Moe Factz 29 - "The Rona"

Moe Factz with Adam Curry for March 14th 2020, Episode number 29
The Rona
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Executive Producer: Sir Seatsitter
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  Adam and Moe are two podcasters socially distanced from each other discussing the corona virus as only they can.
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  DEPO-PROVERA (medroxyprogesterone acetate injectable suspension) | Pfizer
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  Medroxyprogesterone acetate - Wikipedia
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    Not to be confused with
    progesterone, a natural and bioidentical progestogen.
    Medroxyprogesterone acetate Clinical dataPronunciation me- DROKS -ee-proh- JES -tÉr-ohn ASS -i-tayt[2] Trade namesProvera, Depo-Provera, Depo-SubQ Provera 104, Curretab, Cycrin, Farlutal, Gestapuran, Perlutex, Veramix, others[1]Other namesMPA; DMPA; Methylhydroxyprogesterone acetate; Methylacetoxyprogesterone; MAP; Methypregnone; Metipregnone; 6Î±-Methyl-17Î±-hydroxyprogesterone acetate; 6Î±-Methyl-17Î±-acetoxyprogesterone; 6Î±-Methyl-17Î±-hydroxypregn-4-ene-3,20-dione acetate; NSC-26386AHFS/Drugs.comMonograph MedlinePlusa604039 PregnancycategoryRoutes ofadministrationBy mouth, sublingual, intramuscular injection, subcutaneous injectionDrug classProgestogen; Progestin; Progestogen ester; Antigonadotropin; Steroidal antiandrogenATC codeLegal statusLegal statusIn general: 'ž (Prescription only)Pharmacokinetic dataBioavailabilityBy mouth: ~100%[4][6]Protein binding88% (to albumin)[6]MetabolismLiver (hydroxylation (CYP3A4), reduction, conjugation)[3][4][5]Elimination half-life By mouth: 12''33 hours[3][4]IM (aq. susp.): ~50 days[7]SC (aq. susp.): ~40 days[8]ExcretionUrine (as conjugates)[3]Identifiers [(6S,8R,9S,10R,13S,14S,17R)-17-acetyl-6,10,13-trimethyl-3-oxo-2,6,7,8,9,11,12,14,15,16-decahydro-1H-cyclopenta[a]phenanthren-17-yl] acetate CAS NumberPubChem CID IUPHAR/BPSDrugBankChemSpiderUNIIKEGGChEBIChEMBLCompTox Dashboard (EPA) ECHA InfoCard 100.000.689 Chemical and physical dataFormulaC 24H 34O 4Molar mass386.532 g/mol g·mol''13D model (JSmol)C[C@H]1C[C@@H]2[C@H](CC[C@]3([C@H]2CC[C@@]3(C(=O)C)OC(=O)C)C)[C@@]4(C1=CC(=O)CC4)C
    InChI=InChI=1S/C24H34O4/c1-14-12-18-19(22(4)9-6-17(27)13-21(14)22)7-10-23(5)20(18)8-11-24(23,15(2)25)28-16(3)26/h13-14,18-20H,6-12H2,1-5H3/t14-,18+,19-,20-,22+,23-,24-/m0/s1
    Key:PSGAAPLEWMOORI-PEINSRQWSA-N
    (verify) Medroxyprogesterone acetate (MPA), also known as depot medroxyprogesterone acetate (DMPA) in injectable form and sold under the brand name Depo-Provera among others, is a hormonal medication of the progestin type.[9][4] It is used as a method of birth control and as a part of menopausal hormone therapy.[9][4] It is also used to treat endometriosis, abnormal uterine bleeding, abnormal sexuality in males, and certain types of cancer.[9] The medication is available both alone and in combination with an estrogen.[10][11] It is taken by mouth, used under the tongue, or by injection into a muscle or fat.[9]
    Common side effects include menstrual disturbances such as absence of periods, abdominal pain, and headaches.[9] More serious side effects include bone loss, blood clots, allergic reactions, and liver problems.[9] Use is not recommended during pregnancy as it may harm the baby.[9] MPA is an artificial progestogen, and as such activates the progesterone receptor, the biological target of progesterone.[4] It also has weak glucocorticoid activity and very weak androgenic activity but no other important hormonal activity.[4][12] Due to its progestogenic activity, MPA decreases the body's release of gonadotropins and can suppress sex hormone levels.[13] It works as a form of birth control by preventing ovulation.[9]
    MPA was discovered in 1956 and was introduced for medical use in the United States in 1959.[14][15][9] It is on the World Health Organization's List of Essential Medicines, the safest and most effective medicines needed in a health system.[16] The wholesale cost in the developing world is about US$0.59''1.57 per vial.[17] In the United Kingdom this dose costs the NHS about 6.01 pounds.[18] In the United States it costs less than $25 a dose as of 2015.[19] MPA is the most widely used progestin in menopausal hormone therapy and in progestogen-only birth control.[20][21] DMPA is approved for use as a form of long-acting birth control in more than 100 countries.[22][23] In 2016 it was the 252nd most prescribed medication in the United States with more than a million prescriptions.[24]
    Medical uses [ edit ] The most common use of MPA is in the form of DMPA as a long-acting progestogen-only injectable contraceptive to prevent pregnancy in women. It is an extremely effective contraceptive when used with relatively high doses to prevent ovulation. MPA is also used in combination with an estrogen in menopausal hormone therapy in postmenopausal women to treat and prevent menopausal symptoms such as hot flashes, vaginal atrophy, and osteoporosis.[4] It is used in menopausal hormone therapy specifically to prevent endometrial hyperplasia and cancer that would otherwise be induced by prolonged unopposed estrogen therapy in women with intact uteruses.[4][25] In addition to contraception and menopausal hormone therapy, MPA is used in the treatment of gynecological and menstrual disorders such as dysmenorrhea, amenorrhea, and endometriosis.[26] Along with other progestins, MPA was developed to allow for oral progestogen therapy, as progesterone (the progestogen hormone made by the human body) could not be taken orally for many decades before the process of micronization was developed and became feasible in terms of pharmaceutical manufacturing.[27]
    DMPA reduces sex drive in men and is used as a form of chemical castration to control inappropriate or unwanted sexual behavior in those with paraphilias or hypersexuality, including in convicted sex offenders.[28][29] DMPA has also been used to treat benign prostatic hyperplasia, as a palliative appetite stimulant for cancer patients, and at high doses (800 mg per day) to treat certain hormone-dependent cancers including endometrial cancer, renal cancer, and breast cancer.[30][31][32][33][34] MPA has also been prescribed in feminizing hormone therapy for transgender women due to its progestogenic and functional antiandrogenic effects.[35] It has been used to delay puberty in children with precocious puberty but is not satisfactory for this purpose as it is not able to completely suppress puberty.[36] DMPA at high doses has been reported to be definitively effective in the treatment of hirsutism as well.[37]
    Though not used as a treatment for epilepsy, MPA has been found to reduce the frequency of seizures and does not interact with antiepileptic medications. MPA does not interfere with blood clotting and appears to improve blood parameters for women with sickle cell anemia. Similarly, MPA does not appear to affect liver metabolism, and may improve primary biliary cirrhosis and chronic active hepatitis. Women taking MPA may experience spotting shortly after starting the medication but is not usually serious enough to require medical intervention. With longer use amenorrhea (absence of menstruation) can occur as can irregular menstruation which is a major source of dissatisfaction, though both can result in improvements with iron deficiency and risk of pelvic inflammatory disease and often do not result in discontinuation of the medication.[31]
    Birth control [ edit ] Depot medroxyprogesterone acetate (DMPA)BackgroundTypeHormonalFirst use1969[38]Trade namesDepo-Provera, Depo-SubQ Provera 104, othersAHFS/Drugs.comdepo-provera Failure rates (first year)Perfect use0.2%[39]Typical use6%[39]UsageDuration effect3 months(12''14 weeks)Reversibility3''18 monthsUser remindersMaximum interval is just under 3 monthsAdvantages and disadvantagesSTI protectionNoPeriod disadvantagesEspecially in first injection may be frequent spottingPeriod advantagesUsually no periods from 2nd injectionBenefitsEspecially good if poor pill compliance.Reduced endometrial cancer risk.RisksReduced bone density, which may reverse after discontinuationMedical notesFor those intending to start family, suggest switch 6 months prior to alternative method (e.g. POP) allowing more reliable return fertility.DMPA, under brand names such as Depo-Provera and Depo-SubQ Provera 104, is used in hormonal birth control as a long-lasting progestogen-only injectable contraceptive to prevent pregnancy in women.[40][41] It is given by intramuscular or subcutaneous injection and forms a long-lasting depot, from which it is slowly released over a period of several months. It takes one week to take effect if given after the first five days of the period cycle, and is effective immediately if given during the first five days of the period cycle. Estimates of first-year failure rates are about 0.3%.[42] MPA is effective in preventing pregnancy, but offers no protection against sexually transmitted infections (STIs).
    Effectiveness [ edit ] Trussell's estimated perfect use first-year failure rate for DMPA as the average of failure rates in seven clinical trials at 0.3%.[42][43] It was considered perfect use because the clinical trials measured efficacy during actual use of DMPA defined as being no longer than 14 or 15 weeks after an injection (i.e., no more than 1 or 2 weeks late for a next injection).
    Prior to 2004, Trussell's typical use failure rate for DMPA was the same as his perfect use failure rate: 0.3%.[44]
    DMPA estimated typical use first-year failure rate = 0.3% in:Contraceptive Technology, 16th revised edition (1994)[45]Contraceptive Technology, 17th revised edition (1998)[46]Adopted in 1998 by the FDA for its current Uniform Contraceptive Labeling guidance[47]In 2004, using the 1995 NSFG failure rate, Trussell increased (by 10 times) his typical use failure rate for DMPA from 0.3% to 3%.[42][43]
    DMPA estimated typical use first-year failure rate = 3% in:Contraceptive Technology, 18th revised edition (2004)[42]Contraceptive Technology, 19th revised edition (2007)[48]Trussell did not use 1995 NSFG failure rates as typical use failure rates for the other two then newly available long-acting contraceptives, the Norplant implant (2.3%) and the ParaGard copper T 380A IUD (3.7%), which were (as with DMPA) an order of magnitude higher than in clinical trials. Since Norplant and ParaGard allow no scope for user error, their much higher 1995 NSFG failure rates were attributed by Trussell to contraceptive overreporting at the time of a conception leading to a live birth.[42][49][43]
    Advantages [ edit ] DMPA has a number of advantages and benefits:[50][51][41][52]
    Highly effective at preventing pregnancy.Injected every 12 weeks. The only continuing action is to book subsequent follow-up injections every twelve weeks, and to monitor side effects to ensure that they do not require medical attention.No estrogen. No increased risk of deep vein thrombosis, pulmonary embolism, stroke, or myocardial infarction.Minimal drug interactions (compared to other hormonal contraceptives).Decreased risk of endometrial cancer. DMPA reduces the risk of endometrial cancer by 80%.[53][54][55] The reduced risk of endometrial cancer in DMPA users is thought to be due to both the direct anti-proliferative effect of progestogen on the endometrium and the indirect reduction of estrogen levels by suppression of ovarian follicular development.[56]Decreased risk of iron deficiency anemia, pelvic inflammatory disease (PID), ectopic pregnancy,[57][58] and uterine fibroids.Decreased symptoms of endometriosis.Decreased incidence of primary dysmenorrhea, ovulation pain, and functional ovarian cysts.Decreased incidence of seizures in women with epilepsy. Additionally, unlike most other hormonal contraceptives, DMPA's contraceptive effectiveness is not affected by enzyme-inducing antiepileptic drugs.[59]Decreased incidence and severity of sickle cell crises in women with sickle-cell disease.[41]The United Kingdom Department of Health has actively promoted Long Acting Reversible Contraceptive use since 2008, particularly for young people;[60] following on from the October 2005 National Institute for Health and Clinical Excellence guidelines.[61] Giving advice on these methods of contraception has been included in the 2009 Quality and Outcomes Framework "good practice" for primary care.[62]
    Comparison [ edit ] Proponents of bioidentical hormone therapy believe that progesterone offers fewer side effects and improved quality of life compared to MPA.[63] The evidence for this view has been questioned; MPA is better absorbed when taken by mouth, with a much longer elimination half-life leading to more stable blood levels[64] though it may lead to greater breast tenderness and more sporadic vaginal bleeding.[63] The two compounds do not differentiate in their ability to suppress endometrial hyperplasia,[63] nor does either increase the risk of pulmonary embolism.[65] The two medications have not been adequately compared in direct tests to clear conclusions about safety and superiority.[27]
    Available forms [ edit ] MPA is available alone in the form of 2.5, 5, and 10 mg oral tablets, as a 150 mg/mL (1 mL) or 400 mg/mL (2.5 mL) microcrystalline aqueous suspension for intramuscular injection, and as a 104 mg (0.65 mL of 160 mg/mL) microcrystalline aqueous suspension for subcutaneous injection.[66][67] It has also been marketed in the form of 100, 200, 250, 400, and 500 mg oral tablets; 500 and 1,000 mg oral suspensions; and as a 50 mg/mL microcrystalline aqueous suspension for intramuscular injection.[68][69] A 100 mg/mL microcrystalline aqueous suspension for intramuscular injection was previously available as well.[66] In addition to single-drug formulations, MPA is available in the form of oral tablets in combination with conjugated estrogens (CEEs), estradiol, and estradiol valerate for use in menopausal hormone therapy, and is available in combination with estradiol cypionate in a microcrystalline aqueous suspension as a combined injectable contraceptive.[10][11][66][22]
    Depo-Provera is the brand name for a 150 mg microcrystalline aqueous suspension of DMPA that is administered by intramuscular injection. The shot must be injected into thigh, buttock, or deltoid muscle four times a year (every 11 to 13 weeks), and provides pregnancy protection instantaneously after the first injection.[70] Depo-subQ Provera 104 is a variation of the original intramuscular DMPA that is instead a 104 mg microcrystalline dose in aqueous suspension administered by subcutaneous injection. It contains 69% of the MPA found in the original intramuscular DMPA formulation. It can be injected using a smaller injection needle inserting the medication just below the skin, instead of into the muscle, in either the abdomen or thigh. This subcutaneous injection claims to reduce the side effects of DMPA while still maintaining all the same benefits of the original intramuscular DMPA.
    Contraindications [ edit ] MPA is not usually recommended because of unacceptable health risk or because it is not indicated in the following cases:[71][72]
    Conditions where the theoretical or proven risks usually outweigh the advantages of using DMPA:
    Multiple risk factors for arterial cardiovascular diseaseCurrent deep vein thrombosis or pulmonary embolusMigraine headache with aura while using DMPABefore evaluation of unexplained vaginal bleeding suspected of being a serious conditionA history of breast cancer and no evidence of current disease for five yearsActive liver disease: (acute viral hepatitis, severe decompensated cirrhosis, benign or malignant liver tumours)Conditions of concern for estrogen deficiency and reduced HDL levels theoretically increasing cardiovascular risk:Hypertension with vascular diseaseCurrent and history of ischemic heart diseaseHistory of strokeDiabetes for over 20 years or with nephropathy/retinopathy/neuropathy or vascular diseaseConditions which represent an unacceptable health risk if DMPA is used:
    Current or recent breast cancer (a hormonally sensitive tumour)Conditions where use is not indicated and should not be initiated:
    PregnancyMPA is not recommended for use prior to menarche or before or during recovery from surgery.[73]
    Side effects [ edit ] In women, the most common adverse effects of MPA are acne, changes in menstrual flow, drowsiness, and can cause birth defects if taken by pregnant women. Other common side effects include breast tenderness, increased facial hair, decreased scalp hair, difficulty falling or remaining asleep, stomach pain, and weight loss or gain.[26] Lowered libido has been reported as a side effect of MPA in women.[74] DMPA can affect menstrual bleeding. After a year of use, 55% of women experience amenorrhea (missed periods); after 2 years, the rate rises to 68%. In the first months of use "irregular or unpredictable bleeding or spotting, or, rarely, heavy or continuous bleeding" was reported.[75] MPA does not appear to be associated with vitamin B12 deficiency.[76] Data on weight gain with DMPA likewise are inconsistent.[77][78]
    At high doses for the treatment of breast cancer, MPA can cause weight gain and can worsen diabetes mellitus and edema (particularly of the face). Adverse effects peak at five weeks, and are reduced with lower doses. Less frequent effects may include thrombosis (though it is not clear if this is truly a risk, it cannot be ruled out), painful urination, headache, nausea, and vomiting. When used as a form of androgen deprivation therapy in men, more frequent complaints include reduced libido, impotence, reduced ejaculate volume, and within three days, chemical castration. At extremely high doses (used to treat cancer, not for contraception) MPA may cause adrenal suppression and may interfere with carbohydrate metabolism, but does not cause diabetes.[31]
    When used as a form of injected birth control, there is a delayed return of fertility. The average return to fertility is 9 to 10 months after the last injection, taking longer for overweight or obese women. By 18 months after the last injection, fertility is the same as that in former users of other contraceptive methods.[50][51] Fetuses exposed to progestogens have demonstrated higher rates of genital abnormalities, low birth weight, and increased ectopic pregnancy particularly when MPA is used as an injected form of long-term birth control. A study of accidental pregnancies among poor women in Thailand found that infants who had been exposed to DMPA during pregnancy had a higher risk of low birth weight and an 80% greater-than-usual chance of dying in the first year of life.[79]
    Mood changes [ edit ] There have been concerns about a possible risk of depression and mood changes with progestins like MPA, and this has led to reluctance of some clinicians and women to use them.[80][81] However, contrary to widely-held beliefs, most research suggests that progestins do not cause adverse psychological effects such as depression or anxiety.[80] A 2018 systematic review of the relationship between progestin-based contraception and depression included three large studies of DMPA and reported no association between DMPA and depression.[82] According to a 2003 review of DMPA, the majority of published clinical studies indicate that DMPA is not associated with depression, and the overall data support the notion that the medication does not significantly affect mood.[83]
    In the largest study to have assessed the relationship between MPA and depression to date, in which over 3,900 women were treated with DMPA for up to 7 years, the incidence of depression was infrequent at 1.5% and the discontinuation rate due to depression was 0.5%.[82][40][84] This study did not include baseline data on depression,[84] and due to the incidence of depression in the study, the FDA required package labeling for DMPA stating that women with depression should be observed carefully and that DMPA should be discontinued if depression recurs.[82] A subsequent study of 495 women treated with DMPA over the course of 1 year found that the mean depression score slightly decreased in the whole group of continuing users from 7.4 to 6.7 (by 9.5%) and decreased in the quintile of that group with the highest depression scores at baseline from 15.4 to 9.5 (by 38%).[84] Based on the results of this study and others, a consensus began emerging that DMPA does not in fact increase the risk of depression nor worsen the severity of pre-existing depression.[78][84][40]
    Similarly to the case of DMPA for hormonal contraception, the Heart and Estrogen/Progestin Replacement Study (HERS), a study of 2,763 postmenopausal women treated with 0.625 mg/day oral CEEs plus 2.5 mg/day oral MPA or placebo for 36 months as a method of menopausal hormone therapy, found no change in depressive symptoms.[85][86][87] However, some small studies have reported that progestins like MPA might counteract beneficial effects of estrogens against depression.[80][4][88]
    Long-term effects [ edit ] The Women's Health Initiative investigated the use of a combination of oral CEEs and MPA compared to placebo. The study was prematurely terminated when previously unexpected risks were discovered, specifically the finding that though the all-cause mortality was not affected by the hormone therapy, the benefits of menopausal hormone therapy (reduced risk of hip fracture, colorectal and endometrial cancer and all other causes of death) were offset by increased risk of coronary heart disease, breast cancer, strokes and pulmonary embolism.[89] However, the study focused on MPA only and extrapolated the benefits versus risks to all progestogens '' a conclusion that has been challenged by several researchers as unjustified and leading to unnecessary avoidance of HRT for many women as progestogens are not alike.[90]
    When combined with CEEs, MPA has been associated with an increased risk of breast cancer, dementia, and thrombus in the eye. In combination with estrogens in general, MPA may increase the risk of cardiovascular disease, with a stronger association when used by postmenopausal women also taking CEEs. It was because of these unexpected interactions that the Women's Health Initiative study was ended early due the extra risks of menopausal hormone therapy,[91] resulting in a dramatic decrease in both new and renewal prescriptions for hormone therapy.[92]
    Long-term studies of users of DMPA have found slight or no increased overall risk of breast cancer. However, the study population did show a slightly increased risk of breast cancer in recent users (DMPA use in the last four years) under age 35, similar to that seen with the use of combined oral contraceptive pills.[75]
    Results of the Women's Health Initiative (WHI) menopausal hormone therapy randomized controlled trials Clinical outcomeHypothesized effect on riskEstrogen and progestogen(CEs 0.625 mg/day p.o. + MPA 2.5 mg/day p.o.)(n = 16,608, with uterus, 5.2''5.6 years follow up)Estrogen alone(CEs 0.625 mg/day p.o.)(n = 10,739, no uterus, 6.8''7.1 years follow up)HR95% CIARHR95% CIARCoronary heart diseaseDecreased1.241.00''1.54+6 / 10,000 PYs0.950.79''1.15''3 / 10,000 PYsStrokeDecreased1.311.02''1.68+8 / 10,000 PYs1.371.09''1.73+12 / 10,000 PYsPulmonary embolismIncreased2.131.45''3.11+10 / 10,000 PYs1.370.90''2.07+4 / 10,000 PYsVenous thromboembolismIncreased2.061.57''2.70+18 / 10,000 PYs1.320.99''1.75+8 / 10,000 PYsBreast cancerIncreased1.241.02''1.50+8 / 10,000 PYs0.800.62''1.04''6 / 10,000 PYsColorectal cancerDecreased0.560.38''0.81''7 / 10,000 PYs1.080.75''1.55+1 / 10,000 PYsEndometrial cancer''0.810.48''1.36''1 / 10,000 PYs''''''Hip fracturesDecreased0.670.47''0.96''5 / 10,000 PYs0.650.45''0.94''7 / 10,000 PYsTotal fracturesDecreased0.760.69''0.83''47 / 10,000 PYs0.710.64''0.80''53 / 10,000 PYsTotal mortalityDecreased0.980.82''1.18''1 / 10,000 PYs1.040.91''1.12+3 / 10,000 PYsGlobal index''1.151.03''1.28+19 / 10,000 PYs1.011.09''1.12+2 / 10,000 PYsDiabetes''0.790.67''0.930.880.77''1.01Gallbladder diseaseIncreased1.591.28''1.971.671.35''2.06Stress incontinence''1.871.61''2.182.151.77''2.82Urge incontinence''1.150.99''1.341.321.10''1.58Peripheral artery disease''0.890.63''1.251.320.99''1.77Probable dementiaDecreased2.051.21''3.481.490.83''2.66Abbreviations: CEs = conjugated estrogens. MPA = medroxyprogesterone acetate. p.o. = per oral. HR = hazard ratio. AR = attributable risk. PYs = person''years. CI = confidence interval. Notes: Sample sizes (n) include placebo recipients, which were about half of patients. "Global index" is defined for each woman as the time to earliest diagnosis for coronary heart disease, stroke, pulmonary embolism, breast cancer, colorectal cancer, endometrial cancer (estrogen plus progestogen group only), hip fractures, and death from other causes. Sources: See template.Blood clots [ edit ] DMPA has been associated in multiple studies with a higher risk of venous thromboembolism (VTE) when used as a form of progestogen-only birth control in premenopausal women.[93][94][95][96] The increase in incidence of VTE ranges from 2.2-fold to 3.6-fold.[93][94][95][96] Elevated risk of VTE with DMPA is unexpected, as DMPA has little or no effect on coagulation and fibrinolytic factors,[97][98] and progestogens by themselves normally do not increase the risk of thrombosis.[94][95] It has been argued that the higher incidence with DMPA has reflected preferential prescription of DMPA to women considered to be at an increased risk of VTE.[94] Alternatively, it is possible that MPA may be an exception among progestins in terms of VTE risk.[99][100][101] A 2018 meta-analysis reported that MPA was associated with a 2.8-fold higher risk of VTE than other progestins.[100] It is possible that the glucocorticoid activity of MPA may increase the risk of VTE.[4][102][101]
    Bone density [ edit ] DMPA may cause reduced bone density in premenopausal women and in men when used without an estrogen, particularly at high doses, though this appears to be reversible to a normal level even after years of use.
