Stimulation of Leydig and Sertoli Cellular Secretory Function by Anti-Oestrogens: Clomiphene

Leydig and Sertoli cells are essential for the testicular homeostasis. Clinically, the testicular homeostasis is impaired in hypogonadal and subfertile men. Therapeutically, the selective oestrogen receptor modulator clomiphene citrate (CC) is frequently used to treat these patients. In men, the mechanism of action of CC has long been thought to be limited to inhibition of the retro-control by oestrogen on the pituitary gland. However, oestrogen receptors are also expressed in the testis. Therefore, we will explore in this review the systemic effects as well as its action on reproductive function. We will describe in particular the possible effects of CC on the secretory functions of Leydig and Sertoli cells and their implication on the testicular microenvironment. CC is a costeffective and relatively safe off-label treatment for young hypogonadal men actively trying for a child or subfertile men with low testosterone with a positive effect on sperm concentration. Nevertheless, its effects on the oestrogen receptors and other signalling pathways at the testicular level remain poorly investigated. Further research, including combined treatment, could allow improving sperm morphology and sperm motility which do not seem to be significantly enhanced by CC alone.