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Depo Provera

Drugs & Medication

Depo Provera

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Depo Provera
B.C. type Hormonal
First use 1967
Failure rates (per year)
Perfect use 0.3%
Typical use 0.3%
Duration effect 90 days
(12weeks + 5 days)
Reversibility  ?-18+months
User reminders Maximum interval is just under 3 months
Clinic review 12 weeks
Periods Usually no periods from 2nd injection
Benefits Especially if poor pill compliance.
Reduced endometrial cancer risk.
STD protection No
Periods Especially in 1st injection may be frequent spotting
Weight gain Yes
Risks Reduced bone density; possible risk of breast cancer, cervical cancer.
Medical notes
For those intending to start family, suggest switch 6 months prior to alternative method (eg POP) allowing more reliable return fertility.

Depo-Provera is a contraceptive or birth control product which is injected every 3 months.

It is the brand name for medroxyprogesterone acetate manufactured by Pfizer Inc. It is a hormonal birth control method containing the pregnane (17α-hydroxyprogesterone derivative) progestin medroxyprogesterone acetate, without estrogen, and is administered to women in the form of an intramuscular injection once every 11 to 13 weeks. Depo-Provera causes the ovaries to stop releasing eggs.


How it works

The mechanism of action of progestin-only contraceptives depends on the progestin activity and dose.[1][2] High dose progestin-only contraceptives, such as the injectable Depo-Provera, completely inhibit follicular development and ovulation. Like all progestin-only contraceptives, Depo-Provera also has a progestogenic effect of increasing cervical mucus viscosity, thereby inhibiting sperm penetration. In anovulatory cycles using progestin-only contraceptives, the endometrium is thin and atrophic. If the endometrium was also thin and atrophic during an ovulatory cycle, this could theoretically interfere with implantation of a blastocyst (embryo).


  • Near 100% effective at preventing pregnancy.
  • Injected every 3 months. The only continuing action is to book subsequent follow-up injections every twelve weeks, and to monitor side effects to insure that they do not require medical attention.
  • 80% reversible within 12 months and 95% reversible within 18 months
  • Depo-Provera reduces the risk of endometrial cancer by 80%.[3][4][5] The reduced risk of endometrial cancer in Depo-Provera 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.[6]

Pregnancy and breastfeeding

Depo Provera may be used by breast-feeding 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 small 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 possible subgroup of babies with 75% higher incidence of infectious disease was seen in mothers who started Depo Provera at 2 days postpartum.[7] 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." "Unfavorable socioeconomic factors" may therefore result in suboptimal height for 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.[8]

Disadvantages and side effects

Warnings and precautions

  • Takes two weeks to take effect
  • Offers no protection against Sexually transmitted diseases(STDs)
  • Depo Provera can affect menstrual bleeding. After a year of use, 55% of women experience amenorrhoea; 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.[9] Some women may prefer amenorrhea. According to Jerilynn Prior, M.D., professor of endocrinology and metabolism at the University of British Columbia in Vancouver, and board member for the Society for Menstrual Cycle Research,"the most important thing to emphasize about menstrual suppression is that the long-term effects are simply unknown," and "allowing the one vital sign unique to women to go unmonitored...could ultimately lead to an enormous uncontrolled experiment with a woman's health." [10]
  • Return to fertility may be slow. Fifty percent of women may be able to conceive in about 10 months from the last injection, but fertility may be totally suppressed in some women for up to 18 months or more.[9]
  • Long-term studies of users of Depo-Provera have found slight or no increased overall risk of breast cancer. However, one subset of the study population did show an increased risk of breast cancer in recent users (Depo use in the last four years) under age 35.[9]
  • Infants born to women exposed to Depo during pregnancy in one study had an 80% greater chance of dying in the first year of life.[11]

Black box warning

While it has long been known that Depo-Provera causes bone loss, it has recently been discovered that the osteoporotic effects of the injection grow worse the longer Depo-Provera is administered, last long after the injections are stopped, and may be irreversible. For this reason, on November 17, 2004 the United States Food and Drug Administration and Pfizer agreed to put a "black box warning" on Depo-Provera's label.[12] However, the WHO (World Health Organization)—which provided Depo-Provera to developing countries when the US FDA refused to approve it for safety reasons pertaining to breast cancer—advises that the use of Depo Provera should not be restricted.[1][13][14]

