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Testosterone Replacement Therapy (TRT): What the Latest Research Says
TRT
Eileen Quinones
•
6 mins
• Mar 4, 2025
Testosterone Replacement Therapy (TRT) has gained increasing attention as a treatment for men experiencing symptoms of low testosterone (hypogonadism). With growing research on its benefits and risks, there has been a shift in understanding TRT's role in improving metabolic health, sexual function, muscle mass, and even mental well-being. However, misconceptions about its effects on prostate health and cardiovascular risks remain.
This blog will break down the latest scientific findings on TRT, providing clear insights into its benefits, safety, and the most recent innovations in treatment.
Understanding Testosterone Levels: What’s Considered Low?
Determining whether a man has low testosterone requires clear reference ranges. According to recent studies, total testosterone (TT) levels between 12.1–33 nmol/L and free testosterone (FT) levels between 70–141 pg/mL are considered normal. Men with levels below this threshold often experience symptoms such as fatigue, low libido, reduced muscle mass, and depression.
A key takeaway from recent research is that low testosterone is strongly linked to physical dysfunction, sexual dysfunction, and metabolic disorders such as Type 2 diabetes mellitus (T2DM). This has led to an increased emphasis on the importance of properly diagnosing and treating hypogonadism.
TRT and Type 2 Diabetes: A Game-Changer for Metabolic Health?
One of the most exciting findings in TRT research is its potential to prevent or even reverse Type 2 diabetes in men with low testosterone.¹
A 2019 study by Yassin et al. found that long-term TRT in hypogonadal men prevented the progression of prediabetes to full-blown T2DM over an 8-year period.
Another study found that TRT improves insulin sensitivity, lowers fasting blood glucose levels, reduces cholesterol, and helps with weight loss, all of which contribute to better cardiovascular health.
The T4DM trial (2021), a large placebo-controlled study, confirmed that TRT combined with a lifestyle program significantly reduced the risk of developing diabetes in men at high risk.
Key Takeaway:
If you’re struggling with obesity, insulin resistance, or Type 2 diabetes, checking your testosterone levels might be worth considering. TRT, when used appropriately, can have profound metabolic benefits.
How Long Should TRT Be Taken? Is It a Lifelong Treatment?
A major question surrounding TRT is: How long should a man stay on therapy?¹
Research suggests that TRT improves body composition, sexual function, and metabolic markers only while the treatment is ongoing.
In a long-term study of 262 men on TRT, those who stopped treatment experienced a rapid decline in their benefits, including weight gain, worsened urinary symptoms, and reduced libido.
Symptoms such as erectile dysfunction, fatigue, and mood disturbances reappeared once testosterone levels dropped again.
Key Takeaway:
TRT is not a one-time fix—most men will need to stay on therapy to maintain the benefits. However, treatment duration should always be personalized and monitored by a healthcare provider.
Prostate Health and TRT: Does It Increase Cancer Risk?
For decades, there was a widespread belief that higher testosterone levels increased the risk of prostate cancer. However, recent studies debunk this myth and suggest that TRT does not significantly increase prostate cancer risk.¹
The "saturation model" hypothesis proposes that once the prostate’s androgen receptors are saturated, additional testosterone does not fuel cancer growth.
Large studies have found no significant increase in PSA levels or prostate cancer risk among men on long-term TRT.
Men with a history of prostate cancer who were treated successfully have been able to use TRT safely under medical supervision.
Key Takeaway:
TRT does not cause prostate cancer but requires monitoring, especially in men with a history of prostate disease.
TRT and Heart Health: Is It Safe?
One of the most controversial topics regarding TRT is its potential effect on cardiovascular health. Older studies suggested an increased risk of heart attacks, but recent landmark studies tell a different story:²
The TRAVERSE Trial (2023), which followed over 5,000 men for several years, found no increase in major adverse cardiovascular events (heart attacks, strokes, or cardiovascular-related deaths) in men on TRT compared to a placebo group.
In fact, TRT was associated with improved heart health in men with Type 2 diabetes, likely due to its beneficial effects on body fat and metabolism.
The only concerns noted were a slight increase in atrial fibrillation (a type of irregular heartbeat) and a higher chance of mild blood thickening (polycythemia), which can be managed with proper monitoring.
Key Takeaway:
For most men, TRT does not increase heart attack or stroke risk. However, those with existing cardiovascular conditions should be closely monitored during treatment.
