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Depo-Provera is a branded progestogen-only contraceptive, depot medroxyprogesterone acetate (DMPA) long acting reversible hormonal contraceptive birth control drug that is injected every 3 months. It is an aqueous suspension for depot injection of the pregnane 17α-hydroxyprogesterone-derivative progestin medroxyprogesterone acetate.
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.
Mechanism of actionEdit
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.
- the 1995 National Survey of Family Growth (NSFG) — a retrospective survey based on a woman's recall, during a 90-minute interview, of her month-by-month contraceptive use during the preceding 4 to 5 years
- 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.
Pregnancy and breastfeedingEdit
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.
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
- Past history of breast cancer and no evidence of current disease for 5 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:
Disadvantages and side effects Edit
Warnings and precautionsEdit
- 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; 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 Edit
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, may remain long after the injections are stopped, and may be irreversible. For these reasons, 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. However, the World Health Organization (WHO) advises that the use of Depo-Provera should not be restricted.
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. 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. 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 U.S. Food and Drug Administration (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. 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.
In the largest clinical trial of Depo-Provera, the most frequently reported adverse reactions (which may or may not be related to the use of Depo-Provera) were: menstrual irregularities (bleeding or amenorrhea or both), abdominal pain or discomfort, weight changes, headache, asthenia (weakness or fatigue), depression, hair loss and nervousness, skin breakouts. Other, less frequently reported adverse reactions are listed in the patient and physician label information for Depo-Provera.
- A study of 819 women in one city found an association between using Depo-Provera and higher incidence of chlamydia and gonorrhea. A second prospective study in 948 Kenyan women found that Depo-Provera use was associated with higher rates of chlamydial infection, but lower rates of trichomoniasis and pelvic inflammatory disease, when compared to women using no contraception.
- Primate studies of medroxyprogesterone have suggested that it may increase the risk of transmission of simian immunodeficiency virus (SIV), an animal model of HIV. At least one study in humans has suggested an increased rate of HIV infection in Depo-Provera users, while a number of other studies have found no such association. A large prospective clinical trial addressing the issue of Depo-Provera and HIV susceptibility is currently ongoing.
Other uses Edit
Controversy over approvalEdit
Outside the United StatesEdit
- 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 regards to human rights abuses and Medical Experimentation in Africa.
- In 2010, certain members of the feminist movement accused Israel of birth control policy aimed towards Ethiopian Jews, for allowing the prescription of contraceptive drugs like Depo-Provera to the community. Subsequent accusations have indicated that Depo-Provera may have been administered to Ethiopian women without their informed consent  Yet, the drug was administered to women who asked for an "effective birth control solution". It has been followed by an acknowledgment in January 2013 from the Health minister, who has ordered a stop to the practice.
In the United StatesEdit
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 actually 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/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", in spite of the fact that 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.
- Black teenagers in the US using birth control use Depo-Provera at a far higher rate than white teenagers. One activist, Dorothy Roberts, claims this is because black teenagers are disproportionately targeted for the least safe contraceptives.
- ↑ Stacey, Dawn. Depo Provera: The Birth Control Shot Accessed October 13, 2009
- ↑ 2.0 2.1 Leary, Warren E. (October 30, 1992). U.S. Approves Injectable Drug As Birth Control. The New York Times: A.1.
- ↑ Glasier, Anna (2006). "Contraception" DeGroot, Leslie J.; Jameson, J. Larry (eds.) Endocrinology, 5th, 2993–3003, Philadelphia: Elsevier Saunders.
- ↑ Loose, Davis S.; Stancel, George M. (2006). "Estrogens and Progestins" Brunton, Laurence L.; Lazo, John S.; Parker, Keith L. (eds.) Goodman & Gilman's The Pharmacological Basis of Therapeutics, 11th, 1541–1571, New York: McGraw-Hill.
- ↑ 5.0 5.1 5.2 Hatcher, Robert A. (2004). "Depo-Provera Injections, Implants, and Progestin-Only Pills (Minipills)" Hatcher, Robert A.; Trussell, James; Stewart, Felicia H.; Nelson, Anita L.; Cates Jr., Willard; Guest, Felicia; Kowal, Deborah Contraceptive Technology, 18th rev., 461–494, New York: Ardent Media.