It is unclear whether the bone density loss associated with Depo-Provera use is reversible, and if so, how completely. Three studies have suggested that bone loss is reversible after the discontinuation of Depo-Provera, although one notes that bone loss was not reversible in long-term users of Depo-Provera, and the others were conducted in part by a Pfizer consultant. [15][16][17] Other studies have suggested that the effect of Depo-Provera use on post-menopausal bone density is minimal,[18] perhaps because Depo users experience less bone loss at menopause.[19] However, as of 2006, no study has directly examined fracture risk in post-menopausal women who have used Depo-Provera; therefore, the risk is unknown. Pfizer and the FDA recommend that Depo-Provera not be used for longer than 2 years, unless there is no viable alternative method of contraception, due to concerns over bone loss.[12]

Side effects

Depo-Provera may have side effects including irregular menstrual bleeding, no mentrual bleeding, constant bleeding (metrorrhagia), severe headaches, weight gain, weight loss, panic attacks, muscle pain, heart palpitations, pain during sex, acne, abdominal cramps, dizziness, weakness or fatigue, leg cramps, nausea, vaginal discharge or irritation, breast swelling and tenderness, bloating, swelling of the hands or feet, backache, depression,insomnia, pelvic pain, no hair growth or excessive hair loss, rash, hot flashes,joint pain, convulsions, jaundice, urinary tract infections, allergic reactions, fainting, paralysis, deep vein thrombosis, and pulmonary embolus.[9]

Related studies

  • A study of 819 women in one city found an association between using Depo-Provera and higher incidence of chlamydia and gonorrhea.[20]
  • A study of 28 rhesus monkeys linked progesterone implants (similar to, but not identical to Depo Provera) to an eightfold increase in SIV contraction.[21] While studies have not been performed on humans or with HIV, this may suggest an enhanced risk of HIV transmission.[22]
  • A study in mice found that Depo Provera may simultaneously increase susceptibility to the herpesvirus and decrease immune response to the herpesvirus. [23]
  • Depo Provera, exacerbates glutamate excitotoxicity, which may render users more vulnerable to neurodegeneration. [24]


Women with the following conditions should not use Depo Provera:

  • stroke
  • currently pregnant
  • current or past breast cancer
  • liver problems or liver disease
  • blood clots

Other uses

Depo-Provera is also used with male sex offenders as a form of chemical castration as it has the effect of drastically reducing sex drive in males.[2]

Controversy over Approval of Depo

There is a long, controversial history regarding the approval of Depo Provera by the FDA. The original manufacturer, Upjohn, applied repeatedly for approval--which was repeatedly denied. Points in the controversy include:

  • Animal testing for carcinogenicity. Depo Provera 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 Depo Provera which caused malignant mammary tumors in dogs were equivalent to 25 times the amount of the normal luteal phase progesterone level for dogs. (Which is lower than the pregnancy level of progesterone for dogs, and is species-specific.)[3]
    Depo Provera caused endometrial cancer in monkeys--2 of 12 monkeys tested, the first ever recorded cases of endometrial cancer in rhesus monkeys.[25]
    Speaking in comparative terms regarding animal studies of carcinogenicity for drugs, a member of the FDA's Bureau of Drugs testified at an agency Depo hearing, "...Animal data for this drug is more worrisome than any other drug we know of that is to be given to well people."
  • Bias of OB-GYN committee. The OB-GYN Committee, which advised the FDA to approve Depo on the two occaisons when it was not approved, was not capable of objectivity according to senior FDA officials/a former director of the FDA bureau of drugs, because members of the committee were in "the population control business."[25]
  • 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. [26]
  • Coercion and Lack of Informed Consent. Testing/use of Depo was focused almost exclusively on women of color in developing countries, (especially Thailand, during the years that it was a US sponsored military dictatorship) and poor women of color in the US, raising serious questions about coercion and lack of informed consent, particularly for the illiterate[27] and for the mentally retarded, who were given Depo long-term merely to eliminate "menstrual hygiene."[28]
  • Atlanta/Grady Study. Upjohn studied the effect of Depo 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 Depo 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.
  • WHO Review. In 1992, the WHO presented a review of Depo 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--that the WHO could not advise the FDA not to approve Depo after they had already distributed it in developing countries. The WHO's objectivity has recently also been criticized for receiving donations from pharmaceutical companies.[29]. Depo was approved for use in US 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.[4]The Alan Guttmacher Institute has speculated that US approval of Depo may increase its availability and acceptability in developing countries.[5][30]
  • FDA scientists report concern about their ability to voice scientific concern or inform the public about unsafe drugs, something they did not report in the years approval for Depo was rejected.[31]


