Abstract
N. Mogar: None. D. Zhang: None. A. Sarabia Gonzalez: None. L. Chen: None. A.P. Heaney: None.
Clomiphene is a selective estrogen receptor modulator (SERM) that stimulates production of the pituitary gonadotropins, thereby inducing testosterone and estrogen release. Approved to induce ovulation in women, clomiphene is also used “off-label” to increase testosterone production in hypogonadal male patients. Prior studies have shown that estrogen activates SOCS proteins to inhibit JAK/STAT signaling and negatively regulate growth hormone signaling to reduce insulin-like growth factor-1 (IGF-1) levels (1). Prior studies have demonstrated reduced serum IGF-1 levels after administration of oral estrogen to men with intact pituitary function and postmenopausal women, however the literature examining the effect of clomiphene on IGF-1 levels in males with hypogonadism is sparse. We identified 99 male patients prescribed clomiphene citrate for central hypogonadism by APH between 2012 and 2022. 79 of these 99 patients were excluded from the study for medication non-compliance, concomitant diagnosis of acromegaly, insufficient laboratory values prior to and/or after clomiphene therapy, or due to sub-optimal methodology used to measure IGF-1.Fourteen (70%) of the included 20 patients exhibited decreased serum IGF-1 levels on clomiphene with a median decrease (IQR) of -0.87-SD (1.15) within 12 months on clomiphene therapy (p<0.01). In 2 of these patients, the decrease in IGF-1 was > 2 standard deviations below their age- and sex-matched mean value. In contrast, an increase in IGF-1 was seen in 3 patients (15%), and IGF-1 levels remained stable in the final 3 patients (15%). In parallel, all 20 patients (100%) demonstrated an increase in total testosterone levels with a median increase (IQR) of 222 (263) (p<0.0001). Nine patients (45%) also had an increase in serum free testosterone levels with a median increase (IQR) of 23 (96.3) (p<0.05). A further 4 patients (20%) demonstrated a decrease in free testosterone levels, and insufficient values were available in the remaining 6 patients (30%) for analysis. Male hypogonadism is a commonly encountered clinical problem causing a wide variety of debilitating symptoms. Clomiphene is frequently used as therapy as unlike testosterone, it can preserve male fertility and does not cause testicular atrophy. Our study is the first to retrospectively examine the effect of clomiphene on IGF-1 levels in male patients treated only for hypogonadism. We noted a significant decrease in IGF-1 after treatment with clomiphene citrate in the majority of patients (70%), and for some patients, this decrease was > 2SD and could be clinically significant. In summary, our study highlights the need to monitor IGF-1 in clomiphene-treated patients. References: 1.Leung KC, Johannsson G, Leong GM, Ho KK. Estrogen regulation of growth hormone action. Endocr Rev. 2004;25(5):693-721.
Saturday, June 1, 2024