- ↑ 6.0 6.1 6.2 Speroff, Leon; Darney, Philip D. (2005). "Injectable Contraception" A Clinical Guide for Contraception, 4th, 201–220, Philadelphia: Lippincott Williams & Wilkins.
- ↑ 7.0 7.1 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.
- ↑ 8.0 8.1 8.2 8.3 8.4 Trussell, James (2004). "Contraceptive Efficacy" Hatcher, Robert A.; Trussell, James; Stewart, Felicia H.; Nelson, Anita L.; Cates Jr., Willard; Guest, Felicia; Kowal, Deborah Contraceptive Technology, 18th rev., 773–845, New York: Ardent Media.
- ↑ FDA (2005). depo-subQ provera 104 Label Information: U.S. Physician Information and Patient Information. (PDF) URL accessed on 2007-06-21.
- ↑ 10.0 10.1 Fu H, Darroch JE, Haas T, Ranjit N (1999). Contraceptive failure rates: new estimates from the 1995 National Survey of Family Growth. Fam Plann Perspect 31 (2): 56–63.
- ↑ 11.0 11.1 Trussell J, Vaughan B (1999). Contraceptive failure, method-related discontinuation and resumption of use: results from the 1995 National Survey of Family Growth. Fam Plann Perspect 31 (2): 64–72, 93.
- ↑ National Center for Health Statistics (NCHS) (1995). National Survey of Family Growth (NSFG) Cycle 5 Main Study Questionnaire, CAPI Reference Version (PDF), Hyattsville, MD: NCHS.
- ↑ 13.0 13.1 13.2 Trussell J (2004). Contraceptive failure in the United States. Contraception 70 (2): 89–96.
- ↑ 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.
- ↑ Trussell, James (1994). "Contraceptive Failure Rates" Hatcher, Robert A.; Trussell, James; Stewart, Felicia; Stewart, Gary K.; Kowal, Deborah; Guest, Felicia; Cates Jr., Willard; Policar, Michael S. Contraceptive Technology, 16th rev., 637–688, New York: Irvington Publishers.
- ↑ Trussell, James (1998). "Contraceptive Efficacy" Hatcher, Robert A.; Trussell, James; Stewart, Felicia; Cates Jr., Willard; Stewart, Gary K.; Guest, Felicia; Kowal, Deborah Contraceptive Technology, 17th rev., 779–844, New York: Ardent Media.
- ↑ FDA (1998). Guidance for Industry - Uniform Contraceptive Labeling. (PDF) URL accessed on 2007-06-21.
- ↑ Trussell, James (2007). "Contraceptive Efficacy" Hatcher, Robert A.; Trussell, James; Nelson, Anita L.; Cates Jr., Willard; Stewart, Felicia H.; Kowal, Deborah Contraceptive Technology, 19th rev., New York: Ardent Media. URL accessed 2007-06-21.
- ↑ 19.0 19.1 Westhoff C (2003). Depot-medroxyprogesterone acetate injection (Depo-Provera): a highly effective contraceptive option with proven long-term safety. Contraception 68 (2): 75–87.
- ↑ Mishell Jr., Daniel R. (2004). "Contraception" Strauss, Jerome F. III; Barbieri, Robert L. (eds.) Yen and Jaffe's Reproductive Endocrinology, 5th, 899–938, Philadelphia: Elsevier Saunders.
- ↑ 21.0 21.1 Kaunitz AM (2001). Current options for injectable contraception in the United States. Semin Reprod Med 19 (4): 331–7.
- ↑ 22.0 22.1 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.
- ↑ 23.0 23.1 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.
- ↑ Santen, Richard J. (2004). "Endocrinology of Breast and Endometrial Cancer" Strauss, Jerome F. III; Barbieri, Robert L. (eds.) Yen and Jaffe's Reproductive Endocrinology, 5th, 787–809, Philadelphia: Elsevier Saunders.
- ↑ (2011) "Injectable contraceptives" Contraceptive technology, 20th revised, 209–236, New York: Ardent Media. pp. 212–213:
Advantages of DMPA Injectables.(September 2002). Pregnancies diagnosed during Depo-Provera use. Contraception 66 (3): 169-172.
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.
- ↑ includeonly>"Increasing use of long-acting reversible contraception", Nursing Times.net, 21 October 2008. Retrieved on 23009-06-19.
- ↑ CG30 Long-acting reversible contraception: quick reference guide. (PDF) National Institute for Health and Clinical Excellence. URL accessed on 2009-06-19.
