Rate, extent, and modifiers of spermatogenic recovery after hormonal male contraception: an integrated analysis

Abstract

Background: Hormonal methods for safe, reliable, and reversible contraception based on the suppression of spermatogenesis could soon become available. We have investigated the rate, extent, and predictors of reversibility of hormonal male contraception.

Methods: We undertook an integrated multivariate time-to-event analysis of data from individual participants in 30 studies published in 1990-2005, in which sperm output was monitored every month until recovery. The primary outcome was the time for the sperm concentration to recover to a threshold of 20 million per mL, an indicator of fertility. We undertook univariate and multivariate analyses, using Kaplan-Meier and Cox's methods.

Findings: 1549 healthy eugonadal men who were white (n=965), Asian (almost all Chinese men; n=535), or of other origins (n=49) and aged 18-51 years underwent 1283.5 man-years of treatment and 705 man-years of post-treatment recovery. These data represented about 90% of all published data from individuals using androgen or androgen-progestagen regimens. The median times for sperm to recover to thresholds of 20, 10, and 3 million per mL were 3.4 months (95% CI 3.2-3.5), 3.0 months (2.9-3.1), and 2.5 months (2.4-2.7), respectively. Multivariate Cox's analysis showed higher rates of recovery with older age, Asian origin, shorter treatment duration, shorter-acting testosterone preparations, higher sperm concentrations at baseline, faster suppression of spermatogenesis, and lower blood concentrations of luteinising hormone at baseline. The typical probability of recovery to 20 million per mL was 67% (61-72) within 6 months, 90% (85-93) within 12 months, 96% (92-98) within 16 months, and 100% within 24 months.

Interpretation: Hormonal male contraceptive regimens show full reversibility within a predictable time course. Various covariables affect the rate but not the extent of recovery, although their effect sizes are minor. These data are crucial for the further safe and practical development of such regimens.