Clinical trial of transdermal testosterone and oral levonorgestrel for male contraception.

Approaches to hormonal male contraception are predominantly based on injectable testosterone (T) application. As most users would prefer an injection-independent modality, this study was designed to develop a self-applicable hormonal male contraceptive regimen by combining transdermal T with an oral gestagen. Eleven healthy men (23-40 yr old) were treated with oral levonorgestrel and transdermal T for 24 weeks. T was applied daily as a transdermal patch to be worn on the trunk. Levonorgestrel was taken orally at a dose of 250 microg daily up to week 12, followed by 500 microg to week 24 in those volunteers who had not become azoospermic by that time. Within 24 weeks, 2 of 11 volunteers had become azoospermic, and 3 of 11 showed sperm concentrations below 3 million/mL. The sperm concentrations of the remaining volunteers declined, but failed to reach the limit considered compatible with contraception by WHO. Treatment resulted in suppression of LH, FSH, and sex hormone-binding globulin, whereby the volunteers with lower sperm concentrations showed more pronounced suppression than the others. Mean T concentrations remained within the lower limit of normal and on occasions were below this level. There were no complaints of hypoandrogenism. Although mean levels of low density lipoprotein cholesterol, apolipoprotein B, as well as basal and postprandial insulin increased, high density lipoprotein cholesterol and apolipoprotein A-I decreased during the treatment phase. Changes in lipid parameters were normalized within 3 weeks after cessation of medication. Although only 5 of 11 volunteers reached the target sperm counts (<3 million/mL), the study shows that a self-applicable hormonal male contraceptive could be developed.