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Postmenopausal hormone therapy and body composition—a substudy of the estrogen plus progestin trial of the Women's Health Initiative^1,2,3

¹ From the University of Arizona, Tucson, AZ (ZC, TB, and SBG); the University of Pittsburgh, Pittsburgh, PA (JAC); the Ohio State University, Columbus, OH (RDJ); the Fred Hutchinson Cancer Research Center, Seattle, WA (AZL); the Brigham and Women's Hospital, Harvard University, Boston, MA (ML); the Stanford University, Stanford, CA (MLS); and the University of Minnesota, Minneapolis, MN (KLM)

² Supported by the National Heart, Lung, and Blood Institute, US Department of Health and Human Services (the Women's Health Initiative Program) and the National Institute of Arthritis, Musculoskeletal, and Skin Diseases (grant R01-AR049411 to ZC).

³ Reprints not available. Address correspondence to Z Chen, PO Box 245203, Division of Epidemiology and Biostatistics, Mel and Enid Zuckerman College of Public Health, University of Arizona, 1540 E Drachman, Tucson, AZ 85724. E-mail: zchen{at}u.arizona.edu.

	ABSTRACT

TOP ABSTRACT INTRODUCTION SUBJECTS AND METHODS RESULTS DISCUSSION REFERENCES

 
Background: It has been suggested that hormone therapy may help counter undesirable changes in body composition in older women.

Objective: This study was designed to test whether estrogen plus progestin (E+P) therapy favorably affects age-related changes in body composition in postmenopausal women.

Design: The substudy was composed of 835 women from the estrogen plus progestin trial of the Women's Health Initiative who were randomly assigned to receive either E+P therapy (n = 437) or placebo (n = 398). The women had a mean age of 63.1 y and, on average, were 13.8 y past menopause. More than 17% of the participants were from an ethnic minority. No significant differences in baseline body composition (measured with dual-energy X-ray absorptiometry) by intervention assignment were observed.

Results: After 3 y of intervention, the women who received active E+P therapy lost less lean soft tissue mass (–0.04 kg) than did the women who received placebo (–0.44 kg; P = 0.001). Additionally, the women in the E+P group had less upper-body fat distribution than did the women in the placebo group (change in ratio of trunk to leg fat mass: –0.025 for the E+P group and 0.004 for the placebo group; P = 0.003). A sensitivity analysis, which was conducted on the women who took 80% of the study medication during the intervention period, corroborated the findings from the intent-to-treat analysis.

Conclusions: A 3-y E+P intervention significantly reduced both the loss of lean soft tissue mass and the ratio of trunk to leg fat mass in postmenopausal women. However, the effect sizes were small, and whether these changes in body composition lead to significant health benefits remains to be confirmed.

Key Words: Estrogen plus progestin • body composition • Women's Health Initiative • dual-energy X-ray absoptiometry • postmenopausal women

	INTRODUCTION

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Older women may experience increases in body fat mass and redistribution of fat mass from the limbs to a more central or android location (1). These changes can increase the risk of diabetes and cardiovascular diseases in older women. Menopausal therapy may help counter these changes in body composition in postmenopausal women (1–3). Most of the previous studies investigating the effects of menopausal therapy on body composition were limited either to observational studies or to clinical trials with small sample sizes or short intervention periods. The techniques used for assessing body composition have varied widely across these studies; many studies have not used direct measurements of body composition but have instead relied on anthropometric measurements, such as body mass index (BMI) or hip and waist circumferences, as proxies for obesity, lean soft tissue mass, and body fat distribution. These limitations highlight the need for a better understanding of the relation between body composition and hormone therapy in postmenopausal women.

The estrogen plus progestin (E+P) randomized controlled clinical trial of the Women's Health Initiative (WHI) provides a unique opportunity to investigate the effect of hormone therapy on body composition. All the women in the WHI substudy underwent body-composition assessment by dual-energy X-ray absorptiometry (DXA) scans serially throughout the trial. Because of the advantages of the randomized controlled clinical trial, the present substudy had the unique ability to test whether the E+P intervention had positive effects on body composition, including preventing the loss of lean soft tissue mass, reducing the gain in body fat mass, and reducing the redistribution of fat from the limbs to a central or android location.