    On November 17, 2004, the United States Food and Drug Administration put a black box warning on the label, indicating that there were potential adverse effects of loss of bone mineral density.[103][104] While it causes temporary bone loss, most women fully regain their bone density after discontinuing use.[77] The World Health Organization (WHO) recommends that the use not be restricted.[105][106] The American College of Obstetricians and Gynecologists notes that the potential adverse effects on BMD be balanced against the known negative effects of unintended pregnancy using other birth control methods or no method, particularly among adolescents.
    Three studies have suggested that bone loss is reversible after the discontinuation of DMPA.[107][108][109] Other studies have suggested that the effect of DMPA use on postmenopausal bone density is minimal,[110] perhaps because DMPA users experience less bone loss at menopause.[111] Use after peak bone mass is associated with increased bone turnover but no decrease in bone mineral density.[112]
    The FDA recommends that DMPA not be used for longer than 2 years, unless there is no viable alternative method of contraception, due to concerns over bone loss.[104] However, a 2008 Committee Opinion from the American Congress of Obstetricians and Gynecologists (ACOG) advises healthcare providers that concerns about bone mineral density loss should neither prevent the prescription of or continuation of DMPA beyond 2 years of use.[113]
    HIV risk [ edit ] There is uncertainty regarding the risk of HIV acquisition among DMPA users; some observational studies suggest an increased risk of HIV acquisition among women using DMPA, while others do not.[114] The World Health Organization issued statements in February 2012 and July 2014 saying the data did not warrant changing their recommendation of no restriction '' Medical Eligibility for Contraception (MEC) category 1 '' on the use of DMPA in women at high risk for HIV.[115][116] Two meta-analyses of observational studies in sub-Saharan Africa were published in January 2015.[117] They found a 1.4- to 1.5-fold increase risk of HIV acquisition for DMPA users relative to no hormonal contraceptive use.[118][119] In January 2015, the Faculty of Sexual & Reproductive Healthcare of the Royal College of Obstetricians and Gynaecologists issued a statement reaffirming that there is no reason to advise against use of DMPA in the United Kingdom even for women at 'high risk' of HIV infection.[120] A systematic review and meta-analysis of risk of HIV infection in DMPA users published in fall of 2015 stated that "the epidemiological and biological evidence now make a compelling case that DMPA adds significantly to the risk of male-to-female HIV transmission."[121] In 2019, a randomized controlled trial found no significant association between DMPA use and HIV.[122]
    Breastfeeding [ edit ] MPA may be used by breastfeeding mothers. Heavy bleeding is possible if given in the immediate postpartum time and is best delayed until six weeks after birth. It may be used within five days if not breast feeding. While a study showed "no significant difference in birth weights or incidence of birth defects" and "no significant alternation of immunity to infectious disease caused by breast milk containing DMPA", a subgroup of babies whose mothers started DMPA at 2 days postpartum had a 75% higher incidence of doctor visits for infectious diseases during their first year of life.[123]
    A larger study with longer follow-up concluded that "use of DMPA during pregnancy or breastfeeding does not adversely affect the long-term growth and development of children". This study also noted that "children with DMPA exposure during pregnancy and lactation had an increased risk of suboptimal growth in height," but that "after adjustment for socioeconomic factors by multiple logistic regression, there was no increased risk of impaired growth among the DMPA-exposed children." The study also noted that effects of DMPA exposure on puberty require further study, as so few children over the age of 10 were observed.[124]
    Overdose [ edit ] MPA has been studied at "massive" dosages of up to 5,000 mg per day orally and 2,000 mg per day via intramuscular injection, without major tolerability or safety issues described.[125][126][127] Overdose is not described in the Food and Drug Administration (FDA) product labels for injected MPA (Depo-Provera or Depo-SubQ Provera 104).[7][8] In the FDA product label for oral MPA (Provera), it is stated that overdose of an estrogen and progestin may cause nausea and vomiting, breast tenderness, dizziness, abdominal pain, drowsiness, fatigue, and withdrawal bleeding.[3] According to the label, treatment of overdose should consist of discontinuation of MPA therapy and symptomatic care.[3]
    [ edit ] MPA increases the risk of breast cancer, dementia, and thrombus when used in combination with CEEs to treat menopausal symptoms.[73] When used as a contraceptive, MPA does not generally interact with other medications. The combination of MPA with aminoglutethimide to treat metastases from breast cancer has been associated with an increase in depression.[31] St John's wort may decrease the effectiveness of MPA as a contraceptive due to acceleration of its metabolism.[73]
    Pharmacology [ edit ] Pharmacodynamics [ edit ] MPA acts as an agonist of the progesterone, androgen, and glucocorticoid receptors (PR, AR, and GR, respectively),[6] activating these receptors with EC50 values of approximately 0.01 nM, 1 nM, and 10 nM, respectively.[128] It has negligible affinity for the estrogen receptor.[6] The medication has relatively high affinity for the mineralocorticoid receptor, but in spite of this, it has no mineralocorticoid or antimineralocorticoid activity.[4] The intrinsic activities of MPA in activating the PR and the AR have been reported to be at least equivalent to those of progesterone and dihydrotestosterone (DHT), respectively, indicating that it is a full agonist of these receptors.[12][129]
    Progestogenic activity [ edit ] MPA is a potent agonist of the progesterone receptor with similar affinity and efficacy relative to progesterone.[130] While both MPA and its deacetylated analogue medroxyprogesterone bind to and agonize the PR, MPA has approximately 100-fold higher binding affinity and transactivation potency in comparison.[130] As such, unlike MPA, medroxyprogesterone is not used clinically, though it has seen some use in veterinary medicine.[1] The oral dosage of MPA required to inhibit ovulation (i.e., the effective contraceptive dosage) is 10 mg/day, whereas 5 mg/day was not sufficient to inhibit ovulation in all women.[131] In accordance, the dosage of MPA used in oral contraceptives in the past was 10 mg per tablet.[132] For comparison to MPA, the dosage of progesterone required to inhibit ovulation is 300 mg/day, whereas that of the 19-nortestosterone derivatives norethisterone and norethisterone acetate is only 0.4 to 0.5 mg/day.[133]
    The mechanism of action of progestogen-only contraceptives like DMPA depends on the progestogen activity and dose. High-dose progestogen-only contraceptives, such as DMPA, inhibit follicular development and prevent ovulation as their primary mechanism of action.[134][135] The progestogen decreases the pulse frequency of gonadotropin-releasing hormone (GnRH) release by the hypothalamus, which decreases the release of follicle-stimulating hormone (FSH) and luteinizing hormone (LH) by the anterior pituitary. Decreased levels of FSH inhibit follicular development, preventing an increase in estradiol levels. Progestogen negative feedback and the lack of estrogen positive feedback on LH release prevent a LH surge. Inhibition of follicular development and the absence of a LH surge prevent ovulation.[50][51] A secondary mechanism of action of all progestogen-containing contraceptives is inhibition of sperm penetration by changes in the cervical mucus.[136] Inhibition of ovarian function during DMPA use causes the endometrium to become thin and atrophic. These changes in the endometrium could, theoretically, prevent implantation. However, because DMPA is highly effective in inhibiting ovulation and sperm penetration, the possibility of fertilization is negligible. No available data support prevention of implantation as a mechanism of action of DMPA.[136]
    MPA and related steroids at the progesterone receptorCompoundKi (nM)EC50 (nM)aEC50 (nM)bProgesterone4.30.925Medroxyprogesterone2414732Medroxyprogesterone acetate1.20.60.15Footnotes: a = Coactivator recruitment. b = Reporter cell line. Sources: [130] Parenteral potencies and durations of progestogens ProgestogenFormMajor brand namesClassTFD(14 days)POIC-D(2''3 months)CIC-D(month)DurationAlgestone acetophenideOil solutionPerlutal, Topasel, YectamesPregnane?''75''150 mg100 mg '‰ 14''32 daysCyproterone acetateOil solutionAndrocur DepotPregnane?''''300 mg '‰ 20 daysDydrogesteroneaAqueous suspension''Retropregnane?''''100 mg '‰ 16''38 daysGestonorone caproateOil solutionDepostat, PrimostatNorpregnane50 mg''''25''50 mg '‰ 8''13 daysHydroxyprogesterone acetateaAqueous suspension''Pregnane350 mg''''150''350 mg '‰ 9''16 daysHydroxyprogesterone caproateOil solutionDelalutin, Proluton, MakenaPregnane250''500 mgb''250''500 mg65''500 mg '‰ 5''21 daysLevonorgestrel butanoateaAqueous suspension''Gonane?''''5''50 mg '‰ 3''6 monthsLynestrenol phenylpropionateaOil solution''Estrane?''''50''100 mg '‰ 14''30 daysMedroxyprogesterone acetateAqueous suspensionDepo-ProveraPregnane50''100 mg150 mg25 mg50''150 mg '‰ 14''50+ daysMegestrol acetateAqueous suspensionMego-EPregnane?''25 mg25 mg '‰ >14 dayscNorethisterone enanthateOil solutionNoristerat, MesigynaEstrane100''200 mg200 mg50 mg50''200 mg '‰ 11''52 daysOxogestone phenylpropionateaOil solution''Norpregnane?''''100 mg '‰ 19''20 daysProgesteroneOil solutionProgestaject, Gestone, StronePregnane200 mgb''''25''350 mg '‰ 2''6 daysAqueous suspensionAgolutin DepotPregnane50''200 mg''''50''300 mg '‰ 7''14 daysNote: All by intramuscular or subcutaneous injection. All are synthetic except for P4, which is bioidentical. P4 production during the luteal phase is ~25 (15''50) mg/day. The OID of OHPC is 250 to 500 mg/month. Footnotes: a = Never marketed by this route. b = In divided doses (2 — 125 or 250 mg for OHPC, 10 — 20 mg for P4). c = Half-life is ~14 days. Sources: Main: See template.Antigonadotropic and anticorticotropic effects [ edit ] MPA suppresses the hypothalamic''pituitary''adrenal (HPA) and hypothalamic''pituitary''gonadal (HPG) axes at sufficient dosages, resulting decreased levels of gonadotropins, androgens, estrogens, adrenocorticotropic hormone (ACTH), and cortisol, as well as levels of sex hormone-binding globulin (SHBG).[13] There is evidence that the suppressive effects of MPA on the HPG axis are mediated by activation of both the PR and the AR in the pituitary gland.[138][139] Due to its effects on androgen levels, MPA can produce strong functional antiandrogenic effects, and is used in the treatment of androgen-dependent conditions such as precocious puberty in boys and hypersexuality in men.[140] In addition, since the medication suppresses estrogen levels as well, MPA can produce strong functional antiestrogenic effects similarly, and has been used to treat estrogen-dependent conditions such as precocious puberty in girls and endometriosis in women. Due to low estrogen levels, the use of MPA without an estrogen poses a risk of decreased bone mineral density and other symptoms of estrogen deficiency.[141]
    Oral MPA has been found to suppress testosterone levels in men by about 30% (from 831 ng/dL to 585 ng/dL) at a dosage of 20 mg/day, by about 45 to 75% (average 60%; to 150''400 ng/dL) at a dosage of 60 mg/day,[142][143][144] and by about 70 to 75% (from 832''862 ng/dL to 214''251 ng/dL) at a dosage of 100 mg/day.[145][146] Dosages of oral MPA of 2.5 to 30 mg/day in combination with estrogens have been used to help suppress testosterone levels in transgender women.[147][148][149][150][151][152] Very high dosages of intramuscular MPA of 150 to 500 mg per week (but up to 900 mg per week) can suppress testosterone levels to less than 100 ng/dL.[142][153] The typical initial dose of intramuscular MPA for testosterone suppression in men with paraphilias is 400 or 500 mg per week.[142]
    Androgenic activity [ edit ] MPA is a potent full agonist of the AR. Its activation of the AR may play an important and major role in its antigonadotropic effects and in its beneficial effects against breast cancer.[138][154][155] However, although MPA may produce androgenic side effects such as acne and hirsutism in some women,[156][157] it rarely does so, and when such symptoms occur, they tend to be mild, regardless of the dosage used.[138] In fact, likely due to its suppressive actions on androgen levels, it has been reported that MPA is generally highly effective in improving pre-existing symptoms of hirsutism in women with the condition.[158][159] Moreover, MPA rarely causes any androgenic effects in children with precocious puberty, even at very high doses.[160] The reason for the general lack of virilizing effects with MPA, despite it binding to and activating the AR with high affinity and this action potentially playing an important role in many of its physiological and therapeutic effects, is not entirely clear. However, MPA has been found to interact with the AR differently compared to other agonists of the receptor such as dihydrotestosterone (DHT).[12] The result of this difference appears to be that MPA binds to the AR with a similar affinity and intrinsic activity to that of DHT, but requires about 100-fold higher concentrations for a comparable induction of gene transcription, while at the same time not antagonizing the transcriptional activity of normal androgens like DHT at any concentration.[12] Thus, this may explain the low propensity of MPA for producing androgenic side effects.[12]
    MPA shows weak androgenic effects on liver protein synthesis, similarly to other weakly androgenic progestins like megestrol acetate and 19-nortestosterone derivatives.[4][5] While it does not antagonize estrogen-induced increases in levels of triglycerides and HDL cholesterol, DMPA every other week may decrease levels of HDL cholesterol.[4] In addition, MPA has been found to suppress sex hormone-binding globulin (SHBG) production by the liver.[5][161][162] At a dosage of 10 mg/day oral MPA, it has been found to decrease circulating SHBG levels by 14 to 18% in women taking 4 mg/day oral estradiol valerate.[5] Conversely, in a study that combined 2.5 mg/day oral MPA with various oral estrogens, no influence of MPA on estrogen-induced increases in SHBG levels was discerned.[162] In another, higher-dose study, SHBG levels were lower by 59% in a group of women treated with 50 mg/day oral MPA alone relative to an untreated control group of women.[161]
    Unlike the related steroids megestrol acetate and cyproterone acetate, MPA is not an antagonist of the AR and does not have direct antiandrogenic activity.[4] As such, although MPA is sometimes described as an antiandrogen, it is not a "true" antiandrogen (i.e., AR antagonist).[143]
    Glucocorticoid activity [ edit ] As an agonist of the GR, MPA has glucocorticoid activity, and as a result can cause symptoms of Cushing's syndrome,[163] steroid diabetes, and adrenal insufficiency at sufficiently high doses.[164] It has been suggested that the glucocorticoid activity of MPA may contribute to bone loss.[165] The glucocorticoid activity of MPA may also result in an upregulation of the thrombin receptor in blood vessel walls, which may contribute to procoagulant effects of MPA and risk of venous thromboembolism and atherosclerosis.[4] The relative glucocorticoid activity of MPA is among the highest of the clinically used progestins.[4]
    Steroidogenesis inhibition [ edit ] MPA has been found to act as a competitive inhibitor of rat 3Î±-hydroxysteroid dehydrogenase (3Î±-HSD).[166][167][168][169] This enzyme is essential for the transformation of progesterone, deoxycorticosterone, and DHT into inhibitory neurosteroids such as allopregnanolone, THDOC, and 3Î±-androstanediol, respectively.[170] MPA has been described as very potent in its inhibition of rat 3Î±-HSD, with an IC50 of 0.2 Î¼M and a Ki (in rat testicular homogenates) of 0.42 Î¼M.[166][167] However, inhibition of 3Î±-HSD by MPA does not appear to have been confirmed using human proteins yet, and the concentrations required with rat proteins are far above typical human therapeutic concentrations.[166][167]
    MPA has been identified as a competitive inhibitor of human 3Î²-hydroxysteroid dehydrogenase/Î--5-4 isomerase II (3Î²-HSD II).[171] This enzyme is essential for the biosynthesis of sex steroids and corticosteroids.[171] The Ki of MPA for inhibition of 3Î²-HSD II is 3.0 Î¼M, and this concentration is reportedly near the circulating levels of the medication that are achieved by very high therapeutic dosages of MPA of 5 to 20 mg/kg/day (dosages of 300 to 1,200 mg/day for a 60 kg (132 lb) person).[171] Aside from 3Î²-HSD II, other human steroidogenic enzymes, including cholesterol side-chain cleavage enzyme (P450scc/CYP11A1) and 17Î±-hydroxylase/17,20-lyase (CYP17A1), were not found to be inhibited by MPA.[171] MPA has been found to be effective in the treatment of gonadotropin-independent precocious puberty and in breast cancer in postmenopausal women at high dosages, and inhibition of 3Î²-HSD II could be responsible for its effectiveness in these conditions.[171]
    GABAA receptor allosteric modulation [ edit ] Progesterone, via transformation into neurosteroids such as 5Î±-dihydroprogesterone, 5Î²-dihydroprogesterone, allopregnanolone, and pregnanolone (catalyzed by the enzymes 5Î±- and 5Î²-reductase and 3Î±- and 3Î²-HSD), is a positive allosteric modulator of the GABAA receptor, and is associated with a variety of effects mediated by this property including dizziness, sedation, hypnotic states, mood changes, anxiolysis, and cognitive/memory impairment, as well as effectiveness as an anticonvulsant in the treatment of catamenial epilepsy.[170][172] It has also been found to produce anesthesia via this action in animals when administered at sufficiently high dosages.[172] MPA was found to significantly reduce seizure incidence when added to existing anticonvulsant regimens in 11 of 14 women with uncontrolled epilepsy, and has also been reported to induce anesthesia in animals, raising the possibility that it might modulate the GABAA receptor similarly to progesterone.[173][174]
    MPA shares some of the same metabolic routes of progesterone and, analogously, can be transformed into metabolites such as 5Î±-dihydro-MPA (DHMPA) and 3Î±,5Î±-tetrahydro-MPA (THMPA).[173] However, unlike the reduced metabolites of progesterone, DHMPA and THMPA have been found not to modulate the GABAA receptor.[173] Conversely, unlike progesterone, MPA itself actually modulates the GABAA receptor, although notably not at the neurosteroid binding site.[173] However, rather than act as a potentiator of the receptor, MPA appears to act as a negative allosteric modulator.[173] Whereas the reduced metabolites of progesterone enhance binding of the benzodiazepine flunitrazepam to the GABAA receptor in vitro, MPA can partially inhibit the binding of flunitrazepam by up to 40% with half-maximal inhibition at 1 Î¼M.[173] However, the concentrations of MPA required for inhibition are high relative to therapeutic concentrations, and hence, this action is probably of little or no clinical relevance.[173] The lack of potentiation of the GABAA receptor by MPA or its metabolites is surprising in consideration of the apparent anticonvulsant and anesthetic effects of MPA described above, and they remain unexplained.[173]
    Clinical studies using massive dosages of up to 5,000 mg/day oral MPA and 2,000 mg/day intramuscular MPA for 30 days in women with advanced breast cancer have reported "no relevant side effects", which suggests that MPA has no meaningful direct action on the GABAA receptor in humans even at extremely high dosages.[125]
    Appetite stimulation [ edit ] Although MPA and the closely related medication megestrol acetate are effective appetite stimulants at very high dosages,[175] the mechanism of action of their beneficial effects on appetite is not entirely clear. However, glucocorticoid, cytokine, and possibly anabolic-related mechanisms are all thought to possibly be involved, and a number of downstream changes have been implicated, including stimulation of the release of neuropeptide Y in the hypothalamus, modulation of calcium channels in the ventromedial hypothalamus, and inhibition of the secretion of proinflammatory cytokines including IL-1Î±, IL-1Î², IL-6, and TNF-Î±, actions that have all been linked to an increase in appetite.[176]
    Other activity [ edit ] MPA weakly stimulates the proliferation of MCF-7 breast cancer cells in vitro, an action that is independent of the classical PRs and is instead mediated via the progesterone receptor membrane component-1 (PGRMC1).[177] Certain other progestins are also active in this assay, whereas progesterone acts neutrally.[177] It is unclear if these findings may explain the different risks of breast cancer observed with progesterone, dydrogesterone, and other progestins such as medroxyprogesterone acetate and norethisterone in clinical studies.[178]
    Pharmacokinetics [ edit ] Absorption [ edit ] Surprisingly few studies have been conducted on the pharmacokinetics of MPA at postmenopausal replacement dosages.[179][4] The bioavailability of MPA with oral administration is approximately 100%.[4] A single oral dose of 10 mg MPA has been found to result in peak MPA levels of 1.2 to 5.2 ng/mL within 2 hours of administration using radioimmunoassay.[179][180] Following this, levels of MPA decreased to 0.09 to 0.35 ng/mL 12 hours post-administration.[179][180] In another study, peak levels of MPA were 3.4 to 4.4 ng/mL within 1 to 4 hours of administration of 10 mg oral MPA using radioimmunoassay.[179][181] Subsequently, MPA levels fell to 0.3 to 0.6 ng/mL 24 hours after administration.[179][181] In a third study, MPA levels were 4.2 to 4.4 ng/mL after an oral dose of 5 mg MPA and 6.0 ng/mL after an oral dose of 10 mg MPA, both using radioimmunoassay as well.[179][182]
    Treatment of postmenopausal women with 2.5 or 5 mg/day MPA in combination with estradiol valerate for two weeks has been found to rapidly increase circulating MPA levels, with steady-state concentrations achieved after 3 days and peak concentrations occurring 1.5 to 2 hours after ingestion.[4][183] With 2.5 mg/day MPA, levels of the medication were 0.3 ng/mL (0.8 nmol/L) in women under 60 years of age and 0.45 ng/mL (1.2 nmol/L) in women 65 years of age or over, and with 5 mg/day MPA, levels were 0.6 ng/mL (1.6 nmol/L) in women under 60 years of age and in women 65 years of age or over.[4][183] Hence, area-under-curve levels of the medication were 1.6 to 1.8 times higher in those who were 65 years of age or older relative to those who were 60 years of age or younger.[5][183] As such, levels of MPA have been found to vary with age, and MPA may have an increased risk of side effects in elderly postmenopausal women.[5][4][183] This study assessed MPA levels using liquid-chromatography''tandem mass spectrometry (LC''MS/MS), a more accurate method of blood determinations.[183]
