Table 1. Current literature investigating the effects of testosterone replacement therapy on erectile function.
| Study (year) | Study type | Population | Patient No. | Location | Tx | Finding | Note |
|---|---|---|---|---|---|---|---|
| Buvat et al (2011) [60] | RCTb | H | Total-173 T-87 |
France, Italy, Germany, Finland, Spain, the Netherlands, England, United States of America | TG | Addition of testosterone gel to PDE5i is beneficial only in hypogonadal men with baseline T levels <3 ng/mL. | Combination with PDE5i |
| Chiang et al (2007) [61] | RCTb | H | Total-40 T-20 |
Taiwan | TG | Testosterone treated patients had higher IIEF scores at 3 months compared to patients with placebo. | - |
| Giltay et al (2010) [62] | RCTb | H | Total-184 T-113 |
Russia, the Netherlands, United States of America, Germany, United Arab Emirates | TU | There was significant improvement in IIEF-5 scores, most evident in patients with lowest baseline total testosterone levels. | Phase III trial NCT 00696748 |
| Konaka et al (2016) [63] | RCTb | H | Total-334 T-169 |
Japan | TE | The second question on the IIEF-5 was significantly improved in the patients who received testosterone therapy. | EARTH Study Group |
| Shabsigh et al (2004) [64] | RCTb | H | T-75 T-39 |
USA | TG | Testosterone treated subjects had greater improvement in IIEF total score and percentage of IIEF responders. However, no significant correlations were made between IIEF at endpoint. | Combination with PDE5i |
| Spitzer et al (2012) [65] | RCTb | H | T-140 T-70 |
USA | TG | Combination therapy was not superior to sildenafil plus placebo in improving erectile function domain of the IIEF. | Combination with PDE5i, NCT00512707 |
| Amiaz et al (2011) [66] | RCTb | H | Total-100 T-31 |
United States of America, Israel | TG | In a male population with hypogonadism and depression, there was a significant difference in IIEF subscales between men treated with testosterone and men without. | Studied hypogonadal patients with depression. Study was only partially blinded. |
| Yassin et al (2006) [67] | PO | H | Total-69 (varying doses) | Germany, United Arab Emirates | TG | Combination therapy is effective for hypogonadal men who did not respond to PDE5i alone. | Combination with PDE5i |
| Almehmadi et al (2016) [68] | PO | H | Total-261 (all treated) | Germany | TU | Mean IIEEF-5 increased within first 3 months and remained elevated compared to baseline for 5 years. | - |
| Andrade et al (2009) [69] | PO | H | Total-62 T-17 |
Brazil | TC | IIEF-5 scores showed borderline improved sexual potency with hormone replacement. | - |
| Greenstein et al (2005) [70] | PO | H | Total-49 (all treated) | Israel | TG | Combined treatment of PDE5i and TG was beneficial for men that failed testosterone therapy alone. | Combination with PDE5i |
| Hwang et al (2006) [71] | PO | H | Total-32 (all treated) | Taiwan | TU | The study demonstrated that both combination treatment and testosterone only treatment improved IIEF scores compared to baseline. There was no statistical significance in IIEF scores between combination and testosterone alone therapy. | Combination with PDE5i |
| Karazindiyanoğlu and Cayan (2008) [72] | PO | H | Total-25 (all treated) | Turkey | TG | Mean IIEF-5 score significantly increased. | - |
| Kim et al (2013) [73] | PO | H | Total-46 (all treated) | Korea | TE | Combination therapy was more beneficial to patients with severe testosterone depletion. | Combination with PDE5i |
| La Vignera et al (2011) [74] | PO | H | Total-50 T-30 |
Italy | TG | After 6 months, the group with no testosterone therapy showed IIEF-5 score significantly worse than the group with testosterone therapy. | - |
| Moon et al (2010) [75] | PO | H | Total-133 (all treated) | Korea | TU | TU significantly improved total IIEF and all 5 domain scores. | - |
| Mulhall et al (2004) [76] | PO | H | Total-32 (all treated) | USA | TG, TE, TP | In men documented with hypogonadism and ED, normalization of serum testosterone level was associated with only short-term improvement in EF and sexual satisfaction. | - |
| Okada et al (2014) [77] | PO | H | Total-50 (all treated) | Japan | TE | Testosterone therapy led to a significant increase in IIEF-5 score at 6 months. | - |
