Oestradiol enhances testosterone-induced suppression of human spermatogenesis

The aim of this study was to determine for the first time in humans, the efficacy of adding a low dose oestradiol to a suboptimally suppressive testosterone dose in a depot hormonal regimen to suppress spermatogenesis in healthy eugonadal men. Twenty-six healthy men were randomized into groups that were treated by a single subdermal implantation of either 600 mg testosterone 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 increase in peak plasma oestradiol at 1 month and prolonged suppression of plasma LH and FSH leading to significantly enhanced suppression of sperm output. Despite the augmented spermatogenic suppression, there was no significant difference in the proportions achieving azoospermia (6/26, 23%) or severe oligozoospermia (<1 or <3 x 10(6) spermatozoa per ml, 7/26, 27%) and overall these proportions were inadequate to provide reliable contraception according to the standards identified in World Health Organization male contraceptive efficacy studies. Total and free testosterone remained within the eugonadal reference range for young men throughout the study. While the lower oestradiol dosage had minimal spermatogenic suppression effects, the higher dose produced dose-limiting adverse effects of androgen deficiency and/or oestrogen excess between the fourth and sixth month of the study. This appeared to be due to the unexpectedly prolonged, low concentration of oestradiol release from the oestradiol implants. There were no significant treatment-related changes in body composition, lipids, prostate-specific antigen, haematological or biochemical variables. Thus oestradiol has a low therapeutic window and dose-limiting side-effects at dosages that fail to achieve the uniform azoospermia required of an effective male hormonal contraceptive regimen.