Rates of suppression and recovery of human sperm output in testosterone-based hormonal contraceptive regimens

BACKGROUND: Practical hormonal male contraceptive regimens are likely to have delayed onset and offset of reliable contraception dictated by the length of the spermatogenic cycle and clearance rate of pre-formed sperm from the ductular system. While delayed onset of contraceptive efficacy is an accepted feature of vasectomy, reliable time estimates for a hormonal male contraceptive of time to onset and offset of reliable contraception and of resumption of normal male fertility are required. METHODS AND RESULTS: We utilized the sperm output data from three male contraceptive efficacy studies to define quantitative estimates of suppression and recovery rates from an androgen alone (testosterone enanthate) and an androgen/progestin (testosterone/depot medroxyprogesterone acetate) study. Using nearly 14 000 semen samples from World Health Organization (WHO) studies #85921 and #89903 with identical protocols, the rate of suppression of sperm output was best modelled as a two-parameter, single exponential decay function with effective half-time to suppression of 5.5 weeks and times of 6.8 weeks to 10x10(6)/ml, 8.7 weeks to 5x10(6)/ml, 10.0 weeks to 3x10(6)/ml and 13.0 weeks to 1x10(6)/ml. The rate of recovery using absolute sperm concentration was best modelled as a three-parameter, sigmoidal curve with effective time to reach half of the recovery plateau of 10.5 weeks and times of 9.0 weeks to 3x10(6)/ml, 9.9 weeks to 5x10(6)/ml, 11.5 weeks to 10x10(6)/ml, and 13.6 weeks to 20x10(6)/ml. Using relative sperm output, defined as a percentage of the participants' own baseline, recovery approached an asymptotic plateau of similar to 85% of geometric mean pre-treatment sperm concentration. In the combination androgen/progestin study, suppression rate was significantly faster (effective time to reach half maximal suppression of 3.0 weeks) and recovery significantly slower (effective time to reach half of recovery plateau of 14.7 weeks) and less complete (asymptotic recovery plateau of 43% of baseline) than in the androgen-alone WHO studies. CONCLUSION: These findings therefore provide large sample estimates of the suppression and recovery rates from an androgen-alone hormonal male contraceptive regimen as a basis for comparison with other second-generation combination androgen/progestin regimens that are the most promising approach to developing practical male hormonal regimens.