Testosterone Therapy for Late-Onset Hypogonadism Improves Erectile Function: A Systematic Review and Meta-Analysis

<b><i>Introduction:</i></b> Randomized controlled trials (RCTs) of testosterone therapy (TTh) for late-onset hypogonadism are systematically reviewed and a meta-analysis to assess the efficacy of TTh in improving erectile function is performed. <b><i>Methods:</i></b> The PubMed, Cochrane Library, and Web of Science databases were searched to identify RCTs published from 2007. RCTs that assessed erectile function using the erectile function domain of the International Index of Erectile Function (IIEF-EFD) were included in the meta-analysis. <b><i>Results:</i></b> The systematic review included 18 RCTs and the meta-analysis included 6 studies that enrolled a total of 1,458 patients. The overall meta-analysis revealed that the IIEF-EFD score was significantly improved in the TTh group compared with the placebo group (mean difference 1.86; 95% confidence interval 1.01–2.72; <i>p</i> &#x3c; 0.0001). Compared with patients receiving placebo, there was a significant improvement in the IIEF-EFD of patients who received TTh using testosterone gel, those who received TTh for over 30 weeks, and those without diabetes mellitus or metabolic syndrome. <b><i>Conclusion:</i></b> TTh achieved a significant improvement in the IIEF-EFD score of hypogonadal men compared with placebo, especially in those who received testosterone gel, were treated for over 30 weeks, and had no comorbidities.

Differentiation of human induced pluripotent stem cells into testosterone-producing Leydig-like cells

Late-onset hypogonadism (LOH) syndrome due to a partial lack of testosterone, which is mainly secreted by Leydig cells in the testes, decreases the quality of life of older men. Leydig cell transplantation is expected to be a promising alternative to conventional testosterone replacement therapy (TRT) for LOH syndrome. We herein report a simple and robust protocol for directed differentiation of human induced pluripotent stem cells (hiPSCs) into Leydig-like cells by doxycycline-inducible overexpression of NR5A1 and treatment with a combination of 8-bromoadenosine-3’,5’-cyclic monophosphate (8-Br-cAMP) and forskolin. The differentiated cells expressed the steroidogenic enzyme genes STAR, CYP11A1, CYP17A1 and HSD3B2 and the specific markers of adult Leydig cells HSD17B3, INSL3 and LHCGR. Furthermore, we confirmed the secretion of functional testosterone from the cells into the culture supernatant by a testosterone-sensitive cell proliferation assay. These findings showed that the hiPSCs were able to be differentiated into Leydig-like cells, supporting the expectation that hiPSC-derived Leydig-like cells can be novel tools for treating LOH syndrome.