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Effects of testosterone on sexual function in men: results of a meta‐analysis
Abstract
Summary: Objectives The role of androgen decline in the sexual activity of adult males is controversial. To clarify whether sexual function would benefit from testosterone (T) treatment in men with partially or severely reduced serum T levels, we conducted a systematic review and meta‐analysis of placebo‐controlled studies published in the past 30 years. The aim of this study was to assess and compare the effects of T on the different domains of sexual life. Data source A comprehensive search of all published randomized clinical trials was performed in MEDLINE, the Cochrane Library, EMBASE and Current Contents databases. Review methods Guided by prespecified criteria, software‐assisted data abstraction and quality assessed by two independent reviewers, a total of 17 randomized placebo‐controlled trials were found to be eligible. For each domain of sexual function we calculated the standardized mean difference relative to T and reported the results of pooled estimates of T treatment using the random effect model of meta‐analysis. Heterogeneity, reproducibility and consistency of the findings across studies were explored using sensitivity and meta‐regression analysis. Results Overall, 656 subjects were evaluated: 284 were randomized to T, 284 to placebo (P) and 88 treated in cross‐over. The median study length was 3 months (range 1–36 months). Our meta‐analysis showed that in men with an average T level at baseline below 12 nmol/l, T treatment moderately improved the number of nocturnal erections, sexual thoughts and motivation, number of successful intercourses, scores of erectile function and overall sexual satisfaction, whereas T had no effect on erectile function in eugonadal men compared to placebo. Heterogeneity was explored by grouping studies according to the characteristics of the study population. A cut‐off value of 10 nmol/l for the mean T of the study population failed to predict the effect of treatment, whereas the presence of risk factors for vasculogenic erectile dysfunction (ED), comorbidities and shorter evaluation periods were associated with greater treatment effects in the studies performed in hypogonadal, but not in eugonadal, men. Meta‐regression analysis showed that the effects of T on erectile function, but not libido, were inversely related to the mean baseline T concentration. The meta‐analysis of available studies indicates that T treatment might be useful for improving vasculogenic ED in selected subjects with low or low‐normal T levels. The evidence for a beneficial effect of T treatment on erectile function should be tempered with the caveats that the effect tends to decline over time, is progressively smaller with increasing baseline T levels, and long‐term safety data are not available. The present meta‐analysis highlights the need, and pitfalls, for large‐scale, long‐term, randomized controlled trials to formally investigate the efficacy of T replacement in symptomatic middle‐aged and elderly men with reduced T levels and ED.
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“Several studies have previously reported that testosterone levels are linked to a variety of conditions and diseases, such as cardiovascular disease, type-2 diabetes, the metabolic syndrome, erectile dysfunction, depression, obesity, stroke and osteoporosis. 1-7”
From Cigarette smoking has a positive and independent effect on testosterone levels (2013) · cites this paper as [4]
In the citing paper
“Testosterone therapy may be justifiable in patients with some of these conditions, such as men receiving opioids, who may suffer from opioid-induced suppression of testosterone levels 32 and sexual dysfunction, 33 osteoporosis, and/or muscle atrophy.34”
From Who Gets Testosterone? Patient Characteristics Associated with Testosterone Prescribing in the Veteran Affairs System: a Cross-Sectional Study (2017) · cites this paper as [33]
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“T also promotes libido (Isidori et al., 2005) andmoderates responses to social challenges (Archer, 2006; Hermans et al.”
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“The efficacy of TRT for lipid metabolism as well as for insulin resistance has been reported by recent meta-analyses of RCTs with middle-aged and elderly men such that exogenous testosterone reduced the serum level of total cholesterol and LDL cholesterol.(18,54)”
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Which patients with sexual dysfunction are suitable for testosterone replacement therapy?
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“, consisting of 17 randomized controlled trials, testosterone replacement therapy provided a significant improvement of all aspects of sexual function in men with low and low-normal testosterone level in any age [8].”
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“Isidori and coworkers [ 33 ] have recently performed a comprehensive meta-analysis on the effects of T on sexual function showing that, in studies carried out in men with a mean T level 33 ]; and T therapy is appropriate only when clinical symptoms and biochemical evidence of hypogonadism exist.”
