Determinants of the rate and extent of spermatogenic suppression during hormonal male contraception: an integrated analysis.

CONTEXT Male hormonal contraceptive methods require effective suppression of sperm output. OBJECTIVE The objective of the study was to define the covariables that influence the rate and extent of suppression of spermatogenesis to a level shown in previous World Health Organization-sponsored studies to be sufficient for contraceptive purposes (< or =1 million/ml). DESIGN This was an integrated analysis of all published male hormonal contraceptive studies of at least 3 months' treatment duration. SETTING Deidentified individual subject data were provided by investigators of 30 studies published between 1990 and 2006. PARTICIPANTS A total of 1756 healthy men (by physical, blood, and semen exam) aged 18-51 yr of predominantly Caucasian (two thirds) or Asian (one third) descent were studied. This represents about 85% of all the published data. INTERVENTION(S) Men were treated with different preparations of testosterone, with or without various progestins. MAIN OUTCOME MEASURE Semen analysis was the main measure. RESULTS Progestin coadministration increased both the rate and extent of suppression. Caucasian men suppressed sperm output faster initially but ultimately to a less complete extent than did non-Caucasians. Younger age and lower initial blood testosterone or sperm concentration were also associated with faster suppression, but the independent effect sizes for age and baseline testicular function were relatively small. CONCLUSION Male hormonal contraceptives can be practically applied to a wide range of men but require coadministration of an androgen with a second agent (i.e. progestin) for earlier and more complete suppression of sperm output. Whereas considerable progress has been made toward defining clinically effective combinations, further optimization of androgen-progestin treatment regimens is still required.