Depot medroxyprogesterone acetate

Depo-Provera
Background
Type Hormonal
First use 1960[1]
Failure rates (first year)
Perfect use 0.2%[2]
Typical use 6%[2]
Usage
Duration effect 3 months
(12–14 weeks)
Reversibility 3–18 months
User reminders Maximum interval is just under 3 months
Clinic review 12 weeks
Advantages and disadvantages
STD protection No
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
Medical notes
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.

It is an aqueous suspension for depot injection of the pregnane 17α-hydroxyprogesterone-derivative progestin medroxyprogesterone acetate. It is also used for chemical castration.

Effectiveness

Estimates of first-year failure rates are about 0.3%.[3]

Perfect use

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%.[3][4] 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).

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%.[5]

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%.[3][4]

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.[3][10][4]

Benefits

Depo-Provera has several advantages:[11][12][13][14]

The United Kingdom Department of Health has actively promoted Long Acting Reversible Contraceptive use since 2008, particularly for young people;[21] following on from the October 2005 National Institute for Health and Clinical Excellence guidelines.[22] Giving advice on these methods of contraception has been included in the 2009 Quality and Outcomes Framework "good practice" for primary care.[23]

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:[24][25]

Conditions where the theoretical or proven risks usually outweigh the advantages of using Depo-Provera:

Conditions which represent an unacceptable health risk if Depo-Provera is used:

Conditions where use of Depo-Provera is not indicated and should not be initiated:

Side effects

Warnings and precautions

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.[28][29] 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.[30][31] 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.[32][33][34] Other studies have suggested that the effect of Depo-Provera use on post-menopausal bone density is minimal,[35] perhaps because Depo users experience less bone loss at menopause.[36] Use after peak bone mass is associated with increased bone turnover but no decrease in bone mineral density.[37]

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.[29] 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.[38]

HIV risk

There is uncertainty regarding the risk of HIV acquisition among DMPA users; some observational studies suggest an increased risk, others do not.[39] 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.[40][41]

Two meta-analyses of observational studies in sub-Saharan Africa were published in January 2015.[42] They found a 1.4 to 1.5 fold increase risk of HIV acquisition for DMPA users relative to no hormonal contraceptive use.[43][44] 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.[45]

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[46] has been controversial.[47][48][49][50][51]

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.[52]

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.[53]

Other uses

Depo-Provera is also used with male sex offenders as a form of chemical castration as it has the effect of reducing sex drive in males.[54]

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.[55][56] 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.[11][12]

A secondary mechanism of action of all progestogen-containing contraceptives is inhibition of sperm penetration by changes in the cervical mucus.[57]

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.[57]

Society and culture

Commercial products

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.[58] It was approved in the United States by the FDA for contraceptive use on 29 October 1992,[59] 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.

Controversy

Outside the United States

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.[59] Points in the controversy included:

