Depot medroxyprogesterone acetate
|Failure rates (first year)|
|Duration effect||3 months
|User reminders||Maximum interval is just under 3 months|
|Clinic review||12 weeks|
|Advantages and disadvantages|
|Period disadvantages||Especially in first injection may be frequent spotting|
|Period advantages||Usually no periods from 2nd injection|
|Benefits||Especially good if poor pill compliance.
Reduced endometrial cancer risk.
|Risks||Reduced bone density, which may reverse after discontinuation|
|For those intending to start family, suggest switch 6 months prior to alternative method (e.g. POP) allowing more reliable return fertility.|
Depot medroxyprogesterone acetate (DMPA) is a long-acting reversible hormonal contraceptive birth control drug that is injected every three months. It is a progestin-only contraceptive. It is marketed under the brand name Depo-Provera.
- 1 Effectiveness
- 2 Benefits
- 3 Contraindications
- 4 Side effects
- 5 Pregnancy and breastfeeding
- 6 Other uses
- 7 Mechanism of action
- 8 Society and culture
- 9 See also
- 10 References
- 11 External links
Estimates of first-year failure rates are about 0.3%.
Trussell's estimated perfect use first-year failure rate for Depo-Provera as the average of failure rates in seven clinical trials at 0.3%. It was considered perfect use because the clinical trials measured efficacy during actual use of Depo-Provera 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 Depo-Provera was the same as his perfect use failure rate: 0.3%.
- Depo-Provera estimated typical use first-year failure rate = 0.3% in:
- Depo-Provera estimated typical use first-year failure rate = 3% in:
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 Depo-Provera) 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.
- 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 (DVT), pulmonary embolism (PE), stroke, or myocardial infarction.
- Minimal drug interactions (compared to other hormonal contraceptives).
- Decreased risk of endometrial cancer. Depo-Provera reduces the risk of endometrial cancer by 80%. 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.
- Decreased risk of iron deficiency anemia, pelvic inflammatory disease (PID), ectopic pregnancy, 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, Depo-Provera's contraceptive effectiveness is not affected by enzyme-inducing antiepileptic drugs.
- Decreased incidence and severity of sickle cell crises in women with sickle-cell disease.
The United Kingdom Department of Health has actively promoted Long Acting Reversible Contraceptive use since 2008, particularly for young people; following on from the October 2005 National Institute for Health and Clinical Excellence guidelines. Giving advice on these methods of contraception has been included in the 2009 Quality and Outcomes Framework "good practice" for primary care.
The WHO Medical Eligibility Criteria for Contraceptive Use and RCOG Faculty of Family Planning & Reproductive Health Care (FFPRHC) UK Medical Eligibility Criteria for Contraceptive Use list the following as conditions where use of Depo-Provera is not usually recommended or should not be used because of an unacceptable health risk or because it is not indicated:
Conditions where the theoretical or proven risks usually outweigh the advantages of using Depo-Provera:
- Multiple risk factors for arterial cardiovascular disease
- Current deep vein thrombosis (DVT) or pulmonary embolus (PE)
- Migraine headache with aura while using Depo-Provera
- Before evaluation of unexplained vaginal bleeding suspected of being a serious condition
- A history of breast cancer and no evidence of current disease for five years
- Active liver disease: (acute viral hepatitis, severe decompensated cirrhosis, benign or malignant liver tumours)
- Conditions of concern for hypo-estrogenic effects and reduced HDL levels theoretically increasing cardiovascular risk:
Conditions which represent an unacceptable health risk if Depo-Provera is used:
- Current or recent breast cancer (a hormonally sensitive tumour)
Conditions where use of Depo-Provera is not indicated and should not be initiated:
Warnings and precautions
- Takes one week to take effect if given after the first five days of the period cycle. Effective immediately if given during the first five days of the period cycle.
- Offers no protection against sexually transmitted diseases (STDs).
- Depo-Provera can affect menstrual bleeding. After a year of use, 55% of women experience amenorrhoea (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.
- Delayed return of fertility. The average return to fertility is 9 to 10 months after the last injection. By 18 months after the last injection, fertility is the same as that in former users of other contraceptive methods
- Long-term studies of users of Depo-Provera 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 (Depo use in the last four years) under age 35, similar to that seen with the use of combined oral contraceptive pills.
