What is the Optimum TRT Dose for Muscle Growth? : Nelson Vergel Reviews the Data

Landmark Study Reveals How Different Testosterone Doses Affect Muscle, Fat, and Health Markers in Young Men

A deep dive into one of the most influential studies on testosterone dosing reveals key takeaways for anyone interested in hormone optimization—a topic of persistent debate in men's health communities and clinics alike.

Background and Study Design

In 2001, a seminal paper was published in the American Journal of Physiology, Endocrinology and Metabolism. Dr. Shalender Bhasin and colleagues—considered among the top experts on androgens—sought to answer a fundamental question: What are the effects of different weekly testosterone doses on strength, body composition, and key health markers in healthy young men?

The research team recruited approximately 65 men, average age 25, all generally healthy and fit. Each participant’s natural testosterone production was first suppressed with a medication, then replaced in varying increments—25, 50, 125, 300, or 600 mg per week of testosterone cypionate injections for 20 consecutive weeks.

Critically, participants were instructed not to exercise during the study, and their caloric and protein intake was monitored to ensure changes resulted solely from hormone adjustments[1].

Main Findings

Serum Testosterone Levels

25 mg/week: Levels dropped well below baseline; insufficient for replacement.​

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50 mg/week: Some increase, but still suboptimal.​

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125 mg/week: Returned testosterone to baseline (pre-suppression) levels for these young men.​

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300–600 mg/week: Produced supraphysiological levels—common in bodybuilding circles[1].​

Body Composition

Lean Mass (Fat-Free Mass): Significant increases began at 100–125 mg/week and continued at higher doses. These gains were recorded despite no exercise, confirming testosterone’s powerful anabolic potential.​

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Fat Mass: Doses of 100–125 mg/week and above led to reductions in fat mass. Lower doses (25–50 mg/week) paradoxically increased fat mass, suggesting underdosing may be counterproductive[1].​

Muscle Volume and Strength

Thigh and quadriceps volume, measured by MRI, significantly increased at 125 mg/week and higher. Leg press strength and power only improved at high doses (300–600 mg/week)[1].

IGF-1 and Growth Factors

Doses below 125 mg/week did not increase IGF-1. Only high, bodybuilding-type doses (300–600 mg/week) led to statistically significant increases—raising interesting questions about synergy with exercise, which was not tested in this trial[1].

Sexual Function and Libido

Overall, no significant enhancements in sexual activity or libido were noted, regardless of dose. Minor fluctuations occurred, but neither sexual frequency nor desire reached statistical significance. It’s worth noting subjects first received a testosterone blocker before hormone administration, potentially influencing these endpoints[1].

Blood Markers and Safety

Hematocrit and Hemoglobin: Both rose substantially with higher doses, reflecting increased red blood cell mass—a potential cardiovascular risk at extreme levels.​

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HDL Cholesterol: “Good” cholesterol (HDL) decreased in a dose-dependent manner, also raising potential long-term cardiovascular concerns.​

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Prostate-Specific Antigen (PSA): No major changes were observed, likely due to participants’ young age[1].​

Key Practical Insights

• 100–125 mg/week appears optimal for returning serum testosterone and body composition to healthy levels in young adults after suppression.
• Underdosing (25–50 mg/week) is not effective and may increase fat mass.
• Bodybuilding-level doses (300–600 mg/week) yield dramatic increases in testosterone, IGF-1, lean mass, and strength, but at the expense of cardiovascular risk markers like elevated hematocrit and reduced HDL.
• Sexual and cognitive function do not significantly increase simply by raising testosterone above baseline, at least in healthy young men[1].

Study Limitations and Final Thoughts

This remains one of the most comprehensive testosterone dose-response studies to date, especially given its use of direct hormone suppression followed by graded repletion and rigorous controls on diet and exercise. However, its sample was limited to healthy, non-obese men in their 20s who did not work out during the protocol. Results may differ in older or overweight men, or those actively engaged in resistance training.

