Oral Sildenafil in the Treatment of Erectile Dysfunction
Abstract
Background Sildenafil is a potent inhibitor of cyclic guanosine monophosphate hydrolysis [corrected] in the corpus cavernosum and therefore increases the penile response to sexual stimulation. We evaluated the efficacy and safety of sildenafil, administered as needed in two sequential double-blind studies of men with erectile dysfunction of organic, psychogenic, and mixed causes. Methods In a 24-week dose-response study, 532 men were treated with oral sildenafil (25, 50, or 100 mg) or placebo. In a 12-week, flexible dose-escalation study, 329 different men were treated with sildenafil or placebo, with dose escalation to 100 mg based on efficacy and tolerance. After this dose-escalation study, 225 of the 329 men entered a 32-week, open-label extension study. We assessed efficacy according to the International Index of Erectile Function, a patient log, and a global-efficacy question. Results In the dose-response study, increasing doses of sildenafil were associated with improved erectile function (P values for increases in scores for questions about achieving and maintaining erections were Conclusions Oral sildenafil is an effective, well-tolerated treatment for men with erectile dysfunction.
Integrity signals
Registry
Cites
Statistics
Claims the paper makes
Claims other papers make about this one
Each is checked against this paper’s own text: does it say what the citing paper says it does?
Sildenafil is effective (erection with rigidity sufficient for vaginal penetration) after 30-60 minutes from administration.
“It is effective (erection with rigidity sufficient for vaginal penetration) after 30-60 minutes from administration [17].”
From Erectile dysfunction and its pharmacology: An overview (2017) · cites this paper as [17]
Cites
Rajfer, J., Aronson, W. J., Bush, P. A., Dorey, F. J., & Ignarro, L. J. (1992) · New England Journal of Medicine · doi:10.1056/nejm199201093260203 · Cited by 1,006 · see citing works
Flagged first, then by citations
Cited by
Sorted by citations
JOHANNES, C. B., ARAUJO, A. B., FELDMAN, H. A., DERBY, C. A., KLEINMAN, K. P., & McKINLAY, J. B. (2000) · Journal of Urology · doi:10.1016/s0022-5347(05)67900-1 · Cited by 1,158 · see citing works
Shamloul, R., & Ghanem, H. (2013) · The Lancet · doi:10.1016/s0140-6736(12)60520-0 · Cited by 1,091 · see citing works
Endogenous nitric oxide synthesis: Biological functions and pathophysiology
Bredt, D. S. (1999) · Free Radical Research · doi:10.1080/10715769900301161 · Cited by 796 · see citing works
Yafi, F. A., Jenkins, L., Albersen, M., Corona, G., Isidori, A. M., Goldfarb, S., Maggi, M., Nelson, C. J., Parish, S., Salonia, A., et al. (2016) · Nature Reviews Disease Primers · doi:10.1038/nrdp.2016.3 · Cited by 853 · see citing works
Feldman, H. A., Johannes, C. B., Derby, C. A., Kleinman, K. P., Mohr, B. A., Araujo, A. B., & McKinlay, J. B. (2000) · Preventive Medicine · doi:10.1006/pmed.2000.0643 · Cited by 748 · see citing works
Strategies to increase nitric oxide signalling in cardiovascular disease
Lundberg, J. O., Gladwin, M. T., & Weitzberg, E. (2015) · Nature Reviews Drug Discovery · doi:10.1038/nrd4623 · Cited by 576 · see citing works
Modifiable risk factors and erectile dysfunction: can lifestyle changes modify risk?
Derby, C. A., Mohr, B. A., Goldstein, I., Feldman, H. A., Johannes, C. B., & McKinlay, J. B. (2000) · Urology · doi:10.1016/s0090-4295(00)00614-2 · Cited by 552 · see citing works
Self-citationRosen, R. C., Allen, K. R., Ni, X., & Araujo, A. B. (2011) · European Urology · doi:10.1016/j.eururo.2011.07.053 · Cited by 460 · see citing works
Self-citationPrevalence and Risk Factors for Erectile Dysfunction in 2869 Men Using a Validated Questionnaire
PONHOLZER, A., TEMML, C., MOCK, K., MARSZALEK, M., OBERMAYR, R., & MADERSBACHER, S. (2005) · European Urology · doi:10.1016/j.eururo.2004.08.017 · Cited by 361 · see citing works
The Nature of Sexual Desire: A Clinician's Perspective
Levine, S. B. (2003) · Archives of Sexual Behavior · doi:10.1023/a:1023421819465 · Cited by 280 · see citing works
Watkins, C. C., Sawa, A., Jaffrey, S., Blackshaw, S., Barrow, R. K., Snyder, S. H., & Ferris, C. D. (2000) · Journal of Clinical Investigation · doi:10.1172/jci8273 · Cited by 268 · see citing works
