Clinical Review

Menopause in HIV-Infected Women

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

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In a study by Miller et al that focused on 536 HIV-infected women, among whom 37% were perimenopausal, 89% reported psychological symptoms [56]. Ferreira et al found that HIV-infected perimenopausal women had an increased incidence of psychological symptoms compared to non–HIV-infected women [38]. Whether this increased prevalence of psychological symptoms seen in HIV-infected women can be attributed to menopause is unclear since one third to one half of men and women living with HIV experience symptoms of depression [77]. However, in the WIHS, which compared 835 HIV-infected with 335 non-HIV-infected women from all menopausal stages, elevated depressive symptoms were seen in the early perimenopausal period [60]. There was no increased incidence of such symptoms during the premenopausal or postmenopausal period, suggesting the contribution of menopause to depressive symptoms during the perimenopausal period [60].

Persistent menopausal symptoms, especially hot flashes, also predicted elevated depressive symptoms in several studies [56,60] suggesting the importance of appropriately identifying and treating menopausal symptoms. In addition, cognitive decline associated with menopause contributes to depression [78–80].

Other Symptoms

Sleep disturbances are also common among perimenopausal women, with prevalence estimated to be between 38% and 46% [81–84]. Hot flashes, anxiety, and depression appear to be contributing factors [81–84]. In a cross-sectional study of 273 HIV-infected and 264 non-HIV-infected women between 40 and 60 years of age, insomnia was found in 51% of perimenopausal and 53% of postmenopausal HIV-infected women. HIV-infected women had the same prevalence of insomnia compared to non–HIV-infected women [85]. Joint aches are also commonly reported in the perimenopausal period, with prevalence as high as 50% to 60% among perimenopausal women in the United States [52,53]. In HIV-infected women, Miller et al found that 63% of menopausal women reported arthralgia [56].

Treatment

For women experiencing severe hot flashes and vaginal dryness, short-term menopausal hormone therapy (MHT) is indicated to relieve symptoms. MHT should be limited to the shortest period of time at the lowest effective dose as MHT is associated with increased risks of breast cancer, cardiovascular disease, thromboembolism, and increased morbidity [86]. Despite the increased severity of menopausal symptoms experienced among HIV-infected women, the prevalence of the use of MHT in this population is lower compared to non–HIV-infected women [85].

Topical treatment is recommended for women who are experiencing solely vaginal atrophy. First-line treatment is topical nonhormonal therapy such as moisturizers and lubricants [87]. If symptoms are not relieved, then topical vaginal estrogen therapy is recommended [87]. Although topical therapy can result in estrogen absorption into the circulation, it is to a much lesser extent than systemic estrogen therapy [88].

Overall, there is lack of data on the potential interactions between MHT and HAART. Much of the potential interactions are inferred from pharmacokinetic and pharmacodynamics studies between HAART and oral contraceptives. Hormone therapy, protease inhibitors (PIs), colbicistat, and non-nucleoside reverse transcriptase inhibitors (NNRTIs) are all metabolized by the CYP3A4 enzyme [89–91]. Current evidence suggests that concomitant use of hormone therapy with NNRTIs and PIs does not significantly alter the pharmacokinetics of HAART or the clinical outcomes of HIV [91]. However, there is evidence that concomitant use of nevirapine and PIs boosted with ritonavir leads to decrease in estrogen levels so higher doses of MHT may have to be used to achieve symptomatic relief [91]. There is no data on the interaction between PIs boosted with colbicistat and estrogen [92]. Integrase inhibitors, nucleoside and nucleotide reverse transcriptase inhibitors (NRTIs), and the CCR5 antagonist maraviroc have no significant interactions with estrogen containing compounds [89,90,92].