Some of the guys I work out with know that i inject T. It has come up why then do I not put on more gains, I do heavy rssitance training and little cardio. I explained that I am on a theraputic dose. Shoot I take a paltry 30 mg twice a week to keep red blood cells in line, so i could never do the super dosing that alot of body builders do.
At what levels do you begin to see substantial mass gains in the gym? I thought i read where guys may use 1500 mg/ injection when cycling on. I would die of a stroke in a matter of weeks doing that heavy dosage!!!
The Bhasin Testosterone Dose-Response Study: What 125mg Weekly Teaches Us About Optimal TRT Dosing
Published in the American Journal of Physiology: Endocrinology and Metabolism, this study systematically tested five different testosterone doses in healthy young men, measuring everything from muscle mass and strength to body fat, sexual function, and safety parameters. The results established that 125mg per week of testosterone enanthate represents a critical threshold—the lowest dose that produces statistically significant improvements in body composition while maintaining testosterone levels in the high-normal range with minimal adverse effects.
This article provides a comprehensive analysis of the Bhasin study and explains how its findings can inform modern TRT dosing decisions.
Hormonal Suppression: All participants received monthly injections of a long-acting GnRH agonist, which completely suppressed their endogenous testosterone production. This "chemical castration" created a clean slate—ensuring that all circulating testosterone came from the administered injections rather than natural production.
Testosterone Doses: Men were randomized to receive weekly intramuscular injections of testosterone enanthate at one of five doses: 25mg, 50mg, 125mg, 300mg, or 600mg per week for 20 weeks.
Standardized Conditions: Energy and protein intakes were standardized across all groups, eliminating dietary variation as a confounding factor. This is crucial—many studies fail to control for nutrition, making it impossible to isolate testosterone's effects from dietary differences.
Key Insight: The 125mg dose produced trough testosterone levels of 542 ng/dL—solidly in the high-normal range for healthy young men. This is clinically significant because many TRT practitioners aim for trough levels in the 500-700 ng/dL range, suggesting that 125mg weekly represents an evidence-based starting point for physiological testosterone replacement.
The changes in fat-free mass were highly dose-dependent (P = 0.0001) and strongly correlated with log testosterone concentrations (r = 0.73, P = 0.0001). This linear dose-response relationship demonstrates that testosterone's anabolic effects on muscle are predictable and directly proportional to circulating hormone levels—more testosterone equals more muscle, at least within the range studied.
The Clinical Takeaway: Men receiving 25mg or 50mg weekly—resulting in low or low-normal testosterone levels—did not experience statistically significant improvements in lean mass. The 125mg dose was the minimum effective dose for producing meaningful body composition changes.
All three parameters showed the same dose-dependent pattern as fat-free mass:
• Leg Press Strength: Positively correlated with testosterone dose; significant improvements at 125mg and above
• Leg Power: Positively correlated with testosterone dose; demonstrates that muscle quality—not just size—improved
• Thigh Muscle Volume: MRI confirmed that testosterone-induced lean mass gains represented true muscle hypertrophy, not water retention
• Quadriceps Volume: Dose-dependent increases ranging from no change (25-50mg) to +48mL at 600mg
Companion studies using muscle biopsies from the same participants confirmed that the increase in muscle volume was due to true muscle fiber hypertrophy—increases in the cross-sectional area of both Type I (slow-twitch) and Type II (fast-twitch) muscle fibers—rather than intramuscular water or glycogen accumulation.
1. Participants were young, healthy men with normal baseline testosterone and normal sexual function. There was no "floor" to improve from—they were already functioning optimally.
2. Sexual function may have a lower testosterone threshold than muscle anabolism. Once testosterone exceeds a minimum level (perhaps 250-350 ng/dL), additional testosterone may not further enhance libido or sexual performance.
3. Subsequent analysis suggested that doses of 300-600mg weekly showed a slight trend toward increased sexual desire—but this did not reach statistical significance given the small sample sizes.
Clinical Implication: Men with hypogonadism and sexual dysfunction may experience dramatic improvements with TRT because they are starting from deficient levels. But for men already in the normal range, higher doses may not translate to better sexual function.
1. Testosterone Levels in the High-Normal Range: The 125mg dose produced nadir testosterone levels of 542 ng/dL, placing men in the upper-normal physiological range. This is consistent with levels seen in healthy young men and aligns with current clinical targets for TRT (500-700 ng/dL trough).
2. Statistically Significant Body Composition Benefits: Unlike lower doses, 125mg produced meaningful improvements in fat-free mass (+3.4 kg) and reductions in fat mass—benefits that matter for metabolic health, functional capacity, and quality of life.
