Clinical Review

Menopause in HIV-Infected Women

Journal of Clinical Outcomes Management. 2016 January;23(1)

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As these demographics, body habitus, and lifestyle characteristics are frequently found among HIV-infected women, it is not surprising that amenorrhea and anovulation are common in this population [8–14]. In fact, studies show that there is an increased prevalence of amenorrhea and anovulation among HIV-infected women when compared to non–HIV-infected women [8]. Some studies suggest that women with lower CD4 cell counts and higher viral loads have increased frequency of amenorrhea and irregular menstruation compared to those with higher CD4 cell counts and lower viral loads [9,10]. However, it remains unclear if HIV infection itself, instead of the associated social and medical factors, is responsible for the higher frequency of amenorrhea [11–13]. For example, in a prospective study comparing 802 HIV-infected women with 273 non–HIV-infected women, there was no difference in the prevalence of amenorrhea when controlling for BMI, substance use, and age [13].

The World Health Organization (WHO) currently defines natural menopause as the permanent cessation of menstruation for 12 consecutive months without any obvious pathological or physiologic causes [15]. However, given the increased prevalence of amenorrhea in HIV-infected women, amenorrhea seen with HIV infection can be mistaken for menopause. The Women’s Interagency HIV Study (WIHS), a multicenter, observational study of HIV-infected women and non–HIV-infected women of similar socioeconomic status, found that more than half of HIV-infected women with prolonged amenorrhea of at least 1 year had serum follicle-stimulating hormone (FSH) levels in the premenopausal range of less than 25 mIU/mL [16]. Hence, this implies that some of these women may have had prolonged amenorrhea rather than menopause [17]. The traditional definition of menopause may need to be altered in this population.

Age at Menopause

Natural menopause, retrospectively determined by the cessation of menstrual cycles for 12 consecutive months, is a reflection of complete, or near complete, ovarian follicular depletion with subsequent low estrogen levels and high FSH concentrations [18]. In the United States, studies have found the mean age of menopause to be between 50 to 52 years old [19,20]. These studies, however, focused predominantly on menopause in middle class, white women. Early menopause, defined as the permanent cessation of menstruation between 40 to 45 years of age, affects 5% of the women in the United States, while premature menopause or primary ovarian insufficiency, which occurs at younger than 40 years of age, affects 1% of the women [21].

As earlier menopause is associated with increased risks of diabetes [22], cardiovascular disease [23] , stroke [24], and osteoporosis [25], identifying the mean age of menopause is important in the management of HIV-infected women. Among women in the United States, early menopause has been observed in women who are African American, nulliparous, have lower BMI, smoke tobacco, and have more stress, less education, and more unemployment [26–29]. Unhealthy lifestyles can also contribute to an earlier age of menopause. Smoking is one of the most consistent and modifiable risk factors associated with an earlier onset of natural menopause, accelerating menopause by up to 2 years [26,30]. Substances present in cigarettes are associated with irreversible damage of ovarian follicles and impaired liver estrogen metabolism [30]. Cocaine use has also been associated with lower estradiol levels, suggesting possible ovary-toxic effects [7,31].