	SUBJECTS AND METHODS

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Subjects
Between 1993 and 1998, a total of 16 608 postmenopausal women who had not previously undergone a hysterectomy were recruited and enrolled into the WHI E+P trial at 40 WHI clinical centers in the United States. The inclusion criteria were as follows: age of 50-79 y, postmenopausal status, likelihood of residence in the area for 3 y, and provision of written informed consent. All the women were stratified by age and randomly allocated (block randomization by clinical center) into either the E+P group (0.625 mg conjugated equine estrogen combined with 2.5 mg medroxyprogesterone acetate per day) or the placebo group. Women who were taking estrogen therapy at the initial screening were asked to go through a 3-mo washout period before starting E+P therapy. The protocol and consent forms were approved by the review boards of all participating institutions. Details regarding inclusion and exclusion criteria, recruitment procedures, participant characteristics, randomization, blinding, and follow-up for the entire E+P cohort can be found in previously published articles (4, 5).

At 3 WHI clinical centers (Pittsburgh, PA; Birmingham, AL; and Tucson-Phoenix, AZ), body composition was assessed with the use of a DXA scanner at baseline and every 3 y thereafter. The participants who completed the baseline and year 3 DXA scan measurements were included in the substudy. The characteristics of the substudy participants differed from those of the entire WHI cohort in that recruitment was aimed at yielding maximum race-ethnicity and age diversity at the WHI clinical centers where DXA measurements were conducted.

Body-composition measurements
Body-composition measurements, which included measurements of lean soft tissue mass, fat mass, percentage of lean soft tissue mass, and percentage of fat mass, were assessed from whole-body DXA scans (QDR 2000, 2000+, or 4500W; Hologic Inc, Bedford, MA). Both regional and total body-composition measurements were generated from total-body DXA scans. The ratio of trunk to leg fat mass (trunk:leg fat mass), which indicates fat distribution, was calculated by dividing the fat mass of the trunk region by the fat mass of the leg region. The DXA scans were conducted at baseline and every 3 y during the intervention. Because the E+P trial stopped on 7 July 2002, when the mean follow-up time was 5.6 y, few participants had year 6 scans done before the trial ended. Therefore, the present substudy only examined changes in body composition between the measurements made at baseline and those made at year 3.

Standard protocols for positioning and analysis were used by technicians who were trained and certified by the DXA manufacturer and the WHI DXA coordination center at the University of California, San Francisco. The quality assurance program included monitoring of phantom scans; reviewing random samples of all scans and flagging scans with specific problems; controlling changes in hardware and software, which included in vitro and in vivo cross-calibration; and scanning of calibration phantoms across instruments and clinical sites.

Other covariates
Information on age, years since menopause, race and ethnicity, smoking history, recreational physical activities, use of menopausal hormone therapy, energy intake, and alcohol use were assessed with baseline questionnaires. Age at menopause was defined as the age at which the participant last reported any menstrual bleeding, had a bilateral oophorectomy, or began receiving menopausal hormone therapy. Caloric intake was assessed with the use of a validated food-frequency questionnaire, which was based on instruments that were previously used in large-scale dietary intervention trials (6, 7). Recreational physical activity was assessed by questions on the frequency and duration of several types of recreational activities, and metabolic equivalent task scores (defined as the ratio of work metabolic rate to a standard resting metabolic rate, with one metabolic equivalent task roughly equivalent to the resting metabolism while sitting quietly) were computed as the product of days per week, minutes per day, and metabolic equivalent task value for each activity (8). Physical function was measured with the use of the 10-item Medical Outcomes Study Scale (9); a higher score indicates better physical function. Weight was measured to the nearest 0.1 kg on a balance-beam scale while the participant wore indoor clothing and no shoes. Each participant's height was measured to the nearest 0.1 cm with the use of a wall-mounted stadiometer. BMI was calculated as weight (in kg)/height² (in m). Waist and hip circumferences of the participants were measured with the use of measurement tapes at baseline and a year after the randomization for all the E+P participants from the 3 WHI centers where the DXA measurements were conducted. After the first annual visit, the WHI trial only collected waist and hip circumferences in a subcohort of E+P trial participants. In the present WHI substudy, the waist and hip circumference measurements as well as waist-to-hip ratios (WHRs) were repeated in year 3 for only 214 women in the E+P group and 198 women in the placebo group.

