Clomiphene citrate (CC) is a selective estrogen receptor modulator that has been used for the treatment of hypogonadism in men since the 1970s. It acts centrally to increase secretion of luteinizing hormone and follicle-stimulating hormone, thereby increasing testosterone production and serum levels. Unlike testosterone replacement therapy, CC does not suppress the hypothalamic-pituitary-gonadal axis, preserving intratesticular testosterone production and spermatogenesis. This is especially useful in treating hypogonadal men who are interested in fertility.To review the literature regarding the use of CC in the setting of hypogonadism.A review of the relevant literature through September 2018 was performed via PubMed.The data regarding the efficacy and safety of CC when used in the setting of hypogonadism is summarized.Although results are mixed, many studies show CC reduces symptoms in hypogonadal men. Studies have also shown improvement in erectile function and bone mineral density, as well as a reduction in body mass index. There have been few studies investigating fertility rates in hypogonadal men treated with CC, but a metaanalysis of these shows significant improvement in fertility rates. Several studies show improvement in semen parameters. Few studies have investigated adverse effects of the drug. Reports include headache, dizziness, gynecomastia, and exacerbation of psychiatric illnesses. Despite these reports, CC is generally considered to be safe and well tolerated.CC is safe and effective and should remain in the armament of urologists treating hypogonadal men, especially men interested in preservation of fertility. Wheeler KM, Sharma D, Kavoussi PK, et al. Clomiphene citrate for the treatment of hypogonadism. Sex Med Rev 2019;7:272-276.
