Cited by 124Muscle metabolism and nutritionMuscle Physiology and DisordersHormonal and reproductive studies

The DOI matches its Crossref record; 65 of the 66 references it cites were found in a registry or an index; none of the 68 sources its claims cite is checked for support yet.

Testosterone and Progesterone, But Not Estradiol, Stimulate Muscle Protein Synthesis in Postmenopausal Women

Open access

Abstract

CONTEXT: The effect of the female sex steroids, estradiol and progesterone, on muscle protein turnover is unclear. Therefore, it is unknown whether the changes in the hormonal milieu throughout the life span in women contribute to the changes in muscle protein turnover and muscle mass (eg, age associated muscle loss). OBJECTIVE: The objective of this study was to provide a comprehensive evaluation of the effect of sex hormones on muscle protein synthesis and gene expression of growth-regulatory factors [ie, myogenic differentiation 1 (MYOD1), myostatin (MSTN), follistatin (FST), and forkhead box O3 (FOXO3)]. SUBJECTS AND DESIGN: We measured the basal rate of muscle protein synthesis and the expression of muscle growth-regulatory genes in 12 premenopausal women and four groups of postmenopausal women (n=24 total) who were studied before and after treatment with T, estradiol, or progesterone or no intervention (control group). All women were healthy, and pre- and postmenopausal women were carefully matched on body mass, body composition, and insulin sensitivity. RESULTS: The muscle protein fractional synthesis rate was approximately 20% faster, and MYOD1, FST, and FOXO3 mRNA expressions were approximately 40%-90% greater (all P<.05) in postmenopausal than premenopausal women. In postmenopausal women, both T and progesterone treatment increased the muscle protein fractional synthesis rate by approximately 50% (both P<.01), whereas it was not affected by estradiol treatment and was unchanged in the control group. Progesterone treatment increased MYOD1 mRNA expression (P<.05) but had no effect on MSTN, FST, and FOXO3 mRNA expression. T and estradiol treatment had no effect on skeletal muscle MYOD1, MSTN, FST, and FOXO3 mRNA expression. CONCLUSION: Muscle protein turnover is faster in older, postmenopausal women compared with younger, premenopausal women, but these age-related differences do not appear to be explained by the age- and menopause-related changes in the plasma sex hormone milieu.

Overview

AI snapshot

Written from the paper’s full text.

TL;DR

In healthy postmenopausal women, testosterone and progesterone treatment increased basal muscle protein synthesis, whereas estradiol did not. Postmenopausal women also had faster basal muscle protein synthesis and higher expression of several muscle growth-regulatory genes than matched premenopausal women.

Key findings

  • Muscle protein fractional synthesis rate (FSR) was approximately 20% faster in postmenopausal than premenopausal women (P = .02), and MYOD1, FST, and FOXO3 mRNA expression was approximately 40%–90% greater (all P < .05).
  • In postmenopausal women, testosterone and progesterone treatment each increased muscle protein FSR by approximately 50% (both P < .01), while estradiol treatment had no effect and the control group was unchanged.
  • Progesterone treatment increased MYOD1 mRNA expression (P < .05) but had no effect on MSTN, FST, or FOXO3; testosterone and estradiol had no effect on MYOD1, MSTN, FST, or FOXO3 mRNA expression.
  • The authors conclude that age- and menopause-related differences in basal muscle protein turnover in women do not appear to be explained by changes in the plasma sex hormone milieu.

Methods

  • Longitudinal, randomized, controlled study in 12 premenopausal and 24 postmenopausal sedentary, weight-stable women; postmenopausal women were randomized to control, testosterone, estradiol, or progesterone (n = 6 per group).
  • Basal mixed muscle protein FSR was measured with a 5-hour [5,5,5-²H₃]leucine infusion and quadriceps muscle biopsies at 120 and 300 minutes; muscle MYOD1, MSTN, FST, and FOXO3 mRNA expression was measured by real-time PCR.
  • Pre- vs postmenopausal comparisons used t tests or Mann-Whitney U tests; treatment effects used repeated-measures ANOVA with Tukey post hoc tests, and gene expression used Kruskal-Wallis with Bonferroni-corrected Mann-Whitney post hoc analyses.

Limitations

  • The paper states that muscle protein breakdown rates and changes in muscle mass were not measured, so it cannot determine whether progesterone-induced increases in synthesis produce net muscle protein gain or increased muscle mass.
  • The paper states that it cannot determine whether larger pharmacological estradiol doses, more prolonged treatment, or estradiol plus progesterone combination therapy would produce different outcomes; it also notes that the estradiol effect was so small (0.0003% ± 0.011%/h) that more than 50,000 subjects would be needed to detect it.
  • Evident from the text: each postmenopausal treatment group had only 6 women, treatment durations were relatively short (21 days for testosterone; intermittent active treatment over about 71 days for estradiol and progesterone), and participants were healthy, sedentary, weight-stable women, which may limit generalizability.

Model-written summary. Check it against the paper before relying on it.

Integrity signals

Registry

Crossref · 10.1210/jc.2013-2835

Cites

65 of 65 references verified0 citation errors · 0 not checkable

Statistics

Nothing to recompute.

Verification

Claims the paper makes

0 of 68 cited sources checked · 0 supported · 0 flagged

Show all 39 claims

  • Probably not a substantial claim. 20
  • It may state two separate claims as one. 22
  • The quote only partly states this claim. 2
37 of 37
  • The paper relies on this without support.

    Muscle mass is determined by the balance between muscle protein synthesis and breakdown, so a higher synthesis rate with declining muscle mass implies increased breakdown.