Statistical analysis
The analysis was performed on 835 women who had DXA scans done at both baseline and year 3. Because of the replacement of an older DXA machine with a new DXA model, 135 of the women from the Tucson WHI clinic (16% of the 835 women in the present substudy) had their baseline scans done with the QDR2000 model and their year 3 scans with the QDR4500W model. With the use of DXA calibration data from an independent group of 50 women who were scanned with both DXA machines on the same day, linear regression equations were developed for the total and regional body-composition assessments, which predicted QDR2000 values from QDR4500W measurements. These equations were used to correct the measurements from the participants who switched scanners. Three additional women who had different scanner models for their 2 evaluations were eliminated from the analysis because no correction was possible.

An intent-to-treat analysis was used for the primary comparisons between the E+P group and the placebo group. Because the effects of E+P therapy might have been adversely affected by a reduced adherence to the study medication, a sensitivity analysis was conducted in the participants who completed 80% of the intervention assignments. All analyses were conducted with JMP version 5 (SAS Institute, Cary, NC) for Macintosh computers. Descriptive statistics were used for baseline data, and t tests were used for comparisons of body-composition measurements between the 2 intervention groups. All P values were 2-tailed.

	RESULTS

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Descriptive analysis of baseline covariates by intervention
The baseline characteristics of the women by intervention group are shown in Table 1. In this subsample, 398 women were assigned to placebo and 437 were assigned to active E+P therapy. No statistically significant differences between the groups were found in age, years since menopause, dietary energy intake, total weekly expenditure on recreational activities, physical functional score, hormone use, smoking history, or alcohol consumption. A small but statistically significant difference in ethnicity by intervention group was observed (P = 0.03).

Table 2

Table 3

View this table: [in this window] [in a new window]   TABLE 3 Absolute changes () in body-composition measurements between baseline and year 3 by intervention group1

Sensitivity analysis
The sensitivity analysis included a total of 511 women (256 from the placebo group and 255 from the E+P group). The results from this analysis (Table 4) showed significant intervention effects of E+P therapy on changes in lean soft tissue mass (P < 0.001) and changes in the trunk:leg fat mass (P < 0.001) and thus support the findings of the intent-to-treat analysis. The sensitivity analysis suggested an increase (0.11 kg) in lean soft tissue mass in the women who were assigned to the E+P intervention compared with a reduction (–0.45 kg) in the women who were assigned to placebo (P < 0.001). The changes in BMI and the percentage of fat mass were statistically significant by intervention group at the 0.05 level. BMI increased more in the E+P group than in the placebo group (0.56 and 0.04, respectively; P = 0.02). No change in the mean of the percentage of fat mass was observed in the E+P group, but a 0.56% absolute increase in the percentage in fat mass was observed in the placebo group (P = 0.05).

	DISCUSSION

TOP ABSTRACT INTRODUCTION SUBJECTS AND METHODS RESULTS DISCUSSION REFERENCES

Most of the previous studies on the effects of E+P therapy on body weight or body composition were limited by small sample sizes. The sample size in the Postmenopausal Estrogen-Progestin Intervention (PEPI) trial (10) was comparable with our WHI substudy sample. In the PEPI trial, 875 women aged 45–65 y were randomly assigned to 4 hormone therapy regimens or to receive placebo. In that trial, the women who were assigned to E+P therapy had significantly smaller increases in waist and hip circumferences than did the women who were assigned to receive placebo. Although the WHR was reduced by hormone treatment in the PEPI trial, which suggested a reduction in central adiposity, the result was not statistically significant. In addition, the PEPI trial found significantly less weight gain in the hormone treatment groups than in the placebo group, whereas we observed a greater, although not statistically significant, weight gain in the intervention group than in the placebo group. The weight-reduction effect of hormone therapy was also suggested by the Danish Osteoporosis Prevention Study (DOPS), which was a 5-y randomized controlled clinical trial conducted in early postmenopausal women aged 45–58 y. The hormone intervention in DOPS included 2 mg estradiol plus 1 mg nonrethisterone acetate for women with an intact uterus or 2 mg estradiol for women who had undergone a hysterectomy. DOPS results indicated that the reduced weight gain with hormone therapy was due almost entirely to a reduced gain in fat weight (11). In contrast, the greater weight gain observed in the present substudy in the women who were assigned to the E+P therapy resulted primarily from an increase in lean body mass. The WHI participants were older than the PEPI and the DOPS participants, and it is possible that E+P therapy may affect fat gain and lean mass loss differently in younger postmenopausal women than in older postmenopausal women. In addition, differences in other characteristics of the study participants (such as smoking history and different baseline body weights) and in the techniques for the assessment of body composition and fat distribution may explain some of the different results.

