The Relationship between Menopause and Metabolic Syndrome

Abstract

Menopause is the permanent cessation of menstruation due to loss of ovarian activity. Increases in the incidence of obesity in menopausal women raise important public health concerns. Metabolic syndrome is a combination of several factors, including hypertension, dyslipidemia, insulin resistance, obesity, and glucose intolerance. Menopause is associated with an increased risk of metabolic syndrome regardless of age. When postmenopausal women's predisposition to metabolic syndrome is evaluated, the presence of metabolic syndrome and its components causes an increase in inflammatory cytokines, making weight control difficult. It has been suggested that this may be caused by the decrease in estrogen levels that naturally occurs during menopause, which plays an important role in many mechanisms that may be related to menopause and metabolic syndrome. Therefore hormone replacement therapy may yield positive results in postmenopausal or ovariectomized women. Physical activity and nutrition are important in preventing metabolic syndrome in postmenopausal women. When the relationship between protein intake and the risk of early menopause was examined in depth, it was seen that the risk of early menopause could be reduced with a diet pattern in which animal protein sources are moderate, and plant protein sources are predominant. In light of this evidence, women can be advised to follow the Mediterranean type of lifestyle model to prevent early menopause and maintain health during menopause. In this review, the relationship between changes in estrogen levels during menopause and metabolic syndrome is summarized in the current literature.

Keywords

• Abdominal obesity
• nutrition
• menopause
• metabolic syndrome
• estrogen.

Menopoz ve Metabolik Sendrom İlişkisi

Abstract

Menopoz, ovaryum aktivitesinin yitirilmesi sonucunda menstrüasyonun kalıcı olarak sonlanmasıdır. Menopozdaki kadınlarda obezitenin görülme sıklığındaki artışlar önemli halk sağlığı endişelerini doğurmaktadır. Metabolik sendrom; kardiyovasküler hastalık ve tip 2 diyabet geliştirme riskini artıran hipertansiyon, dislipidemi, insülin direnci, obezite ve glukoz intoleransı gibi çeşitli faktörlerin bir araya gelmesidir. Menopoz, yaştan bağımsız olarak artan metabolik sendrom riski ile ilişkilidir. Postmenopozal kadınların metabolik sendroma yatkınlıkları değerlendirildiğinde metabolik sendrom ve bileşenlerinin varlığı inflamatuar sitokinlerde artışa sebep olarak ağırlık denetimini zorlaştırmaktadır. Buna menopoz ve metabolik sendromla ilişkili olabilecek birçok mekanizmada önemli rol alan ve menopozda doğal olarak gerçekleşen östrojen düzeylerindeki azalmanın sebep olabileceği, bu nedenle postmenopozal veya ovariektomili kadınlarda hormon replasman tedavisinin olumlu sonuç verebileceği öne sürülmüştür. Postmenopozal kadınlarda metabolik sendromun önlenmesinde fiziksel aktivite ve beslenme büyük öneme sahiptir. Protein alımının erken menopoz riski ile ilişkisine derinlemesine bakıldığında hayvansal protein kaynaklarının ılımlı, bitkisel protein kaynakları ağırlıklı bir beslenme örüntüsüyle erken menopoz riskinin azalabileceği görülmüştür. Bu kanıtlar ışığında kadınlara erken menopozdan korunma ve menopoz döneminde sağlığın korunması için Akdeniz tipi beslenme modelini takip etmeleri önerilebilir. Bu derlemede, menopoz sürecinde östrojen seviyelerindeki değişimin metabolik sendromla ilişkisi güncel literatür doğrultusunda özetlenmiştir.

Keywords

• Abdominal obezite
• beslenme
• menopoz
• metabolik sendrom
• östrojen.