3. Minimal Adverse Effects: At 125mg, increases in hemoglobin, decreases in HDL, and elevations in IGF-1 were modest and clinically manageable. The 2005 companion study in older men specifically identified 125mg as providing "the best trade-off... associated with high normal testosterone levels, low frequency of adverse events, and significant gains in fat-free mass and muscle strength."
4. The Threshold Effect: The data clearly show that 25mg and 50mg weekly are insufficient for producing anabolic benefits—these doses merely prevent severe hypogonadism without optimizing body composition. For men seeking the benefits of TRT, underdosing represents a missed opportunity.
• Achieves high-normal testosterone levels
• Produces statistically significant improvements in body composition
• Minimizes the risk of supraphysiological exposure and associated adverse effects
• Provides a baseline from which to adjust based on individual response
The key takeaways for men considering or currently on TRT:
• 125mg weekly is the minimum dose for significant body composition benefits —lower doses may not produce meaningful improvements despite achieving "normal" testosterone levels
• More is not always better —supraphysiological doses (300-600mg weekly) produce greater muscle gains but at the cost of increased adverse effects
• Different outcomes have different dose-response curves —sexual function may plateau at lower doses than required for optimal body composition
• Individual monitoring is essential —actual testosterone levels matter more than the dose administered
For clinicians and patients seeking to optimize TRT outcomes while minimizing risks, the 125mg weekly dose (or its equivalent with other formulations and injection frequencies) represents a scientifically grounded starting point—the threshold at which testosterone replacement truly becomes testosterone optimization.
• Responses of Different Doses of Testosterone Injections on Body Composition, Strength, etc. – Original thread with study summary and graphs
• Effect of Low and High Doses of Testosterone Injections on Hematocrit, PSA and HDL – Deep dive into safety parameters at different doses
• What is the Optimum TRT Dose for Muscle Growth? Nelson Vergel Reviews the Data – Video discussion of optimal dosing strategies
• How to Predict Estradiol and DHT at Different Testosterone Doses – Predictive modeling for hormone metabolites
• The 12-Year-Old Study That Proves Testosterone Injections Every Two Weeks Fail – Why injection frequency matters as much as dose
• How Long Does Testosterone Take to Show Effects? – Timeline expectations for TRT benefits
2. Bhasin S, Woodhouse L, Casaburi R, et al. Older men are as responsive as young men to the anabolic effects of graded doses of testosterone on the skeletal muscle. J Clin Endocrinol Metab. 2005;90(2):678-688. [PubMed]
3. Sinha-Hikim I, Artaza J, Woodhouse L, et al. Testosterone-induced increase in muscle size in healthy young men is associated with muscle fiber hypertrophy. Am J Physiol Endocrinol Metab. 2002;283(1):E154-E164. [PubMed]
4. Sinha-Hikim I, Cornford M, Gaytan H, et al. Effects of testosterone supplementation on skeletal muscle fiber hypertrophy and satellite cells in community-dwelling older men. J Clin Endocrinol Metab. 2006;91(8):3024-3033. [PubMed]
5. Pharmacology of testosterone replacement therapy preparations. Transl Androl Urol. 2016;5(6):834-843. [PMC Full Text]
6. Full text of original study. American Physiological Society. [Journal Full Text]
Disclaimer: This article is for informational purposes only and does not constitute medical advice. Testosterone replacement therapy requires a prescription and should be supervised by a qualified healthcare provider. Individual responses to therapy vary, and treatment decisions should be made in consultation with your physician based on your specific clinical circumstances.
About ExcelMale.com: ExcelMale is a men's health forum with over 24,000 members and 20+ years of archived discussions on testosterone replacement therapy, hormone optimization, and sexual health. Founded by Nelson Vergel, author of Testosterone: A Man's Guide and Beyond Testosterone, ExcelMale provides evidence-based information and peer support for men navigating hormone health decisions.
At what levels do you begin to see substantial mass gains in the gym? I thought i read where guys may use 1500 mg/ injection when cycling on. I would die of a stroke in a matter of weeks doing that heavy dosage!!!
The Bhasin Testosterone Dose-Response Study: What 125mg Weekly Teaches Us About Optimal TRT Dosing
By Nelson Vergel | ExcelMale.com | Updated December 2025
In the world of testosterone replacement therapy, one question comes up more than any other: "What's the right dose?" The answer isn't as simple as a single number, but a landmark 2001 study by Dr. Shalender Bhasin and colleagues provides the most rigorous dose-response data we have—and its findings remain remarkably relevant for optimizing TRT protocols today.
