Oestrogen and progestogen hormone replacement therapy for peri-menopausal and post-menopausal women: weight and body fat distribution

Background: Hormone replacement therapy (HRT) is commonly prescribed to treat menopausal symptoms and to prevent post-menopausal bone loss. However, many women are concerned about hormonal replacement therapy because they believe that such treatment will result in weight gain. The effect of HRT on weight and body fat distribution has not yet been examined in systematic reviews. It is an important topic since many women decline oestrogen therapy due to their concerns about resultant weight gain, and thus forego its potential therapeutic benefits.

To evaluate the effect of unopposed oestrogen or combined oestrogen and progestogen hormone replacement therapy (HRT) upon the weight and body fat distribution of perimenopausal and postmenopausal women. Search strategy: The search strategy of the Menstrual Disorders and Subfertility Group was used for the identification of randomised controlled trials (RCTs). Computerised searches of MEDLINE, EMBASE, Current Contents, Biological Abstracts and CINAHL were performed. Attempts were made to identify trials from citation lists of review articles and relevant papers already obtained. In most cases, first authors of each eligible trial were contacted for additional information. All those trials that had been located as at August 1998 were examined for eligibility. Selection criteria: All randomised, placebo or no treatment controlled trials that detailed the effect of HRT on weight or body fat distribution, including studies where HRT was combined with other therapy such as diet, supplements or exercise. Studies were eligible for consideration even though the main focus of the trial may have been on another aspect of HRT. Previous HRT use should have ceased at least one month (in the case of patches, cream or gel) or three months (for oral preparations or subcutaneous pellets) before commencement of the study. Data collection and analysis: Twenty two RCTs were identified that fulfilled the inclusion criteria for this review. The results of one trial were not available in a form that allowed it to be included in the meta-analysis; however, it has been included in the text of the review for discussion. Twenty four RCTs are awaiting assessment pending additional information from first authors. Two reviewers extracted the data independently, and the weighted mean differences for continuous outcomes were estimated from the data. Results for unopposed oestrogen and combined oestrogen were analysed separately, and the effect of each treatment regimen on body weight, BMI, waist-hip ratio, fat mass and skinfold measurement was examined where available. The effect of differing dosage levels on these parameters was also examined. Main results: Outcomes were evaluated separately for unopposed oestrogen and oestrogen/progestogen regimens. Statistical analysis was performed using the weighted mean difference for continuous outcomes as recommended by the Cochrane Menstrual Disorders and Subfertility Group. No statistically significant difference was found in mean weight gain between those using unopposed oestrogen and non-HRT users (0.66 kg, 95% CI -0.62, 1.93). No significant difference was found in mean weight gain between those using oestrogen/progestogen therapy and non-HRT users (-0.47 kg, 95% CI -1.63, 0.69). Insufficient data exist to enable meta-analysis of the effect of unopposed oestrogen on BMI. The reviewers found no statistically significant difference in mean BMI increase between those using oestrogen/progestogen and non-HRT users (-0.50, 95% CI -1.06, 0.06). Insufficient data exist to enable meta-analysis of the effect of HRT on waist-hip ratio, fat mass or skinfold thickness. Reviewer's conclusions: There is evidence of no effect of unopposed oestrogen or combined oestrogen on body weight, indicating that these regimens do not cause extra weight gain in addition to that normally gained at menopause. (ABSTRACT TRUNCATED) Conflict of interest statement There were no conflicts of interest. Figures