    Oral MPA tablets can be administered sublingually instead of orally.[184][185][186] Rectal administration of MPA has also been studied.[187]
    With intramuscular administration of 150 mg microcrystalline MPA in aqueous suspension, the medication is detectable in the circulation within 30 minutes, serum concentrations vary but generally plateau at 1.0 ng/mL (2.6 nmol/L) for 3 months.[188] Following this, there is a gradual decline in MPA levels, and the medication can be detected in the circulation for as long as 6 to 9 months post-injection.[188] The particle size of MPA crystals significantly influences its rate of absorption into the body from the local tissue depot when used as a microcrystalline aqueous suspension via intramuscular injection.[189][190][191] Smaller crystals dissolve faster and are absorbed more rapidly, resulting in a shorter duration of action.[189][190][191] Particle sizes can differ between different formulations of MPA, potentially influencing clinical efficacy and tolerability.[189][190][191][192]
    Distribution [ edit ] The plasma protein binding of MPA is 88%.[4][5] It is weakly bound to albumin and is not bound to sex hormone-binding globulin or corticosteroid-binding globulin.[4][5]
    Metabolism [ edit ] The elimination half-life of MPA via oral administration has been reported as both 11.6 to 16.6 hours[3] and 33 hours,[4] whereas the elimination half-lives with intramuscular and subcutaneous injection of microcrystalline MPA in aqueous suspension are 50 and 40 days, respectively.[7][8] The metabolism of MPA is mainly via hydroxylation, including at positions C6Î², C21, C2Î², and C1Î², mediated primarily via CYP3A4, but 3- and 5-dihydro and 3,5-tetrahydro metabolites of MPA are also formed.[4][5] Deacetylation of MPA and its metabolites (into, e.g., medroxyprogesterone) has been observed to occur in non-human primate research to a substantial extent as well (30 to 70%).[193] MPA and/or its metabolites are also metabolized via conjugation.[73] The C6Î± methyl and C17Î± acetoxy groups of MPA make it more resistant to metabolism and allow for greater bioavailability than oral progesterone.[5]
    Elimination [ edit ] MPA is eliminated 20 to 50% in urine and 5 to 10% in feces following intravenous administration.[194] Less than 3% of a dose is excreted in unconjugated form.[194]
    Level''effect relationships [ edit ] With intramuscular administration, the high levels of MPA in the blood inhibit luteinizing hormone and ovulation for several months, with an accompanying decrease in serum progesterone to below 0.4 ng/mL.[188] Ovulation resumes when once blood levels of MPA fall below 0.1 ng/mL.[188] Serum estradiol remains at approximately 50 pg/mL for approximately four months post-injection (with a range of 10''92 pg/mL after several years of use), rising once MPA levels fall below 0.5 ng/mL.[188]
    Hot flashes are rare while MPA is found at significant blood levels in the body, and the vaginal lining remains moist and creased. The endometrium undergoes atrophy, with small, straight glands and a stroma that is decidualized. Cervical mucus remains viscous. Because of its steady blood levels over the long term and multiple effects that prevent fertilization, MPA is a very effective means of birth control.[188]
    Time''concentration curves [ edit ] Hormone levels with medroxyprogesterone acetate
    Chemistry [ edit ] MPA is a synthetic pregnane steroid and a derivative of progesterone and 17Î±-hydroxyprogesterone.[198][1] Specifically, it is the 17Î±-acetate ester of medroxyprogesterone or the 6Î±-methylated analogue of hydroxyprogesterone acetate.[198][1] MPA is known chemically as 6Î±-methyl-17Î±-acetoxyprogesterone or as 6Î±-methyl-17Î±-acetoxypregn-4-ene-3,20-dione, and its generic name is a contraction of 6Î±-methyl-17Î±-hydroxyprogesterone acetate.[198][1] MPA is closely related to other 17Î±-hydroxyprogesterone derivatives such as chlormadinone acetate, cyproterone acetate, and megestrol acetate, as well as to medrogestone and nomegestrol acetate.[198][1] 9Î±-Fluoromedroxyprogesterone acetate (FMPA), the C9Î± fluoro analogue of MPA and an angiogenesis inhibitor with two orders of magnitude greater potency in comparison to MPA, was investigated for the potential treatment of cancers but was never marketed.[199][200]
    History [ edit ] MPA was independently discovered in 1956 by Syntex and the Upjohn Company.[14][15][201][202] It was first introduced on 18 June 1959 by Upjohn in the United States under the brand name Provera (2.5, 5, and 10 mg tablets) for the treatment of amenorrhea, metrorrhagia, and recurrent miscarriage.[203][204] An intramuscular formulation of MPA, now known as DMPA (400 mg/mL MPA), was also introduced, under the brand name brand name Depo-Provera, in 1960 in the U.S. for the treatment of endometrial and renal cancer.[30] MPA in combination with ethinylestradiol was introduced in 1964 by Upjohn in the U.S. under the brand name Provest (10 mg MPA and 50 Î¼g ethinylestradiol tablets) as an oral contraceptive, but this formulation was discontinued in 1970.[205][206][132] This formulation was marketed by Upjohn outside of the U.S. under the brand names Provestral and Provestrol, while Cyclo-Farlutal (or Ciclofarlutal) and Nogest-S[207] were formulations available outside of the U.S. with a different dosage (5 mg MPA and 50 or 75 Î¼g ethinylestradiol tablets).[208][209]
    Following its development in the late 1950s, DMPA was first assessed in clinical trials for use as an injectable contraceptive in 1963.[210] Upjohn sought FDA approval of intramuscular DMPA as a long-acting contraceptive under the brand name Depo-Provera (150 mg/mL MPA) in 1967, but the application was rejected.[211][212] However, this formulation was successfully introduced in countries outside of the United States for the first time in 1969, and was available in over 90 countries worldwide by 1992.[38] Upjohn attempted to gain FDA approval of DMPA as a contraceptive again in 1978, and yet again in 1983, but both applications failed similarly to the 1967 application.[211][212] However, in 1992, the medication was finally approved by the FDA, under the brand name Depo-Provera, for use in contraception.[211] A subcutaneous formulation of DMPA was introduced in the United States as a contraceptive under the brand name Depo-SubQ Provera 104 (104 mg/0.65 mL MPA) in December 2004, and subsequently was also approved for the treatment of endometriosis-related pelvic pain.[213]
    MPA has also been marketed widely throughout the world under numerous other brand names such as Farlutal, Perlutex, and Gestapuran, among others.[1][10]
    Society and culture [ edit ] Generic names [ edit ] Medroxyprogesterone acetate is the generic name of the drug and its INN, USAN, BAN, and JAN, while medrossiprogesterone is the DCIT and m(C)droxyprogest(C)rone the DCF of its free alcohol form.[198][11][1][214][10] It is also known as 6Î±-methyl-17Î±-acetoxyprogesterone (MAP) or 6Î±-methyl-17Î±-hydroxyprogesterone acetate.[198][11][1][10]
    Brand names [ edit ] MPA is marketed under a large number of brand names throughout the world.[10][11][1] Its most major brand names are Provera as oral tablets and Depo-Provera as an aqueous suspension for intramuscular injection.[10][11][1] A formulation of MPA as an aqueous suspension for subcutaneous injection is also available in the United States under the brand name Depo-SubQ Provera 104.[10][11] Other brand names of MPA formulated alone include Farlutal and Sayana for clinical use and Depo-Promone, Perlutex, Promone-E, and Veramix for veterinary use.[10][11][1] In addition to single-drug formulations, MPA is marketed in combination with the estrogens CEEs, estradiol, and estradiol valerate.[10][11][1] Brand names of MPA in combination with CEEs as oral tablets in different countries include Prempro, Premphase, Premique, Premia, and Premelle.[10][11][1] Brand names of MPA in combination with estradiol as oral tablets include Indivina and Tridestra.[10][11][1]
    Availability [ edit ] Oral MPA and DMPA are widely available throughout the world.[10] Oral MPA is available both alone and in combination with the estrogens CEEs, estradiol, and estradiol valerate.[10] DMPA is registered for use as a form of birth control in more than 100 countries worldwide.[22][23][10] The combination of injected MPA and estradiol cypionate is approved for use as a form of birth control in 18 countries.[22]
    United States [ edit ] As of November 2016[update], MPA is available in the United States in the following formulations:[66]
    Oral pills: Amen, Curretab, Cycrin, Provera '' 2.5 mg, 5 mg, 10 mgAqueous suspension for intramuscular injection: Depo-Provera '' 150 mg/mL (for contraception), 400 mg/mL (for cancer)Aqueous suspension for subcutaneous injection: Depo-SubQ Provera 104 '' 104 mg/0.65 mL (for contraception)It is also available in combination with an estrogen in the following formulations:
    Oral pills: CEEs and MPA (Prempro, Prempro (Premarin, Cycrin), Premphase (Premarin, Cycrin 14/14), Premphase 14/14, Prempro/Premphase) '' 0.3 mg / 1.5 mg; 0.45 mg / 1.5 mg; 0.625 mg / 2.5 mg; 0.625 mg / 5 mgWhile the following formulations have been discontinued:
    Oral pills: ethinylestradiol and MPA (Provest) '' 50 Î¼g / 10 mgAqueous suspension for intramuscular injection: estradiol cypionate and MPA (Lunelle) '' 5 mg / 25 mg (for contraception)The state of Louisiana permits sex offenders to be given MPA.[215]
    Generation [ edit ] Progestins in birth control pills are sometimes grouped by generation.[216][217] While the 19-nortestosterone progestins are consistently grouped into generations, the pregnane progestins that are or have been used in birth control pills are typically omitted from such classifications or are grouped simply as "miscellaneous" or "pregnanes".[216][217] In any case, based on its date of introduction in such formulations of 1964, MPA could be considered a "first-generation" progestin.[218]
    Controversy [ edit ] Outside the United States [ edit ] In 1994, when DMPA was approved in India, India's Economic and Political Weekly reported that "The FDA finally licensed the drug in 1990 in response to concerns about the population explosion in the third world and the reluctance of third world governments to license a drug not licensed in its originating country." [219] Some scientists and women's groups in India continue to oppose DMPA.[220] In 2016, India introduced DMPA depo-medroxyprogesterone IM preparation in the public health system.[221]The Canadian Coalition on Depo-Provera, a coalition of women's health professional and advocacy groups, opposed the approval of DMPA in Canada.[222] Since the approval of DMPA in Canada in 1997, a $700 million class-action lawsuit has been filed against Pfizer by users of DMPA who developed osteoporosis. In response, Pfizer argued that it had met its obligation to disclose and discuss the risks of DMPA with the Canadian medical community.[223]Clinical trials for this medication regarding women in Zimbabwe were controversial with regard to human rights abuses and Medical Experimentation in Africa.A controversy erupted in Israel when the government was accused of giving DMPA to Ethiopian immigrants without their consent. Some women claimed they were told it was a vaccination. The Israeli government denied the accusations but instructed the four health maintenance organizations to stop administering DMPA injections to women "if there is the slightest doubt that they have not understood the implications of the treatment".[224]United States [ edit ] There was a long, controversial history regarding the approval of DMPA by the U.S. Food and Drug Administration. The original manufacturer, Upjohn, applied repeatedly for approval. FDA advisory committees unanimously recommended approval in 1973, 1975 and 1992, as did the FDA's professional medical staff, but the FDA repeatedly denied approval. Ultimately, on October 29, 1992, the FDA approved DMPA for birth control, which had by then been used by over 30 million women since 1969 and was approved and being used by nearly 9 million women in more than 90 countries, including the United Kingdom, France, Germany, Sweden, Thailand, New Zealand and Indonesia.[225] Points in the controversy included:
    Animal testing for carcinogenicity '' DMPA caused breast cancer tumors in dogs. Critics of the study claimed that dogs are more sensitive to artificial progesterone, and that the doses were too high to extrapolate to humans. The FDA pointed out that all substances carcinogenic to humans are carcinogenic to animals as well, and that if a substance is not carcinogenic it does not register as a carcinogen at high doses. Levels of DMPA which caused malignant mammary tumors in dogs were equivalent to 25 times the amount of the normal luteal phase progesterone level for dogs. This is lower than the pregnancy level of progesterone for dogs, and is species-specific.[226]DMPA caused endometrial cancer in monkeys '' 2 of 12 monkeys tested, the first ever recorded cases of endometrial cancer in rhesus monkeys.[227] However, subsequent studies have shown that in humans, DMPA reduces the risk of endometrial cancer by approximately 80%.[53][54][55]Speaking in comparative terms regarding animal studies of carcinogenicity for medications, a member of the FDA's Bureau of Drugs testified at an agency DMPA hearing, "...Animal data for this drug is more worrisome than any other drug we know of that is to be given to well people."Cervical cancer in Upjohn/NCI studies. Cervical cancer was found to be increased as high as 9-fold in the first human studies recorded by the manufacturer and the National Cancer Institute.[228] However, numerous larger subsequent studies have shown that DMPA use does not increase the risk of cervical cancer.[229][230][231][232][233]Coercion and lack of informed consent. Testing or use of DMPA was focused almost exclusively on women in developing countries and poor women in the United States,[234] raising serious questions about coercion and lack of informed consent, particularly for the illiterate[235] and for the mentally challenged, who in some reported cases were given DMPA long-term for reasons of "menstrual hygiene", although they were not sexually active.[236]Atlanta/Grady Study '' Upjohn studied the effect of DMPA for 11 years in Atlanta, mostly on black women who were receiving public assistance, but did not file any of the required follow-up reports with the FDA. Investigators who eventually visited noted that the studies were disorganized. "They found that data collection was questionable, consent forms and protocol were absent; that those women whose consent had been obtained at all were not told of possible side effects. Women whose known medical conditions indicated that use of DMPA would endanger their health were given the shot. Several of the women in the study died; some of cancer, but some for other reasons, such as suicide due to depression. Over half the 13,000 women in the study were lost to followup due to sloppy record keeping." Consequently, no data from this study was usable.[234]WHO Review '' In 1992, the WHO presented a review of DMPA in four developing countries to the FDA. The National Women's Health Network and other women's organizations testified at the hearing that the WHO was not objective, as the WHO had already distributed DMPA in developing countries. DMPA was approved for use in United States on the basis of the WHO review of previously submitted evidence from countries such as Thailand, evidence which the FDA had deemed insufficient and too poorly designed for assessment of cancer risk at a prior hearing.The Alan Guttmacher Institute has speculated that United States approval of DMPA may increase its availability and acceptability in developing countries.[234][237]In 1995, several women's health groups asked the FDA to put a moratorium on DMPA, and to institute standardized informed consent forms.[238]Research [ edit ] DMPA was studied by Upjohn for use as a progestogen-only injectable contraceptive in women at a dose of 50 mg once a month but produced poor cycle control and was not marketed for this use at this dosage.[239] A combination of DMPA and polyestradiol phosphate, an estrogen and long-lasting prodrug of estradiol, was studied in women as a combined injectable contraceptive for use by intramuscular injection once every three months.[240][241][242]
    High-dose oral and intramuscular MPA monotherapy has been studied in the treatment of prostate cancer but was found to be inferior to monotherapy with cyproterone acetate or diethylstilbestrol.[243][244][245] High-dose oral MPA has been studied in combination with diethylstilbestrol and CEEs as an addition to high-dose estrogen therapy for the treatment of prostate cancer in men, but was not found to provide better effectiveness than diethylstilbestrol alone.[246]
    DMPA has been studied for use as a potential male hormonal contraceptive in combination with the androgens/anabolic steroids testosterone and nandrolone (19-nortestosterone) in men.[247] However, it was never approved for this indication.[247]
    MPA was investigated by InKine Pharmaceutical, Salix Pharmaceuticals, and the University of Pennsylvania as a potential anti-inflammatory medication for the treatment of autoimmune hemolytic anemia, Crohn's disease, idiopathic thrombocytopenic purpura, and ulcerative colitis, but did not complete clinical development and was never approved for these indications.[248][249] It was formulated as an oral medication at very high dosages, and was thought to inhibit the signaling of proinflammatory cytokines such as interleukin 6 and tumor necrosis factor alpha, with a mechanism of action that was said to be similar to that of corticosteroids.[248][249] The formulation of MPA had the tentative brand names Colirest and Hematrol for these indications.[248]
    MPA has been found to be effective in the treatment of manic symptoms in women with bipolar disorder.[250]
    Veterinary use [ edit ] MPA has been used to reduce aggression and spraying in male cats.[251] It may be particularly useful for controlling such behaviors in neutered male cats.[251] The medication can be administered in cats as an injection once per month.[251]
    See also [ edit ] Conjugated estrogens/medroxyprogesterone acetateEstradiol/medroxyprogesterone acetateEstradiol cypionate/medroxyprogesterone acetatePolyestradiol phosphate/medroxyprogesterone acetateNotes [ edit ] References [ edit ] ^ a b c d e f g h i j k l m n o Index Nominum 2000: International Drug Directory. Taylor & Francis. January 2000. pp. 638''. ISBN 978-3-88763-075-1. Archived from the original on 2013-06-19. ^ https://www.drugs.com/medroxyprogesterone.html ^ a b c d e f "Provera" (PDF) . FDA. 2015 . Retrieved 31 March 2018 . ^ a b c d e f g h i j k l m n o p q r s t u v w x y z aa Kuhl H (2005). "Pharmacology of estrogens and progestogens: influence of different routes of administration" (PDF) . Climacteric. 8 Suppl 1: 3''63. doi:10.1080/13697130500148875. PMID 16112947. ^ a b c d e f g h i j Stanczyk FZ, Bhavnani BR (September 2015). "Reprint of "Use of medroxyprogesterone acetate for hormone therapy in postmenopausal women: Is it safe? " ". J. Steroid Biochem. Mol. Biol. 153: 151''9. doi:10.1016/j.jsbmb.2015.08.013. PMID 26291834. ^ a b c d Schindler AE, Campagnoli C, Druckmann R, Huber J, Pasqualini JR, Schweppe KW, Thijssen JH (2008). "Classification and pharmacology of progestins". Maturitas. 61 (1''2): 171''80. doi:10.1016/j.maturitas.2008.11.013. PMID 19434889. ^ a b c "Depo_Provera" (PDF) . FDA. 2016 . Retrieved 31 March 2018 . ^ a b c d "depo-subQ Provera" (PDF) . FDA. 2017 . Retrieved 31 March 2018 . ^ a b c d e f g h i "Medroxyprogesterone Acetate". The American Society of Health-System Pharmacists. Archived from the original on 24 December 2016 . Retrieved 8 December 2016 . ^ a b c d e f g h i j k l m n o https://www.drugs.com/international/medroxyprogesterone.html ^ a b c d e f g h i j k Sweetman, Sean C., ed. (2009). "Sex hormones and their modulators". Martindale: The Complete Drug Reference (36th ed.). London: Pharmaceutical Press. pp. 2113''2114. ISBN 978-0-85369-840-1. ^ a b c d e Kemppainen JA, Langley E, Wong CI, Bobseine K, Kelce WR, Wilson EM (March 1999). "Distinguishing androgen receptor agonists and antagonists: distinct mechanisms of activation by medroxyprogesterone acetate and dihydrotestosterone". Molecular Endocrinology. 13 (3): 440''54. doi:10.1210/mend.13.3.0255. PMID 10077001. ^ a b Genazzani AR (15 January 1993). Frontiers in Gynecologic and Obstetric Investigation. Taylor & Francis. p. 320. ISBN 978-1-85070-486-7. Archived from the original on 20 May 2016. ^ a b Stanley M. Roberts (7 May 2013). Introduction to Biological and Small Molecule Drug Research and Development: Chapter 12. Hormone replacement therapy. Elsevier Science. pp. 9''. ISBN 978-0-12-806202-9. [...] medroxyprogesterone acetate, also known as Provera® (discovered simultaneously by Searle and Upjohn in 1956) [..] ^ a b Sneader W (2005). "Chapter 18: Hormone analogs". Drug discovery: a history. New York: Wiley. p. 204. ISBN 0-471-89980-1. ^ World Health Organization (2019). World Health Organization model list of essential medicines: 21st list 2019. Geneva: World Health Organization. hdl:10665/325771. WHO/MVP/EMP/IAU/2019.06. License: CC BY-NC-SA 3.0 IGO. ^ "Medroxyprogesterone Acetate". International Drug Price Indicator Guide . Retrieved 8 December 2016 . ^ British National Formulary : BNF 69 (69th ed.). British Medical Association. 2015. p. 555. ISBN 978-0-85711-156-2. ^ Hamilton R (2015). Tarascon Pocket Pharmacopoeia 2015 Deluxe Lab-Coat Edition. Jones & Bartlett Learning. p. 363. ISBN 9781284057560. ^ A. Wayne Meikle (1 June 1999). Hormone Replacement Therapy. Springer Science & Business Media. pp. 383''. ISBN 978-1-59259-700-0. ^ Special Programme of Research, Development, and Research Training in Human Reproduction (World Health Organization); World Health Organization (2002). Research on Reproductive Health at WHO: Biennial Report 2000-2001. World Health Organization. pp. 17''. ISBN 978-92-4-156208-9. CS1 maint: multiple names: authors list (link) ^ a b c d Bagade O, Pawar V, Patel R, Patel B, Awasarkar V, Diwate S (2014). "Increasing use of long-acting reversible contraception: safe, reliable, and cost-effective birth control" (PDF) . World J Pharm Pharm Sci. 3 (10): 364''392. ISSN 2278-4357. ^ a b Sulochana Gunasheela (14 March 2011). Practical Management of Gynecological Problems. JP Medical Ltd. pp. 39''. ISBN 978-93-5025-240-6. ^ "The Top 300 of 2019". clincalc.com . Retrieved 22 December 2018 . ^ Furness S, Roberts H, Marjoribanks J, Lethaby A (August 2012). "Hormone therapy in postmenopausal women and risk of endometrial hyperplasia". The Cochrane Database of Systematic Reviews (8): CD000402. doi:10.1002/14651858.CD000402.pub4. PMID 22895916. ^ a b "Medroxyprogesterone". MedlinePlus. 