Clinical Review

Hormonal contraception in women with medical conditions

OBG Manag. 2006 September;18(9):37-49

Andrew M. Kaunitz, MD

An interview with Dr. Andrew M. Kaunitz, who assisted in the preparation of the new ACOG Practice Bulletin

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IN THIS ARTICLE

Pill reduces risk of ovarian cancer in BRCA carriers
St. John’s wort lowers hormone levels

References

1. Use of Hormonal Contraception in Women With Coexisting Medical Conditions. ACOG Practice Bulletin #73. American College of Obstetricians and Gynecologists. Obstet Gynecol. 2006;107:1453-1472.

2. Marchbanks PA, McDonald JA, Wilson HG, et al. Oral contraceptives and the risk of breast cancer. N Engl J Med. 2002;346:2025-2032.

3. Davidson NE, Helzlsouer KJ. Good news about oral contraceptives. N Engl J Med. 2002;346:2078-2079.

4. Milne RL, Knight JA, John EM, et al. Oral contraceptive use and risk of early-onset breast cancer in carriers and non-carriers of BRCA1 and BRCA2 mutations. Cancer Epidemiol Biomarkers Prev. 2005;14:350-356.

5. Whittemore AS, Balise RR, Pharoah PD, et al. Oral contraceptive use and ovarian cancer risk among carriers of BRCA1 and BRCA2 mutations. Br J Cancer. 2004;91:1911-1915.

6. Narod SA, Risch H, Moslehi R, et al. Oral contraceptives and the risk of hereditary ovarian cancer. Hereditary Ovarian Cancer Clinical Study Group. N Engl J Med. 1998;339:424-428.

7. Ragueneau-Majlessi I, Levy RH, Janik F. Levetiracetam does not alter the pharmacokinetics of an oral contraceptive in healthy women. Epilepsia. 2002;43:697-702.

8. Griffith SG, Dai Y. Effect of zonisamide on the pharmacokinetics and pharmacodynamics of a combination ethinyl estradiol-norethindrone oral contraceptive in healthy women. Clin Ther. 2004;26:2056-2065.

9. McCann MF, Potter LS. Progestin-only oral contraception: a comprehensive review. Contraception. 1994;50(6 suppl 1):S1-S195.

10. Haukkamaa M. Contraception by Norplant subdermal capsules is not reliable in epileptic patients on anticonvulsant treatment. Contraception. 1986;33:559-565.

11. Bounds W, Guillebaud J. Observational series on women using the contraceptive Mirena concurrently with antiepileptic and other enzyme-inducing drugs. J Fam Plann Reprod Health Care. 2002;187:551-555.

12. Mattson RH, Rebar RW. Contraceptive methods for women with neurologic disorders. Am J Obstet Gynecol. 1993;168:2027-2032.

13. Back DJ, Breckenridge AM, Crawford F, et al. The effect of rifampicin on norethisterone pharmacokinetics. Eur J Clin Pharmacol. 1979;15:193-197.

14. Murphy PA, Kern SE, Stanczyk FZ, Westhoff CL. Interaction of St. John’s wort with oral contraceptives: effects on the pharmacokinetics of norethindrone and ethinyl estradiol, ovarian activity, and breakthrough bleeding. Contraception. 2005;71:402-408.

15. Abdollahi M, Cushman M, Rosendaal F. Obesity: risk of venous thrombosis and the interaction with coagulation factor levels and oral contraceptive use. Thromb Haemost. 2003;89:493-498.

16. Zieman M, Guillebaud J, et al. Contraceptive efficacy and cycle control with Ortho Evra/Evra transdermal system: the analysis of pooled data. Fertil Steril. 2002;77:S13-S18.

17. Holt VL, Scholes D, Wicklund KG, Cushing-Haugen KL, Daling JR. Body mass index, weight, and oral contraceptive failure risk. Obstet Gynecol. 2005;105:46-52.

18. Anderson FD. Hait H and the Seasonale-301 Study Group. A multicenter, randomized study of an extended cycle oral contraceptive. Contraception. 2003;68:89-96.

19. Anderson FD, Gibbons W, Portman D. Safety and efficacy of an extended-regimen oral contraceptive utilizing continuous low-dose ethinyl estradiol. Contraception. 2006;73:229-234.

20. Leiman G. Depo-medroxyprogesterone acetate as a contraceptive agent: its effect on weight and blood pressure. Am J Obstet Gynecol. 1972;114:97-102.

21. Jain J, Jakimiuk AJ, Bode FR, Ross D, Kaunitz AM. Contraceptive efficacy and safety of DMPA-SC. Contraception. 2004;70:269-275.

22. Bermas BL. Oral contraceptives in systemic lupus erythematosus—a tough pill to swallow? N Engl J Med. 2005;353:2602-2604.

23. Petri M, Kim MY, Kalunian KC, et al. Combined oral contraceptives in women with systemic lupus erythematosus. OC-SELENA Trial. N Engl J Med. 2005;353:2550-2558.

24. Sanchez-Guerrero, Urive AG, Jimenez-Santana L, et al. A trial of contraceptive methods in women with systemic lupus erythematosus. N Engl J Med. 2005;353:2539-2549.

25. Orr-Walker BJ, Evans MC, Ames RW, et al. The effect of past use of the injectable contraceptive depot medroxyprogesterone acetate on bone mineral density in normal postmenopausal women. Clin Endocrinol (Oxf). 1998;49:615-618.

