Baseline Gonadotropin Levels and Testosterone Response in Hypogonadal Men Treated With Clomiphene Citrate

Objective: To investigate the role of baseline gonadotropins in predicting the biochemical response to clomiphene citrate (CC) treatment.

Methods: We conducted a retrospective review of data from hypogonadal men treated with CC in 2 high-volume fertility centers between 2013 and 2018. Patient age, body mass index, and baseline hormones (follicle stimulating hormone [FSH], luteinizing hormone [LH], and total testosterone [TT]) were obtained. Response to treatment was measured as changes in TT levels within 6 months of initiating CC treatment. Linear regression models adjusted for age, body mass index, and time on CC therapy were fitted to assess the associations between baseline LH and FSH levels with treatment response.

Results: A total of 332 men with mean ± standard deviation age of 36.2 ± 8.2 years were included. Median time to initial follow-up was 6 weeks (25th-75th interquartile range [IQR]: 4-9 weeks). TT levels increased significantly on CC treatment (mean change: 329.2 ng/dL, 95% CI: 307.4-351.0) with 73% of men having at least 200 ng/dL increase over baseline TT levels. In univariable linear regression models, only age was significantly associated with TT response. Neither the baseline LH nor FSH significantly predicted TT response in linear regression models.

Conclusion: CC treatment results in significant increases in testosterone levels in most men. Baseline gonadotropins are not strong predictors for treatment response to CC. Adequate biochemical response with CC trial can be expected in most patients with normal or slightly elevated baseline gonadotropin levels.