(Redirected from Depo Provera)
'Depot medroxyprogesterone acetate' ('DMPA') is a
progestogen-only
hormonal contraceptive birth control drug which is injected every 3 months.
Depot medroxyprogesterone acetate (DMPA) is an aqueous
suspension for
depot injection of the
pregnane 17α-hydroxyprogesterone-derivative
progestin ''
medroxyprogesterone acetate''.
'Depo-Provera' Contraceptive Injection is the brand name for a 150 mg aqueous suspension of ''
medroxyprogesterone acetate'' for depot
intramuscular injection every 3 months (12–13 weeks) manufactured by
Pfizer.
'depo-subQ provera 104' is the brand name for a 104 mg aqueous suspension of ''medroxyprogesterone acetate'' for depot
subcutaneous injection every 3 months (12–14 weeks) manufactured by Pfizer.
depo-subQ provera 104 was approved in the
United States by the
FDA for contraceptive use on December 17, 2004, and for management of
endometriosis-related pain on March 25, 2005.
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.
[1][2]
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.
[3][4]
A secondary mechanism of action of all progestogen-containing contraceptives is inhibition of
sperm penetration by changes in the
cervical mucus.
[5]
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.
Effectiveness
The
life-table first-year failure rates for 8,183 women using Depo-Provera in seven prospective clinical trials were: 0%, 0%, 0.1%, 0.2%, 0.2%, 0.3%, and 0.7%, with a weighted average of 0.3%.
[6]
The
Pearl Index first-year failure rates for 2,042 women using depo-subQ 104 in three prospective clinical trials were: 0%, 0%, and 0%, with a weighted average of 0%.
[7]
The first-year failure rate for 209 women using Depo-Provera in one retrospective survey was: 2.6%.
[8][9]
★ 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
Perfect use
Trussell's estimated ''perfect use'' first-year failure rate for Depo-Provera is the weighted average of failure rates in seven clinical trials: 0.3%.
★ 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)
Typical use
Prior to 2004, Trussell's ''typical use'' failure rate for Depo-Provera was the same as his ''perfect use'' failure rate: 0.3%.
[12]
★ Depo-Provera estimated ''typical use'' first-year failure rate = 0.3% in:
★
★ ''Contraceptive Technology, 16th revised edition'' (1994)
[13]
★
★ ''Contraceptive Technology, 17th revised edition'' (1998)
[14]
★
★
★ adopted in 1998 by the
FDA for its current ''Uniform Contraceptive Labeling'' guidance
[15]
In 2004, using the 1995 NSFG failure rate, Trussell increased (by 10 times) his ''typical use'' failure rate for Depo-Provera from 0.3% to 3%.
★ Depo-Provera estimated ''typical use'' first-year failure rate = 3% in:
★
★ ''Contraceptive Technology, 18th revised edition'' (2004)
★
★ ''Contraceptive Technology, 19th revised edition'' (2007)
[16]
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.
Benefits
Depo-Provera has several advantages:
★ 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.
★ Culturally acceptable. Some cultures believe injections are especially efficacious. Injections also afford privacy because use is not detectable.
★ Minimal
drug interactions (compared to other
hormonal contraceptives).
★ Decreased risk of
endometrial cancer. Depo-Provera reduces the risk of endometrial cancer by 80%.
[ Current options for injectable contraception in the United States, Kaunitz AM, , , Semin Reprod Med, 2001 ][19][20] 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.
[ Yen and Jaffe's Reproductive Endocrinology, Santen, Richard J., , , Elsevier Saunders, 2004, ISBN 0-7216-9546-9 ]
★ 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.
[21]
★ Decreased incidence and severity of
sickle cell crises in women with sickle-cell disease.
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 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.
[22]
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.
[23]
Disadvantages and side effects
Warnings and precautions
★ Depo-Provera can require up to fourteen days to take effect. This means pregnancy can occur within fourteen days of the first Depo injection.
★ Takes seven days to take effect if given after the first four days of the period cycle. Effective immediately if given during the first four 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.
[24]
★ 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.
[25]
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, may remain 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.
[26]
However, the
World Health Organization (WHO) advises that the use of Depo-Provera should not be restricted.
[27][28]
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.