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to studies excluded from this review Bellantoni 1991 {published data only} - - Bellantoni MF, Harman SM, Cullins VE, Engelhardt SM, Blackman MR. Transdermal estradiol with oral progestin: biological and clinical effects in younger and older postmenopausal women. Journal of Gerontology 1991;46(6):M216‐22. - PubMed Binder 1996 {published data only} - - Binder EF, Birge SJ, Kohrt WM. Effects of endurance exercise and hormone replacement therapy on serum lipids in older women. Journal of the American Geriatric Society 1996;44(3):231‐6. - PubMed Cagnacci 2002 {published data only} - - Cagnacci A, Malmusi S, Arangino S, Zanni A, Rovati L, Cagnacci P. Influence of transdermal estradiol in the regulation of leptin levels of postmenopausal women: A double‐blind, placebo‐controlled study. Menopause 2002;9(1):65‐71. - PubMed Cherry 2002 {published data only} - - Cherry N, Gilmour K, Hanaford P, et al. Oestrogen therapy for prevention of reinfarction in postmenopausal women: a randomised placebo controlled trial. Lancet 2002;360:2001‐8. - PubMed Chung 1996 {published data only} - - Chung TK, Yip SK, Lam P, Chang AM, Haines CJ. A randomized, double‐blind, placebo‐controlled, crossover study on the effect of oral oestradiol on acute menopausal symptoms. Maturitas 1996;25(2):115‐23. - PubMed Davis 2000 {published data only} - - 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(6):395‐401. - PubMed Gambacciani 1995 {published data only} - - Gambacciani M, Spinetti A, Orlandi R, Piaggesi L, Cappagli B, Weiss C, et al. Effects of a new estrogen/progestin combination in the treatment of postmenopausal syndrome. Maturitas 1995;22:115‐20. - PubMed Gambacciani 1997 {published data only} - - Gambacciani M, Ciaponi M, Cappagli B, Piaggesi L, Simone L, Orlandi R. Body weight, body fat distribution, and hormonal replacement therapy in early postmenopausal women. Journal of Clinical Endocrinology and Metabolism 1997;82(2):414‐7. - PubMed Genant 1990 {published data only} - - Genant HK, Baylink DJ, Gallagher JC, Harris ST, Steiger P, Herber M. Effect of estrone sulfate on postmenopausal bone loss. Obstetrics & Gynecology 1990;76(4):579‐84. - PubMed Hanggi 1997 {published data only} - - Hanggi W, Lippuner K, Riesen W, Jaeger P, Birkhauser MH. Long term influence of different postmenopausal hormone replacement regimens on serum lipids and lipoprotein(a): a randomised study. British Journal of Obstetrics & Gynaecology 1997;104(6):708‐17. - PubMed Hosking 1998 {published data only} - - Hosking D, Chilvers CED, Christiansen C, Ravn P, Wasnich R, Ross P, et al. Prevention of bone loss with alendronate in postmenopausal women under 60 years of age. The Early Postmenopausal Intervention Cohort Study Group. New England Journal of Medicine 1998;338(8):485‐92. - PubMed Lindsay 1984 {published data only} - - Lindsay R, Hart DM, Clark DM. The minimum effective dose of estrogen for prevention of postmenopausal bone loss. Obstetrics & Gynaecology 1984;63(6):759‐63. - PubMed Lufkin 1992 {published data only} - - Lufkin EG, Wahner HW, WM OF, Hodgson SF, Kotowicz MA, Lane AW, et al. Treatment of postmenopausal osteoporosis with transdermal estrogen. Annals of Internal Medicine 1992;117(1):1‐9. - PubMed MacLennan 1993 {published data only} - - MacLennan AH, MacLennan A, Wenzel S, Chambers HM, Eckert K. Continuous low‐dose oestrogen and progestogen hormone replacement therapy: a randomised trial. Medical Journal of Australia 1993;159(2):102‐6. - PubMed Morin‐Papunen 2001 {published data only} - - Morin‐Papunen L, Ruokonen A, Vauhkonen I, Tapanainen J, Raudaskoski T. Effects of tibolone versus oestradiol on glucose and lipid metabolism in obese postmenopausal women: a prospective randomised study. Human Reproduction 2001;16(Suppl 1):101. Morrison 1980 {published data only} - - Morrison JC, Martin DC, Blair RA, Anderson GD, Kincheloe BW, Bates GW, et al. The use of medroxyprogesterone acetate for relief of climacteric symptoms. American Journal of Obstetrics & Gynecology 1980;138(1):99‐104. - PubMed Nand 1998 {published data only} - - Nand SL, Webster MA, Baber R, Heller GZ. Menopausal symptom control and side‐effects on continuous estrone sulfate and three doses of medroxyprogesterone acetate. Ogen/Provera Study Group. Climacteric 1998;1(3):211‐8. - PubMed Ongphiphadhanakul {published data only} - - Ongphiphadhanakul B, Chanprasertyothin S, Piaseu N, Chansirikanjana S, Puavilai G, Rajatanavin R. Change in body weight after hormone replacement therapy in postmenopausal women is dependent on basal circulating leptin. Maturitas 1998;30(3):283‐8. - PubMed Pickar 1998 {published data only} - - Pickar JH, Wild RA, Walsh B, Hirvonen E, Lobo RA. Effects of different hormone replacement regimens on postmenopausal women with abnormal lipid levels. Menopause Study Group. Climacteric 1998;1(1):26‐32. - PubMed

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