- ↑ Sexual Health Ruleset. (PDF) New GMS Contract Quality and Outcome Framework - Implementation Dataset and Business Rules. Primary Care Commissioning. URL accessed on 2009-06-19.
* Contraception - Management QOF indicators. NHS Clinical Knowledge Summaries. NHS Institute for Innovation and Improvement. URL accessed on 2009-06-19.
- ↑ 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.
- ↑ 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.
- ↑ WHO (2004). "Progestogen-only contraceptives" Medical Eligibility Criteria for Contraceptive Use, 3rd, Geneva: Reproductive Health and Research, WHO.
- ↑ FFPRHC (2006). The UK Medical Eligibility Criteria for Contraceptive Use (2005/2006). (PDF) URL accessed on 2007-01-11.
- ↑ 34.0 34.1 Pfizer (2004). Depo-Provera Contraceptive Injection, US patient labeling. (PDF) URL accessed on 2007-02-21.
- ↑ (1992) Exposure to DMPA in pregnancy may cause low birth weight. Prog Hum Reprod Res (23): 2–3.
- ↑ 36.0 36.1 FDA. Black Box Warning Added Concerning Long-Term Use of Depo-Provera Contraceptive Injection. URL accessed on 2006-05-12.
- ↑ World Health Organization (2005). Hormonal contraception and bone health. Family Planning. URL accessed on 2006-05-12.
- ↑ Curtis KM, Martins SL (2006). Progestogen-only contraception and bone mineral density: a systematic review. Contraception 73 (5): 470–87.
- ↑ 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.
- ↑ 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.
- ↑ 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.
- ↑ 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.
- ↑ 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.
- ↑ 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.
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- ↑ 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.
- ↑ Baeten J, Nyange P, Richardson B, Lavreys L, Chohan B, Martin H, Mandaliya K, Ndinya-Achola J, Bwayo J, Kreiss J (2001). Hormonal contraception and risk of sexually transmitted disease acquisition: results from a prospective study. Am J Obstet Gynecol 185 (2): 380–5.
- ↑ Preston A. Marx, et al. (1996). Progesterone implants enhance SIV vaginal transmission and early virus load. Nature Medicine 2 (10): 1084–9.
- ↑ Trunova N et al. (2006). Progestin-based contraceptive suppresses cellular immune responses in SHIV-infected rhesus macaques. Virology 352 (1): 169–77.
- ↑ Martin H, Nyange P, Richardson B, Lavreys L, Mandaliya K, Jackson D, Ndinya-Achola J, Kreiss J (1998). Hormonal contraception, sexually transmitted diseases, and risk of heterosexual transmission of human immunodeficiency virus type 1. J Infect Dis 178 (4): 1053–9.
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- ↑ includeonly>"Israel accused of dooming Ethiopian baby boom", RT, 24 February 2010. Retrieved on 15 December 2012.
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- ↑ includeonly>Talila Nesher. "Israel admits Ethiopian women were given birth control shots", Haaretz, 27 January 2013. Retrieved on 29 January 2013.
- ↑ Amy Goodman (February–March 1985). The Case Against Depo-Provera - Problems in the U.S. Multinational Monitor 6 (2 & 3).
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- ↑ 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.
- ↑ 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.
- ↑ 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.
- ↑ 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.
- ↑ Kaunitz A (1996). Depot medroxyprogesterone acetate contraception and the risk of breast and gynecologic cancer. J Reprod Med 41 (5 Suppl): 419–27.
- ↑ 70.0 70.1 Karen Hawkins, Jeff Elliott. Seeking Approval. Albion Monitor. URL accessed on 2006-11-20.
- ↑ (1973) Sterilization of minors leads to controversy. JOICFP Rev 2 (4): 77–8.
- ↑ 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.
- ↑ Singh S (1995). Adolescent knowledge and use of injectable contraceptives in developing countries. J Adolesc Health 16 (5): 396–404.
- ↑ (1995) Clinicians clash with consumer groups over possible Depo ban. Contracept Technol Update 16 (1): 11–4.
- ↑ Moira Brennan (2001). Dorothy Roberts: What we talk about when we talk about reproductive rights. Ms Magazine. URL accessed on 2006-08-22.
- Pfizer official site
- Research on Injectable contraceptives - Family Health International's fact sheet on injectables, including Depo-Provera.
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