Clinical Review

Is hormonal contraception right for your perimenopausal patient?

OBG Manag. 2008 June;20(6):31-38

References

1. Mosher WD, Martinez GM, Chandra A, Abma JC, Willson SJ. Use of contraception and use of family planning services in the United States: 1982–2002. Advance data from vital and health statistics. No. 350. Hyattsville, MD: National Center for Health Statistics, December 10, 2004.

2. Abma JC, Chandra A, Mosher WD, Peterson LS, Piccinino LJ. Fertility, family planning, and women’s health: new data from the 1995 National Survey of Family Growth. Vital and health statistics. Series 23. No. 19. Hyattsville, MD: National Center for Health Statistics, May 1997:1–114. (DHHS publication no. (PHS) 97–1995.)

3. Callaghan WM, Berg CJ. Pregnancy-related mortality among women aged 35 years and older, United States, 1991–1997. Obstet Gynecol. 2003;102:1015-1021.

4. Viegas OA, Leong WP, Ahmed S, Ratnam SS. Obstetrical outcome with increasing maternal age. J Biosoc Sci. 1994;26:261-267.

5. Strauss LT, Herndon J, Chang J, et al. Abortion surveillance—United States, 2001. MMWR Surveill Summ. 2004;53(SS–9):1-32.

6. Nightingale AL, Lawrenson RA, Simpson EL, Williams TJ, MacRae KD, Farmer RDT. The effects of age, body mass index, smoking and general health on the risk of venous thromboembolism in users of combined oral contraceptives. Eur J Contracept Reprod Health Care. 2000;5:265-274.

7. Sidney S, Petitti DB, Soff GA, Cundiff DL, Tolan KK, Quesenberry CP, Jr. Venous thromboembolic disease in users of low-estrogen combined estrogen–progestin oral contraceptives. Contraception. 2004;70:3-10.

8. ACOG Committee on Practice Bulletins–Gynecology. ACOG Practice Bulletin No. 73: Use of hormonal contraceptive in women with coexisting medical conditions. Obstet Gynecol. 2006;107:1453-1472.

9. Gallo MF, Nanda K, Grimes DA, Schulz KF. Twenty micrograms vs. >20 microg estrogen oral contraceptives for contraception: systematic review of randomized controlled trials. Contraception. 2005;71:162-169.

10. Jick SS, Kaye JA, Russman S, Jick H. Risk of nonfatal venous thromboembolism with oral contraceptives containing levonorgestrel. Contraception. 2006;73:566-570.

11. Sidney S, Siscovick DS, Petitti DB, et al. Myocardial infarction and use of low-dose oral contraceptives: a pooled analysis of 2 US studies. Circulation. 1998;98:1058-1063.

12. Schwartz SM, Petitti DB, Siscovick DS, et al. Stroke and use of low-dose oral contraceptives in young women: a pooled analysis of two US studies. Stroke. 1998;29:2277-2284.

13. Margolis KL, Adami H-O, Luo J, Ye W, Weider-pass E. A prospective study of oral contraceptive use and risk of myocardial infarction among Swedish women. Fertil Steril. 2007;88:310-316.

14. MacClellan LR, Giles W, Cole J, et al. Probable migraine with visual aura and risk of ischemic stroke: the stroke prevention in young women study. Stroke. 2007;38:2438-2345.

15. Medical eligibility criteria for contraceptive use. 3rd ed. Geneva: World Health Organization, 2004.

16. Hannaford PC, Selvaraj S, Elliott AM, Angus V, Iversen L, Lee AJ. Cancer risk among users of oral contraceptives: cohort data from the Royal College of General Practitioners’ oral contraception study. BMJ. 2007;335:651.-

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

18. Gill JK, Press MF, Patel AV, Bernstein L. Oral contraceptive use and risk of breast carcinoma in situ (United States). Cancer Causes Control. 2006;17:1155-1162.

19. Strom BL, Berlin JA, Weber AL, et al. Absence of an effect of injectable and implantable progestin-only contraceptives on subsequent risk of breast cancer. Contraception. 2004;69:353-360.

20. Wingo PA, Austin A, Marchbanks PA, et al. Oral contraceptives and the risk of death from breast cancer. Obstet Gynecol. 2007;110:793-800.

21. Silvera SA, Miller AB, Rohan TE. Oral contraceptive use and risk of breast cancer among women with a family history of breast cancer: a prospective cohort study. Cancer Causes Control. 2005;16:1059-1063.