26. Petitti DB, Piaggio G, Mehta S, Cravioto MC, Meirik O. Steroid hormone contraception and bone mineral density: a cross-sectional study in an international population. The WHO Study of Hormonal Contraception and Bone Health. Obstet Gynecol. 2000;95:736-744.

27. Scholes D, LaCroix AZ, Ichikawa LE, Barlow WE, Ott SM. Injectable hormone contraception and bone density: results from a prospective study [published erratum appears in Epidemiology. 2002;13:749]. Epidemiology. 2002;13:581-587.

28. Scholes D, LaCroix AZ, Ichikawa LE, et al. Change in bone mineral density among adolescent women using and discontinuing depot medroxyprogesterone acetate contraception. Arch Pediatr Adolesc Med. 2005;159:139-144.

29. World Health Organization. Medical eligibility criteria for contraceptive use. Annex 1. COCs and antiretroviral therapies. 3rd ed. Geneva: WHO; 2004.

30. Sapire KE. Depo-provera and carbamazapine. Br J Fam Plann. 1990;15:130.-

Dr. Kaunitz has received funding from Barr Laboratories, Berlex, Johnson & Johnson, and the National Institutes of Health. He is a speaker or consultant for the American College of Obstetricians and Gynecologists, the Association of Reproductive Health Professionals, Barr Laboratories, Berlex, Johnson & Johnson, Pfizer, and Procter & Gamble; and holds stock with Noven, Roche, and Sanofi-Aventis.

Fast Track

Women with a family history of breast cancer or BRCA1 or 2 can use the Pill to prevent ovarian cancer without adding to their breast cancer risk

Rifampin is the only antibiotic for which we have solid evidence of substantially lower steroid levels

Combination OCs are safe in lupus patients with stable, mild disease, who are seronegative for antiphospholipid antibodies, with no prior thrombosis

DMPA use by itself is not an indication for bone density measurement

Decisive new data on risks and benefits of hormonal contraception will change how we manage many patients. These findings prompted the American College of Obstetricians and Gynecologists (ACOG) to update its practice bulletin (released in June) on hormonal contraception in women with coexisting medical conditions.¹ Among the most notable areas of change:

Family history of breast cancer or BRCA1 or 2 mutations. Combination oral contraceptives (OCs) do not appear to increase the risk of breast cancer in these women, and do help prevent ovarian cancer.
Concomitant medications. More women are using enzyme-inducing anticonvulsants for conditions other than seizure disorders; some affect steroid levels.
Obesity. Progestin-only and intrauterine methods may be better for obese women older than 35 years, who face an elevated baseline risk of venous thromboembolism.
Lupus. Combination OCs are safe in women with stable, mild disease who are seronegative for antiphospholipid antibodies.
Depot medroxyprogesterone acetate (DMPA). Although bone density declines in women using DMPA, it recovers within 3 years after the drug is discontinued.
Patch and ring. Until method-specific data come in, assume that the patch and ring have the same contraindications as combination OCs.

For the fine points on these and other findings, we talked with Dr. Andrew M. Kaunitz, who assisted ACOG with preparation of the new bulletin.¹

1. Breast cancer risk

OCs do not add to existing high risk

OBG Management: Women who have a family history of breast cancer have a higher-than-average risk of developing the cancer themselves, and it is widely assumed that estrogen further heightens that risk. Should these women avoid combination OCs?

KAUNITZ: No. Although these women have been reluctant to use hormonal contraceptives (as have many caregivers), we now have several lines of reassuring evidence.

Among the studies demonstrating safety of hormonal methods in this population is the 2002 Women’s CARE study, conducted by the Centers for Disease Control and Prevention and sponsored by the National Institute of Child Health and Human Development, which found no elevated risk of breast cancer in women currently or formerly using OCs, compared with women who had never used them.

This study compared 4,575 women who had breast cancer with 4,682 controls. The relative risk of breast cancer was 1.0 (95% confidence interval 0.8–1.3) among current OC users and 0.9 (0.8–1.0) among women who had previously used OCs. The relative risk did not increase consistently with higher doses or longer use.² Nor did use of OCs add risk in women with a family history of breast cancer.²

OBG Management: An editorial accompanying that study said: “The importance of this finding for public health is enormous, because more than 75% of the women in the study had used oral contraceptives.”³

KAUNITZ: Yes, but this does not mean that women with a positive family history have no increased risk of breast cancer—they do. Rather, the use of hormonal contraceptives does not augment that risk further.

OBG Management: What about women with other high-risk factors, such as germline mutations? Do OCs increase their risk of breast cancer?

KAUNITZ: No. In the largest study to date of breast cancer risk associated with prior or current OC use in women 35 to 64 years of age with BRCA1 and 2 mutations, low-dose OC formulations did not increase it.⁴ In fact, OC use was associated with a significantly reduced risk of breast cancer in BRCA1 mutation carriers (odds ratio 0.22; 95% confidence interval 0.10–0.49).⁴

Pill reduces risk of ovarian cancer in BRCA carriers

KAUNITZ: It is also important to remember the higher risk of ovarian cancer in women with BRCA mutations. We now know that use of the Pill reduces ovarian cancer risk in BRCA-positive women, just as it does in the general population. In a study involving 451 women with BRCA1 or 2 mutations, who self-reported their lifetime history of OC use (or nonuse), the odds ratio for ovarian cancer associated with OC use for a minimum of 1 year was 0.85 (95% confidence interval 0.53–1.36) and declined by 5% (1%–9%) with each additional year of use (P for trend=.01). Use for 6 years or more carried an odds ratio of 0.62 (0.35–1.09).⁵