Clinical Review

Hormonal contraception in women with medical conditions

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

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.

3. Obesity

In obese women over 35, avoid combination OCs

OBG Management: ObGyns are seeing increasing numbers of overweight and obese women. Has selection of hormonal contraception for these women changed?

KAUNITZ: Yes. We now have a recognized obesity epidemic on our hands—and obesity, age over 35 years, and use of combination OCs all represent independent risk factors for thrombosis—prompting the question: Are there safer alternatives to combination OCs for obese women older than 35?

Tenfold risk for thromboembolism. Among the evidence addressing this question, a 2003 Dutch study found that women with a body mass index (BMI) greater than 25 who used combination OCs had 10 times the risk of venous thromboembolism of lean controls who did not use the Pill.¹⁵

Thus, progestin-only and intrauterine contraceptive methods may be more appropriate for older obese women. This language about obesity and combination contraceptives was not in the earlier version of the practice bulletin.

No need to rule out the patch

OBG Management: Aren’t some hormonal contraceptives less effective in obese women?

KAUNITZ: In a 2002 analysis of pooled data, women in the highest weight category (≥90 kg) who were using the contraceptive patch had a higher pregnancy rate than lower-weight women.¹⁶ However, this finding does not rule out use of the patch in overweight women who prefer it to less effective methods. Rather, it should be kept in mind when counseling these patients about their options.

Although the new ACOG bulletin cites data from Holt et al¹⁷ suggesting a higher failure rate in obese women using combination OCs, other OC clinical trials have not confirmed this association.^18,19 In a study by Anderson and colleagues,¹⁸ which found no pregnancies among the heaviest women, the mean weight was 155.9 lb, but ranged from 91.0 to 360.0 lb, and the mean BMI was 26.0, but ranged from 15.2 to an extreme of 56.5!

What about DMPA? We also lack evidence of higher pregnancy rates among overweight women using DMPA (150-mg intramuscular or 104-mg subcutaneous formulations).^20,21

4. Lupus

OCs are an option in some women with lupus

OBG Management: As The New England Journal of Medicine observed last year, there has been an “implicit moratorium” on prescribing combination hormonal contraceptives in women with systemic lupus erythematosus (SLE) because clinicians have feared that exogenous estrogens might exacerbate disease.²² This moratorium derives from data suggesting that estrogens worsen SLE, while androgens appear to protect against the condition.

The new practice bulletin now indicates that oral contraceptives are an option for this population. What is behind the change?

KAUNITZ: We now have data from 2 randomized clinical trials^23,24 indicating that women can safely use combination OCs if they:

have stable, mild disease
are seronegative for antiphospholipid antibodies
have no history of thrombosis

Disease remained stable. In the first trial,²⁴ 162 women with mild, stable SLE were randomized to combination OCs, progestin-only pills, or the copper IUD. Their disease level was established at baseline and over 12 months, using the Systemic Lupus Erythematosus Disease Activity Index. Disease remained stable in all 3 groups.

Estrogen did not increase severity of SLE. In the second trial,²³ 183 women with inactive or stable active SLE were randomized to combination OCs or placebo. The primary endpoint for this trial was severe lupus flare: 7 of 91 women (7.7%) in the OC group experienced a flare, compared with 7 of 92 women (7.6%) taking placebo. Thus, estrogen does not appear to increase the severity of SLE.

OBG Management: Isn’t another concern about patients with SLE the substantial risk of thrombosis?

KAUNITZ: Yes. In the first study,²⁴ 2 thromboses occurred in women taking OCs, and 2 occurred in women using the progestin-only pill. All the women with thromboses were seropositive for antiphospholipid antibodies. Hence, we need to exclude the presence of these antibodies in women with SLE prior to prescribing combination estrogen-progestin contraception. In women with lupus and a history of thrombosis, as with all women with a history of thrombosis, we should avoid combination hormonal contraception.

In the second study,²³ which compared women on combination OCs to a placebo group, the OC group experienced 1 case of deep venous thrombosis (DVT) and 1 clotted graft. The placebo group experienced 1 case of DVT, 1 ocular thrombosis, 1 superficial thrombophlebitis, and 1 death (after the trial ended).

5. DMPA and bone density

DMPA does not appear to have long-term impact

OBG Management: There has been some furor over DMPA’s effect on bone mineral density (BMD). What are the latest findings in this area?

KAUNITZ: Studies assessing BMD in former DMPA users, including postmenopausal women, show that prior use of DMPA does not appear to have any long-term impact on BMD.^25,26 In addition, more recent longitudinal data indicate that after DMPA is discontinued BMD fully recovers, which appears to take about 3 years in adults and as little as 1 year in teens.^27,28