Basaria, S., Harman, S. M., Travison, T. G., Hodis, H., Tsitouras, P., Budoff, M., Pencina, K. M., Vita, J., Dzekov, C., Mazer, N. A., et al. (2015) · JAMA · doi:10.1001/jama.2015.8881 · Cited by 268 · see citing works
Eleutherococcus senticosus (Rupr. & Maxim.) Maxim. (Araliaceae) as an adaptogen: a closer look
Davydov, M., & Krikorian, A. D. (2000) · Journal of Ethnopharmacology · doi:10.1016/s0378-8741(00)00181-1 · Cited by 256 · see citing works
Mulhall, J., Land, S., Parker, M., Waters, W. B., & Flanigan, R. C. (2005) · The Journal of Sexual Medicine · doi:10.1111/j.1743-6109.2005.00081_1.x · Cited by 227 · see citing works
The oral microbiome and nitric oxide homoeostasis
Hezel, M., & Weitzberg, E. (2015) · Oral Diseases · doi:10.1111/odi.12157 · Cited by 201 · see citing works
Spitzer, M., Basaria, S., Travison, T. G., Davda, M. N., Paley, A., Cohen, B., Mazer, N. A., Knapp, P. E., Hanka, S., Lakshman, K. M., et al. (2012) · Annals of Internal Medicine · doi:10.7326/0003-4819-157-10-201211200-00004 · Cited by 163 · see citing works
Impact of erectile dysfunction and its subsequent treatment with sildenafil: qualitative study
Tomlinson, J., & Wright, D. (2004) · BMJ · doi:10.1136/bmj.38044.662176.ee · Cited by 147 · see citing works
Jannini, E. A., Screponi, E., Carosa, E., Pepe, M., Lo Giudice, F., Trimarchi, F., & Benvenga, S. (1999) · International Journal of Andrology · doi:10.1046/j.1365-2605.1999.00196.x · Cited by 146 · see citing works
Inventories for male and female sexual dysfunctions
Corona, G., Jannini, E. A., & Maggi, M. (2006) · International Journal of Impotence Research · doi:10.1038/sj.ijir.3901410 · Cited by 146 · see citing works
ÇAYAN, S., BOZLU, M., CANPOLAT, B., & AKBAY, E. (2004) · Journal of Sex & Marital Therapy · doi:10.1080/00926230490465091 · Cited by 143 · see citing works
Carvalheira, A. A., Pereira, N. M., Maroco, J., & Forjaz, V. (2012) · The Journal of Sexual Medicine · doi:10.1111/j.1743-6109.2012.02787.x · Cited by 132 · see citing works
Psychological testing and psychological assessment: A review of evidence and issues.
Meyer, G. J., Finn, S. E., Eyde, L. D., Kay, G. G., Moreland, K. L., Dies, R. R., Eisman, E. J., Kubiszyn, T. W., & Reed, G. M. (2001) · American Psychologist · doi:10.1037//0003-066x.56.2.128 · Cited by 1,469 · see citing works
STEPHENSON, R. A., MORI, M., HSIEH, Y.-C., BEER, T. M., STANFORD, J. L., GILLILAND, F. D., HOFFMAN, R. M., & POTOSKY, A. L. (2005) · Journal of Urology · doi:10.1097/01.ju.0000165342.85300.14 · Cited by 117 · see citing works
Kelly, D. F., Chaloner, C., Evans, D., Mathews, A., Cohan, P., Wang, C., Swerdloff, R., Sim, M.-S., Lee, J., Wright, M. J., et al. (2014) · Journal of Neurotrauma · doi:10.1089/neu.2013.3212 · Cited by 101 · see citing works
Enhancing autophagy in Alzheimer's disease through drug repositioning
Eshraghi, M., Ahmadi, M., Afshar, S., Lorzadeh, S., Adlimoghaddam, A., Rezvani Jalal, N., West, R., Dastghaib, S., Igder, S., Torshizi, S. R. N., et al. (2022) · Pharmacology & Therapeutics · doi:10.1016/j.pharmthera.2022.108171 · Cited by 89 · see citing works
Andropause: Symptom Management for Prostate Cancer Patients Treated With Hormonal Ablation
Thompson, C. A., Shanafelt, T. D., & Loprinzi, C. L. (2003) · The Oncologist · doi:10.1634/theoncologist.8-5-474 · Cited by 84 · see citing works
Mulhall, J., Althof, S. E., Brock, G. B., Goldstein, I., Jünemann, K.-P., & Kirby, M. (2007) · The Journal of Sexual Medicine · doi:10.1111/j.1743-6109.2007.00441.x · Cited by 84 · see citing works
Self-citationSchmidt, H. M., Munder, T., Gerger, H., Frühauf, S., & Barth, J. (2014) · The Journal of Sexual Medicine · doi:10.1111/jsm.12520 · Cited by 84 · see citing works
Corona, G., Rastrelli, G., Burri, A., Jannini, E. A., & Maggi, M. (2016) · Expert Opinion on Drug Safety · doi:10.1517/14740338.2016.1130126 · Cited by 71 · see citing works
Sildenafil increases serum testosterone levels by a direct action on the testes
Spitzer, M., Bhasin, S., Travison, T. G., Davda, M. N., Stroh, H., & Basaria, S. (2013) · Andrology · doi:10.1111/j.2047-2927.2013.00131.x · Cited by 67 · see citing works
The role of the sexual partner in managing erectile dysfunction