It has been suggested that menopause contributes to a change in body fat distribution, irrespective of aging and obesity (12). Although reductions in body fat gain or in android distribution with hormone therapy were not reported by all the studies (13), several intervention studies support the notion that estrogen therapy may attenuate the accumulation of central fat in postmenopausal women (1, 2, 14, 15). At least one prospective observational study has indicated that continuous daily E+P therapy neither prevents nor increases early postmenopausal weight gain and fat accumulation; however, the study also showed that E+P therapy may minimize the shift from gynoid to android fat distribution (16). Another prospective study also found that menopausal hormone therapy significantly reduced fat mass accumulation in women, especially in the trunk region (3). One cross-sectional study reported that waist circumferences were significantly smaller in long-term hormone users than in nonusers who were similar in age, years since menopause, and BMI (17). Research on twins has provided additional evidence of reduced total and central body fat with estrogen therapy (18).

It has been suggested that the beneficial effects of hormone therapy on changes in body fat mass and fat distribution are likely mediated through an increase in insulin sensitivity (19). A recent report from a subcohort of the WHI E+P intervention trial, which excluded women who reported a diagnosis of diabetes at baseline, found that E+P intervention reduced the incidence of diabetes. This reduction possibly resulted from a decrease in insulin resistance because the modified homeostasis assessment was lower in the intervention arm than in the placebo arm, but the treatment effect was not statistically significant (P = 0.08) (20).

Our finding regarding lean body mass loss is consistent with results from a short-term (two 12-wk periods) crossover study in postmenopausal women aged 55 ± 3 y ( ± SD) that used 3 cycles of E+P intervention (Trisequens Forte; Novo Nordisk, Bagsvaerd, Denmark) (2). Their results suggested a significant increase in lean body mass and a reduction in abdominal fat and in the percentage of fat mass in the women who were receiving menopausal hormone therapy. In contrast, a significant reduction in lean soft tissue mass and a significant gain in both total body fat and percentage of fat mass were observed in women who were assigned to receive placebo; however, overall weight changes did not differ in the women before and after the crossover. With the use of urinary creatinine excretion rates as indicators of muscle mass, another study showed that 1 y of E+P therapy was associated with an increase in muscle mass without a change in body weight compared with placebo (21). However, in a randomized trial in postmenopausal women, Aloia et al (13) found no reduction in the loss of lean body mass (measured by using dual-photon absorptiometry) after women received menopausal hormone therapy. No relation between the use of estrogen and lean body mass was observed in cross-sectional studies (22, 23), which may reflect a prescription bias because physicians were more likely to prescribe estrogen to leaner women or to women with menopausal symptoms. Obviously, data related to the effect of hormone therapy on lean body mass are scarce, and more research with direct measurements on lean tissue mass is needed.

The mechanism by which E+P therapy maintains lean body mass is not well understood. Androgens increase lean soft tissue mass in postmenopausal women, but a drop in bioactive-free testosterone was found to be associated with hormone therapy (24). In a cross-sectional study, estrogen users had lower insulin-like growth factor I concentrations than did nonusers (25). However, a 10-mo hormone intervention (2 mg estradiol-valerate and 10 mg dydrogesterone) increased the release of growth hormone and various growth factors (26), which play important roles in muscle growth and development. This finding suggests that the maintenance of lean body mass via E+P therapy may be mediated by growth hormone and growth factors instead of androgens; however, more direct evidence of whether these factors link E+P therapy and body composition is needed.

Maintaining lean body mass in older age may be beneficial for better balance and, in turn, for reducing the number of falls. Central body fat distribution has been linked with insulin resistance. Results from the WHI trial showed that E+P intervention reduced both the risk of fracture (27) and the incidence of diabetes (20). Whether the reductions in the incidence rates of fractures and diabetes were partially mediated through E+P therapy–induced changes in body composition deserves additional investigation.

