Efficacy and Safety of Testosterone Treatment in Male Hypogonadism: a Systematic Review
DOI:
https://doi.org/10.66266/inajemd.v2i2.71Keywords:
Testosterone Replacement Therapy, Hypogonadism, Safety, Efficacy, Systematic ReviewAbstract
Male hypogonadism may occur because of either congenital conditions or dysfunction that arises along the hypothalamic-pituitary-gonadal axis. As part of the lifelong management of male hypogonadism, testosterone replacement therapy (TRT) has been the most important therapy, although its effectiveness and safety are subject to controversy. This systematic review was undertaken to investigate the effectiveness and safety of TRT in men with hypogonadism. Searches were conducted in the literature through MEDLINE, CENTRAL, and ScienceDirect. The inclusion criteria were restricted to RCTs reported within five years. Out of 2,471 published articles, 16 were found eligible for analysis. Results showed that TRT is effective in raising serum testosterone levels in male with hypogonadism no matter the mode of administration, whether injected, oral or topical as in gels. In addition, TRT has improved body composition by decreasing fat and lean muscle mass. An increase in PSA commonly occurs in most patients, yet no research proves that TRT increases the development of prostate cancer and cardiovascular disease. Most commonly, the adverse effects are arrhythmias and increase in blood pressure, especially among those who undergo oral TRT. Amelioration of different symptoms such as erectile dysfunction, decreased libido, and fatigue in patients with hypogonadism was also achieved by TRT. Overall, it can be concluded that, TRT is generally safe and effective but requires close monitoring, but also one where monitoring should regularly be performed because of possible side effects, more research is needed.
Downloads
References
1. Sizar, O., Leslie, S. W. & Schwartz, J.Male
Hypogonadism. (StatPearls Publishing, 2024).
2. Yeo, S. et al. Burden of Male Hypogonadism and
Major Comorbidities, and the Clinical, Economic,
and Humanistic Benefits of Testosterone Therapy:
A Narrative Review. CEOR 13, 31–38 (2021).
3. Liu, Y.-J. et al. Prevalence of late-onset
hypogonadism among middle-aged and elderly
males in China: results from a national survey.
Asian Journal of Andrology 23, 170–177 (2021).
4. Morgentaler, A. & Traish, A. The History of
Testosterone and the Evolution of its Therapeutic
Potential. Sexual Medicine Reviews 8, 286–296
(2020).
5. Patel, A. S., Leong, J. Y., Ramos, L. & Ramasamy,
R. Testosterone Is a Contraceptive and Should
Not Be Used in Men Who Desire Fertility. World
J Mens Health 37, 45 (2019).
6. Swerdloff, R. S. et al. A new oral testosterone
undecanoate formulation restores testosterone
to normal concentrations in hypogonadal men.
J. Clin. Endocrinol. Metab. 105, 2515–2531 (2020).
7. Dudek, P., Kozakowski, J. & Zgliczyński, W. The
effects of testosterone replacement therapy in
men with age-dependent hypogonadism on
body composition, and serum levels of leptin,
adiponectin, and C-reactive protein. Endokrynol.
Pol. 71, 382–387 (2020).
8. Miner, M. et al. Safety, efficacy, and
pharmacokinetics of oral testosterone
undecanoate in males with hypogonadism.
Andrology (2024) doi:10.1111/andr.13747.
9. Bhasin, S. et al. Prostate safety events during
testosterone replacement therapy in men with
hypogonadism: A randomized clinical trial. JAMA
Netw. Open 6, e2348692 (2023).
10. Rasmussen, R. S. et al. Testosterone and resistance
training improved physical performance and
reduced fatigue in frail older men: 1 year followup
of a randomized clinical trial. Aging Male 27,
2403519 (2024).
11. Cunningham, G. R. et al. Prostate-specific
antigen levels during testosterone treatment of
hypogonadal older men: Data from a controlled
trial. J. Clin. Endocrinol. Metab. 104, 6238–6246
(2019).
12. Kienitz, T. & Quinkler, M. Testosterone and blood
pressure regulation. Kidney Blood Press. Res. 31,
71–79 (2008).
13. Lincoff, A. M. et al. Cardiovascular safety of
testosterone-replacement therapy. N. Engl. J.