MethodSelf-citationTestosterone deficiency in the aging male
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“Two different meta-analyses agreed that TRT can improve libido, nocturnal erections, and sexual satisfaction, but the effect in older men is inconsistent and fades with time [Isidori et al. 2005; Bolona et al. 2007].”
BackgroundPrevalence of Sexual Activity and Associated Factors in Men Aged 75 to 95 Years
Hyde, Z., Flicker, L., Hankey, G., Almeida, O., McCaul, K., Chubb, S. A. P., & Yeap, B. (2010) · Annals of Internal Medicine · doi:10.7326/0003-4819-153-11-201012070-00002 · Cited by 69
“Although desire and erectile function have been shown to improve in hypogonadal men who receive testosterone, men with testosterone levels in the normal range obtain little benefit (29, 30).”
BackgroundAmanatkar, H. R., Chibnall, J. T., Seo, B.-W., Manepalli, J. N., & Grossberg, G. T. (2014) · Annals of Clinical Psychiatry · doi:10.1177/104012371402600103 · Cited by 106
“13 In addition, depression is associated with decreased libido, diminished erectile function in men, and decreased sexual activity.”
MECHANISMS IN ENDOCRINOLOGY: Aging and anti-aging: a Combo-Endocrinology overview
Diamanti‐Kandarakis, E., Dattilo, M., Μacut, D., Duntas, L. H., Gonos, E. S., Goulis, D. G., Kanaka‐Gantenbein, C., Καπετάνου, Μ., Koukkou, E. G., Lambrinoudaki, I. V., et al. (2017) · European Journal of Endocrinology · doi:10.1530/eje-16-1061 · Cited by 105
The Burden of Testosterone Deficiency Syndrome in Adult Men: Economic and Quality-of-Life Impact
Maggi, M., Schulman, C., Quinton, R., Langham, S., & Uhl-Hochgräber, K. (2007) · The Journal of Sexual Medicine · doi:10.1111/j.1743-6109.2007.00531.x · Cited by 103
The aging male hypothalamic–pituitary–gonadal axis: Pulsatility and feedback
Veldhuis, J. D., Keenan, D. M., Liu, P. Y., Iranmanesh, A., Takahashi, P. Y., & Nehra, A. X. (2008) · Molecular and Cellular Endocrinology · doi:10.1016/j.mce.2008.09.005 · Cited by 103
“-PA Author M anuscript N IH -PA Author M anuscript et al., 2006; Isidori et al., 2005; Liverman and Blazer 2004), which are significantly reversed by Te supplementation.”
BackgroundRisks and Benefits of Late Onset Hypogonadism Treatment: An Expert Opinion
Corona, G., Vignozzi, L., Sforza, A., & Maggi, M. (2013) · The World Journal of Men s Health · doi:10.5534/wjmh.2013.31.2.103 · Cited by 101
O'Connor, D. B., Corona, G., Forti, G., Tajar, A., Lee, D. M., Finn, J. D., Bártfai, G., Boonen, S., Casanueva, F. F., Giwercman, A., et al. (2008) · The Journal of Sexual Medicine · doi:10.1111/j.1743-6109.2008.00781.x · Cited by 103
Veldhuis, J. D. (2008) · Ageing Research Reviews · doi:10.1016/j.arr.2007.12.005 · Cited by 98
“Among such postulated relationships, low Te availability correlates with reduced grip strength, decreased lean-body mass and increased visceral adiposity in meta-analyses (Isidori et al., 2005).”
Rapid weight gain after birth predicts life history and reproductive strategy in Filipino males
Kuzawa, C. W., McDade, T. W., Adair, L. S., & Lee, N. (2010) · Proceedings of the National Academy of Sciences · doi:10.1073/pnas.1006008107 · Cited by 97
“The axis influences energy needs by regulating resource allocation in support of growth and maintenance of sexually dimorphic, costly traits like muscle (13, 14), while also promoting reproductive behaviors (15, 16).”