22. Narod SA, Dubé MP, Klijn J, et al. Oral contraceptives and the risk of breast cancer in BRCA1 and BRCA2 mutation carriers. J Natl Cancer Inst. 2002;94:1773-1779.

23. Haile RW, Thomas DC, McGuire V, et al. BRCA1 and BRCA2 mutation carriers, oral contraceptive use, and breast cancer before age 50. Cancer Epidemiol Biomarkers Prev. 2006;15:1863-1870.

24. Davis A, Godwin A, Lippman J, Olson W, Kafrissen M. Triphasic norgestimate-ethinyl estradiol for treating dysfunctional uterine bleeding. Obstet Gynecol. 2000;96:913-920.

25. Kaunitz AM. Noncontraceptive health benefits of oral contraceptives. Rev Endocr Metab Disord. 2002;3:277-283.

26. Hurskainen R, Reperi J, Rissanen P, et al. Clinical outcomes and costs with the levonorgestrel-releasing intrauterine system or hysterectomy for treatment of menorrhagia: randomized trial 5-year follow-up. JAMA. 2004;291:1456-1463.

27. Kaunitz AM. Progestin-releasing intrauterine systems and leiomyoma. Contraception. 2007;75 (6 Suppl):S130-S133.

28. Bragheto AM, Caserta N, Bahamondes L, Petta CA. Effectiveness of the levonorgestrel-releasing intrauterine system in the treatment of adenomyosis diagnosed and monitored by magnetic resonance imaging. Contraception. 2007;76:195-199.

29. Kaunitz AM. Depot medroxyprogesterone acetate for contraception. In: Rose BD, ed. UpToDate. Wellesley, MA: UpToDate, 2008.

30. Petitti DB. Combination estrogen–progestin oral contraceptives. N Engl J Med. 2003;349:1443-1450.[Erratum, N Engl J Med. 2004;350:92.]

31. Collaborative Group on Epidemiological Studies of Ovarian Cancer. Ovarian cancer and oral contraceptives: collaborative reanalysis of data from 45 epidemiological studies including 23,257 women with ovarian cancer and 87,303 controls. Lancet. 2008;371:303-314.

32. Schlesselman JJ. Risk of endometrial cancer in relation to use of combined oral contraceptives: a practitioner’s guide to meta-analysis. Hum Reprod. 1997;12:1851-1863.

33. Fernandez E, LaVecchia C, Balducci A, Chatenoud L, Francheschi S, Negri E. Oral contraceptives and colorectal cancer risk: a meta-analysis. Br J Cancer. 2001;84:722-727.

34. Gambacciani M, Cappagli B, Lazzarini V, Ciaponi M, Fruzzetti F, Genazzani AR. Longitudinal evaluation of perimenopausal bone loss: effects of different low dose oral contraceptive preparations on bone mineral density. Maturitas. 2006;54:176-180.

35. Michaëlsson K, Baron JA, Farahmand BY, Persson I, Ljunghall S. Oral-contraceptive use and risk of hip fracture: a case-control study. Lancet. 1999;353:1481-1484.

36. Rosenberg L, Zhang Y, Constant D, et al. Bone status after cessation of use of injectable progestin contraceptives. Contraception. 2007;76:425-431.

37. Casper RF, Dodin S, Reid RL. The effect of 20 μg ethinyl estradiol/1 mg norethindrone acetate (Minestrin), a low-dose oral contraceptive, on vaginal bleeding patterns, hot flashes, and quality of life in symptomatic perimenopausal women. Menopause. 1997;4:139-147.

38. Shargil AA. Hormone replacement therapy in perimenopausal women with a triphasic contraceptive compound: a three-year prospective study. Int J Fertil. 1985;30:15,18-28.

39. Hampton NRE, Rees MCP, Lowe DG, Rauramo I, Barlow D, Guillebaud J. Levonorgestrel intrauterine system (LNG-IUS) with conjugated equine estrogen: a successful regimen for HRT in perimenopausal women. Hum Reprod. 2005;20:2653-2669.

40. North American Menopause Society. Treatment of menopause-associated vasomotor symptoms: position statement of the North American Menopause Society. Menopause. 2004;11:11-33.

41. Gebbie AE, Glasier A, Sweeting V. Incidence of ovulation in perimenopausal women before and during hormone replacement therapy. Contraception. 1995;52:221-222.

