Mechanisms Behind Estrogen's Beneficial Effect on Muscle Strength in Females

Dawn A. Lowe; Kristen A. Baltgalvis; Sarah M. Greising

Disclosures

Exerc Sport Sci Rev. 2010;38(2):61-67. 

In This Article

Evidence that Estrogens are Beneficial to Muscle Strength in Women

The loss of skeletal muscle strength is an undesirable consequence of aging. This decrease in a muscle's ability to generate force is caused in part by age-induced muscle atrophy. However, force generation normalized for muscle size, referred to as specific force or muscle quality, also declines with age. Hurley's group, as part of the Baltimore Longitudinal Study on Aging, found that muscle quality was diminished in arm and leg muscles with age.[12] Moreover, they showed that some of these declines were different between men and women. Pointing toward sex hormones as the underlying cause of these gender differences are studies showing that women have an accelerated decline in strength around the time of menopause. For example, whereas men had gradual decreases in knee extensor and handgrip strength between 20 and 80 yr of age, women had a steep decline after the age of 55 yr.[25] Similarly, Phillips and coworkers[22] reported that the strength of the adductor pollicis muscle was not different between men and women up to the age when menopause occurred, but thereafter, perimenopausal and postmenopausal women had a striking decline in strength (Fig. 1, top panel). The accelerated strength loss of the adductor pollicis muscle in the perimenopausal and postmenopausal women was not caused by enhanced muscle atrophy because the strength data were reported as specific force (maximum voluntary force relative to muscle cross-sectional area).

Figure 1.

Relationship between specific muscle force of the adductor pollicis muscle and age for groups of subjects that did and did not experience loss of estrogens during the sixth decade of life. Within each graph, specific force is expressed as a percent of the mean for subjects aged 45 yr and younger. Top panel: After menopause, women lose muscle strength with age at a greater rate than do men until about the age of 70 yr. Bottom panel: Postmenopausal women who take an estrogen-based hormone therapy (HT) retain muscle strength to a greater extent than do women who do not take the therapy. Data from Phillips et al.[22]

Phillips and coworkers[22] linked the menopause-related strength loss to sex hormones by studying an additional group of women who were on an estrogen-based hormone therapy (HT). They showed that the strength loss was prevented in perimenopausal and postmenopausal women on HT (Fig. 1, bottom panel). Again, the strength differences between groups were not related to muscle size because strength was assessed as specific force. Despite these striking results, the finding that HT prevents muscle weakness in postmenopausal women has not been consistently reported, as was concluded in two narrative review articles on the topic of sex hormones and muscle strength and performance.[13,27]

To address the inconsistent findings in the literature regarding the effect of HT on muscle strength in postmenopausal women, we conducted a systematic review combined with a meta-analysis.[8] Muscle strength data from 23 studies that included nearly 10,000 postmenopausal women who were or were not on HT were analyzed. The major finding was that postmenopausal women who had received HT had approximately 5% greater strength than those who did not receive treatment (effect size, 0.23). Interestingly, when specific force was analyzed from the subset of studies that made that measurement, a trend for a larger effect equating to approximately 10% greater strength for postmenopausal women on HT was revealed (Fig. 2, top panel). Thus, by statistically combining all results from the published literature, it can be concluded that HT is indeed beneficial for muscle strength in postmenopausal women.[8] Results of the meta-analysis also indicate that the effect of HT on muscle strength is due to improving the function of the existing muscle, that is, by improving muscle quality not muscle hypertrophy.

Figure 2.

Forest plots of effect sizes from meta-analyses on studies that reported muscle strength normalized to muscle size (specific force) in subjects that were and were not estrogen deficient. Each square represents the effect size for that study with the size of the square equating to the weight of that study in the meta-analysis. The horizontal line through the square indicates the 95% confidence interval (CI) for that effect size. Within each plot, studies are arranged from lowest to highest effect sizes. Top panel: Results of five studies on postmenopausal women comparing muscle strength between women who were and were not on an estrogen-based hormone therapy. Bottom panel: Results of seven studies on rats or mice comparing specific force between those that were estradiol deficient via ovariectomy and those that were ovary intact or estradiol replaced. Data from Greising et al.;[8] refer to this article for references cited in the figure.

A recent study on postmenopausal monozygotic female twins who were discordant for HT also supports the contention that estrogens are good for muscle function.[24] The purpose of the twin analyses was to determine if long-term HT was associated with better lower limb muscle function in a cohort of women in which potential genetic and early environmental differences were minimized. Although they found that maximal isometric knee extension strength was not significantly different between sisters who did and did not take HT, other measures of muscle function were different. Specifically, HT was associated with significantly better maximal 10-m walking speed and lower-body muscle power. Interestingly, it also was found that sisters on HT had greater relative muscle area and less relative fat area of the thigh than did the non-HT sisters, suggesting that in women, estrogens may have some anabolic and/or metabolic influence. A commentary following the twin article sums up the study and the past literature by stating that this study "incrementally advances the field and in fact tips the balance toward a positive and measureable (beneficial) impact of HRT".[19,24]

In summary, muscle weakness ensues with age and in women tends to become more pronounced when the production of estrogens and progesterone declines at menopause. This accelerated muscle weakness is linked to the loss of sex hormones because HT helps preserve strength. A caveat of the studies on postmenopausal women that precludes the determination of which specific hormone affects muscle function is that differing HT preparations were used across and even within studies.[8] Beyond the hormone preparations used, between-study variations also include population characteristics and type of muscle strength measurement. To circumvent these issues that are inherent to studies on women, more controlled interventions using rodents are reasonable and likely necessary to establish the specific sex hormone that improves strength in females and also to determine the mechanism(s) by which the hormone is working.

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