    “our data from young, premenopausal vs older, postmenopausal women (greater synthesis rate in old compared with young women) and the well-established decline in muscle mass with aging (59 -61) indicate that older women must (by deduction) also have an increased rate of muscle protein breakdown.”
  • The paper relies on this without support.

    Changes in mRNA expression of catabolic genes (FOXO3 and MuRF1) reflect changes in muscle protein breakdown rate.

    “we (present study) and others (44) have observed an age-related upregulation of catabolic genes (ie, FOXO3 and MuRF1 mRNA expression) in muscle that supports this concept and helps explain the ageassociated loss of muscle mass in the face of an increased muscle protein synthesis rate.”
  • The paper relies on this without support.

    Increased MYOD1 mRNA expression reflects increased satellite cell activation.

    “Increased progesterone-induced MYOD1 expression suggests increased satellite cell activation may play a role in this observation.”
3 of 3

Claims other papers make about this one

Each is checked against this paper’s own text: does it say what the citing paper says it does?

Self-check

Percentages, sums and reported differences re-computed from the paper’s own numbers.

Each contradiction between two passages listed here was confirmed by an independent check.

  • IGF-I mass-concentration units differ between tables

    Minor

    Table 1 gives IGF-I concentrations in ng/dL, while Table 2 gives comparable baseline concentrations in ng/mL. Those units differ by a factor of 100, without a corresponding difference in the reported concentrations.

  • Cortisol mass-concentration units differ between tables

    Minor

    Table 1 labels baseline cortisol concentrations in ng/dl, whereas Table 2 labels concentrations for the same study population in ng/mL. The similar numerical values and nM concentrations do not reflect a 100-fold unit change.

  • IGF-BP3 mass-concentration units differ between tables

    Minor

    Table 1 labels IGF-BP3 concentrations in ng/dL, but Table 2 labels comparable baseline concentrations in ng/mL. The numerical values are on the same scale despite the 100-fold difference between those units.

3 of 3

Citations

Cites

Flagged first, then by citations

Show all 66 references

1 of the 66 references couldn’t be matched to a known paper.

Cited by

Sorted by citations

Items 101–124 of 124

Metadata

Authors
Smith, G. I., Yoshino, J., Reeds, D. N., Bradley, D., Burrows, R. E., Heisey, H. D., Moseley, A. C., & Mittendorfer, B.
Affiliations
Washington University in St. Louis (US)
Corresponding author
Mittendorfer, Bettina
Venue
The Journal of Clinical Endocrinology & Metabolism
Published
2014-01
Volume
99
Issue
1
Pages
256-265
ISSN
  • 0021-972X (ISSN-L)
  • 1945-7197
OpenAlex
W1984814458
Cited by
124
References
66
Citations by year
2026: 9 · 2025: 16 · 2024: 11 · 2023: 13 · 2022: 10 · 2021: 13 · 2020: 11 · 2019: 11 · 2018: 7 · 2017: 5 · 2016: 10 · 2015: 3 · 2014: 4
FWCI
3.29
Type
journal article
Language
en
Open access
Locations
  • The Journal of Clinical Endocrinology & Metabolism (publishedVersion)
  • Europe PMC (PubMed Central) (publishedVersion)
  • PubMed Central (publishedVersion)
  • PubMed (publishedVersion)
Funders
  • National Institutes of Health (KL2TR000450, 5p41rr000954-34, UL1TR000448)
  • National Heart, Lung, and Blood Institute (T32HL007456)
  • National Institute of Diabetes and Digestive and Kidney Diseases (DK-94483, DK56341, R01DK094483, P30DK056341)
  • National Center for Research Resources (P41-RR000954, RR024994, RR-024992, RR 00954, KL2RR024994, UL1RR024992)
  • National Center for Advancing Translational Sciences
  • Eunice Kennedy Shriver National Institute of Child Health and Human Development (P50HD057796, HD57796)
Topics
  • Health Sciences › Nursing › Nutrition and Dietetics › Muscle metabolism and nutrition
  • Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › Muscle Physiology and Disorders
  • Health Sciences › Medicine › Endocrinology, Diabetes and Metabolism › Hormonal and reproductive studies
Keywords
muscle protein synthesis, postmenopausal women, testosterone, progesterone, estradiol, sex hormones, muscle protein turnover, myostatin, follistatin, FOXO3, age-related muscle loss, skeletal muscle
MeSH terms
Adult, Blood Glucose, Body Composition, Estradiol, Female, Humans, Insulin, Middle Aged, Muscle Proteins, Progesterone, Testosterone, Gene Expression, Premenopause, Postmenopause, Muscle, Skeletal

About these checks

Registry, retraction, Cites and statistics results are computed, not judged, with one exception: a printed reference that no index lists is read once by a model before it counts as a citation error. Claims are extracted by a model and kept only when their quote appears verbatim in the text; each cited source is then checked, with a model’s help, for whether it says what the claim relies on. Those verdicts can be wrong — read the claim’s quote and the cited source before relying on one.

A language model drew the claims from the paper on 2026-10-09, under version 3 of the claim definition (model deepseek-v4.1-flash, prompt extract-v3).

A second model labelled each claim on 2026-10-09 (model jev-1.13-20260917, definition revision gold-guideline-v0.2).

Statistics and arithmetic are recomputed, not judged.

Confidence bands are shown only for fields calibrated on our annotated test set. None is calibrated yet, so no band is shown.

What counts as a claim ›How we measure confidence ›How we check this ›

Are you an author, or do you see a problem with this page? Request a review