Oestradiol enhances testosterone-induced suppression of human spermatogenesis

The aim of this study was to determine for the first time in humans, the ef ficacy of adding a low dose oestradiol to a suboptimally suppressive testos terone dose in a depot hormonal regimen to suppress spermatogenesis in heal thy eugonadal men. Twenty-six healthy men were randomized into groups that were treated by a single subdermal Implantation of either 600 mg testostero ne alone (T; n = 11) or together with 10 mg (TE10, n = 7) or 20 mg (TE20, ( n = 8) oestradiol, Administration of oestradiol produced a dose-dependent i ncrease in peak plasma oestradiol at 1 month and prolonged suppression of p lasma LH and FSH leading to significantly enhanced suppression of sperm out put. Despite the augmented spermatogenic suppression, there was no signific ant difference in the proportions achieving azoospermia (6/26, 23%) or seve re oligozoospermia <1 or <3 x 10(6) spermatozoa per ml, 7/26, 27%) and over all these proportions were inadequate to provide reliable contraception acc ording to the standards identified in World Health Organization male contra ceptive efficacy studies. Total and free testosterone remained within the e ugonadal reference range for young men throughout the study, While the lowe r oestradiol dosage had minimal spermatogenic suppression effects, the high er dose produced dose-limiting adverse effects of androgen deficiency and/o r oestrogen excess between the fourth and sixth month of the study. This ap peared to be due to the unexpectedly prolonged, low concentration of oestra diol release from the oestradiol implants. There were no significant treatm ent-related changes in body composition, lipids, prostate-specific antigen, haematological or biochemical variables. Thus oestradiol has a low therape utic window and dose-limiting side-effects at dosages that fail to achieve the uniform azoospermia required of an effective male hormonal contraceptiv e regimen.