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Does Hormone Therapy Prevent Muscle Loss in Women? CME / ABIM MOC / CE

News Author: Diana Phillips; CME Author: Charles P. Vega, MD

Posted: 10/25/2019

Clinical Context

Many women have turned against hormone therapy (HT) during menopause, based on the results of studies such as the Women’s Health Initiative. But are these individuals denying themselves an opportunity to improve health-related quality of life (HRQOL) through HT? A previous study by Hess and colleagues, published in the May-June 2008 issue of Menopause, assessed the effects of HT on HRQOL.[1]

The study followed 3102 women over the course of 6 years, 813 of whom initiated HT during this time. Poor emotional and physical functioning during the study period was associated with a lower likelihood of initiating HT. Moreover, the average physical function score declined after initiating HT. In a subgroup analysis, women who reported frequent symptoms before HT had superior outcomes for vitality compared with other women who initiated HT.

The average rate of loss of muscle mass among women older than 50 years is estimated to be approximately 1% annually. Resistance training can protect muscle mass during menopause, but it is unclear what role HT might have in preserving muscle mass. The current meta-analysis addresses this issue.

Study Synopsis and Perspective

HT neither contributes to nor prevents changes in muscle strength in postmenopausal women, a systematic review and meta-analysis has found.[2]

«The small potential benefit for maintaining muscle mass in the general population of postmenopausal women likely does not outweigh the potential risks of prolonged HT,» the researchers write.

Some studies suggest HT may protect against age-related decline in muscle mass and strength or sarcopenia in menopausal and postmenopausal women, on the basis of the hypothesis that declining estrogen levels during the menopause transition accelerate the assault on lean body mass.

Ayesha A. Javed, MS, from the McMaster Institute for Research on Aging at McMaster University in Hamilton, Ontario, Canada, and colleagues conducted a systematic review and meta-analysis of randomized clinical trials comparing postmenopausal women undergoing HT (estrogen only or a combination of estrogen and progesterone) and women not receiving HT. The findings, reported online today in JAMA Network Open, are highly variable but overall indicate no statistically significant difference in lean body mass (LBM) changes between the treatment and control groups.

In total, the analysis included 12 studies comprising 4474 participants (mean age, 59 years). The median duration of follow-up was 2 years. Treatment varied by duration (ranging from 9 to 25 days per month to more than 8 years), formulation (15 of the 22 treatment groups used estrogen-progesterone combination therapy and 7 used estrogen only), and dosage.

The primary outcome of interest was change in LBM. Subgroup analyses looked at between-group differences on the basis of HT type and dosage, duration of follow-up, time since menopause, study quality, and type of LBM measurement.

The main effect analysis showed that across all studies, HT was associated with a nonstatistically significant loss of 0.06 kg less LBM (95% confidence interval [CI], −0.05 to 0.18 kg) compared with the control group.

Similarly, the between-group differences observed in the subgroup analyses did not achieve statistical significance. Specifically, the between-group comparisons showed the following differences in LBM changes:

  • Stratified by therapy type and dosage, HT users lost 0.06 kg more to 0.19 kg less LBM than nonusers.
  • Stratified by duration of follow-up, HT users lost 0.0 to 0.10 kg less LBM than nonusers.
  • Stratified by time since menopause, HT users lost 0.01 to 0.13 kg less LBM than nonusers.
  • Stratified by study quality, HT users lost 0.04 to 0.20 kg less LBM than nonusers.
  • Stratified by type of LBM measurement, HT users lost 0.06 to 0.07 kg less LBM than nonusers.

The nonsignificant reduction in lost LBM observed in the treatment group «is unlikely to be clinically relevant for the average postmenopausal woman,» the authors write.

Women older than 50 years are reported to lose approximately 1% of muscle mass each year, the researchers say. «At this rate, it would take approximately 66 years for a woman of average height and LBM to become sarcopenic according to the cutoff of 7.4 kg/m2 recommended by the European Working Group on Sarcopenia.»

In addition, with respect to the slight increase in sarcopenia-free time associated with treatment, «most women would not live long enough to experience these additional sarcopenia-free years,» the authors stress.

Although it is possible that HT could be beneficial to women with lower muscle mass at baseline, «to our knowledge, no research in this specific population has been conducted,» the authors write.

The study findings are limited by the high risk for bias in many of the studies, the authors write. Despite these limitations, however, «the results of this review remained consistent across subgroups, indicating that the overall body of literature has not shown a meaningful association between HT and muscle mass,» they note.

Given the importance of muscle retention in aging women, interventions other than HT should be investigated, the authors explain. «Further work is also required to determine whether HT is beneficial to muscle strength or function,» they state, noting that muscle strength plays a bigger role in health outcomes than muscle mass.

One study author holds a Tier 1 Canada Research Chair in Geroscience and the Raymond and Margaret Labarge Chair in Research and Knowledge Application for Optimal Aging. The remaining authors have disclosed no relevant financial relationships.

JAMA Network Open. Published online August 28, 2019.

Study Highlights

  • Researchers assessed randomized clinical trials of HT (either estrogen-progesterone or estrogen-only) among community-dwelling women at least 50 years of age.
  • The primary outcome was the effect of HT on lean body mass. Lean body mass could be assessed in different ways, including bioelectrical impedance analysis, dual energy X-ray absorptiometry, or magnetic resonance imaging.
  • Researchers selected 21 studies for full-text review from a total of 8961 articles, and 12 studies with a total of 4474 women were included in the meta-analysis, 6 studies that were conducted in Europe and 6 in the United States. Estrogen-progesterone was assessed twice as often as estrogen-only HT.
  • Overall, the body of research was judged to be at risk for publication bias, and the overall quality of the collected research was low.
  • The average reduction in lean body mass in comparing the HT and control groups was 0.06 kg (95% CI, −0.05 to 0.18 kg).
  • This nonsignificant result was reaffirmed on multiple subgroup analyses, including analyses based on the type of HT, duration of follow-up, time in menopause, and means to measure lean body mass. Study quality also failed to significantly alter the overall negative study outcome.

Clinical Implications

  • A previous study found that women with lower HRQOL scores were less likely to initiate HT, and HT generally did not improve HRQOL among initiators.
  • The current study finds that HT does not improve lean body mass among women older than 50 years, regardless of the type of HT used or time in menopause.
  • Implications for the Healthcare Team: HT can improve vasomotor symptoms of menopause, but has limited utility for other outcomes. The healthcare team should advise women about these limitations before prescribing HT.

Earn Credit



  1. Hess R, Colvin A, Avis NE, et al. The impact of hormone therapy on health-related quality of life: longitudinal results from the Study of Women’s Health Across the Nation. Menopause. 2008;15(3):422-428. Accessed August 28, 2019.
  2. Javed AA, Mayhew AJ, Shea AK, Raina P. Association between hormone therapy and muscle mass in postmenopausal women: a systematic review and meta-analysis. JAMA Netw Open. 2019;2(8):e1910154. Accessed August 28, 2019.