The effect of human chorionic gonadotropin-based hormonal therapy on intratesticular testosterone levels and spermatogonial DNA synthesis in men with non-obstructive azoospermia

Abstract

The use of hormonal therapy in men with non-obstructive azoospermia (NOA) is controversial because no information is available on how it affects intratesticular testosterone (ITT) levels and spermatogenic cells. The aim of this study was to investigate the ITT level and spermatogonial DNA synthesis, as determined by proliferating cell nuclear antigen (PCNA) expression, before and after human chorionic gonadotropin (hCG)-based hormonal therapy in men with NOA. Twenty patients who failed sperm retrieval procedures using microdissection testicular sperm extraction (micro-TESE) were enrolled in hCG-based hormonal therapy prior to a second micro-TESE. The patients' ITT levels were determined from testicular fluid obtained during the micro-TESE. Spermatogonial PCNA expression was determined by immunohistochemical analysis, and the PCNA labelling index (PCNA-LI) was calculated. During the second micro-TESE, spermatozoa were successfully retrieved from three (15%) of the men who had been treated with hormonal therapy. PCNA-positive cells were predominantly in the spermatogonia and primary spermatocytes, and PCNA-LI was significantly increased after the hormonal therapy. A significant increase in the ITT levels before and after the hormonal therapy (p<0.0001, 273.6±134.4 and 1348.1±505.4ng/mL respectively). The sperm-positive group showed a significantly lower basal ITT level compared with the sperm-negative group (p<0.05). There was a marked increase in the PCNA-LI levels of men treated with both recombinant human follicle-stimulating hormone and hCG. In addition, there was a significant negative association between the increase in PCNA-LI and basal ITT levels at the initial micro-TESE (p<0.05), but not the stimulated ITT level at the second micro-TESE. HCG-based hormonal therapy significantly raises the ITT level and stimulates spermatogonial DNA synthesis, potentially improving spermatogenesis. ITT optimization plays, at least in part, an important role for stimulating spermatogenesis in men with NOA.