The major strengths of the present substudy were the relatively large sample size, the randomized and placebo-controlled design, the longer duration of follow-up, and the use of DXA scans (a state-of-the-art technique in assessing body composition) in ambulatory, multiethnic, postmenopausal women. If we had only used weight or BMI as a proxy for body-composition measurements, then a stable body weight or BMI would have masked the gain in fat mass in women who were assigned to the placebo group because a loss in lean tissue mass would cancel out a gain in fat. Similarly, BMI and weight measurements would have suggested that E+P therapy increases adiposity, but, in fact, the women who received E+P therapy gained more weight than did the women who received placebo only because of an increase in lean body mass and not because of an increase in body fat mass.

The present substudy included a subsample of women from the WHI E+P intervention trial from the 3 WHI centers where DXA measurements were conducted. Because the block randomization was done by clinical center, the randomization was well preserved, as indicated by the lack of significant differences in baseline body-composition measurements by intervention group in the subsample. The mean BMI and mean age in the subsample were similar to the mean BMI and mean age of the entire WHI E+P cohort by intervention assignments at baseline (4). Although the subsample differed slightly from the entire E+P cohort in race and ethnicity composition, hormone use, and smoking history, the findings from this substudy would probably be similar if the analyses were done on the entire WHI E+P cohort. In the present substudy, body-composition data were available for only 2 time points: baseline and year 3. This prevented us from assessing any trends in the changes in body composition and also limited the investigation to the effects of E+P therapy on body composition for only the first 3 y of intervention. The effect sizes of E+P therapy on body composition might be larger for the entire average 5.6-y intervention period.

In conclusion, we found that E+P intervention maintains lean body mass and reduces upper-body fat distribution in postmenopausal women. However, the effect sizes observed in this study were small, and the clinical implications of these changes in body composition remain to be investigated.

	ACKNOWLEDGMENTS

 
We thank the WHI investigators and staff at the clinical centers, clinical coordinating center, and project office (Internet: www.whi.org/about) for their contributions.

ZC developed the manuscript and all other authors contributed to the writing of the manuscript. TB provided the resources and participated in the study design. SBG conducted the statistical analyses and helped to interpret the results. JAC contributed to the data collection. RDJ and ML contributed to the study design. AZL contributed to the study design and to the analysis plan. MLS contributed to the interpretation of the study results. KLM contributed to the study design, the analysis plan, and the interpretation of the study results. None of the authors had any conflicts of interest.

