Treatment of male hypogonadism with clomiphene citrate- where do we stay?

Clomiphene citrate (CC) was developed in 1956 as a selective estrogen receptor modulator and was subsequently used in clinical medicine starting in 1967, to treat female infertility. CC has also been used off-label to treat male infertility and hypogonadal symptoms. In this brief review, we will examine and summarize the available literature on CC and assess its efficacy in the treatment of male hypogonadism.

We performed an extensive review of the literature using the PubMed search engine. Our goal was to compare the FDA-approved treatment for male hypogonadism, testosterone, with CC treatment for male hypogonadism. We accessed and reviewed 29 relevant research articles. Our review revealed that CC increased serum testosterone levels, similar to the serum testosterone levels observed following testosterone gel application. We also found support for our contention that CC improves hypogonadal symptoms. An important difference between CC and testosterone is that CC appeared to preserve sperm production and maintain fertility. This is an important feature of CC treatment, as fertility is frequently desired in patients with secondary/tertiary hypogonadism. We also compared the safety of CC to testosterone and found that CC had a similar safety profile. In summary, CC appeared to be a suitable therapy for patients with male factor infertility and associated hypogonadal symptoms. However, based on our review, we found that more research is required to further examine CC’s effectiveness for the treatment of these conditions.