Clomiphene citrate effect on testosterone level and semen parameters in 18 infertile men with low testosterone level and normal/low gonadotropines level.

OBJECTIVE: To determine the effect of a 3-month course of clomiphene citrate (CC) on plasma testosterone (T) level and on semen parameters in 18 infertile men with low T level and normal or low gonadotropines level. STUDY DESIGN: A retrospective study was conducted by reviewing the medical records of men referred to a university fertility medicine unit for infertility management between January 2010 and March 2015. Men treated with CC for at least 3 months were included if they presented with: RESULTS: 18 patients met the inclusion criteria. CC was prescribed for 3 months at the dose of 50 mg every 48 h. Plasma T level was assessed at baseline and after 1 month of CC administration. Semen parameters were assessed at baseline and after 3 months of CC administration. The median pre-treatment T level was 9.1 nmol/l; after 1 month of CC treatment the median post-treatment T level increased to 20.2 nmol/l (p = <0.001). Median baseline sperm concentration was 7 millions/ml with a median progressive motility of 18%. After 3 months of CC, the median post-treatment sperm concentration was 17.5 millions/ml (p = 0.024) and the median post-treatment progressive sperm motility was 18% (p = 0.40). Three natural pregnancies occurred during the treatment period. CONCLUSION: CC is an effective and inexpensive treatment to increase plasma T level in infertile men with low T level and normal or low gonadotropines level. Our study suggests that CC could increase sperm concentration even in oligospermic infertile men, without, however, a significant effect on progressive sperm motility. More powered randomized controlled trials are needed to definitively assess CC effect on sperm parameters and on natural pregnancy rates.

Selective effects of PPARgamma agonists and antagonists on human pre-adipocyte differentiation.

AIM: The insulin sensitizer rosiglitazone (RTZ) acts by activating peroxisome proliferator and activated receptor gamma (PPAR gamma), an effect accompanied in vivo in humans by an increase in fat storage. We hypothesized that this effect concerns PPARgamma(1) and PPARgamma(2) differently and is dependant on the origin of the adipose cells (subcutaneous or visceral). To this aim, the effect of RTZ, the PPARgamma antagonist GW9662 and lentiviral vectors expressing interfering RNA were evaluated on human pre-adipocyte models. METHODS: Two models were investigated: the human pre-adipose cell line Chub-S7 and primary pre-adipocytes derived from subcutaneous and visceral biopsies of adipose tissue (AT) obtained from obese patients. Cells were used to perform oil-red O staining, gene expression measurements and lentiviral infections. RESULTS: In both models, RTZ was found to stimulate the differentiation of pre-adipocytes into mature cells. This was accompanied by significant increases in both the PPARgamma(1) and PPARgamma(2) gene expression, with a relatively stronger stimulation of PPARgamma(2). In contrast, RTZ failed to stimulate differentiation processes when cells were incubated in the presence of GW9662. This effect was similar to the effect observed using interfering RNA against PPARgamma(2). It was accompanied by an abrogation of the RTZ-induced PPARgamma(2) gene expression, whereas the level of PPARgamma(1) was not affected. CONCLUSIONS: Both the GW9662 treatment and interfering RNA against PPARgamma(2) are able to abrogate RTZ-induced differentiation without a significant change of PPARgamma(1) gene expression. These results are consistent with previous results obtained in animal models and suggest that in humans PPARgamma(2) may also be the key isoform involved in fat storage.