BackgroundThe Effect of Statin Therapy on Testosterone Levels in Subjects Consulting for Erectile Dysfunction
Corona, G., Boddi, V., Balercia, G., Rastrelli, G., Vita, G. D., Sforza, A., Forti, G., Mannucci, E., & Maggi, M. (2010) · The Journal of Sexual Medicine · doi:10.1111/j.1743-6109.2009.01698.x · Cited by 99
Corona, G., Mannucci, E., Forti, G., & Maggi, M. (2009) · International Journal of Andrology · doi:10.1111/j.1365-2605.2009.00965.x · Cited by 96
Corona, G., Mondaini, N., Ungar, A., Razzoli, E., Rossi, A., & Fusco, F. (2011) · The Journal of Sexual Medicine · doi:10.1111/j.1743-6109.2011.02473.x · Cited by 96
Men’s Health: Sexual Dysfunction, Physical, and Psychological Health—Is There a Link?
Tan, H. M., Tong, S. F., & Ho, C. C. K. (2011) · The Journal of Sexual Medicine · doi:10.1111/j.1743-6109.2011.02582.x · Cited by 97
Interventions for sexual dysfunction following treatments for cancer
Miles, C., Candy, B., Jones, L., Williams, R., Tookman, A. J., & King, M. (2007) · Cochrane Database of Systematic Reviews · doi:10.1002/14651858.cd005540.pub2 · Cited by 98
Testosterone replacement therapy: for whom, when and how?
Tsametis, C. P., & Isidori, A. M. (2018) · Metabolism · doi:10.1016/j.metabol.2018.03.007 · Cited by 96
Self-citationQuaglio, G., Lugoboni, F., Pattaro, C., Melara, B., Mezzelani, P., & Jarlais, D. C. D. (2008) · Drug and Alcohol Dependence · doi:10.1016/j.drugalcdep.2007.09.025 · Cited by 95
Prospective investigation of risk factors for prostate cancer in the UK Biobank cohort study
Perez‐Cornago, A., Key, T. J., Allen, N. E., Fensom, G. K., Bradbury, K. E., Martin, R. M., & Travis, R. C. (2017) · British Journal of Cancer · doi:10.1038/bjc.2017.312 · Cited by 92
“Men who have not had sex might have erectile dysfunction or low sexual interest, which are both conditions that have been linked to reduced circulating androgen levels (Isidori et al, 2005).”
BackgroundKapoor, D., Clarke, S., Channer, K. S., & Jones, T. H. (2007) · International Journal of Andrology · doi:10.1111/j.1365-2605.2007.00744.x · Cited by 90
Functional significance of men’s testosterone reactivity to social stimuli
Zilioli, S., & Bird, B. M. (2017) · Frontiers in Neuroendocrinology · doi:10.1016/j.yfrne.2017.06.002 · Cited by 88
Male late-onset hypogonadism: pathogenesis, diagnosis and treatment
Huhtaniemi, I., & Forti, G. (2011) · Nature Reviews Urology · doi:10.1038/nrurol.2011.47 · Cited by 88
“However, the evidence for a beneficial effect of testosterone on erectile function was tempered by the progressively smaller effect with increasing baseline testosterone levels and by the declining effect of the treatment over time”
BackgroundJordan, K., Fromberger, P., Stolpmann, G., & Müller, J. L. (2011) · The Journal of Sexual Medicine · doi:10.1111/j.1743-6109.2011.02393.x · Cited by 85
Sexual dysfunction in subjects with Klinefelter’s syndrome
Corona, G., Petrone, L., Paggi, F., Lotti, F., Boddi, V., Fisher, A. D., Vignozzi, L., Balercia, G., Sforza, A., Forti, G., et al. (2009) · International Journal of Andrology · doi:10.1111/j.1365-2605.2009.00986.x · Cited by 80
Kupelian, V. A., Shabsigh, R., Travison, T. G., Page, S. T., de Araújo, A. B., & McKinlay, J. B. (2006) · The Journal of Urology · doi:10.1016/j.juro.2006.08.020 · Cited by 81
Cigarette smoking has a positive and independent effect on testosterone levels
Wang, W., Yang, X., Liang, J., Liao, M., Zhang, H., Qin, X., Mo, L., Lv, W., & Mo, Z. (2013) · Hormones · doi:10.14310/horm.2002.1445 · Cited by 79
Giannetta, E., Gianfrilli, D., Barbagallo, F., Isidori, A. M., & Lenzi, A. (2012) · Best Practice & Research Clinical Endocrinology & Metabolism · doi:10.1016/j.beem.2011.12.005 · Cited by 76
Self-citationTestosterone Associations with Erectile Dysfunction, Diabetes, and the Metabolic Syndrome
Jones, T. H. (2007) · European Urology Supplements · doi:10.1016/j.eursup.2007.07.002 · Cited by 76
Consequences of Anabolic-Androgenic Steroid Abuse in Males; Sexual and Reproductive Perspective
Corona, G., Rastrelli, G., Marchiani, S., Filippi, S., Morelli, A., Sarchielli, E., Sforza, A., Vignozzi, L., & Maggi, M. (2021) · The World Journal of Men s Health · doi:10.5534/wjmh.210021 · Cited by 82
“In fact, in clinical trials, where a standardized dose of T was administered to otherwise eugonadal subjects or in mixed populations, libido increased and did not decrease [43-46] with a null effect on erections.”