Conclusion: The Future of TRT and Its Expanding Role in Men's Health
The latest research on TRT confirms that it offers significant benefits beyond just improving libido and muscle mass. It plays a critical role in metabolic health, diabetes prevention, and overall well-being. While concerns about prostate cancer and heart disease have been widely debated, new evidence suggests that TRT is generally safe when prescribed and monitored properly.
Should You Consider TRT?
If you’re experiencing symptoms of low testosterone—such as fatigue, low libido, depression, weight gain, or difficulty managing blood sugar—it may be worth discussing TRT with your doctor. With newer delivery methods like long-acting injections, transdermal gels, and even nasal testosterone, treatment is becoming more convenient and tailored to individual needs.
Final Thought: TRT is not just about increasing testosterone levels—it’s about improving quality of life, preventing metabolic diseases, and optimizing long-term health. As research continues to evolve, TRT is proving to be a valuable tool in men’s health and longevity.
Sources :
Al-Zoubi RM, Yassin AA, Alwani M, Al-Qudimat A, Aboumarzouk OM, Zarour A, Al Ansari A. A systematic review on the latest developments in testosterone therapy: Innovations, advances, and paradigm shifts. Arab J Urol. 2021 Aug 8;19(3):370-375. doi: 10.1080/2090598X.2021.1959260. PMID: 34552788; PMCID: PMC8451690.
Lincoff, A. M., Bhasin, S., Flevaris, P., Mitchell, L. M., Basaria, S., Boden, W. E., Cunningham, G. R., Granger, C. B., Khera, M., Thompson, I. M., Wang, Q., Wolski, K., Davey, D., Kalahasti, V., Khan, N., Miller, M. G., Snabes, M. C., Chan, A., Dubcenco, E., . . . Nissen, S. E. (2023). Cardiovascular safety of Testosterone-Replacement therapy. New England Journal of Medicine, 389(2), 107–117. https://doi.org/10.1056/nejmoa2215025
Current version
Mar 4, 2025
Written by
Eileen Quinones (Nurse Practitioner)
Balance your hormones
with Enclomiphene or Progesterone
Complete our quick questionnaire to identify if you qualify. (approx 3 min)
Testosterone Replacement Therapy (TRT): What the Latest Research Says
TRT
Eileen Quinones
•
6 mins
• Mar 4, 2025
Testosterone Replacement Therapy (TRT) has gained increasing attention as a treatment for men experiencing symptoms of low testosterone (hypogonadism). With growing research on its benefits and risks, there has been a shift in understanding TRT's role in improving metabolic health, sexual function, muscle mass, and even mental well-being. However, misconceptions about its effects on prostate health and cardiovascular risks remain.
This blog will break down the latest scientific findings on TRT, providing clear insights into its benefits, safety, and the most recent innovations in treatment.
Understanding Testosterone Levels: What’s Considered Low?
Determining whether a man has low testosterone requires clear reference ranges. According to recent studies, total testosterone (TT) levels between 12.1–33 nmol/L and free testosterone (FT) levels between 70–141 pg/mL are considered normal. Men with levels below this threshold often experience symptoms such as fatigue, low libido, reduced muscle mass, and depression.
A key takeaway from recent research is that low testosterone is strongly linked to physical dysfunction, sexual dysfunction, and metabolic disorders such as Type 2 diabetes mellitus (T2DM). This has led to an increased emphasis on the importance of properly diagnosing and treating hypogonadism.
TRT and Type 2 Diabetes: A Game-Changer for Metabolic Health?
One of the most exciting findings in TRT research is its potential to prevent or even reverse Type 2 diabetes in men with low testosterone.¹
A 2019 study by Yassin et al. found that long-term TRT in hypogonadal men prevented the progression of prediabetes to full-blown T2DM over an 8-year period.
Another study found that TRT improves insulin sensitivity, lowers fasting blood glucose levels, reduces cholesterol, and helps with weight loss, all of which contribute to better cardiovascular health.
The T4DM trial (2021), a large placebo-controlled study, confirmed that TRT combined with a lifestyle program significantly reduced the risk of developing diabetes in men at high risk.
Key Takeaway:
If you’re struggling with obesity, insulin resistance, or Type 2 diabetes, checking your testosterone levels might be worth considering. TRT, when used appropriately, can have profound metabolic benefits.
How Long Should TRT Be Taken? Is It a Lifelong Treatment?
A major question surrounding TRT is: How long should a man stay on therapy?¹
Research suggests that TRT improves body composition, sexual function, and metabolic markers only while the treatment is ongoing.