  • In 1995, women's health groups asked the FDA to put a moratorium on Depo Provera, and to institute informed consent forms following a universal standard.[32]
  • Scientists and women's groups in India continue to oppose Depo Provera.[33]In 2002, Depo was removed from the family planning protocol in India.
  • One in five black teenagers using birth control in the US uses Depo Provera--a far higher rate of use than for white teenagers. Activists claim this is because black teenagers are disproportionately targeted for the least safe contraceptives.[34]
  • The Canadian Coalition on Depo-Provera, a coalition of women's health professional and advocacy groups, opposed the approval of Depo in Canada.[35] Since the approval of Depo in Canada in 1997, a $700 million dollar class action lawsuit has been filed against Pfizer.[36]


  1. ^ Glasier, Anna (2006). “Contraception”, in DeGroot, Leslie J.; Jameson, J. Larry (eds.) Endocrinology, 5th edition, Philadelphia: Elsevier Saunders, pp. 2993-3003. ISBN 0-72-160376-9.
  2. ^ Loose, Davis S.; Stancel, George M. (2006). “Estrogens and Progestins”, in Brunton, Laurence L.; Lazo, John S.; Parker, Keith L. (eds.) Goodman & Gilman's The Pharmacological Basis of Therapeutics, 11th ed., New York: McGraw-Hill, pp. 1541-1571. ISBN 0-071-42280-3.
  3. ^ Kaunitz AM (2001). "Current options for injectable contraception in the United States". Semin Reprod Med 19 (4): 331-7. PMID 11727175.
  4. ^ Bigrigg A, Evans M, Gbolade B, Newton J, Pollard L, Szarewski A, Thomas C, Walling M (1999). "Depo Provera. Position paper on clinical use, effectiveness and side effects". Br J Fam Plann 25 (2): 69-76. PMID 10454658.
  5. ^ WHO Collaborative Study of Neoplasia and Steroid Contraceptives (1991). "Depot-medroxyprogesterone acetate (DMPA) and risk of endometrial cancer". Int J Cancer 49 (2): 186-90. PMID 1831802.
  6. ^ Santen, Richard J. (2004). “Endocrinology of Breast and Endometrial Cancer”, in Strauss, Jerome F. III; Barbieri, Robert L. (eds.) Yen and Jaffe's Reproductive Endocrinology, 5th edition, Philadelphia: Elsevier Saunders, pp. 787-809. ISBN 0-72-169546-9.
  7. ^ Dahlberg K (1982). "Some effects of depo-medroxyprogesterone acetate (DMPA): observations in the nursing infant and in the long-term user.". Int J Gynaecol Obstet 20 (1): 43-8. PMID 6126406.
  8. ^ Pardthaisong T, Yenchit C, Gray R (1992). "The long-term growth and development of children exposed to Depo-Provera during pregnancy or lactation.". Contraception 45 (4): 313-24. PMID 1387602.
  9. ^ a b c d Depo Provera - Patient labeling (PDF original). Pfizer (October 2004).
  10. ^ Health experts define menstrual cycle as critical indicator of women's overall health. Medical News Today (September 22, 2004).
  11. ^ (1992) "Exposure to DMPA in pregnancy may cause low birth weight.". Prog Hum Reprod Res (23): 2-3. PMID 12286194.
  12. ^ a b FDA (November 17 2004). Black Box Warning Added Concerning Long-Term Use of Depo-Provera Contraceptive Injection. Retrieved on 2006-05-12.
  13. ^ World Health Organization (September 2005). Hormonal contraception and bone health. Family Planning. Retrieved on 2006-05-12.
  14. ^ Curtis KM, Martins SL (2006). "Progestogen-only contraception and bone mineral density: a systematic review". Contraception 73 (5): 470-87. PMID 16627031.
  15. ^ Cundy T, Cornish J, Evans M, Roberts H, Reid I (1994). "Recovery of bone density in women who stop using medroxyprogesterone acetate.". BMJ 308 (6923): 247-8. PMID 8111260.
