Predicting Biochemical Response to Clomiphene Citrate in Men with Hypogonadism

Introduction Clomiphene citrate (CC) is as an effective treatment for men with hypogonadism (HG). Identifying the ideal candidate for this strategy has to date largely relied upon a patient's interest in preservation of testicular volume and spermatogenesis. Aim This analysis was undertaken to define if predictors existed of robust elevation in serum testosterone (T) levels in response to CC. Methods Seventy-six men with a diagnosis of HG (two separate early morning total T levels <300ng/dL) opting for CC therapy constituted the study population. Demographic, comorbidity data, and physical and laboratory characteristics were recorded. Laboratory tests were conducted 4 weeks after commencement and every 6 months thereafter. Multivariable analysis was conducted to define if predictors of biochemical response could be identified. Parameters included in the model were patient age, mean testicular volume, varicocele presence, and baseline total T, free T, and luteinizing hormone (LH) levels. Main Outcome Measure Successful biochemical response to CC, defined as an increase of 200ng/dL in total T level at 6 months after commencing CC, was the main outcome measure. Results Mean age was 46 +/- 22 years. Mean pretreatment testicular volume was 16 +/- 8mL. Mean baseline T and LH levels were 179 +/- 72ng/dL and 7.2 +/- 5.6IU/mL, respectively. Mean total T on CC was 467 +/- 190ng/dL. Forty-seven patients (62%) met the responder definition, with a mean increase in total T levels of 302 +/- 76 (204-464) ng/dL. In CC responders, the mean LH rise was 5.6 +/- 3.1IU/mL. On multivariable analysis, factors predictive of CC response included: mean testicular volume (adjusted [adj.] r=0.32, P<0.01), mean testicular volume 14mL (hazard ratio [HR] 2.2, P<0.01), LH level (adj. r=0.48, P<0.001), and LH level 6IU/mL (HR 3.5, P<0.001). Conclusion These data indicate that two thirds of men with HG meet a robust responder definition and that pretreatment testicular volume and LH levels (in continuous and dichotomized fashions) are predictors of response. Mazzola CR, Katz DJ, Loghmanieh N, Nelson CJ, and Mulhall JP. Predicting biochemical response to clomiphene citrate in men with hypogonadism. J Sex Med 2014;11:2302-2307.