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Summary

Javed et al. performed a systematic review and meta-analysis to determine whether menopausal hormone therapy (MHT) in postmenopausal women can reduce the age-related decline in lean body mass (LBM), as measured by dual-energy x-ray absorptiometry (DEXA), dual-photon absorptiometry, or bioelectrical impedance analysis [1]. The meta-analysis included twelve studies comprising 4474 postmenopausal women. The mean age of the participants was 59.0 (range 45-75) years, and the median follow-up duration was two years. Across all studies, participants who received MHT lost 0.06 kg (95% confidence interval, -0.05 to 0.18) less LBM than did those who did not receive MHT, but the difference was not statistically significant (p=0.26). The results remained unchanged when stratified based on: 1) MHT type and dosage (estrogen therapy or estrogen-progestogen therapy, equivalent to >=0.625 mg or <0.625 mg of conjugated equine estrogen), 2) duration of follow-up ( >=2 or <2 years), 3) time since menopause (<10 years, <5 years, or >=5 years), 4) study quality (fair/good or poor), 5) type of LBM measurement (DEXA or other). This systematic review and meta-analysis did not show a significant beneficial or detrimental association of MHT with muscle mass.

Commentary

Sarcopenia is defined as an age-related loss in muscle mass and strength [2]. The prevalence of sarcopenia in women increases from the fifth (37%) to sixth (57%) decades, suggesting a link between menopause and the pathogenesis of the condition [3]. Although the mechanism underlying the possible negative effect(s) of estrogen deficiency on the loss of muscle mass and strength has yet to be elucidated, both direct (through estrogen receptors expressed in skeletal muscle cells) and indirect (via increase in pro-inflammatory cytokine levels induced by rapid decline in circulating estrogen) pathways could be involved [2]. In line with this concept, menopausal hormone therapy has been shown to prevent postmenopausal muscle loss in women. A substudy of the estrogen plus progestin trial of the Womens Health Initiative reported that the women who received estrogen-progestin treatment lost less lean soft tissue mass than did women who received a placebo [4]. Including the study mentioned above, Javed et al. conducted the first-ever systematic review and meta-analysis of randomized clinical trials to determine whether MHT prevented postmenopausal muscle loss in women but failed to show its beneficial effects on muscle mass. Although MHT does not seem to be a promising treatment modality in preventing sarcopenia in women, there are still some questions that need answering. Do women with a lower muscle mass at baseline benefit more from MHT? Are there any synergistic effects of exercise and MHT in women? Is there any preferred regimen (sequential or continuous), route of administration (oral or transdermal), or type of progestogen to postpone muscle loss? One of the most critical questions is about the effect of MHT on muscle strength. A previous systematic review and meta-analysis of 23 pooled human studies with diverse types, dosages, and duration of MHT have shown small but significant beneficial effects in preserving skeletal muscle strength [5]. Further studies are warranted to specify the most effective type, dosage, and duration of MHT that protects postmenopausal women against the loss of muscle strength/function and, possibly, muscle mass.

Author(s)

  • Masakazu Terauchi
    Department of Women’s Health, Tokyo Medical and Dental University, Tokyo, Japan

Citations

  1. 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: e1910154.
    https://www.ncbi.nlm.nih.gov/pubmed/31461147
  2. Messier V, Rabasa-Lhoret R, Barbat-Artigas S, Elisha B, Karelis AD, Aubertin-Leheudre M.Menopause and sarcopenia: A potential role for sex hormones. Maturitas. 2011;68: 331-6.
    https://www.ncbi.nlm.nih.gov/pubmed/21353405
  3. Janssen I, Heymsfield SB, Ross R. Low relative skeletal muscle mass (sarcopenia) in older persons is associated with functional impairment and physical disability. J Am Geriatr Soc. 2002;50: 889-96.
    https://www.ncbi.nlm.nih.gov/pubmed/12028177
  4. Chen Z, Bassford T, Green SB, Cauley JA, Jackson RD, LaCroix AZ, Leboff M, Stefanick ML, Margolis KL. Postmenopausal hormone therapy and body composition – a substudy of the estrogen plus progestin trial of the Women’s Health Initiative. Am J Clin Nutr. 2005;82: 651-6.
    https://www.ncbi.nlm.nih.gov/pubmed/16155280
  5. Greising SM, Baltgalvis KA, Lowe DA, Warren GL. Hormone therapy and skeletal muscle strength: a meta-analysis. J Gerontol A Biol Sci Med Sci. 2009;64: 1071-81.
    https://www.ncbi.nlm.nih.gov/pubmed/19561145
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