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Menopause Live - IMS Updates
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Date of release: 06 April, 2009

HRT and sarcopenia


A recently published study is part of a larger research project on postmenopausal sarcopenia and the effects of hormone replacement therapy (HRT) and physical activity [1]. Fifteen 54–62-year-old monozygotic female twin pairs, where one twin in each pair was receiving HRT and the other twin was not, were recruited from the Finnish Twin Cohort. This cohort includes all Finnish same-sex twin pairs born in Finland before 1958 and with both co-twins alive in 1967 (n = 13,888 pairs). Among others, women with chronic musculoskeletal disease, diabetes types 1 and 2, acute cancer, drug or alcohol abuse were excluded. Habitual and maximal walking speeds over 10 meters, thigh muscle composition, lower body muscle power (assessed as vertical jumping height), and maximal isometric hand-grip and knee-extension strengths were measured.


The mean duration of HRT usage was 6.9 ± 4.1 years (range 2–6 years). The maximal walking speed was on average 7% (95% confidence interval (CI) 0.9–13.1%; p = 0.019) and muscle power 16% (95% CI - 0.8 to 32.8%; p = 0.023) greater in the HRT users (estradiol 1–2 mg only or combined with progestogenic compounds, and tibolone 2.5 mg orally) than in their co-twin controls. Thigh muscle cross-sectional area, as taken from CT image analysis, tended to be larger (intra-pair difference = 6%; 95% CI - 0.07 to 12.1%; p = 0.065), relative muscle area greater (8%; 95% CI 0.8–15.0%; p = 0.047) and relative fat area smaller (- 5 %; 95% CI - 11.3 to 1.2%; p = 0.047) in the HRT users than in their co-twins. On the other hand, maximal isometric strengths or habitual walking speeds were not significantly different. Subgroup analysis revealed that estrogen-containing therapies (n = 11 pairs) decreased total body and thigh fat content, whereas tibolone (n = 4 pairs) tended to increase muscle cross-sectional area.

Comment

Reduced muscle diameter, fiber cross-sectional area and strength have been reported in older people and adults with frank growth hormone deficiency. During aging, there is a specific loss of type 2 fibers that may be associated with the loss of muscle power required to rapidly correct changes in position or gait. An effect of recombinant human growth hormone on frail older individuals had been postulated, consisting of a significant change in muscle fiber type [2]. To ascertain whether a therapeutic impact on fiber diameter or absolute fiber numbers may be achieved would require longer-term studies; the possible impact apparently depends on the age at initiation of therapeutic intervention plus the level of physical activity [3].
There is little knowledge on the possible preventive effects of long-term HRT on mobility limitation and disability. The investigators of this Finnish study relate this gap in information to the many years it takes for losses of muscle mass, muscle weakness and their clinical consequences to become apparent. Their strategy for an effective study of long-term HRT was to utilize the unexposed monozygotic twin as a clonal control and thus be able to look at associations of interest independently of an individual’s genetic make-up and shared post-experiences from childhood onwards; any observed difference could therefore be attributed to acquired factors.
A more detailed look at the results satisfies methodological and statistical quality criteria. Assays of steroid hormones and sex hormone binding globulin, anthropometry and total body as well as muscle composition, plus readings of mobility, muscle strength and muscle power are based on fully validated tools. The observed benefits in younger postmenopausal women which have not been seen in older postmenopausal women substantiate similar observations in cardiovascular [4] and neuronal prevention [5]. Muscle power is the product of force and speed of contraction and is not immediately affected by variation in circulating estrogen levels. Muscle power is more sensitive to the aging process and more important in mobility than muscle force alone [6]. Consequently, the authors argue, given the neuroprotective effects of estradiol [7], that their observed difference between the identical sisters in dynamic muscle power (walking speed) but not in muscle strength (hand grip) may rather be due, at least in part, to the possible effects of HRT on peripheral neurons. The missing association, in the Finnish twins, of HRT with isometric muscle strength contrasts with many reports in the literature [8]; this discrepancy may relate to the age of the participants, time since menopause as well as type and duration of HRT. Based on current information and in view of this genetically balanced case–control study utilizing optimal equipment and with sufficient power to detect clinically relevant effects of HRT, the following conclusions appear justified:
 
* HRT is associated with better mobility, greater muscle power and favorable body and muscle composition among younger postmenopausal women. 
* Whether HRT is a preventive agent for muscle weakness and mobility limitation also in older postmenopausal women requires further long-term studies. 
* Resistance training remains the most effective intervention for increasing muscle mass and strength in older people [9]. Elderly people have reduced food intake and increased protein requirements. As a result, adequate nutrition is sometimes a barrier to obtaining full benefits from resistance training. Energy balance, as accomplished in the Finnish study, must be controlled for in studies on sarcopenia and body composition.

Comentario

Hermann P. G. Schneider
Department of Obstetrics and Gynecology, University of Muenster, Germany

    References

  1. Ronkainen PH, Kovanen V, Alen M, et al. Postmenopausal hormone replacement therapy modifies skeletal muscle composition and function: a study with monozygotic twin pairs. J Appl Physiol 2009, epub ahead of print February 26, 2009.
    http://www.ncbi.nlm.nih.gov/pubmed/19246654

  2. Hennessey JV, Chromiak JA, DellaVentura S, et al. Growth hormone administration and exercise effects on muscle fiber type and diameter in moderately frail older people. J Am Geriatr Soc 2001;49:852-8.
    http://www.ncbi.nlm.nih.gov/pubmed/11527474

  3. Woodhouse LJ, Asa SL, Thomas SG, Ezzat S. Measures of submaximal aerobic performance evaluate and predict functional response to growth hormone (GH) treatment in GH-deficient adults. J Clin Endocrinol Metab 1999;84:4570-7.
    http://www.ncbi.nlm.nih.gov/pubmed/10599721

  4. Lobo RA. Postmenopausal hormones and coronary artery disease: potential benefits and risks. Climacteric 2007;10(Suppl 2):21-6.
    http://www.ncbi.nlm.nih.gov/pubmed/17882668

  5. Henderson VW. Alzheimers disease and other neurological disorders. Climacteric 2007;10(Suppl 2):92-6.
    http://www.ncbi.nlm.nih.gov/pubmed/17882682

  6. Bean JF, Leveille SG, Kiely DK, et al. A comparison of leg power and leg strength within the InCHIANTY study: which influences mobility more? J Gerontol A Biol Sci Med Sci 2003;58:728-33
    http://www.ncbi.nlm.nih.gov/pubmed/12902531

  7. Brann DW, Dhandapani K, Wakade C, et al. Neurotrophic and neuroprotective actions of estrogen: basic mechanisms and clinical implications. Steroids 2007;72:381-405.
    http://www.ncbi.nlm.nih.gov/pubmed/17379265

  8. Sipila S, Taaffe DR, Cheng S, et al. Effects of hormone replacement therapy and high-impact physical exercise on skeletal muscle in post-menopausal women: a randomized, placebo-controlled study. Clin Sci (Lond) 2001;101:147-57.
    http://www.ncbi.nlm.nih.gov/pubmed/11473488

  9. Borst SE. Interventions for sarcopenia and muscle weakness in older people. Age Ageing 2004;33:548-55.
    http://www.ncbi.nlm.nih.gov/pubmed/15385272