The average length of human life is currently 75 to 78 years and may increase to 85 years during the coming two decades (1). The most dramatic hormonal change seen in women is menopause. The average age of the onset of menopause (51.4 years) has not changed over time and seems to be largely determined by genetic factors (2). However, due to an increase in life expectancy, the time a woman spends after menopause is more than one third of her life (3).
What is menopause anyway? Menopause is initiated by the exhaustion of the ovarian follicles and changes induced by age in the hypothalamo-pituitary unit (4,5). During the first year post-menopause, the production of estradiol and estrone (female sex hormones) decreases. Serum concentrations of estradiol and estrone decrease 67% and 35% respectively during this first year (6). There is another decrease in both estradiol and estrone production in the following post-menopausal years; however, it is to a much lesser extent. So, during menopause, the pre-menopausal cyclic estradiol production is replaced by a low constant production of ovarian estradiol. Circulating estrone, which is made by the adrenal steroids in the peripheral tissue (mostly adipose tissue), now becomes the most abundant estrogen in the serum after menopause. There is also a decrease in the synthesis of ovarian progesterone with menopause (7).
Menopause and aging are both associated with a decrease in bone density, muscle mass and an increase in adipose tissue (1,8,9). Another characteristic of human aging is a reduction in muscle strength, which contributes to falls, fractures, reduction in quality of life and potentially the loss of a person's ability to live an independent life (7). Estrogen replacement therapy has been associated with preserving bone mass in postmenopausal women (8,9). It has also been suggested that estrogen replacement therapy may have a protective effect on the ratio of muscle strength to muscle cross-sectional area (termed "specific force") in peri- and postmenopausal women (10). Since muscle strength is associated with falls and fractures in aged individuals, this additional effect of estrogen replacement could be of considerable benefit to postmenopausal women (10) Let’s take a closer look at what happens physiologically to muscle with aging and menopause in women.
In the aged individual, a loss of muscle strength (this is also referred to as frailty) plays a large role in determining if a person is capable of living an independent life. Loss of muscle strength is an important factor in the process of older/elderly adults becoming frail. There are many causes to muscle weakness including the aging of muscle fibers and their nerves, osteoarthritis and chronic diseases (11). In addition to the human bodies changing chemistry with age, a sedentary lifestyle and muscle disuse are also important factors in the decline of muscle strength in the elderly. In a study of 100 frail nursing home residents (average age 87 years), lower-extremity muscle mass and strength were closely related (12). Supervised resistance exercise training (for 45 minutes three times per week for 10 weeks) doubled muscle strength and significantly increased gait velocity and stair-climbing power. This demonstrates that frailty can in fact be reduced and perhaps even prevented (12). Also, among non-disabled elderly adults living in the community, measures of lower-extremity function are highly predictive of subsequent disability (13). The main point is that prevention of frailty can be achieved by exercise, but can it be improved more so with hormone replacement therapy?
The physical changes during aging have been considered physiologic; however, there is also evidence that some of these changes are related to this decline in hormonal activity. Sarcopenia refers to the loss of skeletal muscle mass with age. Researchers have found a prevalence of sarcopenia of 22.6% in older postmenopausal women not receiving estrogen (1). The objective of one study was to determine the prevalence of sarcopenia in a population of older, non-obese, community-dwelling women who had been long-term users of estrogen replacement therapy (ERT) (1). The researchers found that sarcopenia is as common in non-obese women who are long-term ERT users as in women not using ERT, suggesting that ERT does not protect against the muscle loss of aging. This data suggests that interventions to target nutrition, strength training and testosterone replacement should be further investigated for their roles in preventing muscle loss with age. Conversely, Phillips et al (10) found that beginning at the time of menopause in women without hormone replacement, there was a dramatic decline in specific force of the adductor pollicis muscle, which was not seen in women on estrogen replacement therapy.
The mechanism for the association between estrogen replacement and muscle strength is unclear at present, although Phillips et al. (10) speculate that hormonal alterations may alter the sensitivity of the actin-myosin cross-bridges to intracellular metabolites and hydrogen ion concentration. Cauley et al. (14) showed a weak association between hand grip strength and estrogen levels in 176 postmenopausal women not on estrogen replacement therapy. However, Kritz-Silverstein and Barrett-Connor (15) showed that, although estrogen use was associated with higher bone density in postmenopausal women, there was no effect seen on grip strength.
Hormone replacement therapies have been developed; however, many of their aspects remain controversial, and increasing blood hormone levels in aging individuals to those found during mid-adult life has not been uniformly proven to be safe and of benefit Currently, the data is mixed as to whether estrogen replacement therapy preserves/improves muscle strength in post-menopausal women. However, it is known that there is a decline in muscle performance after middle age in women, and more research needs to be done in this area. At present, the decision to start hormone replacement at menopause should be carefully considered with the primary healthcare provider based on the individual's risk factors, her attitude toward hormonal treatment and knowledge of its risks and benefits.
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