Published in the American Journal of Physiology: Endocrinology and Metabolism, this study systematically tested five different testosterone doses in healthy young men, measuring everything from muscle mass and strength to body fat, sexual function, and safety parameters. The results established that 125mg per week of testosterone enanthate represents a critical threshold—the lowest dose that produces statistically significant improvements in body composition while maintaining testosterone levels in the high-normal range with minimal adverse effects.
This article provides a comprehensive analysis of the Bhasin study and explains how its findings can inform modern TRT dosing decisions.
Study Design: The Gold Standard for Testosterone Dose-Response Research
What makes the Bhasin study exceptionally valuable is its rigorous methodology. Unlike typical TRT studies that simply compare testosterone to placebo, this study created five distinct hormonal environments by suppressing each participant's endogenous testosterone production and then replacing it at precisely controlled doses.Participants and Protocol
Participants: 61 healthy eugonadal men aged 18-35 years with normal baseline testosterone levels and prior weight-lifting experience. This ensured the study measured testosterone's effects independent of training adaptation.Hormonal Suppression: All participants received monthly injections of a long-acting GnRH agonist, which completely suppressed their endogenous testosterone production. This "chemical castration" created a clean slate—ensuring that all circulating testosterone came from the administered injections rather than natural production.
Testosterone Doses: Men were randomized to receive weekly intramuscular injections of testosterone enanthate at one of five doses: 25mg, 50mg, 125mg, 300mg, or 600mg per week for 20 weeks.
Standardized Conditions: Energy and protein intakes were standardized across all groups, eliminating dietary variation as a confounding factor. This is crucial—many studies fail to control for nutrition, making it impossible to isolate testosterone's effects from dietary differences.
Resulting Testosterone Levels by Dose
The study measured nadir (trough) testosterone levels—the lowest point in the week, typically occurring just before the next injection. These trough values are clinically important because they represent the minimum testosterone exposure:Weekly Dosee | Mean Nadir T (ng/dL) Lower Concentration | Hormonal Status | Clinical Range |
| 25 mg | 253 | Severely hypogonadal | Below range |
50 mg | 306 | Low-normal | Low end of range |
125 mg | 542 | High-normal | Mid-to-upper range |
300 mg | 1,345 | Supraphysiological | Above range |
600 mg | 2,370 | Highly supraphysiological | Steroid-cycle range |
Body Composition Results: The 125mg Threshold Effect
Perhaps the study's most clinically relevant finding was the identification of a clear threshold effect for body composition changes. Not all doses produced equivalent benefits—and statistical significance only emerged at 125mg and above.Fat-Free Mass (Lean Body Mass) Changes
Weekly Dose | Fat-Free Mass Change | Fat Mass Change | Statistical Significance |
| 25 mg | No significant change | Increased | No |
50 mg | No significant change | No change | No |
125 mg | +3.4 kg (7.5 lbs) | Decreased | Yes (P<0.05) |
300 mg | +5.2 kg (11.5 lbs) | Decreased | Yes (P<0.05) |
600 mg | +7.9 kg (17.4 lbs) | Decreased | Yes (P<0.05) |
The Clinical Takeaway: Men receiving 25mg or 50mg weekly—resulting in low or low-normal testosterone levels—did not experience statistically significant improvements in lean mass. The 125mg dose was the minimum effective dose for producing meaningful body composition changes.
Strength and Power: Functional Outcomes Follow the Same Pattern
Body composition changes are only meaningful if they translate to functional improvements. The Bhasin study measured leg press strength (one-repetition maximum), leg power (Nottingham power rig), and muscle volumes (MRI-measured thigh and quadriceps).All three parameters showed the same dose-dependent pattern as fat-free mass:
• Leg Press Strength: Positively correlated with testosterone dose; significant improvements at 125mg and above
• Leg Power: Positively correlated with testosterone dose; demonstrates that muscle quality—not just size—improved
• Thigh Muscle Volume: MRI confirmed that testosterone-induced lean mass gains represented true muscle hypertrophy, not water retention
• Quadriceps Volume: Dose-dependent increases ranging from no change (25-50mg) to +48mL at 600mg
Companion studies using muscle biopsies from the same participants confirmed that the increase in muscle volume was due to true muscle fiber hypertrophy—increases in the cross-sectional area of both Type I (slow-twitch) and Type II (fast-twitch) muscle fibers—rather than intramuscular water or glycogen accumulation.
