Postmenopausal hormone replacement therapy modifies skeletal muscle composition and function: a study with monozygotic twin pairs.

We investigated whether long-term hormone replacement therapy (HRT) is associated with mobility and lower limb muscle performance and composition in postmenopausal women. Fifteen 54- to 62-yr-old monozygotic female twin pairs discordant for HRT were recruited from the Finnish Twin Cohort. Habitual (HWS) and maximal (MWS) walking speeds over 10 m, thigh muscle composition, lower body muscle power assessed as vertical jumping height, and maximal isometric hand grip and knee extension strengths were measured. Intrapair differences (IPD%) with 95% confidence intervals (CI) were calculated. The mean duration of HRT use was 6.9 +/- 4.1 yr. MWS was on average 7% (0.9 to 13.1%, P = 0.019) and muscle power 16% (-0.8 to 32.8%, P = 0.023) greater in HRT users than in their cotwins. Thigh muscle cross-sectional area tended to be larger (IPD% = 6%, 95% CI: -0.07 to 12.1%, P = 0.065), relative muscle area greater (IPD% = 8%, CI: 0.8 to 15.0%, P = 0.047), and relative fat area smaller (IPD% = -5%, CI: -11.3 to 1.2%, P = 0.047) in HRT users than in their sisters. There were no significant differences in maximal isometric strengths or HWS between users and nonusers. Subgroup analyses revealed that estrogen-containing therapies (11 pairs) significantly decreased total body and thigh fat content, whereas tibolone (4 pairs) tended to increase muscle cross-sectional area. This study showed that long-term HRT was associated with better mobility, greater muscle power, and favorable body and muscle composition among 54- to 62-yr-old women. The results indicate that HRT is a potential agent in preventing muscle weakness and mobility limitation in older women.

[1]  G. Grimby Physical activity and muscle training in the elderly. , 2009, Acta medica Scandinavica. Supplementum.

[2]  M. Esbjörnsson,et al.  Expression of both oestrogen receptor alpha and beta in human skeletal muscle tissue , 2009, Histochemistry and Cell Biology.

[3]  D. Mozaffarian,et al.  The perfect storm: obesity, adipocyte dysfunction, and metabolic consequences. , 2008, Clinical chemistry.

[4]  L. Kuller,et al.  Adipose tissue infiltration in skeletal muscle: age patterns and association with diabetes among men of African ancestry. , 2008, The American journal of clinical nutrition.

[5]  F. Tylavsky,et al.  Assessing Body Composition With DXA and Bioimpedance: Effects of Obesity, Physical Activity, and Age , 2008, Obesity.

[6]  Leena Peltonen,et al.  Global Transcript Profiles of Fat in Monozygotic Twins Discordant for BMI: Pathways behind Acquired Obesity , 2008, PLoS medicine.

[7]  O. Itkonen,et al.  Determination of testosterone in serum by liquid chromatography-tandem mass spectrometry , 2008, Scandinavian journal of clinical and laboratory investigation.

[8]  H. Suominen,et al.  Muscular transcriptome in postmenopausal women with or without hormone replacement. , 2007, Rejuvenation research.

[9]  S. Kežić,et al.  Postmenopausal HRT and tibolone in relation to muscle strength and body composition. , 2007, Maturitas.

[10]  D. Brann,et al.  Neurotrophic and neuroprotective actions of estrogen: Basic mechanisms and clinical implications , 2007, Steroids.

[11]  Andrea Riccardo Genazzani,et al.  Estrogen, cognition and female ageing. , 2007, Human reproduction update.

[12]  Taina Rantanen,et al.  Mobility Limitations and Cognitive Deficits as Predictors of Institutionalization among Community-Dwelling Older People , 2006, Gerontology.

[13]  M. Guida,et al.  Serum leptin levels and body composition in postmenopausal women treated with tibolone and raloxifene , 2006, Menopause.

[14]  M. J. Toth,et al.  The effect of hormone replacement therapy on body composition, body fat distribution, and insulin sensitivity in menopausal women: a randomized, double-blind, placebo-controlled trial. , 2006, The Journal of clinical endocrinology and metabolism.

[15]  Stanley Heshka,et al.  Independent association of insulin resistance with larger amounts of intermuscular adipose tissue and a greater acute insulin response to glucose in African American than in white nondiabetic women. , 2005, The American journal of clinical nutrition.