2008-01-09. Archived from the original on 2010-07-12 . Retrieved 2010-07-02 . ^ a b Panay N, Fenton A (February 2010). 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OCLC 781956734. Advantages of DMPA Injectables. 5. Reduced risk of ectopic pregnancy. Compared with women who use no contraceptive at all, women who use DMPA have a reduced risk for having an ectopic pregnancy. Although the overall risk of pregnancy and thus ectopic pregnancy is lowered by DMPA, the possibility of an ectopic pregnancy should be excluded if a woman using DMPA becomes pregnant. One study showed that 1.5% of women who got pregnant on DMPA had an ectopic pregnancy, the same ectopic rate as women who conceived while not using contraception.27 ^ Borgatta L, Murthy A, Chuang C, Beardsley L, Burnhill MS (September 2002). "Pregnancies diagnosed during Depo-Provera use". Contraception. 66 (3): 169''72. doi:10.1016/S0010-7824(02)00340-2. PMID 12384205. ^ O'Brien MD, Guillebaud J (September 2006). "Contraception for women with epilepsy". Epilepsia. 47 (9): 1419''22. doi:10.1111/j.1528-1167.2006.00671.x. PMID 16981856. ^ "Increasing use of long-acting reversible contraception". 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    ^ a b c Holtorf K (January 2009). "The bioidentical hormone debate: are bioidentical hormones (estradiol, estriol, and progesterone) safer or more efficacious than commonly used synthetic versions in hormone replacement therapy?" (PDF) . Postgraduate Medicine. 121 (1): 73''85. doi:10.3810/pgm.2009.01.1949. PMID 19179815. Archived from the original (PDF) on 2011-07-08. ^ Cirigliano M (June 2007). "Bioidentical hormone therapy: a review of the evidence" (PDF) . Journal of Women's Health. 16 (5): 600''31. doi:10.1089/jwh.2006.0311. PMID 17627398. Archived from the original (PDF) on 2011-01-06. ^ Boothby LA, Doering PL (August 2008). "Bioidentical hormone therapy: a panacea that lacks supportive evidence". Current Opinion in Obstetrics and Gynecology. 20 (4): 400''7. doi:10.1097/GCO.0b013e3283081ae9. PMID 18660693. ^ a b c d "Drugs@FDA: FDA Approved Drug Products". United States Food and Drug Administration. Archived from the original on 16 November 2016 . 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Retrieved 2007-01-11 . ^ a b c d "MedroxyPROGESTERone: Drug Information Provided by Lexi-Comp". Merck Manual. 2009-12-01. Archived from the original on 2010-07-24 . Retrieved 2010-07-08 . ^ King SR (9 November 2012). Neurosteroids and the Nervous System. Springer Science & Business Media. pp. 45''. ISBN 978-1-4614-5559-2. Archived from the original on 5 November 2017. ^ a b Pfizer (October 2004). "Depo-Provera Contraceptive Injection, US patient labeling" (PDF) . Archived from the original (PDF) on 2007-02-06 . Retrieved 2007-02-21 . ^ Amatayakul K, Sivasomboon B, Thanangkul O (September 1978). "Vitamin and trace mineral metabolism in medroxyprogesterone acetate users". Contraception. 18 (3): 253''69. doi:10.1016/s0010-7824(78)80019-5. PMID 720068. ^ a b Nelson, Anita L (2014). "DMPA: battered and bruised but still needed and used in the USA". Expert Review of Obstetrics & Gynecology. 5 (6): 673''686. doi:10.1586/eog.10.60. ISSN 1747-4108. ^ a b Jeffrey K. Aronson (15 October 2015). Meyler's Side Effects of Drugs: The International Encyclopedia of Adverse Drug Reactions and Interactions. Elsevier Science. pp. 2''. ISBN 978-0-444-53716-4. Perhaps surprisingly, a consensus seems to be emerging that depot medroxyprogesterone acetate implants do not in fact result in an increase in the incidence of depression or in the severity of pre-existing depression, even after 1 or 2 years, nor do they cause significant weight gain. ^ "Exposure to DMPA in pregnancy may cause low birth weight". Progress in Human Reproduction Research (23): 2''3. 1992. PMID 12286194. ^ a b c Rogerio A. Lobo (5 June 2007). Treatment of the Postmenopausal Woman: Basic and Clinical Aspects. Elsevier. pp. 211''. ISBN 978-0-08-055309-2. ^ Kaunitz AM (1999). "Long-acting hormonal contraception: assessing impact on bone density, weight, and mood". Int J Fertil Womens Med. 44 (2): 110''7. PMID 10338269. Despite the efficacy and increasing acceptability of these long-term methods, some clinicians and women are reluctant to use them because of concerns regarding reduction in bone density with DMPA, and depressive symptoms and body weight issues with both injectables and implants. Recent multicenter experience showed no increase in depressive symptoms after 1 year's DMPA use and 2 years' Norplant use, even among users with the highest mean depressive symptom scores pre-therapy. ^ a b c Worly BL, Gur TL, Schaffir J (February 2018). "The relationship between progestin hormonal contraception and depression: a systematic review". Contraception. 97 (6): 478''489. doi:10.1016/j.contraception.2018.01.010. PMID 29496297. ^ Westhoff C (August 2003). "Depot-medroxyprogesterone acetate injection (Depo-Provera): a highly effective contraceptive option with proven long-term safety". Contraception. 68 (2): 75''87. doi:10.1016/s0010-7824(03)00136-7. PMID 12954518. Another common patient tolerability concern reported with hormonal contraception is the effect on mood [95]. The majority of published reports indicate that DMPA does not cause depressive symptoms. In a large, 1-year, clinical trial of DMPA in 3857 US women, fewer than 2% of users reported depression [15]. Other reports in various settings, including a private practice [96], adolescent clinics [97,98], a psychiatric hospital [99] and inner-city family-planning clinics [100,101], have not found an adverse effect of DMPA on depression. [...] Using a variety of objective indices for depressive symptoms, the overall data for both OCs and DMPA are supportive that these agents have no significant effect on mood. 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ARAgonistsTestosterone derivatives: 4-Androstenediol4-Dehydroepiandrosterone (4-DHEA)4-Hydroxytestosterone4,17Î±-Dimethyltestosterone5-Androstenedione11-Ketotestosterone11Î²-HydroxyandrostenedioneAdrenosterone (11-ketoandrostenedione, 11-oxoandrostenedione)Androstenediol (5-androstenediol)Androstenediol 3Î²-acetateAndrostenediol 17Î²-acetateAndrostenediol diacetateAndrostenediol dipropionateAndrostenedione (4-androstenedione)AtamestaneBoldenoneBoldenone undecylenateBoldione (1,4-androstadienedione)ClostebolClostebol acetateClostebol caproateClostebol propionateCloxotestosteroneCloxotestosterone acetateDehydroandrosteroneDHEA (androstenolone, prasterone; 5-DHEA)DHEA enanthate (prasterone enanthate)DHEA sulfateExemestaneFormestanePlomestaneQuinboloneSilandroneTestosterone# (+dutasteride)Testosterone estersPolytestosterone phloretin phosphateDihydrotestosterone derivatives: 1-Androstenediol1-Androstenedione1-Androsterone (1-andro, 1-DHEA)1-Testosterone3Î±-Androstanediol5Î±-Androst-2-en-17-one7Î²-Hydroxyepiandrosterone11-KetodihydrotestosteroneAndrosteroneBolazineBolazine capronateDihydroethisteroneDihydroethyltestosteroneDihydrofluoxymesteroneDihydromethylandrostenediolDihydrotestosterone (DHT) (androstanolone, stanolone)Dihydrotestosterone estersDrostanoloneDrostanolone propionateEpiandrosteroneEpitiostanolMepitiostaneMesaboloneMesteroloneMesterolone cipionateMethyldiazinolNisterimeNisterime acetateProstanozolStenboloneStenbolone acetateTestifenon (testiphenon, testiphenone)19-Nortestosterone derivatives: 7Î±-Methyl-19-norandrostenedione (MENT dione, trestione)11Î²-Methyl-19-nortestosterone11Î²-Methyl-19-nortestosterone dodecylcarbonate19-Nor-5-androstenediol19-Nor-5-androstenedione19-NordehydroepiandrosteroneBolandiolBolandiol dipropionateBolandione (19-nor-4-androstenedione)Bolmantalate (nandrolone adamantoate)DienedioneDienoloneDimethandroloneDimethandrolone buciclateDimethandrolone dodecylcarbonateDimethandrolone undecanoateLS-1727 (nandrolone 17Î²-N-(2-chloroethyl)-N-nitrosocarbamate)Methoxydienone (methoxygonadiene)NandroloneNandrolone estersNorclostebolNorclostebol acetateNormethandrone (methylestrenolone, normethisterone)OxaboloneOxabolone cipionate (oxabolone cypionate)TrenboloneTrenbolone acetateTrenbolone enanthateTrenbolone hexahydrobenzylcarbonateTrenbolone undecanoateTrendioneTrestolone (MENT)Trestolone acetateTrestolone enanthateDihydrotestosterone and 19-nortestosterone derivatives: 5Î±-Dihydrolevonorgestrel5Î±-Dihydronandrolone5Î±-Dihydronorethandrolone5Î±-Dihydronorethisterone5Î±-Dihydronormethandrone5Î±-Dihydrotrestolone19-Norandrosterone17Î±-Alkylated testosterone derivatives: BolasteroneCalusteroneChlorodehydromethylandrostenediol (CDMA)Chlorodehydromethyltestosterone (CDMT)Chloromethylandrostenediol (CMA)EnestebolEthyltestosteroneFluoxymesteroneFormeboloneHydroxystenozoleMetandienone (methandrostenolone)Methandriol (methylandrostenediol)Methandriol bisenanthoyl acetateMethandriol diacetateMethandriol dipropionateMethandriol propionateMethylclostebol (chloromethyltestosterone)Methyltestosterone (+esterified estrogens)Methyltestosterone 3-hexyl etherOxymesteronePenmesterolTiomesterone17Î±-Alkylated dihydrotestosterone derivatives: AndroisoxazoleDesoxymethyltestosteroneFurazabolMebolazine (dimethazine)MestanoloneMetenoloneMetenolone acetateMetenolone enanthateMethasteroneMethyl-1-testosteroneMethylepitiostanolMethylstenboloneOxandroloneOxymetholoneStanozolol17Î±-Alkylated 19-nortestosterone derivatives: BolenolDimethyldienoloneDimethyltrienoloneEthyldienoloneEthylestrenolMethyldienoloneMethylhydroxynandrolone (MOHN, MHN)MetriboloneMiboleroneNorboletoneNorethandrolonePropetandrolRU-2309Tetrahydrogestrinone17Î±-Vinyltestosterone derivatives: Norvinisterone (vinylnortestosterone)Vinyltestosterone17Î±-Ethynyltestosterone derivatives: Î--4-TiboloneDanazolDesogestrelEthisterone (ethynyltestosterone)EtonogestrelEtynodiolEtynodiol diacetateGestodeneGestrinoneLevonorgestrelLevonorgestrel esters (e.g., levonorgestrel butanoate)LynestrenolLynestrenol phenylpropionateNorethisteroneNorethisterone esters (e.g., norethisterone acetate, norethisterone enanthate)NorgestrelNorgestrienoneQuingestanolQuingestanol acetateTiboloneProgesterone derivatives: Medroxyprogesterone acetateMegestrol acetateOthers/unsorted: 3-Keto-5Î±-abiraterone5Î±-AndrostaneAlternariolCl-4AS-1DrupanolZM-182345Mixed(SARMs)AntagonistsGPRC6AGRAgonistsCortisol-like and related (16-unsubstituted): 3Î±,5Î±-Tetrahydrocorticosterone5Î±-Dihydrocorticosterone9Î±-Fluorocortisone (alfluorone)11-Dehydrocorticosterone (11-oxocorticosterone, 17-deoxycortisone)11-Dehydrocorticosterone acetate11-Deoxycorticosterone (desoxycortone, deoxycortone, desoxycorticosterone)Desoxycortone esters11-Deoxycortisol (cortodoxone, cortexolone)Cortifen (cortiphen, kortifen)Cortodoxone acetate21-DeoxycortisolÎ--7-PrednisoloneÎ--7-Prednisolone 21-acetateAmebucortChloroprednisoneChloroprednisone acetateCloprednolCloprednol acetateCorticosteroneCorticosterone acetateCorticosterone benzoateCortisol (hydrocortisone)Benzodrocortisone (hydrocortisone benzoate)Hydrocortamate (hydrocortisone diethylaminoacetate)Hydrocortisone estersCortisoneCortisone acetateDeprodoneDeprodone propionateDichlorisoneDichlorisone acetateDichlorisone diacetateDifluprednateEndrisone (endrysone)EtiprednolEtiprednol dicloacetate (etiprednol dichloroacetate)Fludrocortisone (fludrocortone)Fludrocortisone acetateFluorometholoneFluorometholone acetateFluperoloneFluperolone acetateFluprednisoloneFluprednisolone estersHalopredoneHalopredone acetate (halopredone diacetate)Isoflupredone (9Î±-fluoroprednisolone)Isoflupredone acetateLoteprednolMazipredone (depersolone)MedrysoneMethylprednisoloneMethylprednisolone estersPrebediolonePrebediolone acetatePrednisolonePrednazatePrednazolinePrednicarbate (prednisolone ethylcarbonate propionate)PrednimustinePrednisolamate (prednisolone diethylaminoacetate)Prednisolone estersPrednisonePrednisone estersPregnenolonePregnenolone acetatePregnenolone succinate (pregnenolone hemisuccinate)ResocortolTipredaneTixocortolButixocort (tixocortol butyrate)Butixocort propionateTixocortol pivalateMethasones and related (16-substituted): 16Î±-Methyl-11-oxoprednisoloneAlclometasoneAlclometasone dipropionateAmelometasoneBeclometasone (beclomethasone)Beclometasone estersBetamethasone (betametasone)Betamethasone estersCortobenzolone (betamethasone salicylate)Ciclometasone (ciclomethasone, cyclomethasone)ClobetasolClobetasol propionateClobetasoneClobetasone butyrateClocortoloneClocortolone estersCloticasoneCloticasone propionateCormetasone (cormethasone)Cormetasone acetateDescinoloneDesoximetasone (desoxymethasone)Dexamethasone (dexametasone)Dexamethasone estersDiflorasoneDiflorasone diacetateDiflucortoloneDiflucortolone pivalateDiflucortolone valerateDimesoneDimesone acetateDoxibetasol (doxybetasol)FlucloroloneFlumetasone (flumethasone)Flumetasone acetateFlumetasone pivalateFluocinoloneFluocortinFluocortin butyl (fluocortin butylate)FluocortoloneFluocortolone estersFluprednidene (fluprednylidene)Fluprednidene acetateFluticasoneFluticasone furoateFluticasone propionateHalocortoloneHalometasoneIcometasoneIcometasone enbutate (icometasone butyrate acetate)IsoprednideneLocicortolone (locicortone)Locicortolone dicibate (locicortone dicibate)MeclorisoneMeclorisone dibutyrateMeprednisone (methylprednisone)Meprednisone acetateMeprednisone hydrogen succinate (methylprednisone hemisuccinate)MometasoneMometasone furoateParamethasoneParamethasone acetateParamethasone disodium phosphateParamethasone phosphatePrednylidenePrednylidene diethylaminoacetateRimexoloneTicabesoneTicabesone propionateTimobesoneTimobesone acetateTriamcinoloneTriamcinolone diacetateUlobetasol (halobetasol)Ulobetasol propionateVamoroloneCyclic ketals (16,17-cyclized): Acrocinonide (triamcinolone acroleinide)Amcinafal (triamcinolone pentanonide)Amcinafide (triamcinolone acetophenide)Amcinonide (triamcinolone acetate cyclopentanonide)BudesonideCiclesonideCicortonideDeflazacort (azacort)Descinolone acetonideDesonide (hydroxyprednisolone acetonide)Desonide disodium phosphateDesonide pivalateDexbudesonideDrocinonideDrocinonide phosphateFluazacortFluclorolone acetonide (flucloronide)Fludroxycortide (flurandrenolone, flurandrenolide)FlumoxonideFlunisolideFlunisolide acetateFluocinolone acetonideCiprocinonide (fluocinolone acetonide cyclopropylcarboxylate)Fluocinonide (fluocinolide, fluocinolone acetonide acetate)Procinonide (fluocinolone acetonide propionate)FormocortalHalcinonideItrocinonideRofleponideRofleponide palmitateTralonideTriamcinolone acetonideFlupamesone (triamcinolone acetonide metembonate)Triamcinolone acetonide estersTriamcinolone aminobenzal benzamidoisobutyrate (TBI-PAB)TriclonideOthers/atypical (other expanded steroid ring systems, homosteroids, and non-pregnane steroids): CortisuzolCortivazolDomoprednateNaflocortNicocortonideNicocortonide acetateNivacortol (nivazol)OxisopredRU-26988RU-28362Non-corticosteroids with some glucocorticoid activity: 15Î²-Hydroxycyproterone acetate17Î±-HydroxyprogesteroneBromoketoprogesteroneChlormadinone acetateCyproteroneCyproterone acetateDanazolDelmadinone acetateDesogestrelDU-41165EtonogestrelFlugestoneFlugestone acetate (flurogestone acetate)Fluoromedroxyprogesterone acetateFluoxymesteroneGestodeneMedrogestoneMedroxyprogesterone acetateMegestrol acetateMetriboloneNorgestometOsaterone acetateProgesteronePromegestoneRU-2309QuingestroneSegesterone acetate (nestorone)TetrahydrogestrinoneNonsteroidal glucocorticoids: AZD-5423GSK-9027Mixed(SEGRMs)AntagonistsOthersPRAgonistsProgesterone derivatives: 3Î²-Dihydroprogesterone5Î±-Dihydroprogesterone9Î±-Bromo-11-ketoprogesterone11-Dehydroprogesterone11-Deoxycorticosterone16Î±-Hydroxyprogesterone20Î±-Dihydroprogesterone20Î²-DihydroprogesteroneDimepregnenDiosgeninP1-185ProgesteroneProgesterone 3-acetyl enol etherQuingestroneRetroprogesterone derivatives: 20Î±-Dihydrodydrogesterone20Î±-DihydrotrengestoneDU-41164DU-41165DydrogesteroneRetroprogesteroneRo 6-3129Trengestone17Î±-Substituted progesterone derivatives: 6Î±-Methyl-17Î±-bromoprogesterone15Î²-Hydroxycyproterone acetate16-Methylene-17Î±-hydroxyprogesterone acetate17Î±-Bromoprogesterone17Î±-Hydroxyprogesterone (hydroxyprogesterone)17Î±-MethylprogesteroneAcetomepregenol (mepregenol diacetate)AlgestoneAlgestone acetonideAlgestone acetophenideAnagestoneAnagestone acetateBromethenmadinoneBromethenmadinone acetateButagest (buterol)ChlormadinoneChlormadinone acetateChlormadinone caproateChlormethenmadinoneChlormethenmadinone acetateCismadinoneCismadinone acetateClogestoneClogestone acetateClomegestoneClomegestone acetateCymegesolateCyproterone acetateDelmadinoneDelmadinone acetateEdogestroneFlugestoneFlugestone acetateFluorometholoneFluorometholone acetateFlumedroxoneFlumedroxone acetateFluoromedroxyprogesterone acetateGestacloneHaloprogesteroneHydromadinoneHydromadinone acetateHydroxyprogesterone acetateHydroxyprogesterone caproate (hydroxyprogesterone hexanoate)Hydroxyprogesterone heptanoate (hydroxyprogesterone enanthate)Hydroxyprogesterone heptanoate benzilic acid hydrazoneMecigestone (pentarane B)MedrogestoneMedroxyprogesteroneMedroxyprogesterone acetateMedroxyprogesterone caproateMegestrolMegestrol acetateMegestrol caproateMelengestrolMelengestrol acetateMethenmadinoneMethenmadinone acetateMethenmadinone caproateMometasoneMometasone furoateOsateroneOsaterone acetatePentagestronePentagestrone acetatePentarane AProligestone19-Norprogesterone derivatives: 17Î±-Methyl-19-norprogesterone18-Methylsegesterone acetate19-NorprogesteroneAmadinoneAmadinone acetateDemegestoneFluoro ethyl norprogesteroneFluoro furanyl norprogesteroneGestadienolGestadienol acetateGestonorone acetate (gestronol acetate)Gestonorone caproate (gestronol hexanoate)Gestronol (gestonorone)NomegestrolNomegestrol acetateNorgestometORG-2058OxogestoneOxogestone phenpropionate (xinogestone)PromegestoneSegesteroneSegesterone acetate (nestorone)TrimegestoneTestosterone derivatives: Progestins: 6,6-Difluoronorethisterone6,6-Difluoronorethisterone acetate17Î±-Allyl-19-nortestosteroneAllylestrenolAltrenogestChloroethynylnorgestrelCingestolDanazolDesogestrelDienogestEthisteroneEthyneroneEtonogestrelEtynodiolEtynodiol diacetateGestodeneGestrinoneLevonorgestrelLevonorgestrel esters (e.g., levonorgestrel butanoate)LynestrenolLynestrenol phenylpropionateMetynodiolMetynodiol diacetateNorelgestrominNorethisterone (norethindrone)Norethisterone esters (e.g., norethisterone acetate, norethisterone enanthate)NoretynodrelNorgesteroneNorgestimateNorgestrelNorgestrienoneNorvinisteroneOxendoloneQuingestanolQuingestanol acetateTiboloneTigestolTosagestin; Anabolic''androgenic steroids: 11Î²-Methyl-19-nortestosterone11Î²-Methyl-19-nortestosterone dodecylcarbonate19-Nor-5-androstenediol19-Nor-5-androstenedione19-NordehydroepiandrosteroneBolandiolBolandiol dipropionateBolandioneDimethisteroneDienedioneDienoloneDimethandroloneDimethandrolone buciclateDimethandrolone dodecylcarbonateDimethandrolone undecanoateDimethyldienoloneDimethyltrienoloneEthyldienoloneEthylestrenol (ethylnandrol)MethyldienoloneMetribolone (R-1881)Methoxydienone (methoxygonadiene)MiboleroneNandroloneNandrolone esters (e.g., nandrolone decanoate, nandrolone phenylpropionate)NorethandroloneNormethandrone (methylestrenolone, normethandrolone, normethisterone)RU-2309TetrahydrogestrinoneTrenbolone (trienolone)Trenbolone esters (e.g., trenbolone acetate, trenbolone enanthate)TrendioneTrestoloneTrestolone acetateSpirolactone derivatives: Canrenoic acidCanrenoneDrospirenoneMespirenonePotassium canrenoateProrenoneSC-5233 (spirolactone)SC-8109SpironolactoneSpirorenoneNonsteroidal: 3,8-DihydrodiligustilideLG-2527LG-100128RiligustilideRWJ-26819RWJ-49853RWJ-60130TanaprogetZM-182345Unknown: ORG-47241ORG-201745Mixed(SPRMs)AntagonistsmPR(PAQR)
  Tuskegee syphilis experiment - Wikipedia
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    A doctor draws blood from one of the Tuskegee test subjects
    Tuskegee Study of Untreated Syphilis in the Negro Male[a] was a clinical study conducted between 1932 and 1972 by the United States Public Health Service.[1][2] The purpose of this study was to observe the natural history of untreated syphilis; the African American men in the study were only told they were receiving free health care from the Federal government of the United States.[3]
    Public Health Service started working on this study in 1932 in collaboration with Tuskegee University, a historically black college in Alabama. Investigators enrolled in the study a total of 600 impoverished, African American sharecroppers from Macon County, Alabama. Of these men, 399 had latent syphilis and 201 did not have the disease and were intentionally infected.[2] The men were given free medical care, meals and free burial insurance for participating in the study. The men were told that the study was only going to last six months, but it actually lasted 40 years.[2] After funding for treatment was lost, the study was continued without informing the men that they would never be treated. None of the men were told that they had the disease, and none were treated with penicillin even after the antibiotic was proven to successfully treat syphilis. According to the Centers for Disease Control and Prevention, the men were told that they were being treated for "bad blood", a colloquialism that described various conditions such as syphilis, anemia and fatigue. "Bad blood"'--specifically the collection of illnesses the term included'--was a leading cause of death within the southern African American community.[2]
    The 40-year Tuskegee Study of Untreated Syphilis in the Negro Male study was a major violation of ethical standards. Researchers knowingly failed to treat patients appropriately after the 1940s validation of penicillin was found as an effective cure for the disease that they were studying. The revelation in 1972 of study failures by a whistleblower, Peter Buxtun, led to major changes in U.S. law and regulation on the protection of participants in clinical studies. Now studies require informed consent,[4] communication of diagnosis and accurate reporting of test results.[5]
    By 1947, penicillin had become the standard treatment for syphilis. Choices available to the doctors involved in the study might have included treating all syphilitic subjects and closing the study, or splitting off a control group for testing with penicillin. Instead, the Tuskegee scientists continued the study without treating any participants; they withheld penicillin and information about it from the patients. In addition, scientists prevented participants from accessing syphilis treatment programs available to other residents in the area.[6] The study continued, under numerous Public Health Service supervisors, until 1972, when a leak to the press resulted in its termination on November 16 of that year.[7] The victims of the study, all African American, included numerous men who died of syphilis, 40 wives who contracted the disease and 19 children born with congenital syphilis.
