Clomiphene citrate improved testosterone and sperm concentration in hypogonadal males

ABSTRACT

When considering empirical medical management (EMT) options for men with unexplained infertility (UI), clomiphene citrate (CC) has been shown to positively influence sperm parameters in hypogonadal men. Unfortunately, the optimal cut point for defining hypogonadism for this patient population has not been established. We hypothesized that hypogonadal men with UI having the lowest serum total testosterone (TT) (<265 ng/dL) would have a significant post-CC improvement in both TT and semen characteristics compared to those in the TT > 264 ng/dL group. We performed our study based on an IRB-approved retrospective chart review of 83 males with UI receiving more than 90 days of 50 mg daily CC. Serum TT and semen characteristics were studied in 83 patients before and in 23 patients after CC treatment. Median TT level increased from 256 ng/dL to 630 ng/dL (p < 0.001, n = 83) and SC increased from 6 (${10}^6$/ml) to 20 (${10}^6$/ml) (p < 0.016, n = 23). Overall, our results demonstrated the following: (1) CC treatment at all currently used serum TT cut-points resulted in significant improvement in both TT (p < 0.001) and sperm concentration (p = 0.03). No significant change in post-CC sperm motility or morphology was noted. (2) Correlation and linear regression analyses demonstrated that CC treatment significantly increased TT in 96% (22 of 23) of patients, and (3) when grouped as two cohorts (≤264 and >264 ng/dL), sperm concentration and TT improved 2.3 to 2.6-fold (p < 0.001) and 1.45 to 2.5-fold (p < 0.01) respectively. Thus, for hypogonadal men with UI, CC significantly improved TT and sperm concentration regardless of pre-treatment, baseline serum TT level. For this reason, CC treatment should be considered in men with UI having a TT < 400 ng/dL.

KEYWORDS:

• Clomiphene citrate
• hypogonadism
• total testosterone
• unexplained infertility
• semen analysis

Ethics approval

An IRB-approved chart review of 83 consecutive male patients with UI treated at our Upstate New York clinic.

Acknowledgments

We thank Patrick Curtin MD and Joseph Hartnett MD for their work on this project and Callum Newton for assistance with database maintenance.

Disclosure statement

Trussell, Delu, Kiltz, and Kuznetsov have no conflict of interest.

Author contributions

Data collection: JT, AD, RK; manuscript preparation, analysis and interpretation: JT, VK; manuscript discussion and review: JT, AD, RK, VK; statistical setup and final version of manuscript writing: VK.

Correction Statement

This article has been republished with minor changes. These changes do not impact the academic content of the article.