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

BACKGROUND: 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). METHOD AND FINDINGS: In 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. CONCLUSION: Even 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.