Hypothalamic-pituitary-testicular axis and seminal parameters in hyperthyroid males

Information on the effect of abnormal thyroid function on male reproduction is less available than that for the female. To assess the effects of hyper thyroidism on hypothalamic-pituitary-testicular axis and on spermogram para meters, 25 male patients (19-47 years old) suffering from active Graves' di sease were studied. Serum luteinizing hormone (LH), follicle stimulating ho rmone (FSH), and prolactin (PRL) were measured before and after administrat ion of 100 mu g GnRH plus 200 mu g thyrotropin-releasing hormone (TRH). Tes tosterone (T), estradiol (E-2), and 17-hydroxyprogesterone (17-OHP) were de termined before and after 5000 IU human chorionic gonadotropin (HCG) admini stration. Serum sex hormone-binding globulin (SHBG), cortisol-binding globu lin (CBG), androstenedione and bioavailable testosterone (bioT), and bioava ilable estradiol (bioE(2)) were also measured. Spermograms according to Wor ld Health Organization (WHO) criteria were determined in 21 patients. Hormo nal and seminal studies were repeated in six patients after 7 to 19 months of euthyroidism achieved after treatment for hyperthyroidism. As a control group, 10 normal men were evaluated. Impaired sexual function, gynecomastia , and low testicular volume were found in 12, 6, and 3 hyperthyroid patient s. Mean basal LH was significantly higher than the control group (7.8 +/- 4 .7 vs. 5.0 +/- 1.9 mIU/mL, respectively, P < 0.02), with hyperresponse to G nRH. The response of PRL to TRH was lower in patients versus control group (30 minutes: 3.9 +/- 3.4 and 12.0 +/- 2.8 ng/mL, P < 0.01). Basal levels of steroids and SHBG were significantly higher in patients than in normal men (T:9.3 +/- 3.3 vs. 5.4 +/- 1.6 ng/mL, P < 0.005; E-2: 62.2 +/- 25.2 vs. 32. 1 +/- 11.0 pg/mL, P < 0.005; 17-OHP: 2.4 +/- 0.9 vs. 1.1 +/- 0.5 ng/mL, P < 0.001; SHBG: 102.3 +/- 37.3 vs. 19.0 +/- 5.0 nmol/L, P < 0.01). The maxima l increment of T and 17-OHP after HCG was lower in hyperthyroid patients th an in normal men (P < 0.019 and p < 0.001, respectively). Basal bioT was lo wer in patients than controls (1.7 +/- 0.8 and 3.1 +/- 1.9 ng/mL, P < 0.02) . The following incidence of abnormal semen parameters was found: asthenosp ermia 85.7%, hypospermia 61.9%, oligospermia 42.9%, necrospermia 42.9% and teratospermia 19.0%. In euthyroidism, a normalization of 85% of seminal alt erations was observed in the limited number of patients evaluated. Our resu lts confirm that hyperthyroidism causes marked alterations of the gonadotro pic and PRL axis and dramatically affects spermatic function. BioT measurem ent was useful to identify hypoandrogenism in these patients in spite of th e high concentration of total testosterone. The restoration of most semen p arameters when euthyroidism was achieved suggests that the alterations were induced by the Graves' disease.