[29][30][31] Other studies have suggested that the effect of Depo-Provera use on post-menopausal bone density is minimal,
[32] perhaps because Depo users experience less bone loss at menopause.
[33] 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.
Side effects
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), and nervousness. Other, less frequently reported adverse reactions are listed in the patient and physician label information for Depo-Provera.
Related studies
★ A study of 819 women in one city found an association between using Depo-Provera and higher incidence of
chlamydia and
gonorrhea.
[35] 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.
[36]
★ Primate studies of medroxyprogesterone have suggested that it may increase the risk of transmission of
simian immunodeficiency virus (SIV), an animal model of
HIV.
[37][38] At least one study in humans has suggested an increased rate of HIV infection in Depo-Provera users,
[39] while a number of other studies have found no such association.
[40][41][42] A large prospective clinical trial addressing the issue of Depo-Provera and HIV susceptibility is currently ongoing.
[43]
Contraindications
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:
[44][45]
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:
★
★
Hypertension with
vascular disease
★
★ Current and history of
ischemic heart disease
★
★ History of
stroke
★
★
Diabetes for > 20 years or with
nephropathy/
retinopathy/
neuropathy or
vascular disease
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:
★
Pregnancy
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.
[1]
Controversy over Approval of Depo-Provera in the United States
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.
[46] 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. (Which is lower than the pregnancy level of progesterone for dogs, and is species-specific.)
[2]Depo-Provera caused endometrial cancer in monkeys—2 of 12 monkeys tested, the first ever recorded cases of endometrial cancer in
rhesus monkeys.
[47] 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.
[48] However, numerous larger subsequent studies have shown that Depo-Provera use does not increase the risk of cervical cancer.
[49][50][51][52][53]
★ Coercion and lack of informed consent. Testing/use of Depo was focused almost exclusively on women in
developing countries and poor women of color in the US,
[54] raising serious questions about coercion and lack of informed consent, particularly for the illiterate
[55] 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.
[56]
★ 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.
[3]The Alan Guttmacher Institute has speculated that US approval of Depo may increase its availability and acceptability in developing countries.
[4][57]
Aftermath
★ In 1995, several women's health groups asked the FDA to put a moratorium on Depo-Provera, and to institute standardized informed consent forms.
[58]
★ 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."
[59] Some scientists and women's groups in India continue to oppose Depo-Provera.
[60] 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.
[61]
★ The Canadian Coalition on Depo-Provera, a coalition of women's health professional and advocacy groups, opposed the approval of Depo in Canada.
[62] 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.
[63]
Footnotes
1. Endocrinology, , Anna, Glasier, Elsevier Saunders, 2006, ISBN 0-7216-0376-9
2. Goodman & Gilman's The Pharmacological Basis of Therapeutics, Loose, Davis S.; Stancel, George M., , , McGraw-Hill, 2006, ISBN 0-07-142280-3
3. Contraceptive Technology, Hatcher, Robert A., , , Ardent Media, 2004, ISBN 0-9664902-5-8
4. A Clinical Guide for Contraception, Speroff, Leon; Darney, Philip D., , , Lippincott Williams & Wilkins, 2005, ISBN 0-7817-6488-2
5. The mechanism of action of hormonal contraceptives and intrauterine contraceptive devices, Rivera R, Yacobson I, Grimes D, , , Am J Obstet Gynecol, 1999
6. Contraceptive Technology, Trussell, James, , , Ardent Media, 2004, ISBN 0-9664902-5-8