In a long-term study of 262 men on TRT, those who stopped treatment experienced a rapid decline in their benefits, including weight gain, worsened urinary symptoms, and reduced libido.
Symptoms such as erectile dysfunction, fatigue, and mood disturbances reappeared once testosterone levels dropped again.
Key Takeaway:
TRT is not a one-time fix—most men will need to stay on therapy to maintain the benefits. However, treatment duration should always be personalized and monitored by a healthcare provider.
Prostate Health and TRT: Does It Increase Cancer Risk?
For decades, there was a widespread belief that higher testosterone levels increased the risk of prostate cancer. However, recent studies debunk this myth and suggest that TRT does not significantly increase prostate cancer risk.¹
The "saturation model" hypothesis proposes that once the prostate’s androgen receptors are saturated, additional testosterone does not fuel cancer growth.
Large studies have found no significant increase in PSA levels or prostate cancer risk among men on long-term TRT.
Men with a history of prostate cancer who were treated successfully have been able to use TRT safely under medical supervision.
Key Takeaway:
TRT does not cause prostate cancer but requires monitoring, especially in men with a history of prostate disease.
TRT and Heart Health: Is It Safe?
One of the most controversial topics regarding TRT is its potential effect on cardiovascular health. Older studies suggested an increased risk of heart attacks, but recent landmark studies tell a different story:²
The TRAVERSE Trial (2023), which followed over 5,000 men for several years, found no increase in major adverse cardiovascular events (heart attacks, strokes, or cardiovascular-related deaths) in men on TRT compared to a placebo group.
In fact, TRT was associated with improved heart health in men with Type 2 diabetes, likely due to its beneficial effects on body fat and metabolism.
The only concerns noted were a slight increase in atrial fibrillation (a type of irregular heartbeat) and a higher chance of mild blood thickening (polycythemia), which can be managed with proper monitoring.
Key Takeaway:
For most men, TRT does not increase heart attack or stroke risk. However, those with existing cardiovascular conditions should be closely monitored during treatment.
Conclusion: The Future of TRT and Its Expanding Role in Men's Health
The latest research on TRT confirms that it offers significant benefits beyond just improving libido and muscle mass. It plays a critical role in metabolic health, diabetes prevention, and overall well-being. While concerns about prostate cancer and heart disease have been widely debated, new evidence suggests that TRT is generally safe when prescribed and monitored properly.
Should You Consider TRT?
If you’re experiencing symptoms of low testosterone—such as fatigue, low libido, depression, weight gain, or difficulty managing blood sugar—it may be worth discussing TRT with your doctor. With newer delivery methods like long-acting injections, transdermal gels, and even nasal testosterone, treatment is becoming more convenient and tailored to individual needs.
Final Thought: TRT is not just about increasing testosterone levels—it’s about improving quality of life, preventing metabolic diseases, and optimizing long-term health. As research continues to evolve, TRT is proving to be a valuable tool in men’s health and longevity.
Current version
Mar 4, 2025
Written by
Eileen Quinones (Nurse Practitioner)
Fact checked by
Eileen Quinones (Nurse Practitioner)
Balanced hormones
with Enclomiphene or Progesterone
Complete our quick questionnaire to identify if you qualify. (approx 3 min)
Balanced hormones
with Enclomiphene or Progesterone
Complete our quick questionnaire to identify if you qualify. (approx 3 min)
Sources :
Al-Zoubi RM, Yassin AA, Alwani M, Al-Qudimat A, Aboumarzouk OM, Zarour A, Al Ansari A. A systematic review on the latest developments in testosterone therapy: Innovations, advances, and paradigm shifts. Arab J Urol. 2021 Aug 8;19(3):370-375. doi: 10.1080/2090598X.2021.1959260. PMID: 34552788; PMCID: PMC8451690.
Lincoff, A. M., Bhasin, S., Flevaris, P., Mitchell, L. M., Basaria, S., Boden, W. E., Cunningham, G. R., Granger, C. B., Khera, M., Thompson, I. M., Wang, Q., Wolski, K., Davey, D., Kalahasti, V., Khan, N., Miller, M. G., Snabes, M. C., Chan, A., Dubcenco, E., . . . Nissen, S. E. (2023). Cardiovascular safety of Testosterone-Replacement therapy. New England Journal of Medicine, 389(2), 107–117. https://doi.org/10.1056/nejmoa2215025