Are declining testosterone levels a major risk factor for ill-health in aging men?
Yeap, B. B. (2008) · International Journal of Impotence Research · doi:10.1038/ijir.2008.60 · Cited by 75
The evolving role of testosterone in the treatment of erectile dysfunction
Shabsigh, R., Rajfer, J., Aversa, A., Traish, A. M., Yassin, A. A., Kalinchenko, S. Y., & BUVAT, J. (2006) · International Journal of Clinical Practice · doi:10.1111/j.1742-1241.2006.01101.x · Cited by 73
Self-citationPaduch, D. A., Polzer, P. K., Ni, X., & Basaria, S. S. (2015) · The Journal of Clinical Endocrinology & Metabolism · doi:10.1210/jc.2014-4434 · Cited by 73
“Given this, and that T therapy may improve other elements of sexual function such as libido and erectile function (22, 23), T replacement could offer benefit in androgen-deficient men with ejaculatory dysfunction.”
BackgroundTestosterone and Erectile Dysfunction
Yassin, A. A., & Saad, F. (2008) · Journal of Andrology · doi:10.2164/jandrol.107.004630 · Cited by 73
Metadata
- Authors
- Isidori, A. M., Giannetta, E., Gianfrilli, D., Greco, E. A., Bonifacio, V., Aversa, A., Isidori, A., Fabbri, A., & Lenzi, A.
- Affiliations
- Sapienza University of Rome (IT)
- University of Rome Tor Vergata (IT)
- Corresponding author
- Isidori, Andrea M.
- ORCID
- Venue
- Clinical Endocrinology
- Publisher
- Wiley
- Published
- 2005-09-03
- Volume
- 63
- Issue
- 4
- Pages
- 381-394
- ISSN
- 0300-0664 (ISSN-L)
- 1365-2265
- OpenAlex
- W2138141643
- Cited by
- 492
- References
- 99
- Citations by year
- 2026: 4 · 2025: 10 · 2024: 12 · 2023: 22 · 2022: 17 · 2021: 12 · 2020: 16 · 2019: 15 · 2018: 26 · 2017: 22 · 2016: 27 · 2015: 25 · 2014: 37 · 2013: 41 · 2012: 31
- FWCI
- 3.03
- Type
- journal article
- Language
- en
- Open access
- closed
- Locations
- Clinical Endocrinology (publishedVersion)
- PubMed (publishedVersion)
- Cineca Institutional Research Information System (Tor Vergata University) (submittedVersion)
- IRIS Research product catalog (Sapienza University of Rome) (submittedVersion)
- 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 › Sperm and Testicular Function
- Keywords
- testosterone replacement therapy, male sexual function, hypogonadism, androgen deficiency, erectile function, vasculogenic erectile dysfunction, sexual desire, nocturnal erections, sexual satisfaction, eugonadal men, treatment effects over time, comorbidities, risk factors for erectile dysfunction, meta-regression, heterogeneity
- MeSH terms
- Adult, Aged, Aging, Data Interpretation, Statistical, Humans, Male, Middle Aged, Placebos, Sexual Dysfunction, Physiological, Testosterone, Randomized Controlled Trials as Topic, Treatment Outcome
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