Mesterolone and idiopathic male infertility: a double‐blind study

Summary A prospective randomized double‐blind study was undertaken to assess the effect on male fertility of 6 months' treatment with the synthetic androgen mesterolone. The study was performed in seven centres and 248 infertile couples were recruited. All men and their partners were investigated according to the standardized WHO protocol—Investigation and Diagnosis of the Infertile Couple. Following this investigation, 157 couples were selected in whom the male diagnosis was primary idiopathic testicular failure or idiopathic low sperm motility; the female partner had no demonstrable cause for infertility or was under successful treatment for a minor endocrine problem. The remaining 91 couples admitted were either incompletely investigated or had some additional factor associated with infertility. Men received either 150 or 75 mg mesterolone daily or placebo. Response was assessed in terms of semen characteristics and the partner's pregnancy rate. The cumulative life table pregnancy rates among all couples 8 months after randomization were 9± 3% (±standard error), 12±4% and 16±4% in the placebo, 75 and 150 mg mesterolone groups, respectively. The ratios of the pregnancy rates compared to placebo were 1.3 (0.5‐3.2) and 1.8 (0.7‐4.4) for the 75 and 150 mg mesterolone groups respectively. Among the subset of 157 couples satisfying the strict eligibility criteria, the pregnancy rates were 11 ±5%, 12 ±5% and 19±6% in the placebo, 75 and 150 mg mesterolone groups, respectively. The corresponding ratios of pregnancy rates to the placebo group were 1.2 (0.4‐3.4) and 1.8 (0.6‐5.3) for the 75 and 150 mg mesterolone groups respectively. There were no significant changes in semen quality during the course of the study, apart from an increase in sperm concentration 3 months after the start of treatment. The increase was greatest among the placebo treated group, but did not differ significantly between treatment groups. Although this study provides no statistically significant evidence for the efficacy of mesterolone for the treatment of male infertility, the power of the study was low as fewer than the anticipated number of couples were recruited, and a number of couples did not satisfy the eligibility criteria. In view of these difficulties and because the improvement in pregnancy rate may represent a true effect of treatment a new two‐arm study has been started using more strict entry criteria to compare mesterolone (150 mg daily) with placebo.