Evaluating the Effects of Testosterone Therapy on Cardiometabolic Health and Well-being in Men with Hypogonadism
DOI:
https://doi.org/10.66266/inajemd.v2i2.69Keywords:
Testosterone Therapy, Hypogonadism, Cardiometabolic Health, Quality of Life, Adverse Cardiovascular EventsAbstract
Testosterone is crucial for male health, and hypogonadism is prevalent, particularly in men with metabolic comorbidities. While Testosterone Therapy (TTh) is used to manage symptoms, its
effects on cardiometabolic health and overall well-being remain debated. This review aimed to synthesize current evidence on the impact of TTh on cardiometabolic parameters, cardiovascular
safety, and quality of life in men with hypogonadism. A literature search (2015-2025) across multiple databases identified relevant studies, including Randomized Controlled Trials (RCTs) and
observational data, which were narratively synthesized. Results show TTh consistently improves body composition (reduced fat, increased muscle) and aspects of sexual function (libido, activity).
However, its effect on glucose metabolism remains controversial, with conflicting findings. While large RCTs indicate no increased risk of major adverse cardiovascular events over the medium term,
TTh is associated with increased specific risks including pulmonary embolism, atrial fibrillation, acute kidney injury, and polycythemia. Benefits on mood/energy are modest, and effects on other
quality of life domains are limited. In conclusion, TTh offers clear benefits for body composition and sexual function. Clinicians must balance these with controversial glucose effects and increased
specific adverse event risks, requiring careful patient selection and monitoring. Further long-term research is needed.
Downloads
References
1. Nassar GN, Leslie SW. Physiology, Testosterone.
2025.
2. Corona G, Giagulli VA, Maseroli E, Vignozzi
L, Aversa A, Zitzmann M, et al. THERAPY
OF ENDOCRINE DISEASE: Testosterone
supplementation and body composition: results
from a meta-analysis study. Eur J Endocrinol
2016;174(3):R99–116.
3. Wittert GA, Grossmann M, Yeap BB, Handelsman
DJ. Testosterone and type 2 diabetes prevention:
translational lessons from the T4DM study.
Journal of Endocrinology 2023;258(3).
4. Rodrigues dos Santos M, Bhasin S. Benefits and
Risks of Testosterone Treatment in Men with
Age-Related Decline in Testosterone. Annu Rev
Med 2021;72(1):75–91.
5. Calderón B, Gómez‐Martín JM, Vega‐Piñero B,
Martín‐Hidalgo A, Galindo J, Luque‐Ramírez M, et
al. Prevalence of male secondary hypogonadism
in moderate to severe obesity and its relationship
with insulin resistance and excess body weight.
Andrology 2016;4(1):62–7.
6. Groti Antonič K, Zitzmann M. Novel perspectives
of testosterone therapy in men with functional
hypogonadism: traversing the gaps of knowledge.
The Aging Male 2024;27(1).
7. Kelly DM, Jones TH. Testosterone and obesity.
Obesity Reviews 2015;16(7):581–606.
8. Meirelles RM da R. Functional Hypogonadism:
Diabetes Mellitus, Obesity, Metabolic Syndrome,
and Testosterone. In: Testosterone. Cham:
Springer International Publishing; 2017. page
147–59.
9. Molina-Vega M, Muñoz-Garach A, Damas-
Fuentes M, Fernández-García J, Tinahones F.
Secondary male hypogonadism: A prevalent
but overlooked comorbidity of obesity. Asian J
Androl 2018;20(6):531.
10. de Silva NL, Grant B, Minhas S, Jayasena CN.
Cardiovascular disease and testosterone therapy
in male hypogonadism. Ann N Y Acad Sci 2024;
11. Kelly DM, Akhtar S, Sellers DJ, Muraleedharan V,
Channer KS, Jones TH. Testosterone differentially
regulates targets of lipid and glucose metabolism
in liver, muscle and adipose tissues of the testicular
feminised mouse. Endocrine 2016;54(2):504–15.
