July 2018

Combined hormonal contraceptives (CHCs) raise the greatest number of clinical issues for patients in the perimenopausal age group, but they may also provide the greatest numbers of noncontraceptive benefits, according Amanda Black and Anita Nelson, writing in the soon to be published 21st edition of Contraceptive Technology.¹ During the perimenopause, CHCs offer healthy candidates effective contraception as well as good cycle control (with the possibility of amenorrhea), decreased blood loss, treatment of vaso¬motor symptoms, at least partial protection against bone loss, and reduction in the risks of several cancers. These benefits must be weighed against additional health issues that can develop with age and that increase the risk of using an estrogen-containing contraceptive method.

In particular, endometrial cancer rates can be reduced by about 50%, regardless of the age of the user.² Ovarian cancer risk reduction has been impressively demonstrated in younger users, but it is not clear how much the risk of ovarian cancer is reduced with CHC use in the later reproductive-age years.³ More recently, the lifetime risk of colorectal cancer has been showed to be reduced by COC use, although the magnitude of the effect is not known when pills are used only during later reproductive years.^4,5

Breast cancer risks alarm women, but the earlier studies that raised the con¬cerns for increased breast cancer risk involved the use of high-dose formu¬lations. Today, there does not appear to be an excess risk of breast cancer associated with long-term use of combined oral contraceptives, either during CHC use or later in life.^6,7

Carefully monitor patients in this age group for development of cate¬gory 4 conditions or combinations of category 3 conditions of the U.S. Medical Eligibility Criteria. Given the prevalence of obesity and under-diagnosed hypertension, diabetes, and cardiovascular risks, thorough periodic analysis of the health status of older CHC users must be done over time. Those found to be healthy without other contra¬indications to estrogen-containing methods can continue to use combined hormonal methods until menopause in the United States. However, the lack of evidence of the safety of CHCs in this population has prompted more conservative approaches in other countries. In Canada and in the United Kingdom, guidelines recommend considering changing at the age of 50 from CHC methods to a progestin-only method.⁸

Some companies have marketed lower-dose oral contraceptives spe¬cifically for this age group, but there is no consistent evidence that for¬mulations with 10 or 20 mcg ethinyl estradiol are safer. Estrogen potency may be important; formulations with weaker estrogens may pose less thrombotic risk.

Specifically for perimenopausal patients, write Carrie Cwiak and Alison Edelman in the new edition of CT,⁹ COCs can reduce irregular menstrual bleeding and the risk of en-dometrial hyperplasia associated with anovulatory cycling. Black and Nelson further advise that, in the late reproductive years, extended-cycle use of combined hormonal contraceptives (oral contraceptive pills and vaginal rings) may be particularly appealing, not only to achieve amenorrhea, but also to avoid development of vasomotor symptoms during hormone-free intervals. Cwiak and Edelman agree, reporting that one 3-year observational study found that 90% of perimenopausal women with vasomotor symp¬toms had relief with COC therapy compared with 40% with placebo.¹⁰ Extended use of COCs may be more effective as users would not experience a drop in EE during the placebo week.

If the user wants scheduled bleeding, try to limit the number of hormone-free days with use of 24/4 formulations or 24/4 ring-use patterns. Some pill formulations have only 2 placebo pills and include low-dose estrogen-only pills during the rest of the scheduled bleeding days; this can reduce symptoms associated with estrogen withdrawal. Of note, the vaginal contraceptive ring increases vaginal lubrication and may help relieve symptoms of vaginal dryness and dyspareunia.
Conclusions
Healthy patients without contraindications to estrogen can safely use COCs until they reach menopause, say Cwiak and Edelman. Though it may be difficult to detect when meno¬pause occurs, because COC users in their 40s or early 50s may not experience traditional symptoms of menopause while taking COCs. They will not experience menstrual irregularities or hot flashes, especially if COCs are used on an extended basis.

1. Black A, Nelson AL. Contraception in the later reproductive years. In: Hatcher RA, Nelson AL, Trussell J, et al. (eds) Contraceptive Technology. 21st edition. New York, NY: Ayer Company Publishers, Inc. In press.
2. Iversen L, Sivasubramaniam S, Lee AJ, Fielding S, Hannaford PC. Lifetime cancer risk and combined oral contraceptives: the Royal College of General Practitioners’ Oral Contraception Study. Am J Obstet Gynecol 2017;216:580.e1-e9.
3. Braem MC, Onland-Moret NC, van den Brandt PA, et al. Reproductive and hormonal factors in association with ovarian cancer in the Netherlands cohort study. Am J Epidemiol 2010;172:1181-9.
4. Gierisch JM, Coeytaux RR, Urrutia RP, et al. Oral contraceptive use and risk of breast, cervical, colorectal, and endometrial cancers: a systematic review. Cancer Epidemiol Biomarkers Prev 2013;22:1931-43.
5. Bosetti C, Bravi F, Negri E, La Vecchia C. Oral contraceptives and colorectal cancer risk: a systematic review and meta-analysis. Hum Reprod Update 2009;15:489-98.
6. Hannaford PC, Iversen L, Macfarlane TV, Elliot AM, Angus V, Lee AJ. Mortality among contraceptive pill users: cohort evidence from Royal College of General Practitioners’ Oral Contraception Study. BMJ 2010;340:c927.
7. Thorbjanardardottir T, Olafsdottir EJ, Valdimarsdottir UA, Olafsson O, Tryggvadottir L. Oral contraceptives, hormone replacement therapy and breast cancer risk: a cohort study of 16,928 women 48 years and older. Acta Oncol 2014;53:752-8.
8. Faculty of Sexual & Reproductive Healthcare CEU. FSRH Guideline: Contraception for women aged over 40 years:2017:1-66.
9. Cwiak C, Edelman AB. Combined oral contraceptives (COCs). In: Hatcher RA, Nelson AL, Trussell J, et al. (eds) Contraceptive Technology. 21st edition. New York, NY: Ayer Company Publishers, Inc. In press.
10. Shargil AA. Hormone replacement therapy in perimenopausal women with a triphasic contraceptive compound: a three-year prospective study. Int J Fertil 1985;30:15, 8-28.