- A study of accidental pregnancies among poor women in Thailand found that infants who had been exposed to Depo-Provera 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.
Black box warning
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. While it causes temporary bone loss, most women regain their bone density after discontinuing use. The World Health Organization (WHO) recommends that the use not be restricted. 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 Depo-Provera. Other studies have suggested that the effect of Depo-Provera use on post-menopausal bone density is minimal, perhaps because Depo users experience less bone loss at menopause. Use after peak bone mass is associated with increased bone turnover but no decrease in bone mineral density.
The FDA recommends 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. 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 Depo-Provera beyond 2 years of use.
There is uncertainty regarding the risk of HIV acquisition among DMPA users; some observational studies suggest an increased risk, others do not. 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.
Two meta-analyses of observational studies in sub-Saharan Africa were published in January 2015. They found a 1.4 to 1.5 fold increase risk of HIV acquisition for DMPA users relative to no hormonal contraceptive use. 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.
A large, four-year randomized controlled trial of hormonal contraception and HIV in sub-Saharan Africa (to provide better evidence than currently available observational studies) that is planned to begin in 2015 has been controversial.
Pregnancy and breastfeeding
The steroid hormone Progesterone is produced in increasingly larger amounts over the course of a pregnancy. The main ingredient in Depo-Provera, medroxyprogesterone acetate, is similar to Progesterone USP but does not support pregnancy. Women who learn they are pregnant should discontinue use of Depo-Provera and visit with her doctor for appropriate health care.
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 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 Depo-Provera at 2 days postpartum had a 75% higher incidence of doctor visits for infectious diseases during their first year of life.
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.
Mechanism of action
The mechanism of action of progestogen-only contraceptives depends on the progestogen activity and dose. High-dose progestogen-only contraceptives, such as injectable DMPA, inhibit follicular development and prevent ovulation as their primary mechanism of action. 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.
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.
Society and culture
Depo-Provera is the brand name for a 150 mg aqueous injection of DMPA depot medroxyprogesterone acetate. It is applied in the form of an intramuscular injection. The shot must be injected into the thigh or buttocks or deltoid four times a year (every 11 to 13 weeks) and provides pregnancy protection instantaneously after the first injection. It was approved in the United States by the FDA for contraceptive use on 29 October 1992, and for management of endometriosis-related pain on 25 March 2005. Depo-subQ Provera 104, also manufactured by Pfizer, is a variation of the original Depo Shot that is instead a 104 mg subcutaneous injection. It contains 69 percent of progestin found in the original Depo-Provera shot. This can be injected using a smaller injection needle inserting the hormone 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 the progestin while still maintaining all the same benefits of the original Depo shot.
Outside the United States
- In 1994, when Depo 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."  Some scientists and women's groups in India continue to oppose Depo-Provera. In 2002, Depo was removed from the family planning protocol in India.
- The Canadian Coalition on Depo-Provera, a coalition of women's health professional and advocacy groups, opposed the approval of Depo in Canada. Since the approval of Depo in Canada in 1997, a $700 million class-action lawsuit has been filed against Pfizer by users of Depo who developed osteoporosis. In response, Pfizer argued that it had met its obligation to disclose and discuss the risks of Depo-Provera with the Canadian medical community.
- Clinical trials for this drug 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 Depo-Provera 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 Depo-Provera injections to women "if there is the slightest doubt that they have not understood the implications of the treatment".
There was a long, controversial history regarding the approval of Depo-Provera 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 Depo-Provera, 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. Points in the controversy included:
- 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. This is lower than the pregnancy level of progesterone for dogs, and is species-specific.
Depo-Provera caused endometrial cancer in monkeys—2 of 12 monkeys tested, the first ever recorded cases of endometrial cancer in rhesus monkeys. However, subsequent studies have shown that in humans, Depo-Provera reduces the risk of endometrial cancer by approximately 80%.
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."
- 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. However, numerous larger subsequent studies have shown that Depo-Provera use does not increase the risk of cervical cancer.
- Coercion and lack of informed consent. Testing or use of Depo was focused almost exclusively on women in developing countries and poor women in the US, raising serious questions about coercion and lack of informed consent, particularly for the illiterate and for the mentally challenged, who in some reported cases were given Depo long-term for reasons of "menstrual hygiene", although they were not sexually active.