  16. ^ Scholes D, LaCroix AZ, Ichikawa LE, Barlow WE, Ott SM (2002). "Injectable hormone contraception and bone density: results from a prospective study". Epidemiology 13 (5): 581-7. PMID 12192229.
  17. ^ Scholes D, LaCroix AZ, Ichikawa LE, Barlow WE, Ott SM (2005). "Change in bone mineral density among adolescent women using and discontinuing depot medroxyprogesterone acetate contraception". Arch Pediatr Adolesc Med 159 (2): 139-44. PMID 15699307.
  18. ^ Orr-Walker B, Evans M, Ames R, Clearwater J, Cundy T, Reid I (1998). "The effect of past use of the injectable contraceptive depot medroxyprogesterone acetate on bone mineral density in normal post-menopausal women.". Clin Endocrinol (Oxf) 49 (5): 615-8. PMID 10197077.
  19. ^ Cundy T, Cornish J, Roberts H, Reid I (2002). "Menopausal bone loss in long-term users of depot medroxyprogesterone acetate contraception.". Am J Obstet Gynecol 186 (5): 978-83. PMID 12015524.
  20. ^ Morrison CS, Bright P, Wong EL, Kwok C, Yacobson I, Gaydos CA, Tucker HT, Blumenthal PD (2004). "Hormonal contraceptive use, cervical ectopy, and the acquisition of cervical infections". Sex Transm Dis 31 (9): 561-7. PMID 15480119.
  21. ^ Preston A. Marx, et al. (1996). "Progesterone implants enhance SIV vaginal transmission and early virus load.". Nature Medicine 2 (10): 1084-9. DOI:10.1038/nm1096-1084. PMID 8837605.
  22. ^ Sara Littlecrow-Russell (Summer 2000). NO. 5 - Time to Take a Critical Look at Depo-Provera (PDF original). Population and Development Program. Hampshire Colledge.
  23. ^ Kaushic, C. et al (2003). "Progesterone increases susceptibility and decreases immune responses to genital herpes infection". Journal of Virological Methods 77. PMID 12663762.
  24. ^ Nilsen, J. et al (2006). "Medroxyprogesterone acetate exacerbates glutamate excitotoxicity". Gynecological endocrinology 22. PMID 16864144.
  25. ^ a b Amy Goodman (February/March 1985). "The Case Against Depo-Provera - Problems in the U.S.". Multinational Monitor Volume 6 (Numbers 2 & 3).
  26. ^ (1977) "Controversy over Depo-Provera.". Wash Drug Device Lett 9 (1): 2. PMID 12335988.
  27. ^ (1973) "Sterilization of minors leads to controversy.". JOICFP Rev 2 (4): 77-8. PMID 12257656.
  28. ^ Egan T, Siegert R, Fairley N (1993). "Use of hormonal contraceptives in an institutional setting: reasons for use, consent and safety in women with psychiatric and intellectual disabilities.". N Z Med J 106 (961): 338-41. PMID 8341476.
  29. ^ Suddenly sick: The hidden big business behind your doctor's diagnosis. Seattle Times. Retrieved on 2006-08-22.
  30. ^ Singh S (1995). "Adolescent knowledge and use of injectable contraceptives in developing countries.". J Adolesc Health 16 (5): 396-404. PMID 7662691.
  31. ^ Inside the FDA: Many FDA Scientists Think Agency Could Do Better on Drug Monitoring. CBS News Healthwatch. Retrieved on 2006-11-3.
  32. ^ (1995) "Clinicians clash with consumer groups over possible Depo ban.". Contracept Technol Update 16 (1): 11-4. PMID 12319319.
  33. ^ Sorojini, NB (Jan-Mar 2005). "Why women's groups oppose injectable contraceptives". Indian Journal of Medical Ethics 13 (1).
  34. ^ Moira Brennan (April*May 2001). Dorothy Roberts: What we talk about when we talk about reproductive rights. Ms Magazine. Retrieved on 2006-08-22.
  35. ^ Madeline Boscoe (December 6 1991). Canadian Coalition on Depo-Provera letter to The Honorable Benoit Bouchard, National Minister of Health and Welfare. Canadian Women's Health Network. Retrieved on 2006-08-22.
  36. ^ Class action suit filed over birth control drug. (Dec 19 2005). Retrieved on 2006-08-22.

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