Menopause Live (21 March, 2011) From IMS

Bea and colleagues [1] have recently reported on results from a Women’s Health Initiative (WHI)-based sub-study that investigated possible effects of hormone therapy (HT) on lean mass, incidence of falls and fractures. The mean age at baseline was 63 years, and the mean time since menopause ranged from 13.3 to 22.5 years. Women were randomly assigned either to estrogen plus progestogen (n = 534) or control (n = 471), or to estrogen alone (n =453) or control (n = 474), all receiving dual-energy X-ray absorptiometry scans to estimate body composition. Falls and fracture occurrence were obtained by annual self-report. Six years post-randomization, the lean body mass did not differ among studied groups. Although lean body mass positively influenced bone mineral density, independent of HT status, the preserved lean body mass observed in the HT arms in the first 3 years did not significantly contribute to models evaluating HT influence on falls and fractures between years 3 and 6. Women taking at least 80% of their medication in the HT arms demonstrated fewer falls compared with those taking placebo; this difference was not attributable to change in lean body mass. The authors concluded that, although lean body mass was preserved with HT during the first 3 years, HT did not ameliorate the age-related, long-term (6 years) loss in body mass.

Comment
Sarcopenia or loss of lean mass during the menopausal transition relates to decreased anabolic hormone secretion (i.e. estrogens, androgens and growth/insulin hormones). Other factors favoring muscle catabolism during this period include cytokine secretion and free radical accumulation which increase inflammation, oxidative stress and muscle fiber apoptosis [2-4]. Prolonged periods of low vitamin D serum levels may also favor motor function alterations and increased bone mass loss and fracture risk [5]. Lean mass decreases by 3 kg for each decade, starting in the fourth [6,7]. This relates to a decrease in functional capacity (muscle strength and neurological coordination) which could, in fact, favor frailty and falls and limit locomotion [5,8,9].

Several studies have demonstrated the importance of exercise in maintaining strength and muscle mass. Loss of lean mass during the aging process is mostly related to a reduction in physical activity and not per se to age or ovarian function decline [9,10]. Nevertheless, it has been postulated that HT during the menopause could prevent these changes [11]. Bea and colleagues [1] demonstrated that treatment with conjugated equine estrogens alone or in combination with medroxyprogesterone acetate reduced lean mass loss at year 3 in comparison to the control group. In addition, compliant patients, taking at least 80% of treatment medications in any of the HT groups, had less falls during this period. Despite all this, the authors indicated that the decreased number of falls could not have been attributed to changes in body lean mass. The beneficial effect of HT over lean mass loss was, however, lost after 6 years of treatment, showing no differences between the groups. Hence, the effect was found to be transient and limited by time. The authors speculated that, if HT had been given to younger women (and at a shorter time since the beginning of menopause), the beneficial effects of HT would have lasted up to the 6th year. Prior studies support this WHI trial observation, demonstrating that, in young postmenopausal women who received HT for 1 year, lean mass was preserved [12] or even increased [13]. Exercise has the property of enhancing estrogenic receptor transcriptional activity in skeletal muscle and response is higher when HT is used [14].

Limitations of the study of Bea (as in any WHI analyses) are based on the characteristics of the participants at the point of HT initiation: their age, body mass index, and time since menopause. It is important to mention that obese women may be at higher risk of falling and suffering fractures, but this factor was not assessed in the HT arms of the study [1]. In addition, obesity is associated with a lower serum vitamin D status [15]. Hence, the effectiveness of HT could have been influenced by endogenous vitamin D levels. Nevertheless, compliance to vitamin D intake in the WHI cohorts (control and users) has also been criticized [5]. 

The results of the study of Bea and colleagues [1] provide information about a specific population who initiated HT at an advanced postmenopausal age. Despite this, HT demonstrated a beneficial effect concerning the physiological, age-related loss of lean mass and, additionally, in regard to fewer falls at 3 years. Until the effects of HT or vitamin D (adequate vs. deficient) can be clearly delineated in a prospective manner, it will be difficult to assert the exact contribution of each factor in maintaining lean body mass and on the risk of falls and fractures. Not less important is the fact that the dramatic changes in HT use during the last decade will make the task of determining the real value of HT in this regard much more difficult. In any case, further studies are indeed warranted.

Peter Chedraui
President, Ecuadorian Menopause Society (Nucleo Guayas)
Guayaquil, Ecuador

References
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http://www.ncbi.nlm.nih.gov/pubmed/20689466
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