Clinical Review

Menopause in HIV-Infected Women

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

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Cardiovascular Risk

Estrogen deficiency resulting from menopause leads to several long-term effects, including cardiovascular disease and osteoporosis. The loss of protective effects of estrogen leads to an increased risk of cardiovascular disease particularly with changes in lipid profiles [93]. Perimenopausal women experience changes in body composition with increased fat mass and waist circumference, as well as dyslipidemia and insulin resistance, all of which are associated with higher risk of cardiovascular disease [94].

HIV infection also incurs a higher risk of cardiovascular disease [95–99]. The inflammatory effects of HIV, HAART, and traditional risk factors including dyslipidemia all contribute to cardiovascular disease but the degree to which each factor contributes to elevated risk is unknown [95,98]. In addition, modifiable risk factors for cardiovascular disease such as decreased fitness and smoking are more commonly seen in HIV-infected women [100]. Even prior to menopause, HIV-infected women experience lipodystrophy syndrome with increase in truncal visceral adiposity and decrease in subcutaneous fat and muscle mass [101,102]. Whether such changes in body composition are exacerbated during the perimenopausal period remain unclear. In the SWEET study, which focused on 702 South African women among whom 21% were HIV-infected, there was lower lean mass but minimal difference in the fat mass of postmenopausal women compared to premenopausal women [103]. As the study was based in South Africa with only 21% HIV-infected, the results of this study should be viewed with caution. While changes in body composition were not observed in postmenopausal women in the SWEET study, increased truncal adiposity seen in premenopausal HIV-infected women is likely to pose an additional risk for cardiovascular disease during the menopause transition.

Several studies have been conducted to demonstrate an increased risk of cardiovascular disease, especially among young HIV-infected men [95–99]. However, no study has focused specifically on the risk of cardiovascular disease in postmenopausal HIV-infected women to date. Despite the lack of studies, it is plausible that the increased risk of cardiovascular disease seen in HIV infection is likely to be compounded with the increased risk seen during menopause. Postmenopausal HIV-infected women may be at significantly higher risk of cardiovascular disease. Appropriate measures such as lipid control, antiplatelet therapy, smoking cessation, and other lifestyle changes should be initiated as in any other population. Further studies are necessary focusing on the effects of menopause on cardiovascular disease risk in HIV-infected women.

Osteoporosis

Menopause, with its associated estrogen deficiency, is the most important risk factor associated with increased bone turnover and bone loss and can worsen HIV associated bone loss [104]. Among HIV-infected individuals, low bone mineral density (BMD) has been described even among premenopausal women and younger men [105–107]. Evidence suggests that the decreased BMD associated with HIV stabilizes or even improves after initiation of HAART in the younger population [105–107]. However, once HIV-infected women enter menopause, they have higher rates of bone loss compared to non–HIV-infected women with significantly increased prevalence of osteoporosis compared to non–HIV-infected women [108–112].

Chronic inflammation by HIV stimulates osteoclast differentiation and resorption [113]. In addition, HAART [114–116], vitamin D deficiency [117], low BMI, poor nutrition [118], inactivity, use of tobacco, alcohol, and illicit drugs [119,120], and coinfection with hepatitis B and C [121] all appear to contribute to decreased BMD among HIV-infected men and women [118]. Among HIV-infected postmenopausal women, those taking ritonavir were found to have increased differentiation of osteoclast cells and increased bone loss [122]. Similarly, methadone use in postmenopausal women has been associated with increased BMD decline [123]. African-American, HIV-infected postmenopausal women appear to be at the greatest risk for bone loss [109].