Association Between Hormone Therapy and Weight Gain in the Menopause Transition and After Menopause: A Systematic Review and Meta-Analysis
DOI:
https://doi.org/10.36311/jhgd.v33.14764Palabras clave:
postmenopause, menopause, climacteric, hormone replacement therapy, body mass index, body weightResumen
Objectives: to conduct a systematic review and meta-analysis in order to assess whether hormone therapy (HT) increases weight in women in the menopausal transition and after menopause.
Method: this article proposes an update to the systematic review published in 2005 by the Cochrane Library (Kongnyuy EJ et al 2005) with reference to studies assessing weight changes in women receiving HT from 1986 to 2005. Following PRISMA recommendations, we included randomized controlled trials (RCTs) ) from May 2005 onwards from Medline, Embase, and the Cochrane CENTRAL databases. Standardized mean differences (SMD) and 95% confidence intervals (CI) were calculated. Two authors independently assessed the risk of biases in the selected studies.
Results: ten RCTs were included, totaling 2,588 HT users and 764 non-users. Different regimens, dosages, and routes of administration in HT users were analyzed and compared to non-users. The results did not show statistically significant differences for most of the HT regimens evaluated. There was significant weight gain only in patients using EEC alone at dosages of 0.45 mg/day and 0.3 mg/day when compared to placebo (p 0.01); as well as in patients receiving esto-progestative combinations of 0.5 mg/day 17-beta-estradiol (E2) + 100 mg/day progesterone, with a 0.7 kg weight increase (p 0.032). On the other hand, the combinations of 1 mg/day estradiol valerate + 3 mg/day drospirenone showed a -1.0 kg reduction (p = 0.04), whereas a -0.2 kg reduction (p = 0.001) was identified in patients using 1 mg /day estradiol (E) + 0.5 mg norethisterone acetate (NETA). Tibolone therapy showed no statistically significant changes in weight. After performing a meta-analysis, the comparative results between users and non-users showed that there was a slight weight increase (+0.279 kg ; CI -1.71 to 2.27) in patients using 0.625 mg/day conjugated equine estrogen (CEE) + 2.5 mg/day medroxyprogesterone acetate (MPA). As for the patients receiving 2.5 mg/day Tibolone, weight gain (+0.670 kg; CI from -1.14 to 2.48) was also observed in them. However, these increases were not significant when compared to non-HT users.
Conclusions: most regimens studied showed that patients using HT in the menopausal transition and after menopause did not show significant weight gain. The only combination that showed weight gain was 0.5 mg/day 17-beta-estradiol (E2) + 100 mg/day progesterone observed, while there was weight reduction in patients using 1 mg/day estradiol valerate + 3 mg/day drospirenone and 1 mg/day estradiol (E) + norethisterone acetate.
Descargas
Referencias
Harlow SD, Gass M, Hall JE, Lobo R, Maki P, Rebar RW, Sherman S, Sluss PM, de Villiers TJ; STRAW + 10 Collaborative Group. Executive summary of the Stages of Reproductive Aging Workshop + 10: addressing the unfinished agenda of staging reproductive aging. J Clin Endocrinol Metab. 2012 Apr;97(4):1159-68. doi: 10.1210/jc.2011-3362. Epub 2012 Feb 16. PMID: 22344196; PMCID: PMC3319184.
Speroff L. The perimenopause: definitions, demography, and physiology. Obstet Gynecol Clin North Am. 2002;29(3):397-410.
Palacios S, Foidart JM, Genazzani AR. Advances in hormone replacement therapy with drospirenone, a unique progestogen with aldosterone receptor antagonism. Maturitas. 2006 Nov 20;55(4):297-307. doi: 10.1016/j.maturitas.2006.07.009. Epub 2006 Sep 1. PMID: 16949774.
Shifren JL, Gass ML; NAMS Recommendations for Clinical Care of Midlife Women Working Group. The North American Menopause Society recommendations for clinical care of midlife women. Menopause. 2014 Oct;21(10):1038-62. doi: 10.1097/GME.0000000000000319. PMID: 25225714.
Kaunitz AM, Manson JE. Management of Menopausal Symptoms. Obstet Gynecol. 2015 Oct;126(4):859-876. doi: 10.1097/AOG.0000000000001058. PMID: 26348174; PMCID: PMC4594172.
