Sildenafil increases serum testosterone levels by a direct action on the testes

Abstract

SUMMARY Phosphodiesterase-5-inhibitors, such as sildenafil, increase intracavernosal cyclic guanosine monophosphate levels, which results in corporal smooth muscle relaxation and penile erection. Here, we determined the effects of sildenafil administration on the hypo-thalamic-pituitary-gonadal axis in men with erectile dysfunction and low testosterone levels. The Testosterone and Erectile Dysfunction trial (ClinicalTrials.gov # NCT00512707) initially administered an optimized dose of sildenafil to 140 men, aged 40–70 years with erectile dysfunction, low serum total testosterone (<11.4 nmol/L; 330 ng/dL) and/or free testosterone (<173 pmol/L; 50 pg/mL) over 3–7 weeks. Sex steroids and gonadotropins were measured at baseline and after sildenafil optimization in a longitudinal study without a separate control group. Serum testosterone, dihydrotestosterone (DHT) and oestrogens were measured using liquid chromatography-tandem mass spectrometry. Administration of an optimized dose of sildenafil was associated with mean increases of 3.6 nmol/L (103 ng/dL; p < 0.001) and 110 pmol/L (31.7 pg/mL; p < 0.001) in total and free testosterone levels respectively. This was accompanied by parallel increases in serum DHT (0.17 nmol/L; 4.9 ng/dL; p < 0.001) and oestradiol (14 pmol/L; 3.7 pg/mL; p < 0.001) and significant suppression of luteinizing hormone (change −1.3 units/L; p = 0.003) levels, suggesting a direct effect at the testicular level. Androstenedione and oestrone increased by 1.3 nmol/L (38 ng/dL; p = 0.011) and 10.7 pmol/L (2.9 pg/mL; p = 0.012), respectively, supporting a possible effect of sildenafil on adrenal steroidogenesis. In conclusion, sildenafil administration was associated with increased testosterone levels likely ascribable to a direct effect on the testis.

Ultrasensitive quantification of serum estrogens in postmenopausal women and older men by liquid chromatography–tandem mass spectrometry

“…For example, a mean value of 20.6 pg/mL was reported for unconjugated serum E2 in six studies of older men, which used the PFBO derivative coupled with GC-MS-based methodology [27,65–69]. The mean unconjugated serum E2 level we found in men was also lower than studies that employed LC-negative ESI/MS (mean 17.2 pg/mL) [70], LC-negative atmospheric pressure photoionization/MS (mean 20 pg/mL) [71], and regular LC-ESI/MS of the E2 dansyl derivative (mean 22.9 pg/mL) [72–74]. This provides further evidence that the NMPS derivative in combination with LC-MS confers high sensitivity and specificity for E2 analysis.…”

Antioxidant Potential and Ability of Phloroglucinol to Decrease Formation of Advanced Glycation End Products Increase Efficacy of Sildenafil in Diabetes-Induced Sexual Dysfunction of Rats

“…Testosterone supplementation increases the erectile response in diabetic rats along with increase in level of nNOS and PDE5 in comparison with diabetic control rats in addition to normalization of RhoA/ROCK pathway upregulation 30, 31, 32. Sildenafil also increases erectile function and serum testosterone level significantly in men with ED associated with low testosterone level 33 . Limitation of this study is lack of data on level of testosterone after sildenafil treatment.…”

Serum testosterone, testosterone replacement therapy and all-cause mortality in men with type 2 diabetes: retrospective consideration of the impact of PDE5 inhibitors and statins

“…Phosphodiesterase 5 inhibitors have beneficial effects on endothelial function, insulin resistance, neuropathy, and nephropathy and possess potentially cardio‐protective properties . They are first‐line treatments for pulmonary hypertension and may increase serum testosterone levels . Gazzaruso et al showed a reduction in MACE with on‐demand PDE5Is in men with diabetes and angiography confirmed coronary artery disease .…”