| Park et al (2015) [78] | PO | H | Total-60 (all treated) | Korea | TU | The combination of testosterone and PDE5i produced significant improvement in erectile function, which was well maintained, even after cessation of treatment. | Combination with PDE5i |
| Pexman-Fieth et al (2014) [79] | PO | H | Total-799 (all treated) | Canada, Russia, Croatia, Germany, Slovenia, Saudi Arabia, Romania, and the United Arab Emirates | TG | Substantial and significant improvements were observed in IIEF score. | - |
| Rastrelli et al (2016) [80] | PO | H | Total-432 T-80 |
Italy | Multiple | Compared to patients that did not start androgen therapy, those who did had significant improvements in all categories of IIEF. | SIAMO-NOI registry |
| Yassin and Saad (2007) [81] | PO | H | Total-22 (all treated) | Germany, United Arab Emirates | TU | Restoring testosterone levels to normal in hypogonadal men improves libido in most subjects, and erectile function in more than 50% of patients. | - |
| Yassin et al (2014) [82] | PO | H | Total-129 (all treated) | Germany | TU | Combination therapy is safe and effective in treating hypogonadal men who failed testosterone therapy alone. | Combination with PDE5i |
| Jeong et al (2011) [83] | RO | H | T-200 (all treated) | Korea | TU | Hypogonadal patients with metabolic syndrome showed less improvement in IIEF. | Studied hypogonadal men with metabolic syndrome |
| Labairu-Huerta et al (2015) [84] | RO | H | Total-1200 T-269 |
Spain | Multiple | The best therapeutic success for ED in this series was achieved through a combination of testosterone+PDE5i. | Combination with PDE5i, PG-E1 |
| Permpongkosol et al (2010) [85] | RO | H | Total-161 (all treated) | Thailand | TU | The mean IIEF-5 and IIEF-15 scores improved significantly. | - |
| Taniguchi et al (2011) [86] | RO | H | Total-33 (all treated) | Japan | Multiple | Scores on the IIEF were all improved significantly in the early stages of treatment and not worsened long after ART was discontinued. | - |
| Tirabassi et al (2015) [87] | RO | H | Total-73 (all treated) | Italy | TU | All IIEF domains significantly improved after TRT p<0.001. This was not the goal of the study, but was reported. | - |
| Gianatti et al (2014) [88] | RCTb | D | Total-88 T-45 |
Australia | TU | Testosterone treatment did not improve constitutional or sexual symptoms in obese, aging men with DM II with mild to moderate symptoms and modest reduction in T levels. | - |
| Hackett et al (2013) [89] | RCTb | D | Total-199 T-92 |
England | TU | TU significantly improved all domains of the IIEF at 30 weeks and more significantly after 52 week open label extension; improvement was most marked in less obese patients, those with lower baseline testosterone, and those without coexisting depression. | Blast trial |
| Mitkov et al (2013) [90] | RCTu | D | Total-45 T-19 |
Bulgaria | TG | Statistically significant improvement in ED indicators in both groups of patients treated with testosterone or treated with alpha-lipoic acid. There were large differences in baseline parameters. | Placebo used was alphalipoic acid |
| Giagulli et al (2015) [91] | RO | D | Total-43 (all treated) | Italy | TU | Testosterone therapy could improve clinical and metabolic parameters in obese, DM II, with ED and overt hypogonadism. The addition of liraglutide to testosterone and metformin therapy allows normal-range testosterone levels to be achieved. | Combination metformin, liraglutide, lifestyle changes, and testosterone |
Summary of current literature describing the effect of testosterone replacement therapy on erectile function. This table demonstrates the heterogeneity of the studies regarding combination with PDE5i, patient populations, and research study design.
Tx: treatment, RCTb: randomized controlled trial blinded, PO: prospective observational, RO: retrospective observational, RCTu: randomized controlled trail unblended, H: hypogonadal, D: diabetes mellitus, TG: testosterone gel, TU: testosterone undecanoate, TE: testosterone enanthate, TC: testosterone cypionate, TP: transdermal patch, PDE5i: phosphodiesterase 5 inhibitor, IIEF: International Index of Erectile Function, ED: erectile dysfunction, ART: androgen replacement therapy, TRT: testosterone replacement therapy, DM: diabetes mellitus, EARTH: Effects of Androgen Replacement Therapy on Hypogonadism, PG-E1: prostagrandin E1.