- 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, as the WHO had already distributed Depo-Provera in developing countries. 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.The Alan Guttmacher Institute has speculated that US approval of Depo may increase its availability and acceptability in developing countries.
- In 1995, several women's health groups asked the FDA to put a moratorium on Depo-Provera, and to institute standardized informed consent forms.
- Trussell, James (2011). "Contraceptive efficacy". In Hatcher, Robert A.; Trussell, James; Nelson, Anita L.; Cates, Willard Jr.; Kowal, Deborah; Policar, Michael S. (eds.). Contraceptive technology (20th revised ed.). New York: Ardent Media. pp. 779–863. ISBN 978-1-59708-004-0. ISSN 0091-9721. OCLC 781956734. Table 26–1 =
- Trussell, James (2004). "Contraceptive Efficacy". In Hatcher, Robert A.; Trussell, James; Stewart, Felicia H.; Nelson, Anita L.; Cates Jr., Willard; Guest, Felicia; Kowal, Deborah. Contraceptive Technology (18th rev. ed.). New York: Ardent Media. pp. 773–845. ISBN 0-9664902-5-8.
- Trussell J (2004). "Contraceptive failure in the United States". Contraception. 70 (2): 89–96. doi:10.1016/j.contraception.2004.03.009. PMID 15288211.
- Trussell J, Hatcher RA, Cates W Jr, Stewart FH, Kost K (1990). "A guide to interpreting contraceptive efficiency studies". Obstet Gynecol. 76 (3 Pt 2): 558–67. PMID 2199875.
- Trussell, James (1994). "Contraceptive Failure Rates". In Hatcher, Robert A.; Trussell, James; Stewart, Felicia; Stewart, Gary K.; Kowal, Deborah; Guest, Felicia; Cates Jr., Willard; Policar, Michael S. Contraceptive Technology (16th rev. ed.). New York: Irvington Publishers. pp. 637–688. ISBN 0-8290-3171-5.
- Trussell, James (1998). "Contraceptive Efficacy". In Hatcher, Robert A.; Trussell, James; Stewart, Felicia; Cates Jr., Willard; Stewart, Gary K.; Guest, Felicia; Kowal, Deborah. Contraceptive Technology (17th rev. ed.). New York: Ardent Media. pp. 779–844. ISBN 0-9664902-0-7.
- FDA (1998). "Guidance for Industry - Uniform Contraceptive Labeling" (PDF). Archived from the original (PDF) on February 25, 2007. Retrieved 2007-06-21.
- Trussell, James (2007). "Contraceptive Efficacy". In Hatcher, Robert A.; Trussell, James; Nelson, Anita L.; Cates Jr., Willard; Stewart, Felicia H.; Kowal, Deborah. Contraceptive Technology (19th rev. ed.). New York: Ardent Media. Retrieved 2007-06-21.
- Trussell J, Vaughan B (1999). "Contraceptive failure, method-related discontinuation and resumption of use: results from the 1995 National Survey of Family Growth" (PDF). Fam Plann Perspect. 31 (2): 64–72, 93. doi:10.2307/2991641. JSTOR 2991641. PMID 10224544.
- Hatcher, Robert A. (2004). "Depo-Provera Injections, Implants, and Progestin-Only Pills (Minipills)". In Hatcher, Robert A.; Trussell, James; Stewart, Felicia H.; Nelson, Anita L.; Cates Jr., Willard; Guest, Felicia; Kowal, Deborah. Contraceptive Technology (18th rev. ed.). New York: Ardent Media. pp. 461–494. ISBN 0-9664902-5-8.
- Speroff, Leon; Darney, Philip D. (2005). "Injectable Contraception". A Clinical Guide for Contraception (4th ed.). Philadelphia: Lippincott Williams & Wilkins. pp. 201–220. ISBN 0-7817-6488-2.
- Westhoff C (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.
- Mishell Jr.; Daniel R. (2004). "Contraception". In Strauss, Jerome F. III; Barbieri, Robert L. Yen and Jaffe's Reproductive Endocrinology (5th ed.). Philadelphia: Elsevier Saunders. pp. 899–938. ISBN 0-7216-9546-9.
- Kaunitz AM (2001). "Current options for injectable contraception in the United States". Semin Reprod Med. 19 (4): 331–7. doi:10.1055/s-2001-18641. PMID 11727175.
