Contraception for the perimenopausal woman: What’s best?

,; ,

Applied Evidence

Contraception for the perimenopausal woman: What’s best?

J Fam Pract. 2015 November;64(11):705-709

PDF Download

References

1. Finer LB, Zolna MR. Unintended pregnancy in the United States: incidence and disparities, 2006. Contraception. 2011;84:478-485.

2. Centers for Disease Control and Prevention (CDC). U.S. medical eligibility criteria for contraceptive use, 2010. MMWR Recomm Rep. 2010;59:1-86.

3. Division of Reproductive Health, National Center for Chronic Disease Prevention and Health Promotion, Centers for Disease Control and Prevention (CDC). U.S. selected practice recommendations for contraceptive use, 2013: adapted from the World Health Organization selected practice recommendations for contraceptive use, 2nd edition. MMWR Recomm Rep. 2013;62:1-60.

4. Lidegaard O, Nielsen LH, Skovlund CW, et al. Venous thrombosis in users of non-oral hormonal contraception: follow-up study, Denmark 2001-10. BMJ. 2012;344:e2990.

5. Committee on gynecologic practice. ACOG committee opinion number 540: Risk of venous thromboembolism among users of drospirenone-containing oral contraceptive pills. Obstet Gynecol. 2012;120:1239-1242.

6. McNamara M, Batur P, DeSapri KT. In the clinic. Perimenopause. Ann Intern Med. 2015;162:ITC1-15.

7. de Bastos M, Stegeman BH, Rosendaal FR, et al. Combined oral contraceptives: venous thrombosis. Cochrane Database Syst Rev. 2014;3:CD010813.

8. Wu CQ, Grandi SM, Filion KB, et al. Drospirenone-containing oral contraceptive pills and the risk of venous and arterial thrombosis: a systematic review. BJOG. 2013;120:801-810.

9. Dinger J, Bardenheuer K, Heinemann K. Cardiovascular and general safety of a 24-day regimen of drospirenone-containing combined oral contraceptives: final results from the international active surveillance study of women taking oral contraceptives. Contraception. 2014;89:253-263.

10. Dinger J, Möhner S, Heinemann K. Cardiovascular risk associated with the use of an etonogestrel-containing vaginal ring. Obstet Gynecol. 2013;122:800-808.

11. Sidney S, Cheetham TC, Connell FA, et al. Recent combined hormonal contraceptives (CHCs) and the risk of thromboembolism and other cardiovascular events in new users. Contraception. 2013;87:93-100.

12. Arowojolu AO, Gallo MF, Lopez LM, et al. Combined oral contraceptive pills for treatment of acne. Cochrane Database Syst Rev. 2012;6:CD004425.

13. Koulianos GT. Treatment of acne with oral contraceptives: criteria for pill selection. Cutis. 2000;66:281-286.

14. Thorneycroft IH. Update on androgenicity. Am J Obstet Gynecol. 1999;180:288-294.

15. Lidegaard Ø, Løkkegaard E, Jensen A, et al. Thrombotic stroke and myocardial infarction with hormonal contraception. N Engl J Med. 2012;366:2257-2266.

16. Peragallo Urrutia R, Coeytaux RR, McBroom AJ, et al. Risk of acute thromboembolic events with oral contraceptive use: a systematic review and meta-analysis. Obstet Gynecol. 2013;122:380-389.

17. U.S. Food and Drug Administration. Safety: Depo-Provera (medroxyprogesterone acetate injectable suspension). U.S. Food and Drug Administration Web site. Available at: http://www.fda.gov/Safety/MedWatch/SafetyInformation/SafetyAlertsforHumanMedicalProducts/ucm154784.htm. Accessed April 20, 2015.

18. Committee Opinion No. 602: Depot medroxyprogesterone acetate and bone effects. Obstet Gynecol. 2014;123:1398-1402.

19. Lanza LL, McQuay LJ, Rothman KJ, et al. Use of depot medroxyprogesterone acetate contraception and incidence of bone fracture. Obstet Gynecol. 2013;121:593-600.

20. Ettinger B, Pressman A, Sklarin P, et al. Associations between low levels of serum estradiol, bone density, and fractures among elderly women: the study of osteoporotic fractures. J Clin Endocrinol Metab. 1998;83:2239-2243.

21. Reginster JY, Sarlet N, Deroisy R, et al. Minimal levels of serum estradiol prevent postmenopausal bone loss. Calcif Tissue Int. 1992;51:340-343.

22. Gaffield ME, Culwell KR, Ravi A. Oral contraceptives and family history of breast cancer. Contraception. 2009;80:372-380.

23. Iodice S, Barile M, Rotmensz N, et al. Oral contraceptive use and breast or ovarian cancer risk in BRCA1/2 carriers: a meta-analysis. Eur J Cancer. 2010;46:2275-2284.

