Effects of hormone replacement therapy and high-impact physical exercise on skeletal muscle in post-menopausal women: a randomized placebo-controlled study

Abstract

An age-related decline in muscle performance is a known risk factor for falling, fracture and disability. In women, a clear deterioration is observed from early menopause. The effect of hormone replacement therapy (HRT) in preserving muscle performance is, however, unclear. This trial examined the effects of a 12-month HRT and high-impact physical exercise regimen on skeletal muscle in women in early menopause. A total of 80 women aged 50-57 years were assigned randomly to one of four groups: exercise (Ex), HRT, exercise+HRT (ExHRT) and control (Co). The exercise groups participated in a high-impact training programme. The administration of HRT (oestradiol/noretisterone acetate) or placebo was carried out double-blind. Knee extension torque and vertical jumping height were evaluated. Lean tissue cross-sectional area (LCSA) and the relative proportion of fat within the muscle compartment were measured for the quadriceps and lower leg muscles. The ExHRT group showed significant increases in knee extension torque (8.3%) and vertical jumping height (17.2%) when compared with the Co group (-7.2%). Vertical jumping height also increased after HRT alone (6.8%). The LCSA of the quadriceps was increased significantly in the HRT (6.3%) and ExHRT (7.1%) groups when compared with the Ex (2.2%) and Co (0.7%) groups. Lower leg LCSA was also increased in the ExHRT group (9.1%) when compared with the Ex (3.0%) and Co (4.1%) groups. In addition, the increase in the relative proportion of fat in the quadriceps in the Co group (16.6%) was significant compared with those in the HRT (4.9%) and ExHRT (-0.6%) groups. Thus, in post-menopausal women, muscle performance, muscle mass and muscle composition are improved by HRT. The beneficial effects of HRT combined with high-impact physical training may exceed those of HRT alone.

Muscular Transcriptome in Postmenopausal Women With or Without Hormone Replacement

“…We have previously reported, in a larger study with the same study subjects, that leg extensor power, assessed by vertical jumping height, 23 and thigh muscle mass increased upon the use of HRT compared to the non-HRT group, where they decreased. 14 Parallel results were obtained with the smaller study sample used in microarray analysis, albeit the functional measurements did not reach statistical significance. Together these results suggest that during early postmenopause, when there is no counteracting medication available, the muscle transcriptome shows notable change; this, in turn, may be related to the deterioration in muscle characteristics in later life.…”

“…14 The study sample was taken from postmenopausal women aged 50-57 years living in the city of Jyväskylä, Finland. Initially 118 women eligible for the study were invited for a clinical examination to assess hormonal menopausal status via serum steroid measurements (DELFIA, Wallac).…”

“…Some of the randomized, controlled trials in postmenopausal women have shown increased muscle mass and/or strength after hormone replacement therapy (HRT), [13][14][15][16] whereas others have failed to…”

Circulating miR-21, miR-146a and Fas ligand respond to postmenopausal estrogen-based hormone replacement therapy – A study with monozygotic twin pairs

“…ERs are also found in the skeletal muscle cells, making skeletal muscle tissue responsive to estrogens (Lemoine, et al 2003, Wiik, et al 2005). There are indications that dramatically decreasing level of circulating 17β-estradiol (E 2 ) at the time of menopause contributes to age-associated muscle weakness (Phillips, et al 1993, Sipila, et al 2001. Our previous studies have shown that the use of estrogen-or estrogen and progesterone -based hormone replacement therapy (HRT) is associated with better muscle quality properties, such as a positive muscle-fat ratio within the muscle compartment, as well as improved muscle performance characteristics like muscle power and mobility (Ronkainen, et al 2009, Finni, et al 2011.…”

Hormone Replacement Therapy Associated White Blood Cell DNA Methylation and Gene Expression are Associated With Within-Pair Differences of Body Adiposity and Bone Mass

“…Aging is typically associated with deterioration of bone properties, reduced skeletal muscle mass and increased ectopic fat accumulation, which affect muscle quality and function. E2 deprivation has been shown to result in gain of fat mass and loss of fat free mass (Shea et al, 2015) as well as in increased risk for osteoporotic changes (Riggs, Khosla, & Melton, 2002;Szulc et al, 2006) while postmenopausal HRT partially counteracts aging related musculoskeletal deteriorations (Cheng et al, 2002;Komulainen et al, 1999;Sipilä et al, 2001;Taaffe et al, 2005). However, there is considerable variation in response to HRT between individuals, which can be partly explained by genetic factors (Langdahl, 2009).…”