Gonadotropin and Sex Steroid Levels in HIV-Infected Premenopausal Women and Their Association With Subclinical Atherosclerosis in HIV-Infected and -Uninfected Women in the Women's Interagency HIV Study (WIHS)

Background: HIV-infected women may experience prolonged amenorrhea, suggesting altered gonadotropin and sex hormone levels. However, the impact of these endocrine disruptions on atherosclerosis has not been evaluated in women living with, or at risk for, HIV infection. We investigated the association of sex hormone and gonadotropin concentrations with subclinical atherosclerosis in HIV-infected and -uninfected premenopausal women in the Women's Interagency HIV Study. Methods: Using B-mode ultrasound, the common carotid artery intima-media thickness and distensibility were measured once. Cycle-specific FSH, total estradiol (E2), and inhibin-B concentrations were measured in 584 (414 HIV infected, 170 HIV uninfected) women. Random concentrations of total T, dehydroepiandrosterone sulphate, and SHBG were measured in 1094 (771 HIV infected, 323 HIV uninfected) women. The endocrine analytes were measured at or before the ultrasound visit. Sex hormones, FSH, and SHBG concentrations were compared between HIV-infected and -uninfected women using nonparametric testing. Linear regression models were used to evaluate the association of sex hormones, FSH, and SHBG with carotid artery intima-media thickness and distensibility adjusted for confounders. Separate analyses were conducted by HIV status. Results: Compared with HIV-uninfected women, E2, T, and dehydroepiandrosterone sulphate concentrations were significantly lower and SHBG was higher in HIV-infected women. Adjusted for the confounders, T was significantly positively associated with distensibility (beta-estimate = .04, P = .0005) among HIV-infected women, and the magnitude of association did not differ by CD4 cell count. E2 was significantly positively associated with distensibility among HIV-infected women with CD4 count less than 350 cells/mu L. Conclusions: HIV-infected women had reduced estrogen and androgen compared with HIV-uninfected premenopausal women. T deficiency is linked with carotid artery stiffness, regardless of immune suppression, whereas E2 deficiency is linked with carotid stiffness among immunocompromised HIV-infected premenopausal women. Further research is warranted to understand the impact of endocrine dysregulation on the accelerated cardiovascular disease risk in HIV-infected women. (J Clin Endocrinol Metab 98: E610-E618, 2013)