What Testosterone Did NOT Change: Sexual Function, Cognition, and PSA
One of the study's most surprising findings was that several outcomes typically associated with testosterone did not show dose-dependent changes:Sexual Function and Libido
Sexual function questionnaires did not show significant changes at any dose—even at 600mg weekly. This may seem counterintuitive, but there are important caveats to consider:1. Participants were young, healthy men with normal baseline testosterone and normal sexual function. There was no "floor" to improve from—they were already functioning optimally.
2. Sexual function may have a lower testosterone threshold than muscle anabolism. Once testosterone exceeds a minimum level (perhaps 250-350 ng/dL), additional testosterone may not further enhance libido or sexual performance.
3. Subsequent analysis suggested that doses of 300-600mg weekly showed a slight trend toward increased sexual desire—but this did not reach statistical significance given the small sample sizes.
Clinical Implication: Men with hypogonadism and sexual dysfunction may experience dramatic improvements with TRT because they are starting from deficient levels. But for men already in the normal range, higher doses may not translate to better sexual function.
Visual-Spatial Cognition and Mood
Cognitive tests measuring visual-spatial abilities and mood assessments showed no significant changes across any dose group. Again, this likely reflects the normal baseline status of the participants rather than a true absence of testosterone effects on brain function.PSA Levels
Prostate-specific antigen (PSA) levels did not change significantly at any dose during the 20-week treatment period. This is reassuring for the safety profile of testosterone therapy in young men, though it should not be extrapolated to older men or longer treatment durations where age-related prostate changes may create a different context.Safety Parameters: Where Higher Doses Show Tradeoffs
While testosterone's anabolic benefits scaled linearly with dose, so did certain adverse effects. The study documented dose-dependent changes in several safety-relevant parameters:Hemoglobin and Hematocrit
Hemoglobin levels increased in a dose-dependent manner, with higher testosterone doses producing greater elevations. This reflects testosterone's stimulatory effect on erythropoiesis (red blood cell production). While modest increases in hemoglobin can be beneficial, excessive elevation (hematocrit >54%) increases blood viscosity and cardiovascular risk. The 125mg dose produced modest hemoglobin increases that remained within safe ranges for most participants.HDL Cholesterol
HDL ("good") cholesterol decreased in a dose-dependent manner—the higher the testosterone dose, the greater the HDL suppression. This is a recognized effect of androgens on hepatic lipid metabolism and represents a potential cardiovascular concern at supraphysiological doses. At 125mg weekly, HDL suppression was minimal and likely clinically insignificant. At 300-600mg weekly, HDL decreases were substantial and warrant consideration in risk-benefit analysis.IGF-1 Levels
Insulin-like growth factor 1 (IGF-1) levels increased with testosterone dose. IGF-1 is an anabolic hormone that contributes to muscle protein synthesis and may partially mediate testosterone's effects on muscle. However, chronically elevated IGF-1 has been associated with increased cancer risk in some epidemiological studies, adding another reason to favor physiological over supraphysiological dosing.Why 125mg Represents the "Sweet Spot" for TRT
The Bhasin study provides compelling evidence that 125mg of testosterone enanthate weekly represents an optimal balance between efficacy and safety for testosterone replacement therapy. Consider the following:1. Testosterone Levels in the High-Normal Range: The 125mg dose produced nadir testosterone levels of 542 ng/dL, placing men in the upper-normal physiological range. This is consistent with levels seen in healthy young men and aligns with current clinical targets for TRT (500-700 ng/dL trough).
2. Statistically Significant Body Composition Benefits: Unlike lower doses, 125mg produced meaningful improvements in fat-free mass (+3.4 kg) and reductions in fat mass—benefits that matter for metabolic health, functional capacity, and quality of life.
3. Minimal Adverse Effects: At 125mg, increases in hemoglobin, decreases in HDL, and elevations in IGF-1 were modest and clinically manageable. The 2005 companion study in older men specifically identified 125mg as providing "the best trade-off... associated with high normal testosterone levels, low frequency of adverse events, and significant gains in fat-free mass and muscle strength."
4. The Threshold Effect: The data clearly show that 25mg and 50mg weekly are insufficient for producing anabolic benefits—these doses merely prevent severe hypogonadism without optimizing body composition. For men seeking the benefits of TRT, underdosing represents a missed opportunity.