    Tuskegee Syphilis Study, cited as "arguably the most infamous biomedical research study in U.S. history",[8] led to the 1979 Belmont Report and to the establishment of the Office for Human Research Protections (OHRP).[9] It also led to federal laws and regulations requiring institutional review boards for the protection of human subjects in studies involving them. The OHRP manages this responsibility within the United States Department of Health and Human Services (HHS).[10]
    On May 16, 1997, President Bill Clinton formally apologized on behalf of the United States to victims of the experiment.
    History [ edit ] Study clinicians [ edit ] For the most part, doctors and civil servants simply did their jobs. Some merely followed orders, others worked for the glory of science.
    The venereal disease section of the U.S. Public Health Service (PHS) formed a study group in 1932 at its national headquarters. Taliaferro Clark was credited with founding it. His initial goal was to follow untreated syphilis in a group of black men for 6 to 9 months, and then follow up with a treatment phase.[12] When he understood the intention of other study members to use deceptive practices, Clark disagreed with the plan to conduct an extended study.[clarification needed ] He retired the year after the study began.
    Although Clark is usually assigned blame for conceiving the Tuskegee Study, Thomas Parran Jr. is equally, if not more, deserving of originating the notion of a non-treatment experiment in Macon County, Alabama. As the Health Commissioner of New York State (and former head of the PHS Venereal Disease Division), Parran was asked by the Rosenwald Fund to make an assessment of their survey and demonstration projects in six Southern states. Among his conclusions was the recommendation that, "If one wished to study the natural history of syphilis in the Negro race uninfluenced by treatment, this county (Macon) would be an ideal location for such a study."[13]
    An official committee at the University of Pittsburgh reported the following on Thomas Parran, M.D., who was a founder of the university's Graduate School of Public Health: ''Dr. Parran's role, and the extent of his influence in approving, funding, and providing oversight of the Tuskegee and Guatemalan studies, is not entirely clear. Based upon the evidence available today, it might not be possible to determine with certainty Dr. Parran's level of knowledge and involvement in the studies.'' Office of Diversity and Inclusion Review Committee on Parran Hall, University of Pittsburgh, Report and Recommendations (June 11, 2018) p. 4.
    Representing the PHS, Clark had solicited the participation of the Tuskegee Institute (a well-known historically black college in Alabama, now known as Tuskegee University) and of the Arkansas regional Public Health Service office. Eugene Heriot Dibble, Jr., an African-American doctor, was head of the John Andrew Hospital at the Tuskegee Institute. (From 1936''1946, he served as director of the Tuskegee Veterans Administration Medical Center, established in 1923 in the city by the federal government on land donated by the Institute.)
    Oliver C. Wenger was the director of the regional PHS Venereal Disease Clinic in Hot Springs, Arkansas. He and his staff took the lead in developing study procedures. Wenger and his staff played a critical role in developing early study protocols. Wenger continued to advise and assist the Tuskegee Study when it was adapted as a long-term, no-treatment observational study after funding for treatment was lost.[14]
    Raymond A. Vonderlehr was appointed on-site director of the research program and developed the policies that shaped the long-term follow-up section of the project. His method of gaining the "consent" of the subjects for spinal taps (to look for signs of neurosyphilis) was by portraying this diagnostic test as a "special free treatment". Participants were not told their diagnosis. Vonderlehr retired as head of the venereal disease section in 1943, shortly after the antibiotic penicillin had first been shown to be a cure for syphilis.[1]
    Several African American health workers and educators associated with Tuskegee Institute helped the PHS to carry out its experimentation and played a critical role in the progress of the study. The extent to which they knew about the full scope of the study is not clear in all cases. Robert Russa Moton, then president of Tuskegee Institute, and Eugene Dibble, head of the Institute's John Andrews Hospital, both lent their endorsement and institutional resources to the government study. Registered nurse Eunice Rivers, who had trained at Tuskegee Institute and worked at its affiliated John Andrew Hospital, was recruited at the start of the study to be the main contact with the participants in the study.
    Vonderlehr advocated for Rivers' participation, as the direct link to the regional African-American community. During the Great Depression of the 1930s, the Tuskegee Study recruited poor lower-class African Americans, who often could not afford health care, by offering them the chance to join "Miss Rivers' Lodge". Patients were told they would receive free physical examinations at Tuskegee University, free rides to and from the clinic, hot meals on examination days, and free treatment for minor ailments.
    Based on the available health care resources, Rivers believed that the benefits of the study to the men outweighed the risks. As the study became long term, Rivers became the chief person with continuity. Unlike the national, regional and on-site PHS administrators, doctors, and researchers, some of whom were political appointees with short tenure and others who changed jobs, Rivers continued at Tuskegee University. She was the only study staff person to work with participants for the full 40 years. By the 1950s, Nurse Rivers had become pivotal to the study: her personal knowledge of the subjects enabled maintenance of long-term follow up.
    In 1943, Congress passed the Henderson Act, a public health law requiring testing and treatment for venereal disease. By the late 1940s, doctors, hospitals and public health centers throughout the country routinely treated diagnosed syphilis with penicillin. However, the Tuskegee experiment continued to avoid treating the men who had the disease.
    In the period following World War II, the revelation of the Holocaust and related Nazi medical abuses brought about changes in international law. Western allies formulated the Nuremberg Code to protect the rights of research subjects. In 1964 the World Health Organization's Declaration of Helsinki specified that experiments involving human beings needed the "informed consent" of participants. But no one appeared to have reevaluated the protocols of the Tuskegee Study according to the new standards and in light of treatment available for the disease which is fatal 8''58% of the time. On July 25, 1972, word of the Tuskegee Study was reported by Jean Heller of the Associated Press; the next day The New York Times carried it on its front page, and the story captured national attention. Peter Buxtun, a whistleblower who was a former PHS interviewer for venereal disease, had leaked information after failing to get a response to his protests about the study within the department. He gave information to the Washington Star and The New York Times. John R. Heller Jr. of PHS, who in later years of the study led the national division, still defended the ethics of the study, stating, "The longer the study, the better the ultimate information we would derive."[15] Author James Jones editorialized about Heller, suggesting that his opinion was, "The men's status did not warrant ethical debate. They were subjects, not patients; clinical material, not sick people."[16]
    Raymond A. Vonderlehr (medical doctor)
    Eugene Dibble (medical doctor)
    Eunice Rivers (nurse)
    Study details [ edit ] Subject blood draw, c. 1953
    A Norwegian study in 1928 had reported on the pathologic manifestations of untreated syphilis in several hundred white males. This study, known as the "Oslo study of untreated syphilis", was a retrospective study, since investigators pieced together information from the histories of patients who had already contracted syphilis but remained untreated for some time.
    Subjects talking with study coordinator, Nurse Eunice Rivers, c.1970
    The Tuskegee study group decided to build on the Oslo work and perform a prospective study to complement it. Researchers could study the natural progression of the disease as long as they did not harm their subjects. The researchers involved with the Tuskegee experiment reasoned that they were not harming the black men involved in the study because they were unlikely to get treatment for their syphilis and further education would not diminish their inherent sex drive. However, even at the beginning of the study, major medical textbooks had recommended that all syphilis be treated, as the consequences were quite severe. At that time, treatment included arsenic therapy and the "606" formula.[1] The researchers reasoned that the knowledge gained would benefit humankind; however, it was determined afterward that the doctors did harm their subjects by depriving them of appropriate treatment once it had been discovered. The study was characterized as "the longest non-therapeutic experiment on human beings in medical history."[6]
    The US Public Health Study of Syphilis at Tuskegee began as a 6-month descriptive epidemiological study of the range of pathology associated with syphilis in the Macon County population. At that time, it was believed that the effects of syphilis depended on the race of those affected. For African Americans, physicians believed that their cardiovascular system was more affected than the central nervous system.[17] Initially, subjects were studied for six to eight months and then treated with contemporary methods, including Salvarsan ("606,") mercurial ointments, and bismuth. These methods were, at best, mildly effective. The disadvantage was that these treatments were all highly toxic. The Tuskegee Institute participated in the study, as its representatives understood the intent was to benefit public health in the local poor population.[18] The Tuskegee University-affiliated hospital effectively loaned the PHS its medical facilities, and other predominantly black institutions and local black doctors participated as well.
    The Rosenwald Fund, a major Chicago-based philanthropy devoted to black education and community development in the South, provided financial support to pay for the eventual treatment of the patients. They had previously collaborated with Public Health Services in a study of syphilis prevalence in over 2,000 black workers in Mississippi's Delta Pine and Land Company in 1928, and helped provide treatment for 25% of the workers who had tested positive for the disease.[19] Study researchers initially recruited 399 syphilitic Black men, and 201 healthy Black men as controls.
    Table from U.S. Public Health Service summarising participants in the study
    Continuing effects of the Stock Market Crash of 1929 and the beginning of the Great Depression led the Rosenwald Fund to withdraw its offer of funding. Study directors issued a final report as they thought this might mean the end of the study once funding to buy medication for the treatment phase of the study was withdrawn.
    Medical ethics considerations were limited from the start and rapidly deteriorated. The PHS asked black Tuskegee Institute physicians to participate in the study by offering funds, employment, and interns to encourage the ongoing participation of the patients. Additionally, the study intentionally employed Eunice Rivers, a black nurse from Macon County, to be primary source of contact and build personal, trusting relationships with patients to promote their participation.[19] To ensure that the men would show up for the possibly dangerous, painful, diagnostic, and non-therapeutic spinal taps, the doctors sent the 400 patients a misleading letter titled "Last Chance for Special Free Treatment".[1] The study also required all participants to undergo an autopsy after death in order to receive funeral benefits. After penicillin was discovered as a cure, researchers continued to deny such treatment to many study participants. Many patients were lied to and given placebo treatments so that researchers could observe the full, long-term progression of the fatal disease.[18]
    Taking a blood sample as part of the Tuskegee Syphilis Study
    The Tuskegee Study published its first clinical data in 1934 and issued its first major report in 1936. This was prior to the discovery of penicillin as a safe and effective treatment for syphilis. The study was not secret since reports and data sets were published to the medical community throughout its duration.
    During World War II, 250 of the subject men registered for the draft. These men were consequently diagnosed as having syphilis at military induction centers and ordered to obtain treatment for syphilis before they could be taken into the armed services.[20] PHS researchers attempted to prevent these men from getting treatment, thus depriving them of chances for a cure. A PHS representative was quoted at the time saying: "So far, we are keeping the known positive patients from getting treatment."[20] Although some of the men in study received arsenical or penicillin treatments elsewhere, for most of them this did not amount to "adequate therapy".[21]
    By 1947 penicillin had become standard therapy for syphilis. The US government sponsored several public health programs to form "rapid treatment centers" to eradicate the disease. When campaigns to eradicate venereal disease came to Macon County, study researchers prevented their patients from participating.[20]
    By the end of the study in 1972, only 74 of the test subjects were alive. Of the original 399 men, 28 had died of syphilis, 100 were dead of related complications, 40 of their wives had been infected, and 19 of their children were born with congenital syphilis. The Tuskegee University Legacy Museum has on display a check issued by the United States government on behalf of Dan Carlis to Lloyd Clements, Jr., a descendant of one of the Tuskegee Syphilis Study participants.[22] Lloyd Clements, Jr.'s great-grandfather Dan Carlis and two of his uncles, Ludie Clements and Sylvester Carlis, were in the study. Original legal paper work for Sylvester Carlis related to the Tuskegee Syphilis Study is on display at the museum as well. Lloyd Clements, Jr. has worked with noted historian Susan Reverby concerning his family's involvement with the Tuskegee Syphilis Study.
    Study termination [ edit ] Group of Tuskegee Experiment test subjects
    Charlie Pollard, survivor
    The first dissenter against the Tuskegee study was Irwin Schatz, a young Chicago doctor only four years out of medical school. In 1965, Schatz read an article about the study in a medical journal, and wrote a letter directly to the study's authors confronting them with a declaration of brazen unethical practice.[23] His letter, read by Anne R. Yobs (one of the study's authors), was immediately ignored and filed away with a brief memo that no reply would be sent.
    In 1966 Peter Buxtun, a PHS venereal-disease investigator in San Francisco, sent a letter to the national director of the Division of Venereal Diseases to express his concerns about the ethics and morality of the extended Tuskegee Study. The Center for Disease Control (CDC), which by then controlled the study, reaffirmed the need to continue the study until completion; i.e., until all subjects had died and been autopsied. To bolster its position, the CDC received unequivocal support for the continuation of the study, both from local chapters of the National Medical Association (representing African-American physicians) and the American Medical Association (AMA).
    In 1968 William Carter Jenkins, an African-American statistician in the PHS, part of the Department of Health, Education, and Welfare (HEW), founded and edited The Drum, a newsletter devoted to ending racial discrimination in HEW. The cabinet-level department included the CDC. In The Drum, Jenkins called for an end to the Tuskegee Study. He did not succeed; it is not clear who read his work.[b]
    Buxtun finally went to the press in the early 1970s. The story broke first in the Washington Star on July 25, 1972. It became front-page news in the New York Times the following day. Senator Edward Kennedy called Congressional hearings, at which Buxtun and HEW officials testified. As a result of public outcry, the CDC and PHS appointed an ad hoc advisory panel to review the study. The panel found that the men agreed to certain terms of the experiment, such as examination and treatment. However, they were not informed of the study's actual purpose.[2] The panel then determined the study was medically unjustified and ordered its termination.
    As part of the settlement of a class action lawsuit subsequently filed by the NAACP on behalf of study participants and their descendants, the U.S. government paid $10 million ($51.8 million in 2019) and agreed to provide free medical treatment to surviving participants and to surviving family members infected as a consequence of the study; Congress created a commission empowered to write regulations to deter such abuses from occurring in the future.[2]
    A collection of materials compiled to investigate the study is held at the National Library of Medicine in Bethesda, Maryland.[24]
    Aftermath [ edit ] In 1974 Congress passed the National Research Act and created a commission to study and write regulations governing studies involving human participants. Within the United States Department of Health and Human Services, the Office for Human Research Protections (OHRP) was established to oversee clinical trials. Now studies require informed consent,[4] communication of diagnosis and accurate reporting of test results.[5] Institutional review boards (IRBs), including laypeople, are established in scientific research groups and hospitals to review study protocols and protect patient interests, to ensure that participants are fully informed.
    In 1994, a multi-disciplinary symposium was held on the Tuskegee study: Doing Bad in the Name of Good?: The Tuskegee Syphilis Study and Its Legacy at the University of Virginia. Following that, interested parties formed the Tuskegee Syphilis Study Legacy Committee to develop ideas that had arisen at the symposium. It issued its final report in May 1996.[25] The Committee had two related goals: (1) President Bill Clinton should publicly apologize for past government wrongdoing related to the study and (2) the Committee and relevant federal agencies should develop a strategy to redress the damages.[26]
    A year later on May 16, 1997, Bill Clinton formally apologized and held a ceremony at the White House for surviving Tuskegee study participants. He said:
    What was done cannot be undone. But we can end the silence. We can stop turning our heads away. We can look at you in the eye and finally say on behalf of the American people, what the United States government did was shameful, and I am sorry... To our African American citizens, I am sorry that your federal government orchestrated a study so clearly racist.[27]
    Five of the eight study survivors attended the White House ceremony.
