Outcomes and Predictors in Hypogonadal Oligospermic Men Treated with Clomiphene Citrate

To determine response rates and predictors of circulating testosterone and sperm concentration improvement in hypogonadal men with oligospermia treated with clomiphene citrate 50 mg daily.

Records of 166 men with testosterone <3.5 ng/mL and sperm concentration <15 million/mL treated for ≥3 months between January 2020-2025 were retrospectively analyzed. Testosterone responders were defined as achieving T ≥3.5 ng/mL. Sperm concentration responders were defined as those with any improvement. Multivariate logistic regression identified predictors of treatment response for both outcomes.

Overall, 151 men (91%) normalized testosterone, with median levels rising from 2.9 (interquartile range 2.8-2.9) to 4.6 (3.9-5.5) ng/mL, a median increase of 1.7 (0.6-2.3) ng/mL (p<0.001). Sperm concentration improved in 118 men (71%), increasing from 4.0 (1.4-8.0) to 5.6 (2.1-10.9) million/mL, a median gain of 1.6 (0.7-2.9) million/mL (p=0.01). However, 48 men (29%) experienced a paradoxical decline, with a median decrease of -3.3 (-6.6 to 0.0) million/mL. Baseline estradiol independently predicted testosterone response (odds ratio [OR] 1.06, 95% confidence interval [CI] 1.01-1.35, p=0.04), while lower baseline sperm concentration predicted greater sperm improvement (OR 0.84, 95% CI 0.70-0.99, p=0.04).

Clomiphene citrate 50 mg daily normalized testosterone in 9 of 10 men with hypogonadism and oligospermia. Baseline estradiol predicted testosterone response, while sperm improvements were more likely in men with lower baseline counts. Although sperm concentration increased in most patients, clinical relevance was modest and nearly one-third worsened. Clomiphene citrate may be considered for testosterone optimization, particularly in men with higher estradiol, but fertility expectations should be managed.