A prolonged hiatus in postmenopausal HRT, does not nullify the therapy's positive impact on ageing related sarcopenia.

Gladys L Onambélé-Pearson,Hans Degens,Christopher I Morse,David J Tomlinson,Martha Asuncion Sánchez-Rodríguez

doi:10.1371/journal.pone.0250813

Gladys L Onambélé-Pearson, Hans Degens + Show 3 more

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https://doi.org/10.1371/journal.pone.0250813

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Abstract

BackgroundPrevious work suggest a positive skeletal muscle effect of hormone replacement therapy (HRT) on skeletal muscle characteristics This study aimed to quantify any continued positive effect of HRT even after a sustained hiatus in treatment, controlling for two key muscle modulation hormones: Estradiol (E2) and Tri-iodo-thyronine (T3).Method and findingsIn 61 untrained women (18-78yrs) stratified as pre-menopausal, post-menopausal without (No_HRT) and post-menopausal with (Used_HRT) HRT history, body composition, physical activity, serum E2 and T3 were assessed by dual energy x-ray absorptiometry, Baecke questionnaire and ELISA. Gastrocnemius medialis (GM) and tibialis anterior (TA) electromyographic profiles (mean power frequency (mPowerF)), isometric plantar-flexion (PF) and dorsi-flexion (DF) maximum voluntary contraction (MVC), rate of torque development (RTD), isokinetic MVC and muscle volume, were assessed using surface electromyography, dynamometry and ultrasonography. Muscle quality was quantified as MVC per unit muscle size. E2 and E2:T3 ratio were significantly lower in postmenopausal participants, and were positively correlated with RTD even after controlling for adiposity and/or age. Pre-menopausal females had greater MVC in 8/8 PF and 2/5 DF (23.7–98.1%; P<0.001–0.049) strength measures compared to No_HRT, but only 6/8 PF (17.4–42.3%; P<0.001–0.046) strength measures compared to Used_HRT. Notably, Used_HRT had significant higher MVC in 7 PF MVC (30.0%-37.7%; P = 0.006–0.031) measures than No_HRT, while premenopausal and Used_HRT had similar uncorrected muscle size or quality. In addition, this cross-sectional data suggest an annual reduction in GM muscle volume corrected for intra-muscular fat by 1.3% in No_HRT and only 0.5% in Used_HRT.ConclusionEven years after cessation of the therapy, a history of HRT is positively associated with negating the expected post-menopausal drop in muscle quantity and quality. Whilst mPowerF did not differ between groups, our work highlights positive associations between RTD against E2 and E2:T3. Notwithstanding our study limitation of single time point for blood sampling, our work is the first to illustrate an HRT attenuation of ageing-related decline in RTD. We infer from these data that high E2, even in the absence of high T3, may help maintain muscle contractile speed and quality. Thus our work is the first to points to markedly larger physiological reserves in women with a past history of HRT.

Highlights

Animal and human models have long shown that ageing is associated with a substantial slowing in contraction duration and half-relaxation time of skeletal muscle fibers [1]
It was hypothesized that: (1) Lower levels of E2 is linked to decreased muscle function, (2) Ageing is associated with perceptible decrements in T3 levels thereby modulating muscle activation profile and potentially indicating fiber type percentage shift towards a slow phenotype; (3) estradiol to Tri-iodo-thyronine ratio (i.e. E2:T3) is a useful endocrine modulator of skeletal muscle phenotype, (4) high body fat in the post-menopausal status alters muscle EMG profile and rate of torque development (RTD), likely through decreasing the fast-to-slow transition of fiber type) in older women
A Kruskal Wallis non-parametric ANOVA revealed a significant difference in age between pre vs post-menopausal women (P

Summary

Introduction

Animal and human models have long shown that ageing is associated with a substantial slowing in contraction duration and half-relaxation time of skeletal muscle fibers [1] These functional changes in the twitch parameters are accompanied with an increase in the relative proportion of slow type I fibers compared with fast type II fibers [1,2,3,4,5]. Two key observations were made: (1) anabolic androstenedione-doped human participants exhibit increased testosterone and subsequently estrogen levels, (2) anabolic androstenedione-doped human participants show significant increases in lean tissue content [11]. Previous work suggest a positive skeletal muscle effect of hormone replacement therapy (HRT) on skeletal muscle characteristics This study aimed to quantify any continued positive effect of HRT even after a sustained hiatus in treatment, controlling for two key muscle modulation hormones: Estradiol (E2) and Tri-iodo-thyronine (T3)

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