Med. 389, 107–117 (2023).
14. Greenberg, D. R., Kohn, T. P., Asanad, K.,
Brannigan, R. E. & Halpern, J. A. Association of
testosterone replacement therapy with atrial
fibrillation and acute kidney injury. The Journal
of Sexual Medicine 21, 1201–1203 (2024).
15. Nackeeran, S. et al. The effect of route of
testosterone on changes in hematocrit: A
systematic review and Bayesian network metaanalysis
of randomized trials. J. Urol. 207, 44–51
(2022).
16. Bhasin, S. et al. Testosterone Therapy in men with
hypogonadism: An Endocrine Society clinical
practice guideline. J. Clin. Endocrinol. Metab. 103,
1715–1744 (2018).
17. Narukawa, T., Soh, J., Kanemitsu, N., Harikai, S.
& Ukimura, O. Efficacy of combined treatment
of intramuscular testosterone injection and
testosterone ointment application for late-onset
hypogonadism: an open-labeled, randomized,
crossover study. Aging Male 23, 1059–1065
(2020).
18. Pencina, K. M. et al. Efficacy of Testosterone
Replacement Therapy in correcting anemia in
men with hypogonadism: A randomized clinical
trial: A randomized clinical trial. JAMA Netw. Open
6, e2340030 (2023).
19. Bøgehave, M. et al. Testosterone therapy
increases the anticoagulant potential in men with
opioid-induced hypogonadism: a randomized,
placebo-controlled study. Endocr. Connect. 12,
e220455 (2023).
20. Elliott, J. et al. Testosterone therapy in
hypogonadal men: a systematic review and
network meta-analysis. BMJ Open 7, e015284
21. Ponce, O. J. et al. The efficacy and adverse
events of testosterone replacement therapy
in hypogonadal men: A systematic review and
meta-analysis of randomized, placebo-controlled
trials. J. Clin. Endocrinol. Metab. 103, 1745–1754
(2018).
22. Ramachandran, S., Hackett, G. I. & Strange, R. C.
Testosterone replacement therapy: Pre-treatment
sex hormone-binding globulin levels and age
may identify clinical subgroups. Andrology 8,
1222–1232 (2020).
23. Tishova, Y. et al. Testosterone therapy reduces
insulin resistance in men with adult-onset
testosterone deficiency and metabolic syndrome.
Results from the Moscow Study, a randomized
controlled trial with an open-label phase.
Diabetes Obes. Metab. 26, 2147–2157 (2024).
24. Cauley, J. A. et al. Effect of testosterone treatment
on the trabecular bone score in older men with
low serum testosterone. Osteoporos. Int. 32,
2371–2375 (2021).
25. Groti Antonič, K. Impact of testosterone therapy
on bone turnover markers in obese males with
type 2 diabetes and functional hypogonadism.
Aging Male 25, 269–277 (2022).
26. Bischoff-Ferrari, H. A. et al. Effects of testosterone
and vitamin D on fall risk in pre-frail hypogonadal
men: a factorial design RCT. J. Nutr. Health Aging
28, 100217 (2024).
27. Gregori, G. et al. Cognitive response to
testosterone replacement added to intensive
lifestyle intervention in older men with obesity
and hypogonadism: prespecified secondary
analyses of a randomized clinical trial. Am. J. Clin.
Nutr. 114, 1590–1599 (2021).
Downloads
Published
Issue
Section
License
Copyright (c) 2025 InaJEMD - Indonesian Journal of Endocrinology Metabolic and Diabetes
This work is licensed under a Creative Commons Attribution-NonCommercial-NoDerivatives 4.0 International License.
Authors retain copyright and grant the Indonesian Journal of Endocrinology, Metabolism and Diabetes (InaJEMD) the right of first publication with the work simultaneously licensed under a Creative Commons Attribution-NonCommercial-NoDerivatives 4.0 International License (CC BY-NC-ND 4.0) that allows others to share the work with an acknowledgement of the work's authorship and initial publication in this journal.
© Indonesian Journal of Endocrinology, Metabolism and Diabetes (InaJEMD). Published by the Indonesian Society of Endocrinology (PERKENI).