	REFERENCES

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1. Gambacciani M, Ciaponi M, Cappagli B, De Simone L, Orlandi R, Genazzani AR. Prospective evaluation of body weight and body fat distribution in early postmenopausal women with and without hormonal replacement therapy. Maturitas 2001;39:125–32.[Medline]
2. Sorensen MB, Rosenfalck AM, Hojgaard L, Ottesen B. Obesity and sarcopenia after menopause are reversed by sex hormone replacement therapy. Obes Res 2001;9:622–6.[Medline]
3. Kristensen K, Pedersen SB, Vestergaard P, Mosekilde L, Richelsen B. Hormone replacement therapy affects body composition and leptin differently in obese and non-obese postmenopausal women. J Endocrinol 1999;163:55–62.[Abstract]
4. Rossouw JE, Anderson GL, Prentice RL, et al. Risks and benefits of estrogen plus progestin in healthy postmenopausal women: principal results from the Women's Health Initiative randomized controlled trial. JAMA 2002;288:321–33.[Abstract/Free Full Text]
5. The Women's Health Initiative Study Group. Design of the Women's Health Initiative clinical trial and observational study. Control Clin Trials 1998;19:61–109.[Medline]
6. Block G, Woods M, Potosky A, Clifford C. Validation of a self-administered diet history questionnaire using multiple diet records. J Clin Epidemiol 1990;43:1327–35.[Medline]
7. Patterson RE, Kristal AR, Coates RJ, et al. Low-fat diet practices of older women: prevalence and implications for dietary assessment. J Am Diet Assoc 1996;96:670–9.[Medline]
8. Ainsworth BE, Haskell WL, Leon AS, et al. Compendium of physical activities: classification of energy costs of human physical activities. Med Sci Sports Exerc 1993;25:71–80.[Medline]
9. Ware JE Jr, Sherbourne CD. The MOS 36-item short-form health survey (SF-36). I. Conceptual framework and item selection. Med Care 1992;30:473–83.[Medline]
10. Espeland MA, Stefanick ML, Kritz-Silverstein D, et al. Effect of postmenopausal hormone therapy on body weight and waist and hip girths. J Clin Endocrinol Metab 1997;82:1549–56.[Abstract/Free Full Text]
11. Jensen LB, Vestergaard P, Hermann AP, 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. J Bone Miner Res 2003;18:333–42.[Medline]
12. Ijuin H, Douchi T, Oki T, Maruta K, Nagata Y. The contribution of menopause to changes in body-fat distribution. J Obstet Gynaecol Res 1999;25:367–72.[Medline]
13. Aloia JF, Vaswani A, Russo L, Sheehan M, Flaster E. The influence of menopause and hormonal replacement therapy on body cell mass and body fat mass. Am J Obstet Gynecol 1995;172:896–900.[Medline]
14. Gambacciani M, Ciaponi M, Cappagli B, et al. Body weight, body fat distribution, and hormonal replacement therapy in early postmenopausal women. J Clin Endocrinol Metab 1997;82:414–7.[Abstract/Free Full Text]
15. Davis SR, Walker KZ, Strauss BJ. Effects of estradiol with and without testosterone on body composition and relationships with lipids in postmenopausal women. Menopause 2000;7:395–401.[Medline]
16. Reubinoff BE, Wurtman J, Rojansky N, et al. Effects of hormone replacement therapy on weight, body composition, fat distribution, and food intake in early postmenopausal women: a prospective study. Fertil Steril 1995;64:963–8.[Medline]
17. Perrone G, Liu Y, Capri O, et al. Evaluation of the body composition and fat distribution in long-term users of hormone replacement therapy. Gynecol Obstet Invest 1999;48:52–5.[Medline]
18. Samaras K, Kelly PJ, Spector TD, Chiano MN, Campbell LV. Tobacco smoking and oestrogen replacement are associated with lower total and central fat in monozygotic twins. Int J Obes Relat Metab Disord 1998;22:149–56.[Medline]
19. Greenfield JR, Samaras K, Jenkins AB, Kelly PJ, Spector TD, Campbell LV. Moderate alcohol consumption, estrogen replacement therapy, and physical activity are associated with increased insulin sensitivity: is abdominal adiposity the mediator? Diabetes Care 2003;26:2734–40.[Abstract/Free Full Text]
20. Margolis KL, Bonds DE, Rodabough RJ, et al. Effect of oestrogen plus progestin on the incidence of diabetes in postmenopausal women: results from the Women's Health Initiative Hormone Trial. Diabetologia 2004;47:1175–87.[Medline]
21. Jensen J, Christiansen C, Rodbro P. Oestrogen-progestogen replacement therapy changes body composition in early post-menopausal women. Maturitas 1986;8:209–16.[Medline]
22. Dittmar M. Comparison of soft tissue body composition in postmenopausal women with or without hormone replacement therapy considering the influence of reproductive history and lifestyle. Ann Hum Biol 2001;28:207–21.[Medline]
23. Bemben DA, Langdon DB. Relationship between estrogen use and musculoskeletal function in postmenopausal women. Maturitas 2002;42:119–27.[Medline]
24. Sarrel P, Dobay B, Wiita B. Estrogen and estrogen-androgen replacement in postmenopausal women dissatisfied with estrogen-only therapy. Sexual behavior and neuroendocrine responses. J Reprod Med 1998;43:847–56.[Medline]
25. Chang S, Wu X, Yu H, Spitz MR. Plasma concentrations of insulin-like growth factors among healthy adult men and postmenopausal women: associations with body composition, lifestyle, and reproductive factors. Cancer Epidemiol Biomarkers Prev 2002;11:758–66.[Abstract/Free Full Text]
26. Hartmann B, Kirchengast S, Albrecht A, Laml T, Bikas D, Huber J. Effects of hormone replacement therapy on growth hormone secretion patterns in correlation to somatometric parameters in healthy postmenopausal women. Maturitas 1995;22:239–46.[Medline]
27. Cauley JA, Robbins J, Chen Z, et al. Effects of estrogen plus progestin on risk of fracture and bone mineral density: the Women's Health Initiative randomized trial. JAMA 2003;290:1729–38.[Abstract/Free Full Text]

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