Wender MCO, Pompei LM, Fernandes CE; Associação Brasileira de Climatério (Sobrac). Consenso brasileiro de terapêutica hormonal da menopausa 2014. São Paulo: Leitura Médica; 2014.
Pardini D. Terapia de reposição hormonal na menopausa [Hormone replacement therapy in menopause]. Arq Bras Endocrinol Metabol. 2014 Mar;58(2):172-81. Portuguese. doi: 10.1590/0004-2730000003044. PMID: 24830594.
Reynolds RF, Obermeyer CM, Walker AM, Guildert D. The role of treatment intentions and concerns about sideeffects in women’s decision to continue postmenopausal hormone therapy. Maturitas 2002;43:83–94.
Hope S, Rees MCP. Why do British women start and stop hormone replacement therapy?. Journal of the British Menopausal Society 1995;October:26–8.
Davis SR, Castelo-Branco C, Chedraui P, Lumsdem MA, Nappi RE, Shah D, et al. Understanding weight gain at menopause. Climacteric. 2012 Oct;15(5):41929. http://dx.doi.org/10.3109/13697137.2012.707385.
Panazzolo DG, Silva LHA, Leão LA, Aguiar LGK. Efeitos da terapia hormonal da menopausa sobre a gordura corporal. HUPE. 2014 2014;13(1):47-53
Kongnyuy EJ, Norman RJ, Flight IHK, Rees MC. Oestrogen and progestogen hormone replacement therapy for peri-menopausal and post-menopausal women: weight and body fat distribution. Cochrane Database of Systematic Reviews 1999, Issue 3. Art. No.: CD001018. DOI: 10.1002/14651858.CD001018. Accessed 16 June 2021.
Higgins_JPT, Green_S, editors. Cochrane Reviewers’ Handbook 4.2.5 [updated May 2005]. http://www.cochrane.org.resources/handbook/hbook.htm (accessed 28 January 2006). The Cochrane Collaboration, 2005.
Page MJ, McKenzie JE, Bossuyt PM, Boutron I, Hoffmann TC, Mulrow CD, et al. The PRISMA 2020 statement: an updated guideline for reporting systematic reviews. BMJ 2021;372:n71. doi: 10.1136/bmj.n71
PROSPERO: International prospective register of systematic reviews. Year of registration. CRD42022240772.https://www.crd.york.ac.uk/prospero/display_record.php?ID=CRD42022240772.
Jadad AR, Moore RA, Carroll D, et al. Assessing the quality of reports of randomized clinical trials: is blinding necessary? Control Clin Trials 1996;17(01):1–12. Doi: 10.1016/0197-2456 (95)00134-4.
Yasui T, Uemura H, Umino Y, Takikawa M, Saito S, Kuwahara A, Matsuzaki T, Maegawa M, Furumoto H, Miura M, Irahara M. Serum estrogen level after hormone replacement therapy and body mass index in postmenopausal and bilaterally ovariectomized women. Maturitas. 2005 Jan 10;50(1):19-29. doi: 10.1016/j.maturitas.2004.03.013. PMID: 15590210.
Chen Z, Bassford T, Green SB, Cauley JA, Jackson RD, LaCroix AZ, Leboff M, Stefanick ML, Margolis KL. Postmenopausal hormone therapy and body composition--a substudy of the estrogen plus progestin trial of the Women’s Health Initiative. Am J Clin Nutr. 2005 Sep;82(3):651-6. doi: 10.1093/ajcn.82.3.651. PMID: 16155280.
Sites CK, L’Hommedieu GD, Toth MJ, Brochu M, Cooper BC, Fairhurst PA. 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. J Clin Endocrinol Metab. 2005 May;90(5):2701-7. doi: 10.1210/jc.2004-1479. Epub 2005 Feb 1. PMID: 15687338.
Tugrul S, Yildirim G, Pekin O, Uslu H, Kutlu T, Eren S. Comparison of two forms of continuous combined hormone replacement therapy with respect to metabolic effects. Arch Gynecol Obstet. 2007 May;275(5):335-9. doi: 10.1007/s00404-006-0265-5. Epub 2006 Oct 19. PMID: 17051405.
