(PNM-14) Predictors of response to clomiphene citrate in men with hypogonadism: a literature review

Abstract Introduction and Objectives Clomiphene citrate (CC) is a safe and effective alternative to exogenous testosterone therapy for men with hypogonadism, particularly those wishing to preserve fertility. It maintains hypothalamic–pituitary-gonadal axis function and offers oral administration at a lower cost. Although 70–75% of patients experience significant increases in total testosterone (TT), reliable predictors of response remain unclear. This review aimed to identify clinical and biochemical factors associated with CC responsiveness. Methods A narrative review was conducted using PubMed and Medline. Clinical studies evaluating CC use in hypogonadal men and analyzing predictors of biochemical response were included. Results In a cohort of 332 men, the mean TT increase was 329 ng/dL, with 73% achieving ≥200 ng/dL. However, baseline LH and FSH levels showed inconsistent correlation with outcomes. Mazzola et al. identified testicular volume ≥ 14 mL and LH ≤6 IU/L as independent predictors of robust response. Hammami et al. found higher prolactin levels associated with improved semen parameters in men with idiopathic oligozoospermia. Randomized trials in obese hypogonadal men showed benefits including increased muscle mass, reduced fat, higher HDL, improved erectile function, and elevated TT. Older age (>55 years) was linked to reduced androgenic response. In late-onset hypogonadism, CC discontinuation led to relapse, though long-term use (up to 52 months) proved safe and effective. Conclusion Despite its efficacy, identifying strong predictors of CC response remains challenging. Preserved testicular volume, LH ≤6 IU/L, and younger age appear favorable. Further research is needed to clarify the role of prolactin and other functional markers in treatment selection. Financing No conflict.