Studies of this rigor and scope are rare—and, given regulatory and ethical barriers, may not be repeated soon. For clinicians and men considering testosterone therapy, this data offers a rare, data-driven roadmap for setting rational expectations and weighing benefits against potential risks[1].

More details: Responses of different doses of testosterone injections on body composition, strength, etc. - Excel Male TRT Forum

 

Briefing Document: Testosterone Dose-Response Relationships in Healthy Young Men​

Source: Bhasin, S., Woodhouse, L., Casaburi, R., et al. (2001). "Testosterone dose-response relationships in healthy young men." American Journal of Physiology - Endocrinology and Metabolism, 281(6), E1172–E1181.

Date of Publication: December 2001

Lead Author/Institution: Shalender Bhasin, Division of Endocrinology, Metabolism, and Molecular Medicine, Charles R. Drew University of Medicine and Science, Los Angeles.

Executive Summary​

This study investigated the dose-dependent effects of testosterone on various physiological processes in healthy young men. By suppressing endogenous testosterone and administering graded doses of testosterone enanthate, researchers established different circulating testosterone levels ranging from subphysiological to supraphysiological. The study found a clear dose- and concentration-dependent relationship between testosterone and changes in fat-free mass, muscle size, strength, power, fat mass, hemoglobin, and IGF-I levels. Conversely, sexual function, visual-spatial cognition, mood, and prostate-specific antigen (PSA) levels did not show significant dose-dependent changes, with some of these functions being maintained even at lower testosterone doses. This indicates that "different androgen-dependent processes have different testosterone dose-response relationships." The study also notes that doses leading to significant muscle gains were associated with reductions in plasma HDL cholesterol, highlighting a potential trade-off between anabolic effects and cardiovascular risk.

Key Findings and Main Themes​

1. Dose-Dependent Effects on Body Composition and Muscle Performance:

• Fat-Free Mass (FFM) and Muscle Size: FFM "increased dose dependently in men receiving 125, 300, or 600 mg of testosterone weekly (change ±3.4, 5.2, and 7.9 kg, respectively)." Changes in FFM were "highly dependent on testosterone dose (P = 0.0001) and correlated with log testosterone concentrations (r = 0.73, P = 0.0001)." Similar dose-dependent increases were observed in thigh muscle and quadriceps muscle volumes. The relationship for FFM and muscle size conformed to a "single log-linear dose-response curve," rather than two separate curves for hypogonadal and supraphysiological ranges.
• Muscle Strength and Power: Leg press strength and leg power also increased in a dose-dependent manner, particularly at the 300-mg and 600-mg doses. Changes in leg press strength correlated with log testosterone levels (r = 0.48, P = 0.0005) and changes in muscle volume and FFM.
• Fat Mass: Fat mass "increased significantly in men receiving the 25- and 50-mg doses but did not change in men receiving the higher doses of testosterone." There was an "inverse correlation between change in fat mass... and log testosterone concentrations (r = -0.60, P = 0.0001)."

1. Differential Dose-Response Relationships for Various Androgen-Dependent Processes:

• Sexual Function, Cognition, and Mood: "Sexual function, visual-spatial cognition and mood, and PSA levels did not change significantly at any dose." This implies that "serum testosterone concentrations at the lower end of male range can maintain some aspects of sexual function."
• Prostate-Specific Antigen (PSA): PSA levels "did not change significantly at any dose," suggesting that even lower doses of testosterone were sufficient to maintain PSA within normal ranges in these eugonadal men. The study did not measure prostate volume.
• Hemoglobin: Hemoglobin levels "decreased significantly in men receiving the 50-mg dose but increased at the 600-mg dose; the changes in hemoglobin were positively correlated with testosterone concentrations (r = 0.66, P = 0.0001)."
• Plasma Lipids (HDL Cholesterol): Changes in plasma HDL cholesterol were "negatively dependent on testosterone dose (P = 0.0049) and correlated with testosterone concentrations (r = -0.40, P = 0.0054)." This is a significant finding regarding potential cardiovascular risk.
• Insulin-like Growth Factor I (IGF-I): IGF-I concentrations "increased dose dependently at the 300- and 600-mg doses (correlation between log testosterone level and change in IGF-I = 0.55, P = 0.0001)."

