Testosterone Induces Relaxation of Human Corpus Cavernosum Tissue of Patients With Erectile Dysfunction

Previous research in the field of cardiovascular diseases suggests a relaxing effect of testosterone (T) on smooth muscle cells. Therefore, it was hypothesized that T could play a significant role in erection development.

To investigate the relaxing effect of T and other molecules of the T signaling pathway on human corpus cavernosum (HCC) tissue.

Samples of the HCC tissue were obtained from men who underwent penile prosthesis implantation (n = 33) for erectile dysfunction. Samples were used for isometric tension measurement in Ex Vivo experiments. Following standardized precontraction with phenylephrine, increasing doses of T or dihydrotestosterone were administered and blocked by NO/H₂S synthesis inhibitors, a K_ATP blocker, and flutamide (androgen receptor inhibitor).

The outcome was relaxation of the HCC tissue, normalized to a maximum precontraction achieved by phenylephrine.

A dose-dependent relaxing effect of dihydrotestosterone and T was observed with a relaxation of, respectively, 24.9% ± 23.4% (P < .0001) and 41.7% ± 19.1% (P = .01) compared with 6.8% ± 15.9% for vehicle (dimethylsulfoxide) at 300 μM. The relaxing effect of T was not countered by blocking NO synthesis, H₂S synthesis, K_ATP channels, or the androgen receptor.

By understanding the underlying mechanisms of T-induced HCC relaxation, potential new therapeutic targets can be identified.

The strength of the study is the use of fresh HCC tissues with reproducible results. The limitation is the need for supraphysiological T levels to induce the observed effect.

Rapid androgen-induced relaxation of HCC is likely to occur via nongenomic mechanisms. Previously suggested mechanisms of action by which T modulates HCC relaxation have been excluded. Van den Broeck T, Soebadi MA, Falter A, et al. Testosterone Induces Relaxation of Human Corpus Cavernosum Tissue of Patients With Erectile Dysfunction. J Sex Med 2019; 8:114-119.