Li, H., Gao, T., & Wang, R. (2016) · Nature Reviews Urology · doi:10.1038/nrurol.2015.315 · Cited by 65 · see citing works
Bajaj, H. S., Gerstein, H. C., Rao-Melacini, P., Basile, J., Colhoun, H., Conget, I., Cushman, W. C., Dagenais, G. R., Franek, E., Hanefeld, M., et al. (2021) · The Lancet Diabetes & Endocrinology · doi:10.1016/s2213-8587(21)00115-7 · Cited by 56 · see citing works
MOORE, T. M., STRAUSS, J. L., HERMAN, S., & DONATUCCI, C. F. (2003) · Journal of Sex & Marital Therapy · doi:10.1080/00926230390224756 · Cited by 51 · see citing works
Barbonetti, A., D’Andrea, S., Cavallo, F., Martorella, A., Francavilla, S., & Francavilla, F. (2019) · The Journal of Sexual Medicine · doi:10.1016/j.jsxm.2019.02.014 · Cited by 49 · see citing works
Riley, A., & Riley, E. (2000) · International Journal of Clinical Practice · doi:10.1111/j.1742-1241.2000.tb11889.x · Cited by 40 · see citing works
Alternative strategies in cardiac preclinical research and new clinical trial formats
Kreutzer, F. P., Meinecke, A., Schmidt, K., Fiedler, J., & Thum, T. (2022) · Cardiovascular Research · doi:10.1093/cvr/cvab075 · Cited by 36 · see citing works
Role of sGC-dependent NO signalling and myocardial infarction risk
Wobst, J., Kessler, T., Dang, T. A., Erdmann, J., & Schunkert, H. (2015) · Journal of Molecular Medicine · doi:10.1007/s00109-015-1265-3 · Cited by 28 · see citing works
Erectile dysfunction and its pharmacology: An overview
Patnaik, S. K., Polimati, H., & Pragada, R. R. (2017) · Asian Journal of Pharmaceutical and Clinical Research · doi:10.22159/ajpcr.2017.v10i2.15183 · Cited by 3 · see citing works
- Authors
- Goldstein, I., Lue, T. F., Padma-Nathan, H., Rosen, R. C., Steers, W. D., & Wicker, P. A.
- Affiliations
- Boston University (US)
- University of Southern California (US)
- University of Medicine and Dentistry of New Jersey (US)
- University of Virginia (US)
- Pfizer (United States) (US)
- Venue
- New England Journal of Medicine
- Publisher
- Massachusetts Medical Society
- Published
- 1998-05-14
- Volume
- 338
- Issue
- 20
- Pages
- 1397-1404
- ISSN
- 0028-4793 (ISSN-L)
- 1533-4406
- OpenAlex
- W22857079
- Cited by
- 2,120
- References
- 1
- Citations by year
- 2026: 30 · 2025: 36 · 2024: 35 · 2023: 39 · 2022: 36 · 2021: 43 · 2020: 67 · 2019: 42 · 2018: 54 · 2017: 39 · 2016: 61 · 2015: 53 · 2014: 51 · 2013: 53 · 2012: 59
- FWCI
- 105.72
- Type
- journal article
- Language
- en
- Open access
- closed
- Locations
- New England Journal of Medicine (publishedVersion)
- PubMed (publishedVersion)
- Topics
- Health Sciences › Medicine › Psychiatry and Mental health › Sexual function and dysfunction studies
- Health Sciences › Medicine › Urology › Urological Disorders and Treatments
- Social Sciences › Psychology › Clinical Psychology › Sexuality, Behavior, and Technology
- Keywords
- sildenafil, erectile dysfunction, phosphodiesterase-5 inhibitors, cyclic GMP, dose-response relationship, dose escalation, International Index of Erectile Function, treatment efficacy, drug safety, adverse effects, organic erectile dysfunction, psychogenic erectile dysfunction
- MeSH terms
- Sildenafil Citrate, Administration, Oral, Adult, Aged, Aged, 80 and over, Coitus, Dose-Response Relationship, Drug, Double-Blind Method, Humans, Erectile Dysfunction, Male, Middle Aged, Phosphodiesterase Inhibitors, Piperazines, Purines, Sulfones, 3',5'-Cyclic-GMP Phosphodiesterases, Treatment Outcome
About these checks
Registry, retraction, Cites and statistics results are computed, not judged, with one exception: a printed reference that no index lists is read once by a model before it counts as a citation error. Claims are extracted by a model and kept only when their quote appears verbatim in the text; each cited source is then checked, with a model’s help, for whether it says what the claim relies on. Those verdicts can be wrong — read the claim’s quote and the cited source before relying on one.
Statistics and arithmetic are recomputed, not judged.
Confidence bands are shown only for fields calibrated on our annotated test set. None is calibrated yet, so no band is shown.
What counts as a claim ›How we measure confidence ›How we check this ›
Are you an author, or do you see a problem with this page? Request a review