1. Study Design and Methodology:

• Participants: 61 healthy eugonadal men, aged 18-35 years, with prior weight-lifting experience. 54 completed the study.
• Intervention: Participants received monthly injections of a GnRH agonist to suppress endogenous testosterone, plus weekly intramuscular injections of testosterone enanthate at doses of 25, 50, 125, 300, or 600 mg for 20 weeks.
• Standardization: Energy and protein intakes were standardized, and participants were instructed "not to undertake strength training or moderate-to-heavy endurance exercise during the study" to isolate the effects of testosterone.
• Outcome Measures: Body composition (underwater weighing, DEXA), muscle size (MRI), strength (leg press 1-RM), power (Nottingham leg extensor power rig), sexual function (daily logs), cognitive function (computerized checkerboard test), mood scales, blood counts, plasma lipids, PSA, and various hormone levels.
• Testosterone Levels Achieved: Mean nadir testosterone concentrations ranged from 253 ng/dl (25 mg dose) to 2,370 ng/dl (600 mg dose), demonstrating successful manipulation of testosterone levels across a wide range.

1. Implications and Future Directions:

• The study clarifies that "different androgen-dependent processes have different testosterone dose-response relationships." This information is crucial for optimizing testosterone replacement regimens for hypogonadal men and for potential uses in sarcopenia.
• A significant trade-off was observed: "Testosterone doses associated with significant gains in fat-free mass, muscle size, and strength were associated with significant reductions in plasma HDL concentrations."
• The authors highlight the need for "further studies... to determine whether clinically significant anabolic effects of testosterone can be achieved without adversely affecting cardiovascular risk."
• The findings support the development of "Selective androgen receptor modulators (SARMs) that preferentially augment muscle mass and strength, but only minimally affect prostate and cardiovascular risk factors."
• The study acknowledges limitations, including the measurement of nadir testosterone levels (fluctuations exist with weekly injections) and the lack of prostate volume measurements. It also questions whether responsiveness to testosterone is attenuated in older men and how other factors like nutritional status and exercise modulate the dose-response.

Critical Considerations​

• Generalizability: While rigorous, the study was conducted on healthy young men with prior weight-lifting experience. The findings may not directly apply to older men, sedentary individuals, or those with chronic illnesses, where testosterone dose-response relationships might differ.
• Long-term Effects: The study duration was 20 weeks. The "long-term effects of androgen administration on the prostate, cardiovascular risk, and behavior are unknown."
• Testosterone Delivery Method: Weekly injections lead to fluctuations in testosterone levels. The authors suggest that "sustained testosterone delivery by a patch or gel might reveal different dose-response relationships, particularly with respect to hemoglobin and HDL cholesterol."
• Individual Variability: Despite clear dose-dependent mean changes, "there was considerable heterogeneity in response to testosterone administration within each group," suggesting that individual factors (e.g., genetics, metabolism) play a role.

 

Nelson are you still progressing in the gym, you are jacked! I'm training 5 or 6 days per week and its tough.. going to failure and 6 to 16 sets per muscle per week.

 

FAQs on Testosterone Dosing and Effects​

What was the purpose and methodology of the 2001 study on testosterone dosing?​

The study, led by Dr. Bhasin and published in the American Journal of Physiology, aimed to determine the effects of different testosterone doses on young, healthy men. Researchers blocked the natural testosterone production of 65 participants (average age 25) and then administered weekly injections of testosterone cypionate at doses of 25 mg, 50 mg, 125 mg, 300 mg, and 600 mg for 20 weeks. Participants were specifically asked not to work out, and their food intake was monitored to ensure changes weren't due to diet. Various metrics were measured, including hormone levels (total and free testosterone, LH, SHBG, IGF-1), body composition (fat-free mass, fat mass), muscle volume, strength, sexual function, and blood work (hemoglobin, hematocrit, PSA, HDL).