24. Marchbanks PA, Curtis KM, Mandel MG, et al. Oral contraceptive formulation and risk of breast cancer. Contraception. 2012;85:342-350.

A large (N=1.6 million) Danish registry study published in 2012 demonstrated a 2-fold increased risk of VTE among vaginal ring users vs women taking COCs.⁴ But a multinational prospective cohort study of more than 33,000 women found no increased VTE risk in ring users,10 and a recent US database study involving more than 800,000 women reported nonsignificant VTE risk estimates for both the ring (RR=1.09; 95% CI, 0.55-2.16) and the patch (RR=1.35; 95% CI, 0.90-2.02) compared with COCs.¹¹

THE BOTTOM LINE For Ms. G, the benefits of contraception likely outweigh any small increase in her absolute risk for VTE. To minimize her risk, however, select a pill that contains a low dose (20-35 mcg) of ethinyl estradiol (EE) combined with a progestin that has not been associated with an increased VTE risk. Because of their mechanism of action, most COCs will improve acne, regardless of the progestin in the formulation.^12-14

CASE 2 › Stephanie T: CV risk

Stephanie T, 47, is in need of contraception and treatment for severe hot flashes. She has no significant past medical history, but she is obese (BMI =36), her blood pressure (BP) is 130/80 mm Hg, and her most recent labs reveal a fasting glucose of 115 and a hemoglobin A1c of 6.1%. Ms. T is concerned about arterial thromboembolic disease because of her family history: Her father had a myocardial infarction (MI) at age 56 and a maternal aunt had a stroke when she was 65.

What evidence should you consider?

Baseline arterial thromboembolic events are considerably more rare in premenopausal women than VTEs (13.2 MIs vs 24.2 thrombotic strokes per 100,000 woman-years).¹⁵ Thus, a small increased RR from a CHC is unlikely to have a significant clinical impact.

Some third-generation progestins appear to be more thrombophilic than firs tor second-generation progestins.

A systemic review and meta-analysis of studies between 1995 and 2012 showed that the odds ratio (OR) of ischemic stroke in users of COCs vs nonusers was 1.9 (95% CI, 1.24–2.91).¹⁶ This study included very few estrogen formulations with <35 mcg EE, however; even so, no increased risk of MI was found (OR=1.34; 95% CI, 0.87–2.08).¹⁶ A 15-year retrospective cohort study of 1.6 million Danish women showed that lowering the dose of EE to 20 mcg (from 30-40 mcg) significantly reduced the risk of arterial events.¹⁵ It is unclear whether the vaginal ring is associated with an increased RR of stroke compared with COCs because studies have had mixed results.^10,15 There is no compelling evidence to suggest a difference in the risk of arterial events based on the type of progestin used in the COC.¹⁵

Hypertension is a key consideration. It is important to remember that perimenopausal women may have comorbid conditions that increase their risk of arterial thromboembolic events. CHCs should be used with caution in women with hypertension, even if BP is adequately controlled—a Category 3 recommendation from the CDC. In such patients, LARC or a progestin-only pill is preferred unless there is a compelling reason to use a CHC, such as acne, vasomotor symptoms, or hirsutism.²

CHCs are contraindicated for women with a BP ≥160/100 mm Hg and/or any manifestation of vascular disease (Category 4).² Although progestin-only methods are often preferred for women with established vascular disease, depot medroxyprogesterone acetate (DMPA) is an exception (Category 3).² DMPA is not a first-line choice for such patients because of its potential to cause weight gain and worsening lipids, glucose, and insulin metabolism. Women with hypertriglyceridemia should have follow-up testing of lipid levels after initiation of hormonal contraception, especially if it contains estrogen.

Diabetes is not an absolute contraindication. Many women with diabetes can safely use CHCs (Category 2). The exceptions: those who have vascular disease, nephropathy, retinopathy, or neuropathy (Category 4) or have had diabetes for >20 years and therefore have the potential for undiagnosed vascular disease.² Generally, the use of insulin should not affect decisions regarding CHCs, and patients can be reassured that the hormones will not worsen their diabetes control.

When caring for women who have multiple risk factors for cardiovascular disease, it is important to exercise clinical judgment regarding the appropriateness of CHCs (Categories 3 and 4). Progestin-only methods have a more favorable risk profile for women at the highest risk and may provide ample relief of perimenopausal symptoms.²

THE BOTTOM LINE Ms. T may benefit from a CHC due to her severe hot flashes. She should be encouraged to adopt healthy lifestyle changes, including diet and exercise, to decrease her risk of arterial thromboembolism and VTE, but she has no contraindications to the use of a CHC at this time.