    The presidential apology led to progress in addressing the second goal of the Legacy Committee. The federal government contributed to establishing the National Center for Bioethics in Research and Health Care at Tuskegee, which officially opened in 1999 to explore issues that underlie research and medical care of African Americans and other under-served people.[28]
    In 2009 the Legacy Museum opened in the Bioethics Center, to honor the hundreds of participants of the Tuskegee Study of Untreated Syphilis in the Negro Male.[28][29]
    Public trust [ edit ] The revelations of mistreatment under the Tuskegee Syphilis Study are believed to have significantly damaged the trust of the black community toward public health efforts in the United States.[30][31] Observers believe that the abuses of the study may have contributed to the reluctance of many poor black people to seek routine preventive care.[32][31] A 1999 survey showed that 80% of African American men believe the men in the Tuskegee Syphilis Experiment had been injected with syphilis.[33] A 2016 paper published by the National Bureau of Economic Research finds "that the historical disclosure of the [Tuskegee experiment] in 1972 is correlated with increases in medical mistrust and mortality and decreases in both outpatient and inpatient physician interactions for older black men. Our estimates imply life expectancy at age 45 for black men fell by up to 1.4 years in response to the disclosure, accounting for approximately 35% of the 1980 life expectancy gap between black and white men."[31] However, other studies, such as the Tuskegee Legacy Project Questionnaire, have challenged the degree to which knowledge of the Tuskegee experiments have kept black Americans from participating in medical research.[34][page needed ] This study shows that, even though black Americans are four times more likely to know about the syphilis trials than are whites, they are two to three times more willing to participate in biomedical studies.[35]Other studies concluded that the Tuskegee Syphilis trial has played a minor role in the decisions of black Americans to decline participation as research subjects.[36] Of the studies that have investigated the willingness of black Americans to participate in medical studies, they have not drawn consistent conclusions related to the willingness and participation in studies by racial minorities. Some of the factors that continue to limit the credibility of these few studies is how awareness differs significantly across studies. For instance, it appears that the rates of awareness differ as a function of method of assessment, study participants who reported awareness of the Tuskegee Syphilis Trials are often misinformed about the results and issues, and awareness of the study is not reliably associated with unwillingness to participate in scientific research.[37][38][39][40][41]
    Distrust of the government, in part formed through the study, contributed to persistent rumors during the 1980s in the black community that the government was responsible for the HIV/AIDS crisis by having deliberately introduced the virus to the black community as some kind of experiment.[42] In February 1992 on ABC's Prime Time Live, journalist Jay Schadler interviewed Dr. Sidney Olansky, Public Health Services director of the study from 1950 to 1957. When asked about the lies that were told to the study subjects, Olansky said, "The fact that they wereilliterate was helpful, too, because they couldn't read the newspapers. If they were not, as things moved on they might have been reading newspapers and seen what was going on."[19]
    On January 3, 2019, a U.S. District Judge stated that Johns Hopkins University, Bristol-Myers Squibb and the Rockefeller Foundation must face a $1 billion lawsuit for their roles in a similar experiment affecting Guatemalans.[43]
    Ethical implications [ edit ] This section
    needs expansion.
    You can help by adding to it. ( March 2010 )Depression-era U.S. poster advocating early syphilis treatment. Although treatments were available, participants in the study did not receive them.
    Tuskegee highlighted issues in race and science.[44] The aftershocks of this study, and other human experiments in the United States, led to the establishment of the National Commission for the Protection of Human Subjects of Biomedical and Behavioral Research and the National Research Act. The latter requires the establishment of institutional review boards (IRBs) at institutions receiving federal support (such as grants, cooperative agreements, or contracts). Foreign consent procedures can be substituted which offer similar protections and must be submitted to the Federal Register unless a statute or Executive Order requires otherwise.
    Writer James Jones said that physicians were fixated on African American sexuality, and believing that African Americans willingly had sexual relations with those who were infected (although none had been told his diagnosis) resulted in their believing that individuals were solely responsible for contracting the disease.[45] One researcher critiqued how the study was administered and its change in purpose. He said that it was "the economic exploitation of humans as a natural resource of a disease that could not be cultivated or animals in order to establish and sustain U.S. superiority in patented commercial biotechnology".[46]
    Due to the lack of information, the participants were manipulated into continuing the study without full knowledge of their role or their choices.[47] Since the late 20th century, IRBs established in association with clinical studies require that all involved in study be willing and voluntary participants.[48]
    In popular culture [ edit ] ComicsTruth: Red, White, and Black (published January''July 2003) is a seven-issue Marvel comic book series inspired by the Tuskegee trials. Written as a prequel to the Captain America series, Truth: Red, White, and Black explores the exploitation of certain races for scientific research, as in the Tuskegee syphilis trials.[35]FilmsIn the movie Half Baked (1998), the character Thurgood Jenkins states that his grandfather was in the Tuskegee experiments.LiteratureDavid Feldshuh's stage play Miss Evers' Boys (1992), based on the history of the Tuskegee study, was a runner-up for the 1992 Pulitzer Prize in drama.[49]MusicThe lyrics of Gil Scott-Heron's 33-second song, "Tuskeegee #626", featured on the Bridges (1977) LP, detail and condemn the Tuskegee syphilis experiments.The hip hop duo Pete Rock & CL Smooth's song, "Anger in the Nation", from the LP Mecca and the Soul Brother (1992), references the experiments.TelevisionIn the House episode "Needle in a Haystack" (season 3, episode 13), Dr. Eric Foreman mentions the Tuskegee experiments in conversation with a Romani father who is concerned about the hospital potentially practicing unethical medical science on his son, alluding to their treatment by the Nazi regime in World War II. Dr. Foreman, who is African-American, mentions the Tuskegee experiments to establish his understanding of the father's concern.Miss Evers' Boys (1997), the HBO made-for-TV adaptation of David Feldshuh's eponymous 1992 stage play, was nominated for eleven Emmy Awards[50] and won in four categories.[51]In the 2019 TV series The Passage episode ''I Want to Know What You Taste Like'' (season 1), Dr. Tim Fanning refers to the doctors in Tuskegee experiment as monsters.See also [ edit ] Notes [ edit ] ^ Also known as the Tuskegee Syphilis Study or Tuskegee Syphilis Experiment ( tus- KEE -ghee) or the United States Public Health Services Study of Untreated Syphilis in Black Males ^ Bill Jenkins left the PHS in the mid-1970s for doctoral studies. In 1980, he joined the CDC Division of Sexually Transmitted Diseases, where he managed the Participants Health Benefits Program that ensured health services for survivors of the Tuskegee Study. References [ edit ] ^ a b c d Allan M. Brandt (December 1978). "Racism and Research: The Case of the Tuskegee Syphilis Study" (PDF) . The Hastings Center Report. 8 (6): 21''9. doi:10.2307/3561468. JSTOR 3561468. PMID 721302. ^ a b c d e f "Tuskegee Study - Timeline". NCHHSTP. CDC. June 25, 2008 . Retrieved December 4, 2008 . ^ 1946-, Reverby, Susan M. (2009). Examining Tuskegee : the infamous syphilis study and its legacy. Chapel Hill: University of North Carolina Press. ISBN 9780807833100. OCLC 496114416. ^ a b "Code of Federal Regulations Title 45 Part 46 Protections of Human Subjects 46.1.1(i)" (PDF) . U.S. Department of Health and Humand Services. January 15, 2009 . Retrieved February 22, 2010 . ^ a b "Final Report of the Tuskegee Syphilis Study Legacy Committee". Tuskegee Syphilis Study Legacy Committee. May 20, 1996 . Retrieved December 4, 2008 . ^ a b Jones J (1981). Bad Blood: The Tuskegee Syphilis Experiment. New York: Free Press. ISBN 978-0-02-916676-5. ^ " " I Didn't Want to Believe It": Lessons from Tuskegee 40 Years Later". Planned Parenthood Advocates of Arizona. November 25, 2012 . Retrieved November 25, 2012 . ^ Katz RV, Kegeles SS, Kressin NR, et al. (November 2006). "The Tuskegee Legacy Project: willingness of minorities to participate in biomedical research". J Health Care Poor Underserved. 17 (4): 698''715. doi:10.1353/hpu.2006.0126. PMC 1780164 . PMID 17242525. ^ Office for Human Research Protections (OHRP) (June 23, 2005). "Protection of Human Subjects". Title 45, Code of Federal Regulations, Part 46. US Department of Health and Human Services . Retrieved December 4, 2008 . ^ "Office for Human Research Protections". Department of Health and Human Services. September 28, 2008 . Retrieved December 4, 2008 . ^ Cockburn, Alexander; Jeffrey St. Clair (1998). Whiteout: The CIA, Drugs and the Press . London: Verso. p. 67. ISBN 978-1-85984-139-6. some merely followed orders, others worked for the glory of science . ^ Jones, James H. (1981). Bad Blood: The Tuskegee Syphilis Experiment. New York: The Free Press. p. 99. ISBN 978-0029166703. ^ Bender W (July 20, 2017). "Did a U.S surgeon general come up with the idea of the notorious Tuskegee syphilis experiment". Philadelphia Inquirer. ^ DiClemente RJ, Blumenthal DS (2003). Community-based health research: issues and methods. New York: Springer Pub. p. 50. ISBN 978-0-8261-2025-0. ^ Jones, James H. Bad Blood: The Tuskegee Syphilis Experiment, p. 179. ^ Jones, James H. Bad Blood: The Tuskegee Syphilis Experiment, p. 179. (N.B.: This quote is often falsely attributed to Heller himself.) ^ Murphy, Timothy F. "The Tuskegee Syphilis Studies," in Case Studies in Biomedical Research Ethics. Cambridge: MIT, 2004. 21. Print. ^ a b Parker, Laura (April 28, 1997). " ' Bad Blood' Still Flows In Tuskegee Study". USA Today. Archived from the original on December 8, 2008 . Retrieved December 4, 2008 . ^ a b c Thomas, Stephen B.; Crouse Quinn, Sandra (2000). "Light on the Shadow of the Syphilis Study at Tuskegee" (PDF) . Health Promotion Practice. 1 (3): 234''7. doi:10.1177/152483990000100306. Archived from the original (PDF) on June 16, 2016 . Retrieved December 12, 2014 . ^ a b c "Doctor of Public Health Student Handbook" (PDF) . University of Kentucky College of Public Health. 2004. p. 17. Archived from the original (PDF) on December 9, 2008. ^ Benedek, Thomas G.; Erlen, Jonathon (1999). "The Scientific Environment of the Tuskegee Study of Syphilis, 1920-1960". Perspectives in Biology and Medicine. 43 (1): 24''5. doi:10.1353/pbm.1999.0034. PMID 10701219. ^ "Tuskegee Syphilis Experiment". Encyclopine. Archived from the original on September 16, 2014 . Retrieved May 8, 2015 . ^ "Dr. Irwin Schatz, the first, lonely voice against infamous Tuskegee study, dies at 83". Washington Post. ^ "Documents on the origin and development of the Tuskegee syphilis study 1921-1973". National Library of Medicine. ^ "Bad Blood: The Tuskegee Syphilis Study". University of Virginia Claude Moore Health Sciences Library . Retrieved December 2, 2014 . ^ "Bad Blood: The Tuskegee Syphilis Study: Final Report of the Tuskegee Syphilis Study Legacy Committee". University of Virginia Claude Moore Health Sciences Library . Retrieved December 2, 2014 . ^ "Remarks by the President in apology for study done in Tuskegee". Office of the Press Secretary, The White House. May 16, 1997. Archived from the original on October 11, 2014 . Retrieved September 6, 2009 . ^ a b "Bad Blood: The Tuskegee Syphilis Study: Final Report of the Tuskegee Syphilis Study Legacy Committee". University of Virginia Claude Moore Health Sciences Library . Retrieved December 2, 2014 . ^ "The Legacy Museum". Tuskegee University. Archived from the original on May 14, 2017 . Retrieved December 2, 2014 . ^ Thomas SB, Quinn SC (November 1991). "The Tuskegee Syphilis Study, 1932 to 1972: implications for HIV education and AIDS risk education programs in the black community". Am J Public Health. 81 (11): 1498''505. doi:10.2105/AJPH.81.11.1498. PMC 1405662 . PMID 1951814. ^ a b c Alsan, Marcella; Wanamaker, Marianne (2018). "Tuskegee and the Health of Black Men" (PDF) . Quarterly Journal of Economics. 133 (1): 407''455. doi:10.1093/qje/qjx029. PMC 6258045 . PMID 30505005. ^ Cohen E (February 26, 2007). "Tuskegee's ghosts: Fear hinders black marrow donation". CNN . Retrieved December 4, 2008 . ^ Katz, Ralph V.; Green, B. Lee; Kressin, Nancy R.; Kegeles, S. Stephen; Wang, Min Qi; James, Sherman A.; Russell, Stefanie L.; Claudio, Cristina; McCallum, Jan M. (November 1, 2008). "The legacy of the Tuskegee Syphilis Study: assessing its impact on willingness to participate in biomedical studies". Journal of Health Care for the Poor and Underserved. 19 (4): 1168''1180. doi:10.1353/hpu.0.0067. ISSN 1049-2089. PMC 2702151 . PMID 19029744. ^ Reverby, Susan (2009). Examining Tuskegee:The Infamous Syphilis Study and its Legacy. Chapel Hill: The University of North Carolina Press. ^ a b Katz, R.; Kegeles, S.; Kressin, N. R.; Green, B.; James, S.A.; Wang, M.; James, J.; Russel, S.; Claudio, C. (2008). "Awareness of the Tuskegee Syphilis Study and the US Presidential Apology and Their Influence on Minority Participation in Biomedical Research". 98 (6). American Journal of Public Health: 1137''1142. ^ Crenner, Christopher (February 12, 2011). "The Tuskegee Syphilis Study and the Scientific Concept of Racial Nervous Resistance". Journal of the History of Medicine and Allied Sciences. 67 (2): 244''80. doi:10.1093/jhmas/jrr003. PMID 21317423. ^ N. Poythress Ph. D.; M. Epstein Ph. D.; P. Stiles J. D. Ph. D.; J. Edens Ph. D. (October 9, 2011). "Awareness of the Tuskegee Syphilis Study: Impact on Offenders' Decisions to Decline Research Participation". Behavioral Sciences and the Law. 29 (6): 821''828. doi:10.1002/bsl.1012. PMID 21984035. ^ "Did Tuskegee damage trust on clinical trials?". CNN. Montgomery, AL. AP. March 17, 2008. Archived from the original on May 12, 2008 . Retrieved December 4, 2008 . ^ Ralph V. Katz DMD MPH; S. Steven Kegeles; Nancy R. Kressin; B. Lee Green; Min Qi Wang; Sherman A. James; Stefanie L. Russell DDS MPH; Cristina Claudio (November 2006). "The Tuskegee Legacy Project: Willingness of Minorities to Participate in Biomedical Research". Journal of Health Care for the Poor and Underserved. 17 (4): 698''715. doi:10.1353/hpu.2006.0126. PMC 1780164 . PMID 17242525. ^ Brandon DT; Isaac LA; LaVeist TA. (2005). "The legacy of Tuskegee and trust in medical care: is Tuskegee responsible for race differences in mistrust of medical care?". J Natl Med Assoc. 97 (7): 951''6. PMC 2569322 . PMID 16080664. ^ Ralph V. Katz DMD MPH; S. Stephen Kegeles; Nancy R. Kressin; B. Lee Green; Sherman A. James; Min Qi Wang; Stefanie L. Russell DDS MPH; Cristina Claudio (September 2008). "Awareness of the Tuskegee Syphilis Study and the US Presidential Apology and Their Influence on Minority Participation in Biomedical Research". American Journal of Public Health. 98 (6): 1137''1142. doi:10.2105/AJPH.2006.100131. PMC 2377291 . PMID 17901437. ^ Jones, James (1993). Bad Blood: New and Expanded Edition. Simon and Schuster. pp. 220''241. ISBN 978-0-02-916676-5. ^ Stempel, Jonathan (January 4, 2019). "Johns Hopkins, Bristol-Myers must face $1 billion syphilis infections suit". Reuters . Retrieved January 4, 2019 . ^ Chadwick A (July 25, 2002). "Remembering the Tuskegee Experiment". NPR . Retrieved December 4, 2008 . ^ Jones, James H. "A Notoriously Syphilis-Soaked Race." Bad Blood. New York: Free Press, 1993. 22''23. ^ Russert, Britt (2009). " " A Study in Nature": The Tuskegee Experiments and the New South Plantation". Journal of Medical Humanities. 30 (3): 155''171. doi:10.1007/s10912-009-9086-4. PMID 19603260. ^ Ralph Katz; Rueben Warren (2011). the Search for the Legacy of the USPHS Syphilis Study at Tuskegee. Lanham: Lexington Books. ^ Perkiss, Abigail (2008). "Public Accountability And The Tuskegee Syphilis Experiments: A Restorative Justice Approach". 10 (70). Berkeley Journal of African-American Law & Policy. ^ "The Pulitzer Prizes: Drama". The Pulitzer Prizes. Columbia University. ^ Geddes, Darryl (September 11, 1997). "HBO's adaptation of Feldshuh's play Miss Evers' Boys is up for 12 Emmys". Cornell Chronicle. ^ "Awards for Miss Evers' Boys". Cornell University. Further reading [ edit ] "Nurse Eunice Rivers". msu.edu. "The Tuskegee Syphilis Study and Its Implications for the 21st Century". socialworker.com. "Tuskegee Syphilis Study article". Encyclopedia of Alabama. "Tuskegee re-examined by Richard A Shweder, Cultural anthropologist (sp!ked article)". Primary sources [ edit ] Caldwell, J. G; E. V. Price; et al. (1973). "Aortic regurgitation in the Tuskegee study of untreated syphilis". J Chronic Dis. 26 (3): 187''94. doi:10.1016/0021-9681(73)90089-1. PMID 4695031. Hiltner, S. (1973). "The Tuskegee Syphilis Study under review". Christ Century. 90 (43): 1174''6. PMID 11662609. Kampmeier, R. H. (1972). "The Tuskegee study of untreated syphilis". South Med J. 65 (10): 1247''51. doi:10.1097/00007611-197210000-00016. PMID 5074095. Kampmeier, R. H. (1974). "Final report on the "Tuskegee syphilis study". South Med J. 67 (11): 1349''53. doi:10.1097/00007611-197411000-00019. PMID 4610772. Olansky, S.; L. Simpson; et al. (1954). "Environmental factors in the Tuskegee study of untreated syphilis". Public Health Rep. 69 (7): 691''8. doi:10.2307/4588864. JSTOR 4588864. PMC 2024316 . PMID 13177831. Rockwell, D. H.; A. R. Yobs; et al. (1964). "The Tuskegee Study of Untreated Syphilis; the 30th Year of Observation". Arch Intern Med. 114 (6): 792''8. doi:10.1001/archinte.1964.03860120104011. PMID 14211593. Schuman, S. H.; S. Olansky; et al. (1955). "Untreated syphilis in the male negro; background and current status of patients in the Tuskegee study". J Chronic Dis. 2 (5): 543''58. doi:10.1016/0021-9681(55)90153-3. PMID 13263393. Photocopied documents from the studyThe Tuskegee Study Group Letter inviting subjects to receive "special treatment", actually a diagnostic lumbar puncture
    Document from Tuskegee Syphilis Study, requesting that after test subjects die, an autopsy be performed, and the results sent to the National Institutes of Health
    Draft report of study results up to 1949, page 1
    Draft report of study results up to 1949, page 2
    Table depicting number of subjects with syphilis and number of controlled non-syphlitic patients, and how many of the subjects have died during the experiments, 1969
    Memo ordering termination of the study
    Secondary sources [ edit ] Gjestland T (1955). "The Oslo study of untreated syphilis: an epidemiologic investigation of the natural course of the syphilitic infection based upon a re-study of the Boeck-Bruusgaard material". Acta Derm Venereol. 35 (Suppl 34): 3''368. Gray, Fred D. (1998). The Tuskegee Syphilis Study: The Real Story and Beyond. Montgomery, Alabama: NewSouth Books. Jones, James H. (1981). Bad Blood: The Tuskegee Syphilis Experiment. New York: Free Press. The Deadly Deception, by Denisce DiAnni, PBS/WGBH NOVA documentary video, 1993.Reverby, Susan M. (1998). "History of an Apology: From Tuskegee to the White House". Research Nurse. Reverby, Susan M. (2000). Tuskegee's Truths: Rethinking the Tuskegee Syphilis Study. University of North Carolina Press. Reverby, Susan M. (2009). Examining Tuskegee: The Infamous Syphilis Study and its Legacy. University of North Carolina Press. Thomas, Stephen B; Sandra Crouse Quinn (1991). "The Tuskegee Syphilis Study, 1932''1972: Implications for HIV Education and AIDS Risk Programs in the Black Community". American Journal of Public Health. 81 (1503): 1498''1505. doi:10.2105/AJPH.81.11.1498. PMC 1405662 . PMID 1951814. Carlson, Elof Axel (2006). Times of triumph, times of doubt : science and the battle for the public trust. Cold Spring Harbor Press. ISBN 978-0-87969-805-8. Washington, Harriet A. (2007). Medical Apartheid: The Dark History of Medical Experimentation on Black Americans From Colonial Times to the Present. External links [ edit ] "Bad Blood: The Tuskegee Syphilis Study". Claude Moore Health Sciences Library, University of Virginia. "Patient medical files". National Archives and Records Administration Southeast Region. Morrow, GA. August 15, 2016. "Review of the TSS". Michigan State University. "U.S. Public Health Service Syphilis Study at Tuskegee". Center for Disease Control. October 3, 2018.