12. Liu Y, Zhang D, Yuan J, Song L, Zhang C, Lin Q,
et al. Hyperbaric Oxygen Ameliorates Insulin
Sensitivity by Increasing GLUT4 Expression in
Skeletal Muscle and Stimulating UCP1 in Brown
Adipose Tissue in T2DM Mice. Front Endocrinol
(Lausanne) 2020;11:32.
13. Su CL, Chen M, Xu W, Lin JF. The impacts
of testosterone on insulin sensitivity and
chronic low-grade. Zhonghua Yi Xue Za Zhi
2017;97(1):47–52.
14. Kurniawan LB. Hypotestosterone in Male with
Obesity. INDONESIAN JOURNAL OF CLINICAL
PATHOLOGY AND MEDICAL LABORATORY
2021;27(2):217–23.
15. Stárka L, Hill M, Pospíšilová H, Dušková M.
Estradiol, obesity and hypogonadism. Physiol
Res 2020;69(Suppl 2):S273–8.
16. Miller C, Madden-Doyle L, Jayasena C, McIlroy
M, Sherlock M, O’Reilly MW. Mechanisms
in endocrinology: hypogonadism and
metabolic health in men—novel insights
into pathophysiology. Eur J Endocrinol
2024;191(6):R1–17.
17. Grossmann M. Hypogonadism and male obesity:
Focus on unresolved questions. Clin Endocrinol
(Oxf) 2018;89(1):11–21.
18. Babcock MC, DuBose LE, Witten TL, Stauffer
BL, Hildreth KL, Schwartz RS, et al. Oxidative
Stress and Inflammation Are Associated With
Age-Related Endothelial Dysfunction in Men
With Low Testosterone. J Clin Endocrinol Metab
2022;107(2):e500–14.
19. van Koeverden ID, de Bakker M, Haitjema S,
van der Laan SW, de Vries JPPM, Hoefer IE,
et al. Testosterone to oestradiol ratio reflects
systemic and plaque inflammation and predicts
future cardiovascular events in men with severe
atherosclerosis. Cardiovasc Res 2019;115(2):453–
62.
20. 20. Rovira-Llopis S, Bañuls C, de Marañon AM,
Diaz-Morales N, Jover A, Garzon S, et al. Low
testosterone levels are related to oxidative stress,
mitochondrial dysfunction and altered subclinical
atherosclerotic markers in type 2 diabetic male
patients. Free Radic Biol Med 2017;108:155–62.
21. Zhao J, Liu GL, Wei Y, Jiang LH, Bao PL, Yang
QY. Low-dose testosterone alleviates vascular
damage caused by castration in male rats in
puberty via modulation of the PI3K/AKT signaling
pathway. Mol Med Rep 2016;14(3):2518–26.
22. Lotti F, Maggi M. Sexual dysfunction and male
infertility. Nat Rev Urol 2018;15(5):287–307.
23. Zitzmann M. Testosterone, mood, behaviour and
quality of life. Andrology 2020;8(6):1598–605.
24. Wittert G, Bracken K, Robledo KP, Grossmann
M, Yeap BB, Handelsman DJ, et al. Testosterone
treatment to prevent or revert type 2 diabetes in
men enrolled in a lifestyle programme (T4DM):
a randomised, double-blind, placebo-controlled,
2-year, phase 3b trial. Lancet Diabetes Endocrinol
2021;9(1):32–45.
25. Yassin A, Haider A, Haider KS, Caliber M, Doros
G, Saad F, et al. Testosterone Therapy in Men
With Hypogonadism Prevents Progression
From Prediabetes to Type 2 Diabetes: Eight-
Year Data From a Registry Study. Diabetes Care
2019;42(6):1104–11.
26. Haider KS, Haider A, Saad F, Doros G, Hanefeld
M, Dhindsa S, et al. Remission of type 2 diabetes
following long‐term treatment with injectable
testosterone undecanoate in patients with
hypogonadism and type 2 diabetes: 11‐year data
from a real‐world registry study. Diabetes Obes
Metab 2020;22(11):2055–68.