Clinical Applications: Translating Research to Practice
Starting Dose Recommendations
Based on the Bhasin data, 100-125mg of testosterone cypionate or enanthate weekly represents a reasonable starting dose for most men initiating TRT. This dose:• Achieves high-normal testosterone levels
• Produces statistically significant improvements in body composition
• Minimizes the risk of supraphysiological exposure and associated adverse effects
• Provides a baseline from which to adjust based on individual response
Individual Variability Requires Monitoring
The study reports mean values, but individual responses varied considerably. Some men achieved much higher or lower testosterone levels than average at the same dose due to differences in absorption, metabolism, SHBG levels, and other factors. This underscores the importance of checking actual testosterone levels (ideally trough values) after initiating therapy and adjusting the dose to achieve target levels rather than treating based on a fixed dose.Injection Frequency Considerations
The Bhasin study used once-weekly injections. However, modern TRT practice increasingly favors twice-weekly or even more frequent injections to minimize peak-to-trough fluctuations and maintain more stable testosterone levels. A man receiving 125mg weekly could alternatively inject 62.5mg twice weekly or 40-42mg every other day, potentially achieving better symptom control with fewer side effects related to hormonal peaks and troughs.Conclusion: The Enduring Relevance of the Bhasin Dose-Response Data
More than two decades after publication, the Bhasin testosterone dose-response study remains the definitive reference for understanding how testosterone dose affects body composition, strength, and safety parameters. Its findings have stood the test of time and continue to inform evidence-based TRT practice.The key takeaways for men considering or currently on TRT:
• 125mg weekly is the minimum dose for significant body composition benefits —lower doses may not produce meaningful improvements despite achieving "normal" testosterone levels
• More is not always better —supraphysiological doses (300-600mg weekly) produce greater muscle gains but at the cost of increased adverse effects
• Different outcomes have different dose-response curves —sexual function may plateau at lower doses than required for optimal body composition
• Individual monitoring is essential —actual testosterone levels matter more than the dose administered
For clinicians and patients seeking to optimize TRT outcomes while minimizing risks, the 125mg weekly dose (or its equivalent with other formulations and injection frequencies) represents a scientifically grounded starting point—the threshold at which testosterone replacement truly becomes testosterone optimization.
Related ExcelMale Forum Discussions
Explore these community discussions for additional insights:• Responses of Different Doses of Testosterone Injections on Body Composition, Strength, etc. – Original thread with study summary and graphs
• Effect of Low and High Doses of Testosterone Injections on Hematocrit, PSA and HDL – Deep dive into safety parameters at different doses
• What is the Optimum TRT Dose for Muscle Growth? Nelson Vergel Reviews the Data – Video discussion of optimal dosing strategies
• How to Predict Estradiol and DHT at Different Testosterone Doses – Predictive modeling for hormone metabolites
• The 12-Year-Old Study That Proves Testosterone Injections Every Two Weeks Fail – Why injection frequency matters as much as dose
• How Long Does Testosterone Take to Show Effects? – Timeline expectations for TRT benefits
Key References
1. Bhasin S, Woodhouse L, Casaburi R, et al. Testosterone dose-response relationships in healthy young men. Am J Physiol Endocrinol Metab. 2001;281(6):E1172-E1181. [PubMed]2. Bhasin S, Woodhouse L, Casaburi R, et al. Older men are as responsive as young men to the anabolic effects of graded doses of testosterone on the skeletal muscle. J Clin Endocrinol Metab. 2005;90(2):678-688. [PubMed]
3. Sinha-Hikim I, Artaza J, Woodhouse L, et al. Testosterone-induced increase in muscle size in healthy young men is associated with muscle fiber hypertrophy. Am J Physiol Endocrinol Metab. 2002;283(1):E154-E164. [PubMed]
4. Sinha-Hikim I, Cornford M, Gaytan H, et al. Effects of testosterone supplementation on skeletal muscle fiber hypertrophy and satellite cells in community-dwelling older men. J Clin Endocrinol Metab. 2006;91(8):3024-3033. [PubMed]
5. Pharmacology of testosterone replacement therapy preparations. Transl Androl Urol. 2016;5(6):834-843. [PMC Full Text]
6. Full text of original study. American Physiological Society. [Journal Full Text]
Disclaimer: This article is for informational purposes only and does not constitute medical advice. Testosterone replacement therapy requires a prescription and should be supervised by a qualified healthcare provider. Individual responses to therapy vary, and treatment decisions should be made in consultation with your physician based on your specific clinical circumstances.
About ExcelMale.com: ExcelMale is a men's health forum with over 24,000 members and 20+ years of archived discussions on testosterone replacement therapy, hormone optimization, and sexual health. Founded by Nelson Vergel, author of Testosterone: A Man's Guide and Beyond Testosterone, ExcelMale provides evidence-based information and peer support for men navigating hormone health decisions.
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