Testicular Pathologic Changes and the Pituitary-Testicular Axis During Human Immunodeficiency Virus Infection

Abstract

To chronicle pituitary-testicular axis dysfunction and its clinicopathologic features in homosexual men. Between 1984 and 1992, 84 homosexual men underwent longitudinal follow-up for 4 years. At entry into the study, 28 were seronegative and 56 were seropositive for human immunodeficiency virus (HIV). Although 40 subjects remained asymptomatic (nonprogressors), 16 had progression to acquired immunodeficiency syndrome (AIDS). Of those 16 patients with progression, 8 had AIDS within 2 years (early progressors) and 8 demonstrated AIDS within 4 years after enrollment (late progressors), and all died. The testes of five patients were examined at autopsy. The control group had similar follow-up. Luteinizing hormone (LH), follicle-stimulating hormone (FSH), testosterone, and bioavailable testosterone (bio-T) were measured in stored sera collected at 2-year intervals. The last hormonal measurement was between 3 and 24 months before autopsy. Comparison was made between autopsied and nonautopsied patients with AIDS as well as between HIV nonprogressors and control seronegative men. The correlation between pathologic findings and hormonal status was examined by regression analysis. At baseline, testosterone, bio-T, LH, and FSH were not significantly different among all patients and subjects. During the study period, testosterone, bio-T, and serum gonadotropin levels remained unchanged in the seronegative homosexual men. In nonprogressors, serum FSH and LH concentrations remained unchanged, whereas testosterone and bio-T levels decreased significantly during this 4-year period. After progression to AIDS (in both groups of progressors), the serum FSH and LH levels were higher and the serum testosterone and bio-T were lower in comparison with values in the seronegative men. In late progressors to AIDS, FSH and LH increased, whereas serum testosterone and bio-T decreased significantly from baseline. All five patients with AIDS on whom autopsy was done had boundary wall thickening of the seminiferous tubules and decreased spermatogenesis. No significant differences were found in serum testosterone, bio-T, and LH between those in whom autopsy was or was not done; however, FSH was significantly higher in the autopsied cases. The serum testosterone and bio-T levels were negatively correlated with the interstitial inflammation. A significant correlation was also observed between change of bio-T and weight loss. We conclude that dysfunction of the pituitary-gonadal axis is common in HIV-infected men. All patients in whom autopsy was done because of AIDS-related diseases had been hypogonadal 3 to 24 months before death. Decreased spermatogenesis, subacute interstitial inflammation, or both were seen at autopsy of patients with AIDS. Pathologic damage to the testes during AIDS was associated with decreased testosterone and bio-T as well as increased serum gonadotropin levels. In a substantial proportion of men with progression to AIDS, compensated hypogonadism (normal serum testosterone and increased serum LH levels) preceded the development of low serum testosterone level.