Odabasi AR, Yuksel H, Kafkas S, Demircan S, Karul A, Kozaci D, Koseoglu K, Onur E. Effects of tibolone on abdominal subcutaneous fat, serum leptin levels, and anthropometric indices: a 6-month, prospective, randomized, placebo-controlled, double-blind study. Adv Ther. 2006 Nov-Dec;23(6):926-37. doi: 10.1007/BF02850215. PMID: 17276962.
Yüksel H, Odabaşi AR, Demircan S, Karul A, Kozaci LD, Köseoğlu K, Kizilkaya K, Başak O. Effects of oral continuous 17beta-estradiol plus norethisterone acetate replacement therapy on abdominal subcutaneous fat, serum leptin levels and body composition. Gynecol Endocrinol. 2006 Jul;22(7):381-7. doi: 10.1080/09513590600842281. PMID: 16864148.
Tommaselli GA, Di Carlo C, Di Spiezio Sardo A, Bifulco G, Cirillo D, Guida M, Capasso R, Nappi C. Serum leptin levels and body composition in postmenopausal women treated with tibolone and raloxifene. Menopause. 2006 Jul-Aug;13(4):660-8. doi: 10.1097/01.gme.0000227335.27996.d8. PMID: 16837888.
Zang H, Carlström K, Arner P, Hirschberg AL. Effects of treatment with testosterone alone or in combination with estrogen on insulin sensitivity in postmenopausal women. Fertil Steril. 2006 Jul;86(1):136-44. doi: 10.1016/j.fertnstert.2005.12.039. Epub 2006 Jun 5. PMID: 16750207.
Thorneycroft IH, Lindsay R, Pickar JH. Body composition during treatment with conjugated estrogens with and without medroxyprogesterone acetate: analysis of the women’s Health, Osteoporosis, Progestin, Estrogen (HOPE) trial. Am J Obstet Gynecol. 2007 Aug;197(2):137.e1-7. doi: 10.1016/j.ajog.2007.05.042. PMID: 17689624.
Yüksel H, Odabasi AR, Demircan S, Köseoğlu K, Kizilkaya K, Onur E. Effects of postmenopausal hormone replacement therapy on body fat composition. Gynecol Endocrinol. 2007 Feb;23(2):99-104. doi: 10.1080/09513590601152177. PMID: 17454160.
Dedeoğlu EN, Erenus M, Yörük P. Effects of hormone therapy and tibolone on body composition and serum leptin levels in postmenopausal women. Fertil Steril. 2009 Feb;91(2):425-31. doi: 10.1016/j.fertnstert.2007.11.061. Epub 2008 Feb 4. PMID: 18249383.
Ziaei S, Moaya M, Faghihzadeh S. Comparative effects of continuous combined hormone therapy and tibolone on body composition in postmenopausal women. Climacteric. 2010 Jun;13(3):249-53. doi: 10.3109/13697130903318240. PMID: 19848555.
Paoletti AM, Cagnacci A, Di Carlo C, Orrù MM, Neri M, D’Alterio MN, Melis GB. Clinical effect of hormonal replacement therapy with estradiol associated with noretisterone or drospirenone. A prospective randomized placebo controlled study. Gynecol Endocrinol. 2015 May;31(5):384-7. doi: 10.3109/09513590.2014.1003294. Epub 2015 Feb 23. PMID: 25703254.
Deng Y, Xue W, Wang Y, Zhu S, Ma X, Sun A. Effects of different menopausal hormone replacement regimens on body composition in Chinese women. Climacteric. 2018 Dec;21(6):607-612. doi: 10.1080/13697137.2018.1523387. Epub 2018 Oct 31. PMID: 30380948.
Black DR, Minkin MJ, Graham S, Bernick B, Mirkin S. Effects of combined 17β-estradiol and progesterone on weight and blood pressure in postmenopausal women of the REPLENISH trial. Menopause. 2020 Sep 14;28(1):32-39. doi: 10.1097/GME.0000000000001659. PMID: 32932401; PMCID: PMC7769186.
Limpaphayom K, Taechakraichana N, Jaisamrarn U. Hormonal replacement and lipid changes in postmenopausal women. Journal of Medical Association of Thailand. 1996 Jan; 79 (1):10-5. PMID: 8867395.
Descargas
Publicado
Número
Sección
Licencia
Derechos de autor 2023 Murbach IG, Martins VFM, Cristófalo MM, Fukunaga ET, Aldrighi JM
Esta obra está bajo una licencia internacional Creative Commons Atribución 4.0.
