Clinical Review

UPDATE ON CONTRACEPTION

OBG Manag. 2012 August;24(8):29-35

References

1. Finer LB, Henshaw SK. Disparities in rates of unintended pregnancy in the united states 1994 and 2001. Perspect Sex Reprod Health. 2006;38(2):90-6.

2. Jones RK, Kooistra K. Abortion incidence and access to services in the United States 2008. Perspect Sex Reprod Health. 2011;43(1):41-50.

3. Centers for Disease Control and Prevention (CDC). Ten great public health achievements—United States 1900-1999. MMWR. 1999;48(12):241-243.

4. Hubacher D, Finer LB, Espey E. Renewed interest in intrauterine contraception in the United States: evidence and explanation. Contraception. 2011;83(4):291-294.

5. Grimes DA, Lopez LM, Schulz KF, Van Vliet HA, Stanwood NL. Immediate post-partum insertion of intrauterine devices. Cochrane Database Syst Rev. 2010;(5):CD003036.-

6. Chen BA, Reeves MF, Hayes JL, Hohmann HL, Perriera LK, Creinin MD. Postplacental or delayed insertion of the levonorgestrel intrauterine device after vaginal delivery: a randomized controlled trial. Obstet Gynecol. 2010;116(5):1079-1087.

7. World Health Organization Collaborative Study of Cardiovascular Disease and Steroid Hormone Contraception. Venous thromboembolic disease and combined oral contraceptives: results of international multicentre case-control study. Lancet. 1995;346(8990):1575-1582.

8. Fuhrmann U, Krattenmacher R, Slater EP, Fritzemeier KH. The novel progestin drospirenone and its natural counterpart progesterone: biochemical profile and antiandrogenic potential. Contraception. 1996;54(4):243-251.

9. Dinger JC, Heinemann LA, Kuhl-Habich D. The safety of a drospirenone-containing oral contraceptive: final results from the European Active Surveillance Study on oral contraceptives based on 142475 women-years of observation. Contraception. 2007;75(5):344-354.

10. Raymond EG, Burke AE, Espey E. Combined hormonal contraceptives and venous thromboembolism: putting the risks into perspective. Obstet Gynecol. 2012;119(5):1039-1044.

11. Lidegaard O, Lokkegaard E, Svendsen AL, Agger C. Hormonal contraception and risk of venous thromboembolism: national follow-up study. BMJ. 2009;339:b2890.-

12. World Health Organization. Hormonal contraception and HIV: a technical statement. 2012. http://www.who.int/reproductivehealth/topics/family_planning/Hormonal_contraception_and_HIV.pdf. Accessed June 1 2012.

13. 1Martin HL Jr, Nyange PM, Richardson BA, et al. Hormonal contraception, sexually transmitted diseases, and risk of heterosexual transmission of human immunodeficiency virus type 1. J Infect Dis. 1998;178(4):1053-1059.

14. Heikinheimo O, Lahteenmaki P. Contraception and HIV infection in women. Hum Reprod Update. 2009;15(2):165-176.

15. Morrison CS, Richardson BA, Mmiro F, et al. Hormonal Contraception and the Risk of HIV Acquisition (HC-HIV) Study Group. Hormonal contraception and the risk of HIV acquisition. AIDS. 2007;21(1):85-95.

VTE risk, postpartum hormonal contraception, and progestin type

Centers for Disease Control and Prevention. Update to CDC’s U.S. medical eligibility criteria for contraceptive use, 2010: Revised recommendations for the use of contraceptive methods during the postpartum period. MMWR Morb Mortal Wkly Rep. 2011;60(26):878–883.

Lidegaard O, Nielsen LH, Skovlund CW, Skjeldestad FE, Lokkegaard E. Risk of venous thromboembolism from use of oral contraceptives containing different progestogens and oestrogen doses: Danish cohort study, 2001–9. BMJ. 2011;343:d6423.

