Impact level of dihydrotestosterone on the hypothalamic‐pituitary‐leydig cell axis in men

Abstract

Dihydrotestosterone (DHT) the physiologically most potent androgen cannot be aromatised into oestrogen. DHT is used as a treatment for idiopathic gynaecomastia. In order to investigate the different sites of action of DHT on the hypothalamic-pituitary-testicular axis, two groups of adult men were studied. Group I included 10 gonadotropin-releasing hormone (GnRH)-deficient men who were evaluated before and during a pulsatile infusion of GnRH alone for 2 weeks and then in association with DHT given transdermally at doses used in the treatment of gynaecomastia for further two weeks. Luteinizing hormone (LH) pulsatility was assessed at the end of each step of the study. Plasma LH levels were measured every 15 min. Plasma testosterone (T), DHT, oestradiol (E2), free alpha-subunit (FAS) of glycoproteic hormones and LH bioactivity were measured on pooled plasma samples. Group II included 12 healthy men in whom plasma T, DHT and E2 were measured before and then 24, 48 and 72 h after the injection of 5000 IU hCG alone or in combination with either DHT or the pure anti-androgen nilutamide. Two weeks separated each of the 3 hCG testing. In group I, except for bioactive/immunoreactive (B/I) LH ratio which was unchanged, GnRH treatment induced significant rises (p < 0.01) in all plasma hormone levels, LH pulse amplitude and frequency. During treatment with GnRH+DHT, plasma DHT levels increased up to 16.8 +/- 2.5 nm, while plasma hormone levels, B/I LH ratio, LH pulse amplitude and frequency were similar to those obtained with GnRH alone. In group II, the peak of hCG-induced T rise was not modified by either DHT or nilutamide. In contrast, DHT reduced by 50% (p < 0.01) the E2 peak in response to hCG. These data show that DHT exerts no direct action on the pituitary to retroregulate LH secretion and to modify either B/I LH ratio or FAS secretion. Its reducing effect on LH secretion is likely mediated at the hypothalamic level. DHT does not appear to have a physiological influence on Leydig cells steroidogenesis. Administered at therapeutic doses, DHT directly reduces testicular aromatase activity that combined with its antigonadotropic effect leads to the gain in the symptomatic treatment of gynaecomastia.