- 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.
- 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. doi:10.1002/ijc.2910490207. PMID 1831802.
- Santen, Richard J. (2004). "Endocrinology of Breast and Endometrial Cancer". In Strauss, Jerome F. III; Barbieri, Robert L. Yen and Jaffe's Reproductive Endocrinology (5th ed.). Philadelphia: Elsevier Saunders. pp. 787–809. ISBN 0-7216-9546-9.
- Bartz, Deborah; Goldberg, Alisa B. (2011). "Injectable contraceptives". In Hatcher, Robert A.; Trussell, James; Nelson, Anita L.; Cates, Willard Jr.; Kowal, Deborah; Policar, Michael S. (eds.). Contraceptive technology (20th revised ed.). New York: Ardent Media. pp. 209–236. ISBN 978-1-59708-004-0. ISSN 0091-9721. OCLC 781956734. pp. 212–213:
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
- O'Brien MD, Guillebaud J (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". Nursing Times.net. 21 October 2008. Retrieved 2009-06-19.
- "CG30 Long-acting reversible contraception: quick reference guide" (PDF). National Institute for Health and Clinical Excellence. Retrieved 2009-06-19.
- "Sexual Health Ruleset" (PDF). New GMS Contract Quality and Outcome Framework - Implementation Dataset and Business Rules. Primary Care Commissioning. 1 May 2009. Retrieved 2009-06-19.
* "Contraception - Management QOF indicators". NHS Clinical Knowledge Summaries. NHS Institute for Innovation and Improvement. Retrieved 2009-06-19.
- WHO (2004). "Progestogen-only contraceptives". Medical Eligibility Criteria for Contraceptive Use (3rd ed.). Geneva: Reproductive Health and Research, WHO. ISBN 92-4-156266-8.
- FFPRHC (2006). "The UK Medical Eligibility Criteria for Contraceptive Use (2005/2006)" (PDF). Archived from the original (PDF) on June 19, 2007. Retrieved 2007-01-11.
- Pfizer (October 2004). "Depo-Provera Contraceptive Injection, US patient labeling" (PDF). Retrieved 2007-02-21.
- "Exposure to DMPA in pregnancy may cause low birth weight". Prog Hum Reprod Res (23): 2–3. 1992. PMID 12286194.
- "Depot medroxyprogesterone acetate and bone effects. Committee Opinion #602". June 2014. Retrieved 2015-05-03.
- FDA (November 17, 2004). "Black Box Warning Added Concerning Long-Term Use of Depo-Provera Contraceptive Injection". Archived from the original on 2005-12-21. Retrieved 2006-05-12.
- World Health Organization (September 2005). "Hormonal contraception and bone health". Family Planning. Retrieved 2006-05-12.
- Curtis KM, Martins SL (2006). "Progestogen-only contraception and bone mineral density: a systematic review". Contraception. 73 (5): 470–87. doi:10.1016/j.contraception.2005.12.010. PMID 16627031.
- 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. doi:10.1136/bmj.308.6923.247. PMC . PMID 8111260.
- 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. doi:10.1097/00001648-200209000-00015. PMID 12192229.
- 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. doi:10.1001/archpedi.159.2.139. PMID 15699307.
- 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. doi:10.1046/j.1365-2265.1998.00582.x. PMID 10197077.
- 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. doi:10.1067/mob.2002.122420. PMID 12015524.
- Walsh JS, Eastell R, Peel NF (November 2008). "Depot medroxyprogesterone acetate use after peak bone mass is associated with increased bone turnover but no decrease in bone mineral density". Fertil. Steril. 93 (3): 697–701. doi:10.1016/j.fertnstert.2008.10.004. PMID 19013564.
- &Na; (2008). "ACOG Committee Opinion No. 415: Depot Medroxyprogesterone Acetate and Bone Effects". Obstetrics & Gynecology. 112 (3): 727–730. doi:10.1097/AOG.0b013e318188d1ec. PMID 18757687.
- Polis, Chelsea B.; Phillips, Sharon J.; Curtis, Kathyrn M.; Westreich, Daniel J.; Steyn, Petrus S.; Raymond, Elizabeth; Hannaford, Philip; Turner, Abigail Norris (July 23, 2014). "Hormonal contraceptive methods and risk of HIV acquisition in women: a systematic review of epidemiological evidence". Contraception. 90 (4): 360–390. doi:10.1016/j.contraception.2014.07.009. PMID 25183264.
