Serum total estradiol, but not testosterone is associated with reduced bone mineral density (BMD) in HIV-infected men: a cross-sectional, observational study
TO THE EDITOR—We read with interest the updated human immunodeficiency virus (HIV) primary care guidelines by Aberg et al in Clinical Infectious Diseases on 1 January 2014  and would like to bring an additional comment to readers’ attention. We agree with the authors that the preferred initial assay for hypogonadism diagnosis in HIV-infected men has not been definitively established, although experts in the field have advocated using morning free testosterone (FT) as the initial assay in HIV-infected men for 10 years . HIV-infected men have elevated sex hormone binding globulin levels, which can make total testosterone (TT) appear normal even in the setting of inadequate testosterone production . Clinical data supporting the use of morning FT for initial diagnosis of hypogonadism in HIV-infected men have been sparse. Therefore, we recently performed an analysis using data from the Multicenter AIDS Cohort Study . Data were analyzed from >500 HIVinfected and -uninfected men not on testosterone replacement therapy in whom morning TT and FT levels were available. Biochemical hypogonadism (FT <50 pg/ mL or TT <300 ng/dL) was present in 7.2% of HIV-uninfected men and 9.3% of HIV-infected men. Of the men with biochemical hypogonadism (n = 46), 11 of 34 of the HIV-infected men had normal TT but low FT. In contrast, all of the HIV-uninfected men had both low TT and low FT. The implication of our finding is that if morning TT alone were used as the initial diagnostic test for hypogonadism in HIV-infected men, one-third of the men would be missed. We also examined characteristics of the HIV-infected men who had normal TT but low FT compared with those who had both low TT and low FT. Hepatitis C virus (HCV) infection was significantly associated with having normal TT but low FT. Therefore, HIV/HCV-coinfected patients may be particularly likely to be missed if TT is used. For these reasons, we suggest using morning FT as the initial diagnostic test for hypogonadism in HIV-infected men to improve diagnostic sensitivity.