Reduced IGF-1 Levels Following Clomiphene Treatment for Male Hypogonadism

The selective estrogen receptor modulator clomiphene stimulates pituitary-derived gonadotropins to generate sex steroids including estrogen. Estrogen activates SOCS-3, which can inhibit growth hormone-directed JAK/STAT signaling to reduce serum insulin-like growth factor (IGF)-1 levels.

We sought to examine the effects of clomiphene therapy on IGF-1 levels in nonacromegalic male patients treated with clomiphene for underlying hypogonadism.

We identified 20 male subjects with hypogonadism treated with clomiphene citrate for at least 3 months. These patients were treated in an ambulatory, academic, tertiary medical center. The 20 male patients ranged from 27 to 76 years of age and hypogonadism was due to several etiologies, including prolactinomas, clinically nonfunctioning pituitary tumors, Rathke cleft cysts, colloid cysts, or idiopathic causes. Clomiphene citrate 50 mg 3 days per week was administered for a minimum of 3 months. IGF-1 was measured by liquid chromatography-mass spectroscopy before and after clomiphene therapy.

Fifteen of 20 (75%) of hypogonadal men treated with clomiphene exhibited a decrease in median (IQR) serum IGF-1 levels of -0.60 (-1.2-0.0) (P < .01). Two of the 20 patients (10%) exhibited a decrease in IGF-1 >2 SD below their age- and sex-matched mean value.

Clomiphene therapy can result in a significant reduction in serum IGF-1 levels in some treated hypogonadal men. Given that the decrease in IGF-1 can be >2 SD in some patients and potentially clinically significant, we recommend interval monitoring of serum IGF-1 levels and symptoms of growth hormone deficiency in patients with hypogonadism treated with clomiphene citrate.