[16]  A. Kenny,et al.  Effects of Ultra‐Low‐Dose Estrogen Therapy on Muscle and Physical Function in Older Women , 2005, Journal of the American Geriatrics Society.

[17]  S. Souza,et al.  Estrogen Regulation of Adiposity and Fuel Partitioning , 2005, Journal of Biological Chemistry.

[18]  J. Kaprio,et al.  Contribution of genetic and environmental factors to individual differences in maximal walking speed with and without second task in older women. , 2005, The journals of gerontology. Series A, Biological sciences and medical sciences.

[19]  A. Newman,et al.  Estrogen replacement, muscle composition, and physical function: The Health ABC Study. , 2005, Medicine and science in sports and exercise.

[20]  H. Suominen,et al.  The effect of hormone replacement therapy and/or exercise on skeletal muscle attenuation in postmenopausal women: a yearlong intervention , 2005, Clinical physiology and functional imaging.

[21]  M. Boyanov,et al.  Effects of tibolone on body composition in postmenopausal women: a 1-year follow up study. , 2005, Maturitas.

[22]  S. Rubin,et al.  Muscle mass, muscle strength, and muscle fat infiltration as predictors of incident mobility limitations in well-functioning older persons. , 2005, The journals of gerontology. Series A, Biological sciences and medical sciences.

[23]  Vinjar Fønnebø,et al.  Endogenous sex hormones in relation to age, sex, lifestyle factors, and chronic diseases in a general population: the Tromsø Study. , 2004, The Journal of clinical endocrinology and metabolism.

[24]  R. Baumgartner,et al.  Sarcopenic obesity predicts instrumental activities of daily living disability in the elderly. , 2004, Obesity research.

[25]  J. Guralnik,et al.  Physical disability and muscular strength in relation to obesity and different body composition indexes in a sample of healthy elderly women , 2004, International Journal of Obesity.

[26]  Ravinder J. Singh,et al.  Liquid chromatography-tandem mass spectrometry assay for simultaneous measurement of estradiol and estrone in human plasma. , 2004, Clinical chemistry.

[27]  O. Johansson,et al.  Oestrogen receptor beta is expressed in adult human skeletal muscle both at the mRNA and protein level. , 2003, Acta physiologica Scandinavica.

[28]  Luigi Ferrucci,et al.  A comparison of leg power and leg strength within the InCHIANTI study: which influences mobility more? , 2003, The journals of gerontology. Series A, Biological sciences and medical sciences.

[29]  R. Porcher,et al.  Changes in body composition during post-menopausal hormone therapy: a 2 year prospective study. , 2003, Human reproduction.

[30]  L. Fried,et al.  Handgrip Strength and Cause‐Specific and Total Mortality in Older Disabled Women: Exploring the Mechanism , 2003, Journal of the American Geriatrics Society.

[31]  P. Delamarche,et al.  Estrogen receptor alpha mRNA in human skeletal muscles. , 2003, Medicine and science in sports and exercise.

[32]  S. Going,et al.  Effects of exercise training and hormone replacement therapy on lean and fat mass in postmenopausal women. , 2003, The journals of gerontology. Series A, Biological sciences and medical sciences.

[33]  P. Vestergaard,et al.  Hormone Replacement Therapy Dissociates Fat Mass and Bone Mass, and Tends to Reduce Weight Gain in Early Postmenopausal Women: A Randomized Controlled 5‐Year Clinical Trial of the Danish Osteoporosis Prevention Study , 2003, Journal of bone and mineral research : the official journal of the American Society for Bone and Mineral Research.

[34]  S. Kritchevsky,et al.  Association between regional adipose tissue distribution and both type 2 diabetes and impaired glucose tolerance in elderly men and women. , 2003, Diabetes care.

[35]  A. Kenny,et al.  Prevalence of sarcopenia and predictors of skeletal muscle mass in healthy, older men and women. , 2002, The journals of gerontology. Series A, Biological sciences and medical sciences.

[36]  J. Kaprio,et al.  Genetic and Environmental Factors in Complex Diseases: The Older Finnish Twin Cohort , 2002, Twin Research.

[37]  E. Ribom,et al.  Six months of hormone replacement therapy does not influence muscle strength in postmenopausal women. , 2002, Maturitas.