Combined hormonal contraception (CHC) increases a woman’s risk of venous thromboembolism (VTE), an effect that has been attributed to the thrombogenic effects of estrogen.⁷ The combined risk of VTE from CHC and the known independent risk of VTE postpartum has prompted the CDC to recommend against the use of any combined (i.e., estrogen-containing) method for 21 days postpartum. Although no direct evidence exists of a higher rate of VTE with CHC immediately postpartum, indirect evidence of increased risk should be considered very seriously.

Evidence from retrospective and database studies continues to suggest that one of the newer progestins, drospirenone, may play a larger role in VTE than previously understood, reigniting the debate over the risk of VTE and combined oral contraceptives (OCs).

Drospirenone was introduced in 2001 in combination with ethinyl estradiol in an OC that had the added benefits of alleviating acne and controlling premenstrual symptoms.⁸ A large (142,475 woman-years) prospective trial examining the role of drospirenone showed no significant difference between this hormone and other forms of progesterone in regard to adverse cardiovascular events.⁹ This study had minimal loss to follow-up (2.4%) and is the only cohort to confirm VTE outcomes based on medical records review (rather than insurance claims databases or national registries).¹⁰

A national cohort study in Denmark, published in 2009, found that the risk of VTE was directly related to duration of use and the dosage of estrogen.¹¹ More significantly, those investigators found that specific progestin types, including drospirenone, desogestrel, and gestodene, were also associated with increased VTE risk.

Danish researchers conducted another retrospective study to assess the VTE risk associated with drospirenone in CHC—a review that included other progestins, the levonorgestrel-releasing IUD, and progestin-only pills. The results again suggested that contraceptives that contain drospirenone, desogestrel, or gestodene were associated with more than twice the risk of VTE, compared with OCs that contain levonorgestrel.

For gestodene and desogestrel, increasing the dosage of estrogen increased the risk of VTE; for drospirenone, however, the dosage of estrogen did not affect the rate of VTE. No association was found between the levonorgestrel-releasing IUD or progestin-only pills with VTE. Overall, the absolute number of VTE was small (4,307 VTE among 1.3 million women using hormonal contraception), which is reassuring, considering that this was a large cohort study.

WHAT THIS EVIDENCE MEANS FOR PRACTICE

No combination hormonal contraception (CHC) of any type should be prescribed for use during the 3 weeks after delivery, given indirect evidence of increased risk of VTE during this period and the known VTE risk posed by CHC.

For women who are beyond that window and who want CHC, the question becomes: How should you counsel them about progestins in different formulations?

A decade of research has yielded equivocal data on drospirenone and the risk of VTE. The only large prospective study did not show any increase in the risk of VTE; newer studies contain important retrospective data but, by their design, are inherently weaker in regard to their conclusions.

Lastly, database reviews that cannot fully control for confounding and do not include chart review for confirmation of diagnosis do not provide a rationale for avoiding certain CHC formulations, especially if one of those formulations is strongly preferred by your patient.¹⁰

Does DMPA lead to HIV?

Heffron R, Donnell D, Rees H, et al; Partners in Prevention HSV/HIV Transmission Study Team. Use of hormonal contraceptives and risk of HIV-1 transmission: a prospective cohort study. Lancet Infect Dis. 2012;12(1):19–26.

Much controversy has arisen in recent years over the role of hormonal contraception and HIV acquisition. This led the World Health Organization (WHO) to convene an international meeting of stakeholders earlier this year to address guidelines for hormonal contraception, especially injectables, in women who are living with HIV or are at high risk of acquiring the virus¹² (see “What this evidence means for practice” on page 35 for more about this meeting).

Fifteen years ago, a well-designed cohort study showed that female sex workers in Kenya who used depot medroxyprogesterone acetate (sold in the United States as Depo-Provera) for contraception were twice as likely to acquire HIV than sex workers who used a nonhormonal method.¹³ Since then, numerous published studies on this topic have yielded equivocal results¹⁴: for example, the largest one, of 1,536 DMPA users in Uganda and Zimbabwe, showed no increased risk of HIV acquisition with DMPA use.¹⁵