  Operation Paperclip - Wikipedia
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    Sat, 14 Mar 2020 15:15
    Operation Paperclip was a secret program of the Joint Intelligence Objectives Agency (JIOA) largely carried out by special agents of Army CIC, in which more than 1,600 German scientists, engineers, and technicians, such as Wernher von Braun and his V-2 rocket team, were taken from Germany to the United States, for U.S. government employment, primarily between 1945 and 1959. Many were former members, and some were former leaders, of the Nazi Party.[1][2]
    The primary purpose for Operation Paperclip was U.S. military advantage in the Soviet''American Cold War, and the Space Race. The Soviet Union was more aggressive in forcibly recruiting more than 2,200 German specialists'--a total of more than 6,000 people including family members'--with Operation Osoaviakhim during one night on October 22, 1946.[3]
    The Joint Chiefs of Staff (JCS) established the first secret recruitment program, called Operation Overcast, on July 20, 1945, initially "to assist in shortening the Japanese war and to aid our postwar military research".[4] The term "Overcast" was the name first given by the German scientists' family members for the housing camp where they were held in Bavaria.[5] In late summer 1945, the JCS established the JIOA, a subcommittee of the Joint Intelligence Community, to directly oversee Operation Overcast and later Operation Paperclip.[6] The JIOA representatives included the army's director of intelligence, the chief of naval intelligence, the assistant chief of Air Staff-2 (air force intelligence), and a representative from the State Department.[7] In November 1945, Operation Overcast was renamed Operation Paperclip by Ordnance Corps (United States Army) officers, who would attach a paperclip to the folders of those rocket experts whom they wished to employ in America.[5]
    In a secret directive circulated on September 3, 1946, President Truman officially approved Operation Paperclip and expanded it to include one thousand German scientists under "temporary, limited military custody".[8][9][10]
    Osenberg List [ edit ] In the later part of World War II, Nazi Germany found itself at a logistical disadvantage, having failed to conquer the USSR with Operation Barbarossa (June''December 1941), the Siege of Leningrad (September 1941 '' January 1944), Operation Nordlicht ("Northern Light", August''October 1942), and the Battle of Stalingrad (July 1942 '' February 1943). The failed conquest had depleted German resources, and its military-industrial complex was unprepared to defend the GroŸdeutsches Reich (Greater German Reich) against the Red Army's westward counterattack. By early 1943, the German government began recalling from combat a number of scientists, engineers, and technicians; they returned to work in research and development to bolster German defense for a protracted war with the USSR. The recall from frontline combat included 4,000 rocketeers returned to Peenem¼nde, in northeast coastal Germany.[11][12]
    Overnight, Ph.D.s were liberated from KP duty, masters of science were recalled from orderly service, mathematicians were hauled out of bakeries, and precision mechanics ceased to be truck drivers.
    '--'‰Dieter K. Huzel, Peenem¼nde to Canaveral
    The Nazi government's recall of their now-useful intellectuals for scientific work first required identifying and locating the scientists, engineers, and technicians, then ascertaining their political and ideological reliability. Werner Osenberg, the engineer-scientist heading the Wehrforschungsgemeinschaft (Defense Research Association), recorded the names of the politically cleared men to the Osenberg List, thus reinstating them to scientific work.[13]
    In March 1945, at Bonn University, a Polish laboratory technician found pieces of the Osenberg List stuffed in a toilet; the list subsequently reached MI6, who transmitted it to U.S. Intelligence.[14][15] Then U.S. Army Major Robert B. Staver, Chief of the Jet Propulsion Section of the Research and Intelligence Branch of the U.S. Army Ordnance Corps, used the Osenberg List to compile his list of German scientists to be captured and interrogated; Wernher von Braun, Germany's premier rocket scientist, headed Major Staver's list.[16]
    Identification [ edit ] In Operation Overcast, Major Staver's original intent was only to interview the scientists, but what he learned changed the operation's purpose. On May 22, 1945, he transmitted to the U.S. Pentagon headquarters Colonel Joel Holmes's telegram urging the evacuation of German scientists and their families, as most "important for [the] Pacific war" effort.[15] Most of the Osenberg List engineers worked at the Baltic coast German Army Research Center Peenem¼nde, developing the V-2 rocket. After capturing them, the Allies initially housed them and their families in Landshut, Bavaria, in southern Germany.
    Beginning on July 19, 1945, the U.S. JCS managed the captured ARC rocketeers under Operation Overcast. However, when the "Camp Overcast" name of the scientists' quarters became locally known, the program was renamed Operation Paperclip in November 1945.[17] Despite these attempts at secrecy, later that year the press interviewed several of the scientists.[15][16][18]
    Capture and detention [ edit ] The Allied zones of occupation in post-war Germany, highlighting the Soviet zone (red), the inner German border (heavy black line) and the zone from which British and American troops withdrew in July 1945 (purple). The provincial boundaries are those of
    Nazi Germany, before the present
    L¤nder (federal states) were established.
    Early on, the United States created the Combined Intelligence Objectives Subcommittee (CIOS). This provided the information on targets for the T-Forces that went in and targeted scientific, military and industrial installations (and their employees) for their know-how. Initial priorities were advanced technology, such as infrared, that could be used in the war against Japan; finding out what technology had been passed on to Japan; and finally to halt the research.
    A project to halt the research was codenamed "Project Safehaven", and it was not initially targeted against the Soviet Union; rather the concern was that German scientists might emigrate and continue their research in countries such as Spain, Argentina or Egypt, all of which had sympathized with Nazi Germany.[citation needed ] In order to avoid the complications involved with the emigration of German scientists, the CIOS was responsible for scouting and kidnapping high-profile individuals for the deprivation of technological advancements in nations outside of the US.
    Much U.S. effort was focused on Saxony and Thuringia, which by July 1, 1945, would become part of the Soviet Occupation zone. Many German research facilities and personnel had been evacuated to these states, particularly from the Berlin area. Fearing that the Soviet takeover would limit U.S. ability to exploit German scientific and technical expertise, and not wanting the Soviet Union to benefit from said expertise, the United States instigated an "evacuation operation" of scientific personnel from Saxony and Thuringia, issuing orders such as:
    On orders of Military Government you are to report with your family and baggage as much as you can carry tomorrow noon at 1300 hours (Friday, 22 June 1945) at the town square in Bitterfeld. There is no need to bring winter clothing. Easily carried possessions, such as family documents, jewelry, and the like should be taken along. You will be transported by motor vehicle to the nearest railway station. From there you will travel on to the West. Please tell the bearer of this letter how large your family is.
    By 1947 this evacuation operation had netted an estimated 1,800 technicians and scientists, along with 3,700 family members. Those with special skills or knowledge were taken to detention and interrogation centers, such as one code-named DUSTBIN,[19] to be held and interrogated, in some cases for months.[citation needed ]
    A few of the scientists were gathered up in Operation Overcast, but most were transported to villages in the countryside where there were neither research facilities nor work; they were provided stipends and forced to report twice weekly to police headquarters to prevent them from leaving. The Joint Chiefs of Staff directive on research and teaching stated that technicians and scientists should be released "only after all interested agencies were satisfied that all desired intelligence information had been obtained from them".[citation needed ]
    On November 5, 1947, the Office of Military Government of the United States (OMGUS), which had jurisdiction over the western part of occupied Germany, held a conference to consider the status of the evacuees, the monetary claims that the evacuees had filed against the United States, and the "possible violation by the US of laws of war or Rules of Land Warfare". The OMGUS director of Intelligence R. L. Walsh initiated a program to resettle the evacuees in the Third World, which the Germans referred to as General Walsh's "Urwald-Programm" (jungle program); however, this program never matured. In 1948, the evacuees received settlements of 69.5 million Reichsmarks from the U.S., a settlement that soon became severely devalued during the currency reform that introduced the Deutsche Mark as the official currency of western Germany.[citation needed ]
    John Gimbel concludes that the United States held some of Germany's best minds for three years, therefore depriving the German recovery of their expertise.[20]
    Arrivals [ edit ] In May 1945, the U.S. Navy "received in custody" Herbert A. Wagner, the inventor of the Hs 293 missile; for two years, he first worked at the Special Devices Center, at Castle Gould and at Hempstead House, Long Island, New York; in 1947, he moved to the Naval Air Station Point Mugu.[21]
    In August 1945, Colonel Holger Toftoy, head of the Rocket Branch of the Research and Development Division of the U.S. Army's Ordnance Corps, offered initial one-year contracts to the rocket scientists; 127 of them accepted. In September 1945, the first group of seven rocket scientists (aerospace engineers) arrived at Fort Strong, located on Long Island in Boston harbor: Wernher von Braun, Erich W. Neubert, Theodor A. Poppel, August Schulze, Eberhard Rees, Wilhelm Jungert, and Walter Schwidetzky.[15]
    Beginning in late 1945, three rocket-scientist groups arrived in the United States for duty at Fort Bliss, Texas, and at White Sands Proving Grounds, New Mexico, as "War Department Special Employees".[11]: 27 [17]
    In 1946, the United States Bureau of Mines employed seven German synthetic fuel scientists at a Fischer-Tropsch chemical plant in Louisiana, Missouri.[22]
    On June 1, 1949, the Chief of Ordnance of the United States Army designated Redstone Arsenal in Huntsville, Alabama, as the Ordnance Rocket Center, its facility for rocket research and development. On April 1, 1950, the Fort Bliss missile development operation'--including von Braun and his team of over 130 Paperclip members'--was transferred to Redstone Arsenal.
    In early 1950, legal U.S. residency for some of the Project Paperclip specialists was effected through the U.S. consulate in Ciudad Jurez, Chihuahua, Mexico; thus, German scientists legally entered the United States from Latin America.[11]: 226 [16]
    Between 1945 and 1952, the United States Air Force sponsored the largest number of Paperclip scientists, importing 260 men, of whom 36 returned to Germany and one (Walter Schreiber) reemigrated to Argentina.[23]
    Eighty-six aeronautical engineers were transferred to Wright Field, Ohio, where the United States had Luftwaffe aircraft and equipment captured under Operation Lusty (Luftwaffe Secret Technology).[24]
    The United States Army Signal Corps employed 24 specialists '' including the physicists Georg Goubau, Gunter Guttwein, Georg Hass, Horst Kedesdy, and Kurt Lehovec; the physical chemists Rudolf Brill, Ernst Baars, and Eberhard Both; the geophysicist Helmut Weickmann; the optician Gerhard Schwesinger; and the engineers Eduard Gerber, Richard Guenther, and Hans Ziegler.[25]
    In 1959, 94 Operation Paperclip men went to the United States, including Friedwardt Winterberg and Friedrich Wigand.[21]
    Overall, through its operations to 1990, Operation Paperclip imported 1,600 men, as part of the intellectual reparations owed to the US and the UK, valued at $10 billion in patents and industrial processes.[21][26]
    Major awards (in the United States) [ edit ] The NASA Distinguished Service Medal is the highest award which may be bestowed by the National Aeronautics and Space Administration (NASA). After more than two decades of service and leadership in NASA, four Operation Paperclip members were awarded the NASA Distinguished Service Medal in 1969: Kurt Debus, Eberhard Rees, Arthur Rudolph, and Wernher von Braun. Ernst Geissler was awarded the medal in 1973.
    The Department of Defense Distinguished Civilian Service Award is the highest civilian award given by the United States Department of Defense. After two decades of service, Operation Paperclip member Siegfried Knemeyer was awarded the Department of Defense Distinguished Civilian Service Award in 1966.
    The Goddard Astronautics Award is the highest honor bestowed for notable achievements in the field of astronautics by the American Institute of Aeronautics and Astronautics (AIAA).[27] For their service, three Operation Paperclip members were awarded the Goddard Astronautics Award: Wernher von Braun (1961), Hans von Ohain (1967), and Krafft Arnold Ehricke (1984).
    The U.S. Space & Rocket Center in Huntsville, Alabama, owns and operates the U.S. Space Camp. Several Operation Paperclip members are members of the Space Camp Hall of Fame (which began in 2007): Wernher von Braun (2007), Georg von Tiesenhausen (2007), and Oscar Holderer (2008).
    The New Mexico Museum of Space History includes the International Space Hall of Fame. Two Operation Paperclip members are members of the International Space Hall of Fame: Wernher von Braun (1976)[28] and Ernst Steinhoff (1979).[29] Hubertus Strughold was inducted in 1978 but removed as a member in 2006. Other closely related members include Willy Ley (1976),[30] a German-American science writer, and Hermann Oberth (1976),[31] a German scientist who advised von Braun's rocket team in the U.S. from 1955 to 1958.
    Two lunar craters are named after Paperclip scientists: Debus after Kurt Debus, the first director of NASA's Kennedy Space Center, and von Braun.
    Scientific accomplishments [ edit ] Wernher von Braun was chief architect of the Saturn V launch vehicle, the key instrument in getting man to the moon.[32]
    Adolf Busemann was the mind behind the swept wing, which improved aircraft performance at high speeds.[33][34]
    Controversy and investigations [ edit ] Before his official approval of the program, President Truman, for sixteen months, was indecisive on the program.[10] Years later in 1963, Truman recalled that he was not in the least reluctant to approve Paperclip; that because of relations with Russia "this had to be done and was done".[35]
    Several of the Paperclip scientists were later investigated because of their links with the Nazi Party during the war. Only one Paperclip scientist, Georg Rickhey, was formally tried for any crime, and no Paperclip scientist was found guilty of any crime, in America or Germany. Rickhey was returned to Germany in 1947 to stand trial at the Dora Trial, where he was acquitted.[36]
    In 1951, weeks after his U.S. arrival, Walter Schreiber was linked by the Boston Globe to human experiments conducted by Kurt Blome at Ravensbr¼ck, and he emigrated to Argentina with the aid of the U.S. military.
    In 1984, Arthur Rudolph, under perceived threat of prosecution relating to his connection'--as operations director for V-2 missile production'--to the use of forced labor from Mittelbau-Dora at the Mittelwerk, renounced his U.S. citizenship and moved to West Germany, which granted him citizenship.[37]
    For fifty years, from 1963 to 2013, the Strughold Award'--named after Hubertus Strughold, The Father of Space Medicine, for his central role in developing innovations like the space suit and space life support systems'--was the most prestigious award from the Space Medicine Association, a member organization of the Aerospace Medical Association.[38] On October 1, 2013, in the aftermath of a Wall Street Journal article published on December 1, 2012, which highlighted his connection to human experiments during WW2, the Space Medicine Association's Executive Committee announced that the Space Medicine Association Strughold Award had been retired.[38][39]
    Key recruits [ edit ] Advisors brought into the United StatesHermann OberthAeronautics and rocketryHans Amtmann,[40] Herbert Axster, Anton Flettner, Erich Ball,[41] Oscar Bauschinger,[42] Hermann Beduerftig,[43] Rudi Beichel,[44] Anton Beier,[45] Herbert Bergeler,[46] Magnus von Braun, Wernher von Braun, Theodor Buchhold, Walter Burose,[47] Adolf Busemann, GN Constan,[48] Werner Dahm, Konrad Dannenberg, Kurt H. Debus, Gerd De Beek,[49] Walter Dornberger, Gerhard Drawe,[50] Friedrich Duerr,[51] Ernst R. G. Eckert, Otto Eisenhardt,[52] Krafft Arnold Ehricke, Alfred Finzel,[53] Edward Fischel,[54] Karl Fleischer,[55] Anselm Franz, Herbert Fuhrmann,[56] Ernst Geissler, Werner Gengelbach,[57] Dieter Grau, Hans Gruene,[58] Herbert Guendel,[59] Fritz Haber,[60] Heinz Haber, Karl Hager,[61] Guenther Haukohl,[62] Karl Heimburg,[63] Emil Hellebrand,[64] Gerhard Heller,[65] Bruno Helm,[66] Rudolf Hermann,[67] Bruno Heusinger,[68] Hans Heuter,[69] Guenther Hintze,[70] Sighard F. Hoerner, Kurt Hohenemser, Oscar Holderer, Hans Henning Hosenthien, Dieter Huzel,[71][circular reference ] Walter Jacobi, Erich Kaschig,[72] Ernst Klaus,[73] Theodore Knacke,[74] Siegfried Knemeyer, Heinz-Hermann Koelle, Gustav Kroll,[75] Werner Kuers,[76] Hermann Kurzweg,[77] Hermann Lange,[78] Hans Lindenberg,[79] Hans Lindenmayer,[80] Alexander Martin Lippisch, Robert Lusser, Hans Maus,[81] Helmut Merk,[82] Joseph Michel,[83] Hans Milde,[84] Heinz Millinger,[85] Rudolf Minning,[86] Willi Mrazek,[87] Hans Multhopp, Erich Neubert,[88] Gerhard Neumann, Hans von Ohain (designer of German jet engines), Robert Paetz,[89] Hans Palaoro,[90] Kurt Patt,[91] Hans Paul,[92] Arnold Peter,[93] Theodor Poppel,[94] Werner Rosinski,[95] Heinrich Rothe,[96] Ludwig Roth, Arthur Rudolph, Friedrich von Saurma, Edgar Schaeffer, Martin Schilling,[97] Helmut Schlitt,[98] Albert Schuler,[99] August Schulze,[100] Walter Schwidetzky,[101] Ernst Steinhoff, Wolfgang Steurer,[102] Ernst Stuhlinger, Kurt Tank, Bernhard Tessmann, Adolf Thiel, Georg von Tiesenhausen, Werner Tiller,[103] JG Tschinkel,[104] Arthur Urbanski,[105] Fritz Vandersee,[106] Richard Vogt, Woldemar Voigt (designer of Messerschmitt P.1101), Werner Voss,[107] Theodor Vowe,[108] Herbert A. Wagner, Hermann Weidner,[109] G¼nter Wendt and Walter Fritz Wiesemann.[110](see List of German rocket scientists in the US).