- WHO Department of Reproductive Health and Research (February 16, 2012). "Technical Statement: Hormonal contraception and HIV". Geneva: World Health Organization.
- WHO Department of Reproductive Health and Research (July 23, 2014). "2014 Guidance Statement: Hormonal contraceptive methods for women at high risk of HIV and living with HIV" (PDF). Geneva: World Health Organization.
- AVAC (January 27, 2015). "News from the HC-HIV front: it's raining meta (analyses)!". New York: AIDS Vaccine Advocacy Coalition.
- Ralph, Lauren J.; McCoy, Sandra I.; Shiu, Karen; Padian, Nancy S. (January 8, 2015). "Hormonal contraceptive use and women's risk of HIV acquisition: a meta-analysis of observational studies". Lancet Infectious Diseases. 15 (2): 181–189. doi:10.1016/S1473-3099(14)71052-7. PMID 25578825.
- Morrison, Charles S.; Chen, Pai-Lien; Kwok, Cynthia; Baeten, Jared M.; Brown, Joelle; Crook, Angela M.; Van Damme, Lut; Delany-Moretlwe, Sinead; Francis, Suzanna C.; Friedland, Barbara A.; Hayes, Richard J.; Heffron, Renee; Kapiga, Saidi; Karim, Quarraisha Abdool; Karpoff, Stephanie; Kaul, Rupert; McClelland, R. Scott; McCormack, Sheena; McGrath, Nuala; Myer, Landon; Rees, Helen; van der Straten, Ariane; Watson-Jones, Deborah; van de Wijgert, Janneke H. H. M.; Stalter, Randy; Low, Nicola (January 22, 2015). "Hormonal contraception and the risk of HIV acquisition: an individual participant data meta-analysis". PLoS Medicine. 12 (1): e1001778. doi:10.1371/journal.pmed.1001778. PMC . PMID 25612136.
- Faculty of Sexual; Reproductive Healthcare (January 2015). "CEU Statement: Depot medroxyprogesterone acetate (DMPA, Depo-Provera) and risk of HIV acquisition" (PDF). London: Royal College of Obstetricians and Gynaecologists.
- FHI 360 (July 2014). "Research on hormonal contraception and HIV acquisition" (PDF). Durham, N.C.: FHI 360.
- Westhoff, Carolyn L.; Winikoff, Beverly (August 8, 2014). "DMPA and HIV: do we need a trial? (editorial)". Contraception. 90 (4): 353. doi:10.1016/j.contraception.2014.08.008. PMID 25183262.
- Rees, Helen; Evidence for Contraceptive Options and HIV Outcomes (ECHO) Consortium (August 7, 2014). "DMPA and HIV: why we need a trial (commentary)". Contraception. 90 (4): 354–356. doi:10.1016/j.contraception.2014.08.007. PMID 25183263.
- Jones, Heidi (June 2, 2014). "Time to focus on improving the contraceptive method mix in high HIV prevalence settings and let go of unanswerable questions (commentary)". Contraception. 90 (4): 354–356. doi:10.1016/j.contraception.2014.05.014. PMID 24993486.
- Lancet Infectious Diseases (January 8, 2015). "End of the debate on hormonal contraception and HIV risk? (editorial)". Lancet Infectious Diseases. 15 (2): 131. doi:10.1016/S1473-3099(15)70011-3.
- Colvin, Christopher J.; Harrison, Abigail (January 8, 2015). "Broadening the debate over HIV and hormonal contraception (comment)". Lancet Infectious Diseases. 15 (2): 135–136. doi:10.1016/S1473-3099(14)71076-X. PMID 25578824.
- 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. doi:10.1016/0020-7292(82)90044-3. PMID 6126406.
- 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. doi:10.1016/0010-7824(92)90053-V. PMID 1387602.
- "The chemical knife". Retrieved 2009-01-22.
- Glasier, Anna (2006). "Contraception". In DeGroot, Leslie J.; Jameson, J. Larry. Endocrinology (5th ed.). Philadelphia: Elsevier Saunders. pp. 2993–3003. ISBN 0-7216-0376-9.