7. depo-subQ provera 104 Label Information: U.S. Physician Information and Patient Information FDA
8. Contraceptive failure rates: new estimates from the 1995 National Survey of Family Growth, Fu H, Darroch JE, Haas T, Ranjit N, , , Fam Plann Perspect, 1999
9. Contraceptive failure, method-related discontinuation and resumption of use: results from the 1995 National Survey of Family Growth, Trussell J, Vaughan B, , , Fam Plann Perspect, 1999
10. National Survey of Family Growth (NSFG) Cycle 5 Main Study Questionnaire, CAPI Reference Version, National Center for Health Statistics (NCHS), , , NCHS, 1995,
11. Contraceptive failure in the United States, Trussell J, , , Contraception, 2004
12. A guide to interpreting contraceptive efficacy studies, Trussell J, Hatcher RA, Cates W Jr, Stewart FH, Kost K, , , Obstet Gynecol, 1990
13. Contraceptive Technology, Trussell, James, , , Irvington Publishers, 1994, ISBN 0-8290-3171-5
14. Contraceptive Technology, Trussell, James, , , Ardent Media, 1998, ISBN 0-9664902-0-7
15. Guidance for Industry - Uniform Contraceptive Labeling FDA
16. Contraceptive Technology, Trussell, James, , , Ardent Media, 2007,
17. Depot-medroxyprogesterone acetate injection (Depo-Provera): a highly effective contraceptive option with proven long-term safety, Westhoff C, , , Contraception, 2003
18. Yen and Jaffe's Reproductive Endocrinology, Mishell Jr., Daniel R., , , Elsevier Saunders, 2004, ISBN 0-7216-9546-9
19. Depo Provera. Position paper on clinical use, effectiveness and side effects, Bigrigg A, Evans M, Gbolade B, Newton J, Pollard L, Szarewski A, Thomas C, Walling M, , , Br J Fam Plann, 1999
20. Depot-medroxyprogesterone acetate (DMPA) and risk of endometrial cancer, WHO Collaborative Study of Neoplasia and Steroid Contraceptives, , , Int J Cancer, 1991
21. Contraception for women with epilepsy, O'Brien MD, Guillebaud J, , , Epilepsia, 2006
22. Some effects of depo-medroxyprogesterone acetate (DMPA): observations in the nursing infant and in the long-term user., Dahlberg K, , , Int J Gynaecol Obstet, 1982
23. The long-term growth and development of children exposed to Depo-Provera during pregnancy or lactation., Pardthaisong T, Yenchit C, Gray R, , , Contraception, 1992
24. Depo-Provera Contraceptive Injection, US patient labeling Pfizer
25. Exposure to DMPA in pregnancy may cause low birth weight., , , , Prog Hum Reprod Res, 1992
26. Black Box Warning Added Concerning Long-Term Use of Depo-Provera Contraceptive Injection FDA
27. Hormonal contraception and bone health World Health Organization
28. Progestogen-only contraception and bone mineral density: a systematic review, Curtis KM, Martins SL, , , Contraception, 2006
29. Recovery of bone density in women who stop using medroxyprogesterone acetate., Cundy T, Cornish J, Evans M, Roberts H, Reid I, , , BMJ, 1994
30. Injectable hormone contraception and bone density: results from a prospective study, Scholes D, LaCroix AZ, Ichikawa LE, Barlow WE, Ott SM, , , Epidemiology, 2002
31. Change in bone mineral density among adolescent women using and discontinuing depot medroxyprogesterone acetate contraception, Scholes D, LaCroix AZ, Ichikawa LE, Barlow WE, Ott SM, , , Arch Pediatr Adolesc Med, 2005
32. The effect of past use of the injectable contraceptive depot medroxyprogesterone acetate on bone mineral density in normal post-menopausal women., Orr-Walker B, Evans M, Ames R, Clearwater J, Cundy T, Reid I, , , Clin Endocrinol (Oxf), 1998
33. Menopausal bone loss in long-term users of depot medroxyprogesterone acetate contraception., Cundy T, Cornish J, Roberts H, Reid I, , , Am J Obstet Gynecol, 2002
34. Depo-Provera Contraceptive Injection, US physician information Pfizer
35. Hormonal contraceptive use, cervical ectopy, and the acquisition of cervical infections, Morrison CS, Bright P, Wong EL, Kwok C, Yacobson I, Gaydos CA, Tucker HT, Blumenthal PD, , , Sex Transm Dis, 2004
36. Hormonal contraception and risk of sexually transmitted disease acquisition: results from a prospective study., Baeten J, Nyange P, Richardson B, Lavreys L, Chohan B, Martin H, Mandaliya K, Ndinya-Achola J, Bwayo J, Kreiss J, , , Am J Obstet Gynecol, 2001