27. Tishova Y, Kalinchenko S, Mskhalaya G, Hackett G,
Livingston M, König C, et al. Testosterone therapy
reduces insulin resistance in men with adultonset
testosterone deficiency and metabolic
syndrome. Results from the Moscow Study, a
randomized controlled trial with an open‐label
phase. Diabetes Obes Metab 2024;26(6):2147–57.
28. Bhasin S, Lincoff AM, Nissen SE, Wannemuehler
K, McDonnell ME, Peters AL, et al. Effect of
Testosterone on Progression From Prediabetes
to Diabetes in Men With Hypogonadism. JAMA
Intern Med 2024;184(4):353.
29. Lincoff AM, Bhasin S, Flevaris P, Mitchell LM,
Basaria S, Boden WE, et al. Cardiovascular Safety
of Testosterone-Replacement Therapy. New
England Journal of Medicine 2023;389(2):107–17.
30. Hudson J, Cruickshank M, Quinton R, Aucott
L, Aceves-Martins M, Gillies K, et al. Adverse
cardiovascular events and mortality in men
during testosterone treatment: an individual
patient and aggregate data meta-analysis. Lancet
Healthy Longev 2022;3(6):e381–93.
31. Etminan M, Skeldon SC, Goldenberg SL, Carleton
B, Brophy JM. Testosterone Therapy and Risk of
Myocardial Infarction: A Pharmacoepidemiologic
Study. Pharmacotherapy: The Journal of Human
Pharmacology and Drug Therapy 2015;35(1):72–
8.
32. Wallis CJD, Lo K, Lee Y, Krakowsky Y, Garbens A,
Satkunasivam R, et al. Survival and cardiovascular
events in men treated with testosterone
replacement therapy: an intention-to-treat
observational cohort study. Lancet Diabetes
Endocrinol 2016;4(6):498–506.
33. Pencina KM, Travison TG, Cunningham GR,
Lincoff AM, Nissen SE, Khera M, et al. Effect of
Testosterone Replacement Therapy on Sexual
Function and Hypogonadal Symptoms in Men
with Hypogonadism. J Clin Endocrinol Metab
2024;109(2):569–80.
34. Bhasin S, Seidman S, Travison TG, Pencina
KM, Lincoff AM, Nissen SE, et al. Depressive
Syndromes in Men With Hypogonadism in the
TRAVERSE Trial: Response to Testosterone-
Replacement Therapy. J Clin Endocrinol Metab
2024;109(7):1814–26.
35. Grossmann M, Robledo KP, Daniel M, Handelsman
DJ, Inder WJ, Stuckey BGA, et al. Testosterone
Treatment, Weight Loss, and Health-related
Quality of Life and Psychosocial Function in
Men: A 2-year Randomized Controlled Trial. J
Clin Endocrinol Metab 2024;109(8):2019–28.
36. Hackett G, Cole N, Mulay A, Strange RC,
Ramachandran S. Long‐term testosterone
therapy in type 2 diabetes is associated with
reduced mortality without improvement in
conventional cardiovascular risk factors. BJU Int
2019;123(3):519–29.
37. Khera M, Orozco Rendon D, Saffati G, Morgentaler
A. Lessons learned from the TRAVERSE trial. J Sex
Med 2024;21(9):746–8.
38. Krishnan S, Aldana-Bitar J, Golub I, Kianoush
S, Benzing T, Ichikawa K, et al. Testosterone
replacement therapy and cardiovascular risk:
TRAVERSE with caution. Prog Cardiovasc Dis
2024;86:73–4.
39. Budoff MJ. Testosterone Repletement. JACC:
Advances 2023;2(10):100742.
40. Hackett G, Ramachandran S. Making Sense of
the TRAVERSE Trials. Androgen Society2024;
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).