[38]  Charles Kooperberg,et al.  Risks and benefits of estrogen plus progestin in healthy postmenopausal women: principal results From the Women's Health Initiative randomized controlled trial. , 2002, JAMA.

[39]  S. Kritchevsky,et al.  Leg Muscle Mass and Composition in Relation to Lower Extremity Performance in Men and Women Aged 70 to 79: The Health, Aging and Body Composition Study , 2002, Journal of the American Geriatrics Society.

[40]  Suzanne G. Leveille,et al.  The Relationship Between Leg Power and Physical Performance in Mobility‐Limited Older People , 2002, Journal of the American Geriatrics Society.

[41]  C. Schneeberger,et al.  Production and actions of estrogens. , 2002, The New England journal of medicine.

[42]  M. Samson,et al.  The effect of tibolone on fat mass, fat-free mass, and total body water in postmenopausal women. , 2001, Endocrinology.

[43]  H. Suominen,et al.  Effects of hormone replacement therapy and high-impact physical exercise on skeletal muscle in post-menopausal women: a randomized placebo-controlled study. , 2001, Clinical science.

[44]  S. Humphries,et al.  Angiotensin-I converting enzyme genotype-dependent benefit from hormone replacement therapy in isometric muscle strength and bone mineral density. , 2001, The Journal of clinical endocrinology and metabolism.

[45]  R. Woledge,et al.  Follow-up study of the benefits of hormone replacement therapy on isometric muscle strength of adductor pollicis in postmenopausal women. , 2001, Clinical science.

[46]  H. Kloosterboer Tibolone: a steroid with a tissue-specific mode of action , 2001, The Journal of Steroid Biochemistry and Molecular Biology.

[47]  Suzanne G. Leveille,et al.  Coimpairments as Predictors of Severe Walking Disability in Older Women , 2001, Journal of the American Geriatrics Society.

[48]  V. Hughes,et al.  Sarcopenia: current concepts. , 2000, The journals of gerontology. Series A, Biological sciences and medical sciences.

[49]  R Ross,et al.  Skeletal muscle attenuation determined by computed tomography is associated with skeletal muscle lipid content. , 2000, Journal of applied physiology.

[50]  M. Samson,et al.  Relationships between physical performance measures, age, height and body weight in healthy adults. , 2000, Age and ageing.

[51]  A. Vermeulen,et al.  A critical evaluation of simple methods for the estimation of free testosterone in serum. , 1999, The Journal of clinical endocrinology and metabolism.

[52]  P. Vestergaard,et al.  Hormone replacement therapy affects body composition and leptin differently in obese and non-obese postmenopausal women. , 1999, The Journal of endocrinology.

[53]  K. Yano,et al.  Effects of walking on coronary heart disease in elderly men: the Honolulu Heart Program. , 1999, Circulation.

[54]  R. Woledge,et al.  Hormone replacement therapy increases isometric muscle strength of adductor pollicis in post-menopausal women. , 1999, Clinical science.

[55]  Suzanne G. Leveille,et al.  Midlife hand grip strength as a predictor of old age disability. , 1999, JAMA.

[56]  R. Kronmal,et al.  High body fatness, but not low fat-free mass, predicts disability in older men and women: the Cardiovascular Health Study. , 1998, The American journal of clinical nutrition.

[57]  C. Bouchard,et al.  Serum lipids, lipoproteins, and lipid metabolizing enzymes in identical twins discordant for obesity. , 1998, The Journal of clinical endocrinology and metabolism.

[58]  F. Horber,et al.  Differential impact of conventional oral or transdermal hormone replacement therapy or tibolone on body composition in postmenopausal women , 1998, Clinical endocrinology.

[59]  D. Kiel,et al.  Body fat and skeletal muscle mass in relation to physical disability in very old men and women of the Framingham Heart Study. , 1998, The journals of gerontology. Series A, Biological sciences and medical sciences.

[60]  J. Kaprio,et al.  Relationship of leisure-time physical activity and mortality: the Finnish twin cohort. , 1998, JAMA.

[61]  K. Yano,et al.  Effects of walking on mortality among nonsmoking retired men. , 1998, The New England journal of medicine.

[62]  E Heikkinen,et al.  Physical Activity and the Changes in Maximal Isometric Strength in Men and Women from the Age of 75 to 80 Years , 1997, Journal of the American Geriatrics Society.

