Sildenafil increases serum testosterone levels by a direct action on the testes
Open accessAbstract
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 hypothalamic-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.
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The increase in testosterone with sildenafil is consistent with evidence that resumption of sexual activity by itself can increase testosterone by 30%.
“Though sildenafil may have a direct action on the testes (41), this increase is also consistent with evidence that resumption of sexual activity by itself can increase testosterone by 30% (42).”
From A Perspective on Middle-Aged and Older Men With Functional Hypogonadism: Focus on Holistic Management (2017) · cites this paper as [41]
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Bazid, H. A. S., Attia, A. M., Sonbol, A. A., & Ghanem, M. M. M. (2026) · Egyptian Journal of Dermatology and Venerology · doi:10.4103/ejdv.ejdv_37_25
- Authors
- Spitzer, M., Bhasin, S., Travison, T. G., Davda, M. N., Stroh, H., & Basaria, S.
- Affiliations
- Valley Medical Group; Endocrinology Department; Greenfield Health Center; Greenfield MA USA
- Brigham and Women's Hospital (US)
- Boston University (US)
- Corresponding author
- Spitzer, M.
- Venue
- Andrology
- Publisher
- Wiley
- Published
- 2013-09-18
- Volume
- 1
- Issue
- 6
- Pages
- 913-918
- ISSN
- 2047-2919 (ISSN-L)
- PMC
- PMC6036338
- OpenAlex
- W2019612900
- Cited by
- 67
- References
- 34
- Citations by year
- 2026: 1 · 2025: 5 · 2024: 1 · 2023: 6 · 2022: 6 · 2021: 1 · 2020: 6 · 2019: 6 · 2018: 10 · 2017: 6 · 2016: 10 · 2015: 6 · 2014: 3
- FWCI
- 4.98
- Type
- journal article
- Language
- en
- Open access
- green
- europepmc.org
- Locations
- Andrology (publishedVersion)
- PubMed (publishedVersion)
- Europe PMC (PubMed Central) (acceptedVersion)
- PubMed Central (acceptedVersion)
- Funders
- National Institutes of Health (5r01hd047722-03, 5p30ag031679-15)
- Clinical and Translational Science Institute, Boston University
- National Institute on Aging (5 P30 AG031679, P30-AG031679)
- National Institute of Child Health and Human Development
- National Center for Research Resources (UL1RR025771)
- Eunice Kennedy Shriver National Institute of Child Health and Human Development (R01 HD047722, 5R01HD047722)
- Topics
- Health Sciences › Medicine › Endocrinology, Diabetes and Metabolism › Hormonal and reproductive studies
- Health Sciences › Medicine › Psychiatry and Mental health › Sexual function and dysfunction studies
- Health Sciences › Medicine › Reproductive Medicine › Hypothalamic control of reproductive hormones
- Keywords
- sildenafil, testosterone, erectile dysfunction, androgen deficiency, phosphodiesterase-5 inhibitors, hypothalamic-pituitary-gonadal axis, luteinizing hormone suppression, dihydrotestosterone, estradiol, adrenal steroidogenesis, androstenedione, estrone
- MeSH terms
- Sildenafil Citrate, Adult, Aged, Androstenedione, Estradiol, Estrone, Humans, Erectile Dysfunction, Luteinizing Hormone, Male, Middle Aged, Piperazines, Purines, Dihydrotestosterone, Sulfones, Testis, Testosterone, Phosphodiesterase 5 Inhibitors
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