Effect of clomiphene citrate treatment on the Sertoli cellsof dysmetabolic obese men with low testosterone levels.

Clomiphene citrate (CC) has been shown to restore the hypothalamic pituitary-gonadal (HPG) axis by increasing testosterone (T) levels to physiological levels in patients with dysmetabolic conditions such as obesity, metabolic syndrome and type 2 diabetes mellitus (T2DM). However, the data are unclear regarding the effects on Sertoli cell (SC) function.To study SC function by assessing Inhibin B (IB) and Anti-Mullerian Hormone (AMH) levels at baseline and after 3 month of CC treatment.This is an ancillary study of a cross-over, randomised, double-blind, placebo-controlled trial performed to evaluate androgen response to CC treatment in dysmetabolic obese subjects with low T levels treated with metformin. We evaluated SC function by assessing IB and AMH levels at baseline and after three months of each treatment in ten dysmetabolic obese subjects with low T levels. In all subjects,the influence of the clinical characteristics, metabolic and hormonal baseline parameters on SC and Leydig (LC) function, evaluated respectively with AMH, IB, FSH and T levels, were tested.No significant changes were observed for IB and AMH concentrations after each treatment period. Whereas T and estradiol (E2) levels were shown to be significantly higher in the CC plus metformin phase (CC/Met) only. No clinical, metabolic or hormonal parameters showed significant effects on serum AMH at baseline or after treatments. However, baseline T, dihydrotestosterone (DHT) andE2 positively affected IB levels during CC/Met therapy (P=0.003, P=0.038 and P=0.049 respectively). Baseline leptin, and FSH had a negative (P=0,031) and positive (P=0.048) respectively role on T levels during CC/Met, as they were statistically significant compared to the placebo period (Plac/Met).Unlike the LC activity, CC was unable to influence SC function, as shown by the lack of IB and AMH serum modifications, thus suggesting an intrinsic non-reversible defect of SC cells in patients with dysmetabolic conditions.