37. Progesterone implants enhance SIV vaginal transmission and early virus load., Preston A. Marx, ''et al.'', , , Nature Medicine, 1996
38. Progestin-based contraceptive suppresses cellular immune responses in SHIV-infected rhesus macaques, Trunova N et al, , , Virology, 2006
39. Hormonal contraception, sexually transmitted diseases, and risk of heterosexual transmission of human immunodeficiency virus type 1., Martin H, Nyange P, Richardson B, Lavreys L, Mandaliya K, Jackson D, Ndinya-Achola J, Kreiss J, , , J Infect Dis, 1998
40. Incident HIV-1 infection in a cohort of young women in Butare, Rwanda., Bulterys M, Chao A, Habimana P, Dushimimana A, Nawrocki P, Saah A, , , AIDS, 1994
41. Hormonal contraceptive use and HIV-1 infection in a population-based cohort in Rakai, Uganda., Kiddugavu M, Makumbi F, Wawer M, Serwadda D, Sewankambo N, Wabwire-Mangen F, Lutalo T, Meehan M, Gray R, , , AIDS, 2003
42. Prospective study of hormonal contraception and women's risk of HIV infection in South Africa., , , , Int J Epidemiol,
43. Prospective clinical trials designed to assess the use of hormonal contraceptives and risk of HIV acquisition., Morrison C, Richardson B, Celentano D, Chipato T, Mmiro F, Mugerwa R, Padian N, Rugpao S, Salata R, , , J Acquir Immune Defic Syndr,
44. Medical Eligibility Criteria for Contraceptive Use, WHO, , , Reproductive Health and Research, WHO, 2004, ISBN 92-4-156266-8
45. The UK Medical Eligibility Criteria for Contraceptive Use (2005/2006) FFPRHC
46. U.S. Approves Injectable Drug As Birth Control, Leary, Warren E., , , The New York Times, 1992
47.
48. Controversy over Depo-Provera., , , , Wash Drug Device Lett, 1977
49. Cervical carcinoma in situ and use of depot-medroxyprogesterone acetate (DMPA). WHO Collaborative Study of Neoplasia and Steroid Contraceptives., Thomas D, Ye Z, Ray R, , , Contraception, 1995
50. Depot-medroxyprogesterone acetate (DMPA) and risk of invasive squamous cell cervical cancer. The WHO Collaborative Study of Neoplasia and Steroid Contraceptives., , , , Contraception, 1992
51. Depot-medroxyprogesterone acetate (DMPA) and risk of invasive adenocarcinomas and adenosquamous carcinomas of the uterine cervix. WHO Collaborative Study of Neoplasia and Steroid Contraceptives., Thomas D, Ray R, , , Contraception, 1995
52. Risk of invasive cancer of the cervix in relation to the use of injectable progestogen contraceptives and combined estrogen/progestogen oral contraceptives (South Africa)., Shapiro S, Rosenberg L, Hoffman M, Kelly J, Cooper D, Carrara H, Denny L, du Toit G, Allan B, Stander I, Williamson A, , , Cancer Causes Control, 2003
53. Depot medroxyprogesterone acetate contraception and the risk of breast and gynecologic cancer., Kaunitz A, , , J Reprod Med, 1996
54. > Seeking Approval Karen Hawkins, Jeff Elliott
55. Sterilization of minors leads to controversy., , , , JOICFP Rev, 1973
56. Use of hormonal contraceptives in an institutional setting: reasons for use, consent and safety in women with psychiatric and intellectual disabilities., Egan T, Siegert R, Fairley N, , , N Z Med J, 1993
57. Adolescent knowledge and use of injectable contraceptives in developing countries., Singh S, , , J Adolesc Health, 1995
58. Clinicians clash with consumer groups over possible Depo ban., , , , Contracept Technol Update, 1995
59. Contraceptives. Case for public enquiry., , , , Economic and Political Weekly, 1994
60. Why women's groups oppose injectable contraceptives, Sorojini, NB, , , Indian Journal of Medical Ethics, 2005
61. Dorothy Roberts: What we talk about when we talk about reproductive rights Moira Brennan
62. Canadian Coalition on Depo-Provera letter to The Honorable Benoit Bouchard, National Minister of Health and Welfare Madeline Boscoe
63. Class action suit filed over birth control drug
External links
★
Pfizer official site
★
Research on Injectable contraceptives - Family Health International's fact sheet on injectables, including Depo-Provera.
★
ContraceptINFO: Information for Consumers about Depo-Provera
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