[63]  F. Petraglia,et al.  Modulatory effects of a synthetic steroid (tibolone) and estradiol on spontaneous and GH-RH-induced GH secretion in postmenopausal women. , 1997, Maturitas.

[64]  Y. Kuryshev,et al.  Corticotropin releasing hormone inhibits an inwardly rectifying potassium current in rat corticotropes , 1997, The Journal of physiology.

[65]  T. Reilly,et al.  Effects of acute changes in oestrogen on muscle function of the first dorsal interosseus muscle in humans. , 1997, The Journal of physiology.

[66]  W. Ollier,et al.  The human immunoglobulin V(H) gene repertoire is genetically controlled and unaltered by chronic autoimmune stimulation. , 1996, The Journal of clinical investigation.

[67]  M. Sheehan,et al.  The influence of menopause and hormonal replacement therapy on body cell mass and body fat mass. , 1995, American journal of obstetrics and gynecology.

[68]  S. Cummings,et al.  Is postmenopausal estrogen therapy associated with neuromuscular function or falling in elderly women? Study of Osteoporotic Fractures Research Group. , 1995, Archives of internal medicine.

[69]  S. Cummings,et al.  Is Postmenopausal Estrogen Therapy Associated With Neuromuscular Function or Falling in Elderly Women , 1995 .

[70]  J. M. Davies,et al.  Strength, power and related functional ability of healthy people aged 65-89 years. , 1994, Age and ageing.

[71]  E Heikkinen,et al.  Maximal isometric strength and mobility among 75-year-old men and women. , 1994, Age and ageing.

[72]  C. Christiansen,et al.  Postmenopausal hormone replacement therapy prevents central distribution of body fat after menopause. , 1991, Metabolism: clinical and experimental.

[73]  V. Salomaa,et al.  Body fat distribution in the Finnish population: environmental determinants and predictive power for cardiovascular risk factor levels. , 1991, Journal of epidemiology and community health.

[74]  J. Selby,et al.  Concordance for dyslipidemic hypertension in male twins. , 1991, JAMA.

[75]  A Tremblay,et al.  The response to long-term overfeeding in identical twins. , 1990, The New England journal of medicine.

[76]  J. Tobin,et al.  The role of muscle loss in the age-related decline of grip strength: cross-sectional and longitudinal perspectives. , 1990, Journal of gerontology.

[77]  J. Kaprio,et al.  Decreased beta-adrenergic receptor density and catecholamine response in male cigarette smokers. A study of monozygotic twin pairs discordant for smoking. , 1988, Circulation.

[78]  J. Morley,et al.  Endocrinology in aging. , 1988, Disease-a-month : DM.

[79]  C. Ankarberg-Lindgren,et al.  A purification step prior to commercial sensitive immunoassay is necessary to achieve clinical usefulness when quantifying serum 17beta-estradiol in prepubertal children. , 2008, European journal of endocrinology.

[80]  T. Rantanen,et al.  Endogenous hormones, muscle strength, and risk of fall-related fractures in older women. , 2006, The journals of gerontology. Series A, Biological sciences and medical sciences.

[81]  K. Korach,et al.  Signal transduction. A new mediator for an old hormone? , 2005, Science.

[82]  Paavo V. Komi,et al.  A simple method for measurement of mechanical power in jumping , 2004, European Journal of Applied Physiology and Occupational Physiology.

[83]  P. Era,et al.  Muscle strength in male athletes aged 70–81 years and a population sample , 2004, European Journal of Applied Physiology and Occupational Physiology.

[84]  Ack,et al.  LOWER-EXTREMITY FUNCTION IN PERSONS OVER THE AGE OF 70 YEARS AS A PREDICTOR OF SUBSEQUENT DISABILITY , 2001 .

[85]  H. Suominen,et al.  Effects of strength and endurance training on thigh and leg muscle mass and composition in elderly women. , 1995, Journal of applied physiology.

[86]  R. Woledge,et al.  Muscle weakness in women occurs at an earlier age than in men, but strength is preserved by hormone replacement therapy. , 1993, Clinical science.

[87]  J. Kaprio,et al.  The Finnish Twin Registry: formation and compilation, questionnaire study, zygosity determination procedures, and research program. , 1978, Progress in clinical and biological research.