Clomiphene Citrate and Male Infertility: Investigation of Treatment on Spermatogenesis and Testicular Histomorphology in a Rat Model

Clomiphene citrate (CC) is used off‐label as a treatment for selected cases of male infertility, acting as a competitive selective‐estrogen receptor modulator. Although CC is used clinically, there have only been a small number of randomized controlled human studies that have yielded inconclusive findings. Here we have used a prospective animal model for studying CC treatment to determine if this drug increases spermatogenesis for treatment of male infertility. We treated sexually mature Sprague‐Dawley rats with CC via oral gavage for either 1 or 2 rat spermatogenic cycles (13 days for 1 cycle or 26 days for 2 cycles) at a dose of 0.6 mg/kg. This dose was chosen as it is a similar dose to what is clinically used in humans. Testes were weighed and sperm counts were measured from rats treated with CC and control animals. Testes were fixed in modified Davidson's solution and stained with HE for histopathological and morphometric analysis. No differences in sperm count and no histomorphologic differences were noted in the testes treated with CC as compared to control. Seminiferous tubule minimum diameter and tubular epithelial height were measured and the number of retained spermatozoa was also scored with no significant differences compared to control. Although previous studies have shown that rats treated with much higher doses of CC (>20 mg/kg) have decreased spermatogenesis, we can conclude that CC treatment at a therapeutic dose of 0.6 mg/kg in rats does not appear to have an effect on spermatogenesis. That said; CC may play a more indirect role in male infertility which may include changes in accessory reproductive organs or alterations in hormonal levels. Support or Funding Information Internal funding; Department of Urology, University of Iowa