Sildenafil Increases Serum Testosterone Levels by a Direct Action on the Testes

Program: Abstracts - Orals, Featured Poster Presentations, and Posters
Session: SUN 524-553-Male Reproductive Endocrinology
Bench to Bedside
Sunday, June 16, 2013: 1:45 PM-3:45 PM
Expo Halls ABC (Moscone Center)

Poster Board SUN-528
Matthew Johnathan Spitzer*, Shalender Bhasin, Thomas G Travison, Maithili Davda, Helene Stroh and Shehzad Sultan Basaria
Boston University Medical Center, Boston, MA
Phosphodiesterase-5-inhibitors, such as sildenafil, increase intracavernosal cyclic guanosine monophosphate levels, which results in corporal vasodilatation and induces penile erection. Administration of sildenafil to male rats has been shown to increase serum testosterone levels by directly stimulating testicular Leydig cells. However, the effect of sildenafil on the hypothalamic-pituitary-gonadal axis in humans has not been evaluated in the setting of a large clinical trial. The Testosterone and Erectile Dysfunction trial (ClinicalTrials.gov # NCT00512707) administered an optimized dose of sildenafil in an initial run-in period to 140 men, age 40-70 years with erectile dysfunction and low testosterone levels (< 330ng/dL) and then randomized them to either transdermal testosterone or placebo gel. Serum testosterone, dihydrotestosterone and estrogens were measured using LC-MS/MS. Administration of an optimized dose of sildenafil was associated with mean increases of 103ng/dL (P < 0.001) and 60.1pg/mL (P < 0.001) in total and free testosterone levels, respectively. This was accompanied by parallel increases in serum dihydrotestosterone (48.8pg/mL; P < 0.001), estradiol (3.7pg/mL; P < 0.001), and estrone (2.9pg/mL; P = 0.012) levels, and significant suppression of luteinizing hormone (change -1.3units/L; P = 0.003) levels, suggesting a direct effect at the testicular level. FSH and inhibin B levels remained unchanged. Conclusion: Sildenafil administration was associated with increased testosterone levels likely due to a direct effect on the testis.

Nothing to Disclose: MJS, SB, TGT, MD, HS, SSB

*Please take note of The Endocrine Society's News Embargo Policy at http://www.endo-society.org/endo2013/media.cfm

Sources of Research Support: National Institute of Child Health and Human Development (5R01HD047722); Boston University Clinical and Translational Science Institute (1UL1RR025771); Boston Claude D. Pepper Older Americans Independence Center (5P30AG031679 from the National Institute on Aging)