See also

References

  1. http://www.accessdata.fda.gov/drugsatfda_docs/label/2016/012541s084lbl.pdf
  2. 1 2 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 = Table 3–2 Percentage of women experiencing an unintended pregnancy during the first year of typical use and the first year of perfect use of contraception, and the percentage continuing use at the end of the first year. United States.
  3. 1 2 3 4 5 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.
  4. 1 2 3 Trussell J (2004). "Contraceptive failure in the United States". Contraception. 70 (2): 89–96. doi:10.1016/j.contraception.2004.03.009. PMID 15288211.
  5. 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.
  6. 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.
  7. 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.
  8. FDA (1998). "Guidance for Industry - Uniform Contraceptive Labeling" (PDF). Archived from the original (PDF) on February 25, 2007. Retrieved 2007-06-21.
  9. 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.
  10. 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.
  11. 1 2 3 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.
  12. 1 2 3 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.
  13. 1 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.
  14. 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.
  15. 1 2 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.
  16. 1 2 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.
  17. 1 2 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.
  18. 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.
  19. 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
    Borgatta, Lynn; Murthy, Amitasrigowri; Chuang, Cynthia; Beardsley, Leah; Burnhill, Michael S. (September 2002). "Pregnancies diagnosed during Depo-Provera use". Contraception. 66 (3): 169–172. doi:10.1016/S0010-7824(02)00340-2. PMID 12384205.
  20. 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.
  21. "Increasing use of long-acting reversible contraception". Nursing Times.net. 21 October 2008. Retrieved 2009-06-19.
  22. "CG30 Long-acting reversible contraception: quick reference guide" (PDF). National Institute for Health and Clinical Excellence. Retrieved 2009-06-19.
  23. "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.
    Sumarised at
    * "Contraception - Management QOF indicators". NHS Clinical Knowledge Summaries. NHS Institute for Innovation and Improvement. Retrieved 2009-06-19.
  24. WHO (2004). "Progestogen-only contraceptives". Medical Eligibility Criteria for Contraceptive Use (3rd ed.). Geneva: Reproductive Health and Research, WHO. ISBN 92-4-156266-8.
  25. 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.
  26. 1 2 Pfizer (October 2004). "Depo-Provera Contraceptive Injection, US patient labeling" (PDF). Retrieved 2007-02-21.
  27. "Exposure to DMPA in pregnancy may cause low birth weight". Prog Hum Reprod Res (23): 2–3. 1992. PMID 12286194.
  28. "Depot medroxyprogesterone acetate and bone effects. Committee Opinion #602". June 2014. Retrieved 2015-05-03.
  29. 1 2 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.
  30. World Health Organization (September 2005). "Hormonal contraception and bone health". Family Planning. Retrieved 2006-05-12.
  31. 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.
  32. 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 2539337Freely accessible. PMID 8111260.
  33. 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.
  34. 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.
  35. 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.
  36. 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.
  37. 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.
  38. &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.
  39. 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.
  40. WHO Department of Reproductive Health and Research (February 16, 2012). "Technical Statement: Hormonal contraception and HIV". Geneva: World Health Organization.
  41. 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.
  42. AVAC (January 27, 2015). "News from the HC-HIV front: it's raining meta (analyses)!". New York: AIDS Vaccine Advocacy Coalition.
  43. 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.
  44. 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 4303292Freely accessible. PMID 25612136.
  45. 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.
  46. FHI 360 (July 2014). "Research on hormonal contraception and HIV acquisition" (PDF). Durham, N.C.: FHI 360.
  47. 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.
  48. 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.
  49. 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.
  50. 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.
  51. 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.
  52. 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.
  53. 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.
  54. "The chemical knife". Retrieved 2009-01-22.
  55. 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.
  56. 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.
  57. 1 2 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.
  58. Stacey, Dawn. Depo Provera: The Birth Control Shot Accessed October 13, 2009
  59. 1 2 Leary, Warren E. (October 30, 1992). "U.S. Approves Injectable Drug As Birth Control". The New York Times: A.1. PMID 11646958.
  60. "Contraceptives. Case for public enquiry". Economic and Political Weekly. 29 (15): 825–6. 1994. Popline database document number 096527.
  61. 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.
  62. 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.
  63. "Class action suit filed over birth control drug". CTV.ca. December 19, 2005. Retrieved 2006-08-22.
  64. "http://www.haaretz.com/news/israel/israeli-minister-appointing-team-to-probe-ethiopian-birth-control-shot-controversy-1.506266
  65. "Progestins (IARC Summary & Evaluation, Supplement7, 1987)". Retrieved 15 October 2016.
  66. Amy Goodman (February–March 1985). "The Case Against Depo-Provera - Problems in the U.S". Multinational Monitor. 6 (2 & 3).
  67. "Controversy over Depo-Provera". Wash Drug Device Lett. 9 (1): 2. 1977. PMID 12335988.
  68. 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.
  69. 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.
  70. 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.
  71. 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.
  72. 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.
  73. 1 2 Karen Hawkins; Jeff Elliott (1996-05-05). "Seeking Approval". Albion Monitor. Retrieved 2006-11-20.
  74. "Sterilization of minors leads to controversy". JOICFP Rev. 2 (4): 77–8. 1973. PMID 12257656.
  75. 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.
  76. 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.
  77. "Clinicians clash with consumer groups over possible Depo ban". Contracept Technol Update. 16 (1): 11–4. 1995. PMID 12319319.
This article is issued from Wikipedia - version of the 12/2/2016. The text is available under the Creative Commons Attribution/Share Alike but additional terms may apply for the media files.