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To evaluate endocrine profile and hypothalamic-pituitary-testis (HPT) axis in male depressed patients with selective serotonin reuptake inhibitor (SSRI)-induced sexual dysfunction (SDF).Eighty-six fertile depressed male patients with SSRI-induced SDF, aged 18 to 50 years, were enrolled in the study (group 1). Sixty-two age-matched depressed fertile patients who currently receive one of the SSRIs but without SDF (group 2), and 68 age-matched healthy fertile men who had never received a psychiatric diagnosis (group 3) served as controls. Pretreatment evaluation included history and physical examination and International Index of Erectile Function. Two blood samples were drawn from each subject at 20-minute intervals for the determination of the resting levels of the following hormones: luteinizing hormone (LH), follicle-stimulating hormone (FSH), testosterone, prolactin, and estradiol. The HPT axis was also assessed using the gonadotropin-releasing hormone test.The prevalence of hormonal abnormalities in groups 1, 2, and 3 were 83.7% (72), 51.6% (32), and 11.8% (7), respectively (P = 0.001 vs group 1 and 0.007 vs group 2). Compared with normal controls, the subjects taking SSRIs had significantly lower serum levels of LH, FSH, and testosterone. In addition, there were significantly decreased LH and FSH responses to gonadotropin-releasing hormone test in groups 1 and 2 compared with normal controls. Of patients in groups 1 and 2, 68 (79.1%) and 27 (43.5%) had elevated serum levels of prolactin (P = 0.0001 vs group 1 and 0.001 vs group 2).Most depressed subjects taking SSRIs with and without SDF had diminished HPT axis function. This should be replicated in further studies.