    ArchitectureHeinz Hilten [111] and Hannes Luehrsen.[112]Electronics - including guidance systems, radar and satellitesWilhelm Angele,[113] Ernst Baars, Josef Boehm,[114] Hans Fichtner, Hans Friedrich,[115] Eduard Gerber,[116] Georg Goubau, Walter Haeussermann, Otto Heinrich Hirschler,[117] Otto Hoberg,[118] Rudolf Hoelker,[119] Hans Hollmann, Helmut H¶lzer, Horst Kedesdy,[120] Kurt Lehovec, Kurt Lindner,[121] JW Muehlner,[122] Fritz Mueller, Johannes Plendl, Fritz Karl Preikschat, Eberhard Rees, Gerhard Reisig,[123] Harry Ruppe,[124] Heinz Schlicke, Werner Sieber,[125] Othmar Stuetzer,[126] Albin Wittmann,[127] Hugo Woerdemann,[128] Albert Zeiler,[129] and Hans K. Ziegler.Material Science (high temperature)Claus Scheufelen [130] and Rudolf Schlidt.[131]Medicine '' including biological weapons, chemical weapons, and space medicineTheodor Benzinger, Rudolf Brill, Konrad Johannes Karl B¼ttner, Richard Lindenberg, Walter Schreiber, Hubertus Strughold, Hans Georg Clamann, and Erich Traub.PhysicsGunter Guttein, Gerhard Schwesinger,[132] Gottfried Wehner, Helmut Weickmann,[133] and Friedwardt Winterberg.Chemistry and Chemical engineeringHelmut Pichler, Leonard Alberts; Ernst Donath, Hans Schappert, Max Josenhaus, Kurt Bretschneider, Erich FreseSimilar operations [ edit ] APPLEPIE: Project to capture and interrogate key Wehrmacht, RSHA AMT VI, and General Staff officers knowledgeable of the industry and economy of the USSR.[134]DUSTBIN (counterpart of ASHCAN): An Anglo-American military intelligence operation established first in Paris, then in Kransberg Castle, at Frankfurt.[135][136]: 314 ECLIPSE (1944): An unimplemented Air Disarmament Wing plan for post-war operations in Europe for destroying V-1 and V-2 missiles.[136][137]: 44 Safehaven: US project within ECLIPSE meant to prevent the escape of Nazi scientists from Allied-occupied Germany.[16]Field Information Agency; Technical (FIAT): US Army agency for securing the "major, and perhaps only, material reward of victory, namely, the advancement of science and the improvement of production and standards of living in the United Nations, by proper exploitation of German methods in these fields"; FIAT ended in 1947, when Operation Paperclip began functioning.[136]: 316 On April 26, 1946, the Joint Chiefs of Staff issued JCS Directive 1067/14 to General Eisenhower instructing that he "preserve from destruction and take under your control records, plans, books, documents, papers, files and scientific, industrial and other information and data belonging to ... German organizations engaged in military research";[15]: 185 and that, excepting war-criminals, German scientists be detained for intelligence purposes as required.[138]National Interest/Project 63: Job placement assistance for Nazi engineers at Lockheed, Martin Marietta, North American Aviation, and other aeroplane companies, whilst American aerospace engineers were being laid off work.[21]Operation Alsos, Operation Big, Operation Epsilon, Russian Alsos: Soviet, American and British efforts to capture German nuclear secrets, equipment, and personnel.Operation Backfire: A British effort at recovering rocket and aerospace technology, followed by assembling and testing rockets at Cuxhaven.Fedden Mission: British mission to gain technical intelligence concerning advanced German aircraft and their propulsion systems.Operation Lusty: US efforts to capture German aeronautical equipment, technology, and personnel.Operation Osoaviakhim (sometimes transliterated as "Operation Ossavakim"), a Soviet counterpart of Operation Paperclip, involving German technicians, managers, skilled workers and their respective families who were relocated to the USSR in October 1946.[139]Operation Surgeon: British operation for denying German aeronautical expertise to the USSR, and for exploiting German scientists in furthering British research.[140]Special Mission V-2: April''May 1945 US operation, by Maj. William Bromley, that recovered parts and equipment for 100 V-2 missiles from a Mittelwerk underground factory in Kohnstein within the Soviet zone. Major James P. Hamill co-ordinated the transport of the equipment on 341 railroad cars with the 144th Motor Vehicle Assembly Company, from Nordhausen to Erfurt, just before the Soviets arrived.[141] (See also Operation Blossom, Broomstick Scientists, Hermes project, Operations Sandy and Pushover)Target Intelligence Committee: US project to exploit German cryptographers.See also [ edit ] Brain drainOperation OsoaviakhimCarmel OffieFort BlissList of Axis personnel indicted for war crimesOperation BloodstoneOperation Lusty '-- targeting advanced aircraft of the defeated LuftwaffeRatlines (World War II)Unit 731 '-- Japanese human experimenters recruited for their biological weapons technology.Upper Atmosphere Research PanelProject MKNAOMINotes [ edit ] ^ Jacobsen, Annie (2014). Operation Paperclip: The Secret Intelligence Program to Bring Nazi Scientists to America. New York: Little, Brown and Company. p. Prologue, ix. ISBN 978-0-316-22105-4. ^ "Joint Intelligence Objectives Agency". U.S. National Archives and Records Administration . Retrieved October 9, 2008 . ^ "Operation "Osoaviakhim " ". Russian space historian Anatoly Zak . Retrieved May 4, 2018 . ^ Project Paperclip: German Scientists and the Cold War, 1971, Clarence G. Lasby, et al. p. 79 ^ a b Project Paperclip: German Scientists and the Cold War, 1971, Clarence G. Lasby, et al. p. 155 ^ Jacobsen, pp. 191. ^ Jacobsen, pp. 193. ^ The Paperclip Conspiracy: The Hunt for the Nazi Scientists, 1987, Tom Bower, et al. p. 178 ^ Jacobsen, pp. 229. ^ a b Lasby, pp. 177. ^ a b c Huzel, Dieter K (1960). Peenem¼nde to Canaveral. Englewood Cliffs NJ: Prentice Hall. pp. 27, 226. ^ Braun, Wernher von; Ordway III; Frederick I (1985) [1975]. Space Travel: A History. & David Dooling Jr. New York: Harper & Row. p. 218. ISBN 978-0-06-181898-1. ^ Forman, Paul; Snchez-Ron, Jos(C) Manuel (1996). National Military Establishments and the Advancement of Science and Technology. Boston Studies in the Philosophy of Science. Kluwer Academic Publishers. p. 308. ISBN 9780792335412. ^ MI6: Inside the Covert World of Her Majesty's Secret Intelligence Service (2000), by Steven Dorril, p. 138. ^ a b c d e McGovern, James (1964). Crossbow and Overcast . New York: W. Morrow. pp. 100, 104, 173, 207, 210, 242. ^ a b c d Ordway, Frederick I, III; Sharpe, Mitchell R (1979). The Rocket Team. Apogee Books Space Series 36. New York: Thomas Y. Crowell. pp. 310, 313, 314, 316, 325, 330, 406. ISBN 978-1-894959-00-1. ^ a b Laney, Monique (2015). German Rocketeers in the Heart of Dixie: Making Sense of the Nazi Past During the Civil Rights Era. New Haven and London: Yale University Press. p. 26. ISBN 978-0-300-19803-4. ^ Boyne, Walter J. (June 2007). "Project Paperclip". Air Force. Air Force Association . Retrieved October 17, 2008 . ^ Note: Located first in Paris and then moved to Kransberg Castle outside Frankfurt. ^ "U.S. Policy and German Scientists: The Early Cold War", Political Science Quarterly, Vol. 101, No. 3, (1986), pp. 433''451 ^ a b c d Hunt, Linda (1991). Secret Agenda: The United States Government, Nazi Scientists, and Project Paperclip, 1945 to 1990. New York: St.Martin's Press. pp. 6, 21, 31, 176, 204, 259. ISBN 978-0-312-05510-3. ^ "Fischer-Tropsch.org". Fischer-Tropsch.org. Archived from the original on September 24, 2015 . Retrieved December 22, 2011 . ^ Project Paperclip: German Scientists and the Cold War, 1975, Clarence G. Lasby, et al. p. 257 ^ "The End of World War II". (television show, Original Air Date: 2-17-05). A&E. Archived from the original on September 27, 2007 . Retrieved June 4, 2007 . ^ Fred Carl. "Operation Paperclip and Camp Evans". Campevans.org. Archived from the original on March 9, 2012 . Retrieved December 22, 2011 . ^ Naimark. 206 (Naimark cites Gimbel, John Science Technology and Reparations: Exploitation and Plunder in Postwar Germany) The $10 billion compare to the 1948 US GDP $258 billion, and to the total Marshall plan (1948''52) expenditure of $13 billion, of which Germany received $1.4 billion (partly as loans). ^ "Goddard Astronautics Award". AAIA: Shaping the Future of Aerospace. American Institute of Aeronautics and Astronautics . Retrieved August 22, 2017 . ^ "International Space Hall of Fame '' Wernher von Braun". New Mexico Museum of Space History. New Mexico Department of Cultural Affairs . Retrieved August 22, 2017 . ^ "International Space Hall of Fame '' Ernst A. Steinhoff". New Mexico Museum of Space History. New Mexico Department of Cultural Affairs . Retrieved August 22, 2017 . ^ "International Space Hall of Fame '' Willy Ley". New Mexico Museum of Space History. New Mexico Department of Cultural Affairs . Retrieved August 22, 2017 . ^ "International Space Hall of Fame '' Hermann J. Oberth". New Mexico Museum of Space History. New Mexico Department of Cultural Affairs . Retrieved August 22, 2017 . ^ Harbaugh, Jennifer (February 18, 2016). "Biography of Wernher Von Braun". NASA . Retrieved May 1, 2018 . ^ AP. "Adolf Busemann, 85, Dead; Designer of the Swept Wing" . Retrieved May 1, 2018 . ^ "Operation Paperclip | Defense Media Network". Defense Media Network . Retrieved May 1, 2018 . ^ Lasby, pp. 177, citing Personal Interview, President Harry S. Truman, Independence, Missouri, June 3, 1963. ^ Michael J. Neufeld (2008). Von Braun: Dreamer of Space, Engineer of War Vintage Series. Random House, Inc. p. 235. ISBN 978-0-307-38937-4. ^ Hunt, Linda (May 23, 1987). "NASA's Nazis". Literature of the Holocaust. ^ a b "Strughold Award". ^ Lagnado, Lucette (December 1, 2012). "A Scientist's Nazi-Era Past Haunts Prestigious Space Prize" '' via Wall Street Journal. ^ https://www.amazon.com/Hans-H.-Amtmann/e/B001KMFDZ4 ^ "Ball, Erich". www.astronautix.com. ^ "Bauschinger". www.astronautix.com. ^ "Beduerftig". www.astronautix.com. ^ "Beichel". www.astronautix.com. ^ "Beier". www.astronautix.com. ^ "Bergeler". www.astronautix.com. ^ "Burose". www.astronautix.com. ^ "Constan". www.astronautix.com. ^ "De Beek". www.astronautix.com. ^ "Drawe". www.astronautix.com. ^ "Duerr". www.astronautix.com. ^ "Eisenhardt". www.astronautix.com. ^ "Finzel". www.astronautix.com. ^ "Fischel". www.astronautix.com. ^ "Fleischer". www.astronautix.com. ^ "Fuhrmann". www.astronautix.com. ^ "Werner K. Gengelbach". National Air and Space Museum. January 16, 2016. ^ "Gruene". www.astronautix.com. ^ "Guendel". www.astronautix.com. ^ Burkhart, Ford (August 29, 1998). "Fritz Haber, 86, Dies; Simulated Weightlessness of Space" '' via NYTimes.com. ^ "Hager". www.astronautix.com. ^ "Haukohl". www.astronautix.com. ^ "Heimburg". www.astronautix.com. ^ Ap (December 19, 1981). "Emil Hellebrand Dead; Rocket Expert Was 67" '' via NYTimes.com. ^ "Heller". www.astronautix.com. ^ "Helm". www.astronautix.com. ^ "Hermann, Rudolf". www.astronautix.com. ^ "Heusinger". www.astronautix.com. ^ "Hueter". www.astronautix.com. ^ "Hintze". www.astronautix.com. ^ "Dieter Huzel". www.de.wikipedia.org. ^ "Kaschig". www.astronautix.com. ^ "Klaus". www.astronautix.com. ^ "Theodore W. Knacke, USA". National Air and Space Museum. January 16, 2016. ^ "Kroll". www.astronautix.com. ^ "Kuers". www.astronautix.com. ^ Darling, David. "Kurzweg, Hermann H. (1908-2000)". www.daviddarling.info. ^ "Lange". www.astronautix.com. ^ "Lindenberg". www.astronautix.com. ^ "Lindenmayer". www.astronautix.com. ^ "Maus". www.astronautix.com. ^ "Merk". www.astronautix.com. ^ "Michel, Josef". www.astronautix.com. ^ "Milde". www.astronautix.com. ^ "Millinger". www.astronautix.com. ^ "Minning". www.astronautix.com. ^ "Mrazek". www.astronautix.com. ^ "Neubert". www.astronautix.com. ^ "Paetz". www.astronautix.com. ^ "Palaoro". www.astronautix.com. ^ "Patt". www.astronautix.com. ^ "Paul". www.astronautix.com. ^ Trotter, Megan. "Cookevillian recalls secret Operation Paperclip". Herald Citizen. ^ "Poppel". www.astronautix.com. ^ "Rosinski". web.archive.org. September 12, 2010. ^ "Rothe". www.astronautix.com. ^ "Schilling". www.astronautix.com. ^ "Schlitt". www.astronautix.com. ^ "Schuler". www.astronautix.com. ^ "Schulze". www.astronautix.com. ^ "Schwidetzky". www.astronautix.com. ^ "Steurer". www.astronautix.com. ^ "Tiller". www.astronautix.com. ^ "Tschinkel". www.astronautix.com. ^ "Urbanski". www.astronautix.com. ^ "Vandersee". www.astronautix.com. ^ "Voss, Werner". www.astronautix.com. ^ "Vowe". www.astronautix.com. ^ "Weidner". www.astronautix.com. ^ "Wiesemann". www.astronautix.com. ^ Roop, Lee (January 26, 2016). "Rare architect's drawings show Huntsville's change from cotton town to Rocket City". al.com. ^ "Luehrsen". www.astronautix.com. ^ Saxon, Wolfgang (September 1, 1996). "Wilhelm Angele, 91, Engineer in Space Program" '' via NYTimes.com. ^ "Boehm". www.astronautix.com. ^ "Friedrich". www.astronautix.com. ^ Ballato, A. (January 1, 1987). "In Memoriam Eduard A. Gerber". IEEE Transactions on Ultrasonics, Ferroelectrics, and Frequency Control. 34 (1): 2. doi:10.1109/T-UFFC.1987.26903. ^ Saxon, Wolfgang (February 9, 2001). "H. Otto Hirschler, 87, Aided Space Program" '' via NYTimes.com. ^ "Hoberg". www.astronautix.com. ^ Saxon, Wolfgang (June 20, 2003). "Rudolf F. Hoelker, 91, Space Flight Scientist" '' via NYTimes.com. ^ " " OPERATION PAPERCLIP" - ARCHIVE OF DR. HORST KEDESDY on LiveAuctioneers". LiveAuctioneers. ^ "Lindner". www.astronautix.com. ^ "Muehlner". www.astronautix.com. ^ "Reisig". www.astronautix.com. ^ "Ruppe". www.astronautix.com. ^ "Sieber". www.astronautix.com. ^ "Albuquerque Journal Obituaries". obits.abqjournal.com. ^ "Wittmann". www.astronautix.com. ^ "Woerdemann". www.astronautix.com. ^ "Albert Zeiler". October 18, 1975 '' via NYTimes.com. ^ "Scheufelen". www.astronautix.com. ^ "Schlidt". www.astronautix.com. ^ "Variable focal length focusing lens system and device therefor". google.com. ^ "Historical Overview of NSSL: We build on the foundations established by our predecessors". www.nssl.noaa.gov. ^ "List Of Terms, Code Names, Operations, and Other Search Terminology To Assist Review and Identification Activities Required by the Act". U.S. National Archives and Records Administration . Retrieved December 19, 2008 . ^ Buchholz, Dr. Annemarie (2003). "The New Form of Government: Bombocracy". Current Concerns. Switzerland. Archived from the original on September 28, 2007 . Retrieved October 18, 2008 . ^ a b c Ziemke, Earl F (1990) [1975]. "Chapter XI:Getting Ready for "The Day " ". The U.S. Army in the Occupation of Germany 1944''1946. Washington DC: United States Army Center of Military History. p. 163. CMH Pub 30-6. ^ Cooksley, Peter G (1979). Flying Bomb. New York: Charles Scribner's Sons. p. 44. ^ Beyerchen, Alan (1982). "German Scientists and Research Institutions in Allied Occupation Policy". History of Education Quarterly. 22 (3): 289''299. doi:10.2307/367770. JSTOR 367770. Much of the FIAT information was adapted commercially, to the degree that the office of the Assistant Secretary of State for Occupied Areas requested that the peace treaty with Germany be redacted to protect US industry from lawsuits. ^ Pennacchio, Charles F. (Fall 1995). "The East German Communists and the Origins of the Berlin Blockade Crisis" (DOC) . East European Quarterly. 29 (3) . Retrieved June 29, 2010 . October 21, 1946, marked the initiation of "Operation Ossavakim", which forcibly transferred to Soviet soil thousands of German technicians, managers and skilled personnel, along with their family members and the industrial tools they would operate. ^ "UK 'fears' over German scientists", BBC News, March 31, 2006 ^ Breuer, William B. (2000). Top Secret Tales of World War II. Wiley. pp. 220''224. ISBN 978-0-471-35382-9. References [ edit ] Yves Beon, Planet Dora. Westview Press, 1997. ISBN 0-8133-3272-9.Giuseppe Ciampaglia: "Come ebbe effettivo inizio a Roma l'Operazione Paperclip". Roma 2005. In: Strenna dei Romanisti 2005. Edit. Roma AmorHenry Stevens, Hitler's Suppressed and Still-Secret Weapons, Science and Technology. Adventures Unlimited Press, 2007. ISBN 1-931882-73-8John Gimbel, "Science Technology and Reparations: Exploitation and Plunder in Postwar Germany" Stanford University Press, 1990 ISBN 0-8047-1761-3Linda Hunt, Arthur Rudolph of Dora and NASA, Moment 4, 1987 (Yorkshire Campaign for Nuclear Disarmament)Linda Hunt, Secret Agenda:The United States Government, Nazi Scientists, and Project Paperclip, 1945 to 1990. St Martin's Press '' Thomas Dunne Books, 1991. ISBN 0-312-05510-2Linda Hunt, U.S. Coverup of Nazi Scientists The Bulletin of the Atomic Scientists. April 1985.Matthias Judt; Burghard Ciesla, Technology Transfer Out of Germany After 1945 Harwood Academic Publishers, 1996. ISBN 3-7186-5822-4Michael C. Carroll, Lab 257: The Disturbing Story of the Government's Secret Germ Laboratory. Harper Paperbacks, 2005. ISBN 0-06-078184-XJohn Gimbel "U.S. Policy and German Scientists: The Early Cold War", Political Science Quarterly, Vol. 101, No. 3 (1986), pp. 433''51Clarence G., Lasby Project Paperclip: German Scientists and the Cold War Scribner (February 1975) ISBN 0-689-70524-7Christopher Simpson, Blowback: America's Recruitment of Nazis and Its Effects on the Cold War (New York: Weidenfeld & Nicolson, 1988)Wolfgang W. E. Samuel American Raiders: The Race to Capture the Luftwaffe's Secrets (University Press of Mississippi, 2004)Koerner, Steven T. "Technology Transfer from Germany to Canada after 1945: A Study in Failure?". Comparative Technology Transfer and Society, Volume 2, Number 1, April 2004, pp. 99''124John Farquharson "Governed or Exploited? The British Acquisition of German Technology, 1945''48" Journal of Contemporary History, Vol. 32, No. 1 (January 1997), pp. 23''421995 Human Radiation Experiments Memorandum: Post-World War II Reccruitment of German Scientists '' Project PaperclipEmployment of German scientists and technicians: denial policy UK National archives releases March 2006."Objective List of German and Austrian Scientists" (Microsoft Word) . Joint Intelligence Objectives Agency . Retrieved April 10, 2007 . Dr. Wernher von Braun First Center Director, July 1, 1960 - Jan. 27, 1970. NASA Marshall Space Flight Center History Office. Retrieved December 31, 2017.Further reading [ edit ] Annie Jacobsen (2014). Operation Paperclip: The Secret Intelligence Program that Brought Nazi Scientists to America. New York: Little, Brown and Company. ISBN 978-0-316-22104-7. OCLC 827257574. Brian E. Crim. 2018. Our Germans: project paperclip and the national security state. Johns Hopkins University Press.Eric Lichtblau (2014). The Nazis Next Door: How America Became a Safe Haven for Hitler's Men. Mariner Books. ISBN 0-544-57788-4Simpson, Christopher (1988). Blowback: America's Recruitment of Nazis and Its Effects on the Cold War. New York: Weidenfeld & Nicolson. ISBN 978-1-55584-106-5.External links [ edit ] In Cold War, U.S. Spy Agencies Used 1,000 Nazis. Eric Lichtblau for The New York Times. October 26, 2014.The Nazis Next Door: Eric Lichtblau on how the CIA & FBI Secretly Sheltered Nazi War Criminals '' video report by Democracy Now!, October 31, 2014
  NMA President Oliver T. Brooks Biography
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    Oliver Tate Brooks, M.D. received his undergraduate degree in biology from Morehouse College in Atlanta, Georgia in 1977, graduating in three years. While at Morehouse, he received the Frederick E. Mapp Prize in Biology for excellence in biology. Dr. Brooks received his medical degree in 1981 from Howard University College of Medicine, where he was a summer instructor in biochemistry. He completed a residency in Pediatrics at Children's Hospital-Oakland, where he practiced for four years before accepting a position at Watts Healthcare Corporation.
    Dr. Brooks is Medical Director and past Chief of Pediatric and Adolescent Medicine at Watts Healthcare Corporation in Los Angeles, California (CA) where he also serves as the Medical Director of the Jordan and Locke High School Wellness Centers. He is a Medical Director for L.A. Care Health Plan, one of the nation's largest Medicaid managed care plans whose mission is ''to provide access to quality health care for Los Angeles County's vulnerable and low-income communities and residents''. He holds staff appointments at Centinela Hospital in Inglewood, CA where he was Chair of the Peer Review Committee and at Martin Luther King Community Hospital in South Los Angeles, CA where he is Vice-Chair of the OB/Pediatrics Department and is a member of its Executive Committee. Dr. Brooks is Chairman of the Community Clinic Association of Los Angeles County, a consortium of 30 community health centers in the southern California area.
    Dr. Brooks has held several leadership positions within the National Medical Association, including the immediate past Speaker, House of Delegates (HOD), Vice-Speaker and Secretary, HOD, and Chairman of the Constitutional and By-Laws Committee. At the state and local level, he served as Past President of the Golden State (CA) Medical Association and Past President of the Miller-Lawrence Medical and Dental Society.
    Dr. Brooks is Immediate Past President of the California Immunization Coalition and Chairman of the Immunize LA Families Coalition. He is a member of the national leadership panel for the Adolescent Immunization Initiative (AII), which advocated successfully for adding a column on the Advisory Committee on Immunization Practice's Center for Disease Control and Prevention yearly vaccine recommendations in 2017. Dr. Brooks is often requested to speak to the media on issues related to immunizations and is a vocal and passionate advocate for reduced disparities in immunization rates among disadvantaged communities. He is frequently asked to speak to physicians and other medical groups on the science and the implementation perspective of vaccine utilization. His community service extends beyond health and wellness and includes serving as Past President of the Long Beach Museum of Art's Board of Trustees.
    Dr. Brooks has received numerous honors and awards, most recently in 2018, he was honored by the National Council of Negro Women, Long Beach, CA for Outstanding Service to the Community and in 2017, he was the Wall of Excellence for Medicine awardee for Long Beach Black History Month. In 2019, Dr. Brooks was honored as one of the Top Blacks in Health Care by BlackDoctor.org.
    Dr. Brooks is a member of the Kappa Alpha Psi and Sigma Pi Phi (the Boule) fraternities. He is married to his wife of 32 years, Lisa and has two children, Alana and Joseph.
  Debbie Birx, AIDS Expert, To Help U.S. Coronavirus Response : NPR
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    U.S. global AIDS coordinator Debbie Birx was named as Vice President Pence's point person on the coronavirus response on Thursday. Riccardo Savi/Getty Images hide caption
    toggle caption Riccardo Savi/Getty Images U.S. global AIDS coordinator Debbie Birx was named as Vice President Pence's point person on the coronavirus response on Thursday.
    Riccardo Savi/Getty Images Updated at 5 :45 p.m.
    The White House sought to show it was shoring up its efforts to corral the spread of coronavirus on Thursday, naming an internationally recognized HIV/AIDS expert as its new coronavirus response coordinator.
    Debbie Birx is a State Department ambassador-at-large who works on global health diplomacy issues. Vice President Pence said Birx would be detailed to his office.
    President Trump put Pence in charge of the response after the stock market plunged and federal health officials warned that Americans should prepare for disruptions if the new COVID-19 coronavirus worsens in the United States.
    The issue has quickly become political, and Democrats in Congress and on the campaign trail have panned Trump for minimizing the risks and failing to appoint a "czar" to lead to the response.
    Birx will also join Trump's coronavirus task force, led by Health and Human Services Secretary Alex Azar, which is charged with responding to the virus. On Thursday, Pence also bolstered its ranks by adding Treasury Secretary Steven Mnuchin and Trump's economic adviser Larry Kudlow '-- signaling concerns about the growing economic threat posed by the virus. Surgeon General Jerome Adams will also join the task force, Pence said.
    Pence toured the Health and Human Services operations center with Secretary Alex Azar after a coronavirus task force meeting. Andrew Harnik/AP hide caption
    toggle caption Andrew Harnik/AP Pence toured the Health and Human Services operations center with Secretary Alex Azar after a coronavirus task force meeting.
    Andrew Harnik/AP Birx directed the Centers for Disease Control and Prevention's global HIV/AIDS division before she became the U.S. global AIDS coordinator in 2014.
    Her new role was applauded by former President Barack Obama's Ebola response coordinator Ron Klain, who was less formally known as the "Ebola czar." But Klain '-- a close adviser to former Vice President and current Democratic primary candidate Joe Biden '-- noted there are now layers of top responders to the virus.
    Amb. Brix is great. But who, exactly, is in charge? Her? Pence? Azar?
    '-- Ronald Klain (@RonaldKlain) February 27, 2020Pence sought to make clear on Thursday that he was in charge. "I'm leading the task force, will continue to rely on the secretary's role as chairman of the task force and the leader of Health and Human Services," Pence said after meeting with the task force.
    "But the president wanted to make it clear to the American people that we're going to bring a whole-of-government approach to this," he said.
Music in this episode
  Intro: Future - Mask Off x
  Outro: Going Spaceward - Quarantine with Me
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