← All studies
New England Journal of Medicine / AJP-Endocrinology · 1996 / 2001Muscle & body composition

Testosterone dose–response relationships in healthy young men

Bhasin et al. suppressed endogenous production and assigned healthy men to graded weekly testosterone doses. The controlled design helped isolate how circulating testosterone relates to lean mass, fat mass, strength and physical power.

Bhasin S. et al.Open the publication DOI: 10.1152/ajpendo.2001.281.6.E1172

Design

Controlled dose-response

Endogenous production suppressed

Doses

25–600 mg/week

Five graded weekly doses

Measured

Lean mass, strength, fat

Fat-free mass, leg strength and power

Result

Graded response

Gains rose across the dose range

Structured abstract

Method

Endogenous testosterone production was suppressed so that every participant started from the same place. Healthy men were then assigned to one of five graded weekly testosterone doses, so the resulting serum levels — and their effects — could be attributed to the dose rather than to individual differences.

Result

Fat-free mass increased progressively across the tested dose range. Leg strength and power rose with higher exposure, and fat mass decreased at the higher doses. The tissue effects did not plateau at the top of the ordinary physiological range.

Conclusion

Muscle and fat respond in proportion to how much hormone is actually circulating. The trials describe dose response; they do not define a universal treatment target and do not establish long-term safety at supraphysiological doses.

Why it matters

Fat-free mass and power rose across the graded weekly doses.

Study design

Same men, same conditions, only the dose changed

The design is tightly controlled because the starting point was set by the investigators rather than observed.

Step one

Suppression

The participants' own testosterone production was switched off, removing individual baseline differences from the comparison.

Step two

Five graded doses

Men were assigned to weekly doses from 25 mg to 600 mg, producing a wide and deliberately spaced range of serum levels.

Step three

Direct measurement

Fat-free mass, muscle size, leg strength and leg power were measured rather than inferred from how participants felt.

Body composition

Fat-free mass and fat mass

Function

Leg strength and leg power

Exposure

Serum testosterone per dose group

Duration

20 weeks of treatment

Five weekly doses, five different outcomes

The lowest doses did not simply do less — at the bottom of the range, men lost lean mass and gained body fat.

Fat-free mass

Progressive

Lean mass rose across the whole tested dose range, without plateauing inside the ordinary physiological range.

Leg strength and power

Rising

Strength and power increased with higher circulating testosterone.

Fat mass at higher doses

Falling

Fat mass decreased at the higher doses, completing the graded body-composition response.

The detailed per-dose figures used elsewhere on this site — including the mean on-treatment testosterone for each group — are shown in the dose-response graphic in the article library, drawn from the same publication.

Why the low-dose result matters most

The clinically interesting part of this experiment is not the top of the range but the bottom of it.

Low doses were not neutral in this trial

At the lowest doses, participants lost lean mass and gained body fat while still nominally being treated.

Lowest dose groups in the same trial

Tissue versus mood

Muscle and fat kept responding as exposure rose, whereas drive, mood and libido tend to level off within the ordinary range.

Interpretation across the wider literature

Why protocols differ

In this trial, body-composition response scaled with circulating level; it did not measure symptoms or long-term outcomes.

Practical reading of the dose-response curve

Clinical interpretation

Level, not label

In this trial, response tracked the level actually achieved rather than the fact of being treated, which may help explain why men on similar therapy respond differently.

It does not show which level is right for an individual man; that is a clinical judgement made with a physician.

None of this justifies supraphysiological dosing. The two highest arms are evidence about biology, not a protocol, and long-term safety at those levels was not established here.

Your own numbers

In this trial, response tracked the level reached.

Before any of this applies to you, the starting point has to be measured properly.

  • Total testosterone and SHBG by LC-MS/MS
  • Free testosterone calculated from both
  • Haematocrit as a baseline safety marker
  • A physician to set and review the target