Smith · The Journal of clinical endocrinology and metabolism 2014 · Randomized controlled trial with cross-sectional comparison · n=36

Testosterone and progesterone, but not estradiol, stimulate muscle protein synthesis in postmenopausal women.

Cited 126 times in the scientific literature.

Level 2 - randomized trial

Randomized controlled trial evaluating hormone interventions in postmenopausal women with a cross-sectional comparison group.

PubMed 24203065 · doi:10.1210/jc.2013-2835 · record verified 2026-08-29

What was done

Researchers measured the basal muscle protein fractional synthesis rate and skeletal muscle gene expression of growth-regulatory factors (MYOD1, MSTN, FST, FOXO3) in 12 healthy premenopausal women and 24 postmenopausal women matched for body mass, body composition, and insulin sensitivity. Postmenopausal women were studied before and after assignment to one of four parallel groups: testosterone, estradiol, progesterone, or no intervention (control).

What was found

Basal muscle protein fractional synthesis rate was approximately 20% faster, and MYOD1, FST, and FOXO3 mRNA expressions were approximately 40%-90% greater in postmenopausal compared to premenopausal women (all P < .05). In postmenopausal women, both testosterone and progesterone treatment increased muscle protein fractional synthesis rate by approximately 50% (both P < .01), whereas estradiol and control showed no change. Progesterone treatment increased MYOD1 mRNA expression (P < .05) without altering MSTN, FST, or FOXO3. Testosterone and estradiol treatments had no effect on MYOD1, MSTN, FST, or FOXO3 expression.

Why it matters

This study shows that testosterone and progesterone, but not estradiol, stimulate acute muscle protein synthesis in postmenopausal women. It suggests that age-related differences in female muscle protein turnover are not driven by menopause-related changes in circulating estradiol.

Limits

The total sample size was small (n=36 overall; n=6 per postmenopausal arm). The abstract does not disclose the specific doses, routes of administration, or treatment durations used, nor did it measure muscle protein breakdown or longitudinal functional outcomes.

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