EFFICACY OF CLOMIPHENE CITRATE IN SUBFERTILE MEN STRATIFIED BY PRE-TREATMENT SEX HORMONE LEVELS AND SPERM CONCENTRATION

Abstract

Selective estrogen receptor modulators (SERMs) are known to improve sperm count. Men with low testosterone (T), luteinizing hormone (LH), and follicle stimulating hormone (FSH) are thought to benefit most from SERMs like clomiphene citrate (CC), though predictors of efficacy have not been robustly characterized. We sought to identify changes in sperm counts with CC, stratifying by pre-treatment sex hormones and semen parameters. With IRB approval, we retrospectively reviewed sex hormone levels and semen parameters in subfertile men before and after 3 months of CC use (25 mg qd or 50 mg qod) during 10/2015-6/2020. Men were stratified by initial hormone levels (T≥300 vs T<300, LH≥7 vs LH<7, FSH≥7 vs FSH<7) and separately by initial sperm concentration (azoospermia, oligozoospermia, and normospermia). Men who previously underwent hormone therapy, genital surgery, or had previously conceived were excluded. Men with or without varicoceles were included. Student t-test was conducted with alpha=0.05. Out of 137 patients, 34% improved, 13% worsened, and 53% had no change in sperm concentration with CC use. 77% of azoospermic men had no change in sperm concentration. Table 1 summarizes changes in T and sperm concentration stratified by initial parameters. No significant difference was found in magnitude of changes in semen parameters stratified by testosterone. Men with lower LH had greater improvements in total sperm count (TSC) and total motile sperm count. Men with lower FSH had greater improvements in T, sperm concentration, and TSC. Azoospermic men showed least improvement across all semen parameters. No significant differences in magnitude of improvement were observed between oligozoospermia sub-categorizations (mild, moderate, severe) and normospermia. Not all patients experience the same benefit from CC. Our data suggest that men with nonobstructive azoospermia do not significantly benefit from CC use. Degree of oligospermia did not affect magnitude of improvement. Men with lower gonadotropin levels may expect greater degree of improvement in both hormone and semen parameters.