- Loose, Davis S.; Stancel, George M. (2006). "Estrogens and Progestins". In Brunton, Laurence L.; Lazo, John S.; Parker, Keith L. Goodman & Gilman's The Pharmacological Basis of Therapeutics (11th ed.). New York: McGraw-Hill. pp. 1541–1571. ISBN 0-07-142280-3.
- Rivera R, Yacobson I, Grimes D (1999). "The mechanism of action of hormonal contraceptives and intrauterine contraceptive devices". Am J Obstet Gynecol. 181 (5 Pt 1): 1263–9. doi:10.1016/S0002-9378(99)70120-1. PMID 10561657.
- Stacey, Dawn. Depo Provera: The Birth Control Shot Accessed October 13, 2009
- Leary, Warren E. (October 30, 1992). "U.S. Approves Injectable Drug As Birth Control". The New York Times: A.1. PMID 11646958.
- "Contraceptives. Case for public enquiry". Economic and Political Weekly. 29 (15): 825–6. 1994. Popline database document number 096527.
- Sorojini, NB (January–March 2005). "Why women's groups oppose injectable contraceptives". Indian Journal of Medical Ethics. 13 (1). Archived from the original (– Scholar search) on May 6, 2006.
- 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. Archived from the original on 5 Feb 2007. Retrieved 2006-08-22.
- "Class action suit filed over birth control drug". CTV.ca. December 19, 2005. Retrieved 2006-08-22.
- "Progestins (IARC Summary & Evaluation, Supplement7, 1987)". Retrieved 15 October 2016.
- Amy Goodman (February–March 1985). "The Case Against Depo-Provera - Problems in the U.S". Multinational Monitor. 6 (2 & 3).
- "Controversy over Depo-Provera". Wash Drug Device Lett. 9 (1): 2. 1977. PMID 12335988.
- Thomas D, Ye Z, Ray R (1995). "Cervical carcinoma in situ and use of depot-medroxyprogesterone acetate (DMPA). WHO Collaborative Study of Neoplasia and Steroid Contraceptives". Contraception. 51 (1): 25–31. doi:10.1016/0010-7824(94)00007-J. PMID 7750280.
- The Who Collaborative Study Of Neop, (1992). "Depot-medroxyprogesterone acetate (DMPA) and risk of invasive squamous cell cervical cancer. The WHO Collaborative Study of Neoplasia and Steroid Contraceptives". Contraception. 45 (4): 299–312. doi:10.1016/0010-7824(92)90052-U. PMID 1387601.
- Thomas D, Ray R (1995). "Depot-medroxyprogesterone acetate (DMPA) and risk of invasive adenocarcinomas and adenosquamous carcinomas of the uterine cervix. WHO Collaborative Study of Neoplasia and Steroid Contraceptives". Contraception. 52 (5): 307–12. doi:10.1016/0010-7824(95)00215-V. PMID 8585888.
- Shapiro S, Rosenberg L, Hoffman M, Kelly J, Cooper D, Carrara H, Denny L, du Toit G, Allan B, Stander I, Williamson A (2003). "Risk of invasive cancer of the cervix in relation to the use of injectable progestogen contraceptives and combined estrogen/progestogen oral contraceptives (South Africa)". Cancer Causes Control. 14 (5): 485–95. doi:10.1023/A:1024910808307. PMID 12946044.
- Kaunitz A (1996). "Depot medroxyprogesterone acetate contraception and the risk of breast and gynecologic cancer". J Reprod Med. 41 (5 Suppl): 419–27. PMID 8725705.
- Karen Hawkins; Jeff Elliott (1996-05-05). "Seeking Approval". Albion Monitor. Retrieved 2006-11-20.
- "Sterilization of minors leads to controversy". JOICFP Rev. 2 (4): 77–8. 1973. PMID 12257656.
- 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.
- Singh S (1995). "Adolescent knowledge and use of injectable contraceptives in developing countries". J Adolesc Health. 16 (5): 396–404. doi:10.1016/S1054-139X(94)00060-R. PMID 7662691.
- "Clinicians clash with consumer groups over possible Depo ban". Contracept Technol Update. 16 (1): 11–4. 1995. PMID 12319319.
- Pfizer official site (last live version from Wayback Machine)
- Research on Injectable contraceptives (last live version from Wayback Machine) - Family Health International's fact sheet on injectables, including Depo-Provera.