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.
Keywords: Clomiphene, male infertility, hypogonadism, adverse effect, spermatogenesis, testosterone, leydig cell, sertoli cell.
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