How did different testosterone doses affect total and free testosterone levels?​

As expected, both total and free testosterone levels increased with higher doses of injected testosterone. Interestingly, the 25 mg per week dose actually led to a decrease in total testosterone from baseline (e.g., from ~593 to 253 ng/dL), indicating it was insufficient to replace natural production. A dose of 125 mg per week brought total testosterone back to approximate baseline levels. Doses of 300 mg and 600 mg per week resulted in significantly elevated total testosterone levels (1300-2300 ng/dL), far exceeding typical physiological ranges.

What impact did testosterone dosing have on body composition and muscle growth, even without exercise?​

The study showed significant improvements in fat-free mass (lean mass) and decreases in fat mass with increasing testosterone doses. Doses of 125 mg per week and above led to clear positive changes. Notably, the lower doses (25 mg and 50 mg) actually resulted in an increase in fat mass, suggesting that underdosing can be detrimental. MRI measurements of thigh and quad muscle volume also showed significant increases starting at the 125 mg dose, even though participants were not exercising. This highlights the powerful anabolic effects of testosterone itself.

Did different testosterone doses significantly impact sexual function and desire?​

The study's findings on sexual activity and desire were not statistically significant across the different doses. While some individual variations were observed, there wasn't a clear or strong correlation between testosterone dose and changes in sexual activity scores or intensity of sexual desire (libido). The small sample size per group (12 participants) might have contributed to this lack of statistical significance. It's important to remember that these were young men whose natural testosterone was blocked before treatment, which could also influence the observed sexual responses.

What were the effects of testosterone dosing on IGF-1 and strength markers?​

IGF-1 (insulin-like growth factor 1), a metabolite of growth hormone, did not show statistically significant changes at lower testosterone doses (25 mg, 50 mg, 125 mg). However, at higher, "bodybuilding" doses of 300 mg and 600 mg per week, a statistically significant increase in IGF-1 was observed. Regarding strength, leg press strength and leg power significantly increased at the 300 mg and 600 mg doses, even though the participants were explicitly instructed not to work out. This indicates that higher testosterone levels alone can improve strength.

What were the notable changes observed in blood markers, such as hemoglobin, hematocrit, and HDL cholesterol?​

Higher testosterone doses led to increases in hemoglobin and red blood cell count (hematocrit), which is a known effect of testosterone. The study notes ongoing debate about the "magic highest number" for hematocrit before cardiovascular issues arise. Critically, the "good" cholesterol, HDL, significantly decreased as the testosterone dose increased. The presenter highlights that the rise in hemoglobin/hematocrit and the decrease in HDL are "prices to pay" for higher doses, as they indicate an increased cardiovascular risk. PSA (Prostate-Specific Antigen) showed only minor, non-significant changes.

What is considered a "replacement" dose versus a "bodybuilding" dose based on this study?​

Based on this study, a weekly testosterone cypionate dose of approximately 100-125 mg was found to be effective in bringing total testosterone levels back to baseline in young men whose natural production was suppressed. This range could be considered a "replacement" or physiological dose. Doses of 300 mg and 600 mg per week are characterized as "bodybuilding" doses, as they significantly elevated total testosterone, IGF-1, muscle mass, and strength, beyond typical physiological replacement levels.

What are the main takeaways or limitations of this study?​

This study provides valuable insights into the dose-dependent effects of testosterone, particularly its anabolic effects on muscle and fat mass even without exercise. It highlights that underdosing (25-50 mg/week) can be counterproductive, while higher doses significantly improve strength and body composition but come with potential risks like decreased HDL and increased hematocrit. The study's limitations include its focus on young, healthy men (results may differ for older or less healthy populations), the relatively small sample size per dose group, and the unique methodology of blocking natural testosterone before administering exogenous doses. The presenter emphasizes that such a comprehensive study, especially with high doses, is unlikely to be replicated today due to ethical and logistical considerations.