42. Creinin MD. Laboratory criteria for menopause in women using oral contraceptives. Fertil Steril. 1996;66:101-104.

43. Kaunitz AM. Hormonal contraception in women of older reproductive age. N Engl J Med. 2008;358:1262-1270.

In the Women’s Contraceptive and Reproductive Experiences (CARE) study, current or previous users of OCs had no increased risk of invasive or in situ breast cancer, compared with never-users.^17,18 This study did include a subgroup of women who had started using OCs after age 40. Nor did the CARE study find an association between progestin-only injectable DMPA or implantable contraceptives and breast cancer.¹⁹

Last, a population-based case-control study in the United States found no increased risk of death from breast cancer among previous users of OCs, compared with women who had never used them.²⁰ This study included an analysis limited to women who had begun using OCs at 30 years of age or older.

OBG Management: What about women who have a family history of breast cancer? Do OCs and other hormonal contraceptives elevate their risk further?

Kaunitz: Women who have a family history of breast cancer are often cautioned that it would be unsafe for them to use hormonal contraception. However, use of hormonal contraception does not appear to impact the risk of breast cancer in women who have a family history of the disease.

A large prospective study from Canada involving women who had a family history of breast cancer and a mean age of 49 found no increased risk of breast cancer among former or current OC users.²¹ This study did not assess risk by BRCA mutation status.

A separate study found that the risk of breast cancer increased slightly among women who had a BRCA1 mutation, with an odds ratio of 1.20 (95% confidence interval, 1.02–1.40), but not among women who had a BRCA2 mutation.²² Another study found no significant increase in the risk of breast cancer among women who had either a BRCA1 or BRCA2 mutation.²³

Benefits include improved bleeding patterns

OBG Management: Many perimenopausal women who have fibroids or adenomyosis experience menorrhagia or dysfunctional uterine bleeding (DUB) and opt for surgery such as endometrial ablation or hysterectomy. Can OCs or other hormonal contraceptives alleviate these patterns without the need for surgery?

Kaunitz: Yes. OCs can restore physiologic bleeding in older women who have DUB. One study involving women 15 to 50 years of age who had DUB found improved bleeding patterns in more than 80% of women randomized to OCs, compared with less than 50% of women randomized to placebo.²⁴ In addition, women who have menorrhagia have reported a significant reduction of blood loss after using OCs.²⁵

Another effective option for women who have menorrhagia is the levonorgestrel-releasing intrauterine system (LNG-IUS), even in women who have menorrhagia associated with fibroids and adenomyosis.^26-28

Because long-term use of injectable forms of contraception tends to lead to amenorrhea, some physicians recommend DMPA as a treatment for menorrhagia. Data supporting this strategy are scant, however.²⁹

OCs reduce the risk of three cancers

OBG Management: Oral contraceptives are known to reduce the risk of ovarian, endometrial, and colorectal cancer to varying degrees. Does this benefit hold up for older women, too?

Kaunitz: Yes. And because the incidence of ovarian cancer, in particular, increases with age, the protection afforded by combination OCs may be especially beneficial for women of older reproductive age.

OBG Management: Just how much protection against ovarian cancer does OC use afford?

Kaunitz: Among users of low-dose combination OCs, the risk of epithelial ovarian cancer declines by at least 50%, compared with women who have never used the pill—and, the longer the use, the greater the protection.^16,30,31 Once OCs are discontinued, the protection diminishes over time, but some degree of reduced risk persists for three decades or longer.³¹

OBG Management: What about endometrial cancer?

Kaunitz: Not just OCs, but also DMPA, are associated with a significant reduction in the risk of endometrial cancer: 50% with use of OCs formulated with 30 μg or more of estrogen, and 80% with use of DMPA. In the case of OCs, the reduced risk is greater with longer use, and it persists after discontinuation for at least 20 years.^25,32

OBG Management: Is the protection against colorectal cancer as great as the protection against these other cancers?

Kaunitz: No, it isn’t, but the protection is still significant. OC use reduces the risk of colorectal cancer by approximately 20%, but the protection against colorectal cancer does not appear to increase with duration of use.^16,33 It also may be that more recent OC use (past 5 years) affords greater protection than use in the more distant past.^16,33

OCs may reduce fracture risk postmenopausally

OBG Management: What effect do combination OCs and other forms of hormonal contraception have on the bone loss that accelerates around the time of menopause?