References

1. Birleşmiş Milletler, United Nations Department of Economic and Social Affairs. Population Division 2022 World Population Prospects. New York; 2022. Erişim tarihi: 14. Şubat 2024 https://population.un.org/ wpp/Download/Standard/Population/
2. Türkiye İstatistik Kurumu (TÜİK). İstatistiklerle Kadın. Ankara; 2022. Erişim tarihi: 14. Şubat 2024 https://data.tuik.gov.tr/Bulten/ Index?p=Istatistiklerle-Kadin-2022-49668.
3. Dünya Sağlık Örgütü, World Health Organization (WHO). Menopause. Geneva; 2022. Erişim tarihi: 14. Şubat 2024 https://www.who.int/news-room/fact-sheets/detail/menopause.
4. Eshtiaghi R, Esteghamati A, Nakhjavani M. Menopause is an independent predictor of metabolic syndrome in Iranian women. Maturitas. 2010;65(3):262-6. DOI: 10.1016/j.maturitas.2009.11.004.
5. Reiss NA. Ontogeny and estrogen responsiveness of creatine kinase and glycolytic enzymes in brain and uterus of rat. Neurosci Lett.1988; 84 (2):197-202. DOI: 10.1016/0304-3940(88)90407-7.
6. Awa WL, Fach E, Krakow D, Welp R, Kunder J, Voll A, et al. Initiative and the German BMBF Competence Networks Diabetes mellitus and Obesity, Type 2 diabetes from pediatric to geriatric age: analysis of gender and obesity among 120 183 patients from the German/Austrian DPV database. Eur J Endocrinol. 2012; 167 (2): 245–254. DOI: 10.1530/ EJE-12-0143.
7. Wietlisbach V, Marques-Vidal P, Kuulasmaa K, Karvanen J, Paccaud F, WHO MONICA Project. The relation of body mass index and abdominal adiposity with dyslipidemia in 27 general populations of the WHO MONICA Project. Nutr Metab Cardiovasc Dis. 2013; 23 (5):432–442. DOI: 10.1016/j.numecd.2011.09.002.
8. Miranda PJ, DeFronzo RA, Califf RM, Guyton JR. Metabolic syndrome: definition, pathophysiology, and mechanisms. Am Heart J. 2005; 149 (1):33–45. DOI: 10.1016/j.ahj.2004.07.013.

9. Expert Panel on Detection, Evaluation, and Treatment of High Blood Cholesterol in Adults; Executive Summary of The Third Report of The National Cholesterol Education Program (NCEP) Expert Panel on Detection, Evaluation, And Treatment of High Blood Cholesterol In Adults (Adult Treatment Panel III). JAMA. 2001 ; 285 (19):2486–2497. DOI: 10.1001/jama.285.19.2486.
10. Sinatora RV, Chagas EFB, Mattera FOP, Mellem LJ, Santos AROD, Pereira LP, et al. Relationship of Inflammatory Markers and Metabolic Syndrome in Postmenopausal Women. Metabolites. 2022; 12(1):73. DOI: 10.3390/metabo12010073.
11. Garcia-Alfaro P, Bergamaschi L, Marcos C, Garcia S, Rodríguez I. Prevalence of ocular surface disease symptoms in peri- and postmenopausal women. Menopause. 2020; 27(9):993-998. DOI: 10.1097/GME.0000000000001565.
12. Grundy SM, Cleeman JI, Daniels SR, Donato KA, Eckel RH, Franklin BA, et al. Diagnosis and management of the metabolic syndrome: an American Heart Association/National Heart, Lung, and Blood Institute Scientific Statement. Circulation. 2005; 112(17): 2735–2752. DOI: 10.1161/CIRCULATIONAHA.105.169404.
13. Cybulska AM, Schneider-Matyka D, Bosiacki M, Chlubek D, Panczyk M, Grochans E. The Levels of Bioelements in Postmenopausal Women with Metabolic Syndrome. Nutrients. 2022; 14(19):4102. DOI: 10.3390/ nu14194102.
14. Crispo A, Augustin LSA, Luongo A, Calderaio C, Breda J, Coluccia S, et al. Central obesity, body mass index, metabolic syndrome and mortality in Mediterranean breast cancer patients. Sci Rep. 2023 Dec 1;13(1):21208. DOI: 10.1038/s41598-023-45439-y.
15. Jeong HG, Park H. Metabolic Disorders in Menopause. Metabolites. 2022; 8;12(10):954. DOI: 10.3390/metabo12100954.
16. Avhan N. Diabetes mellitusun beslenme tedavisinde protein alımı. (ed: Mercanlıgil SM) Proteinlerin Sağlıkta, Hastalıklarda ve Bazı Özel Durumlarda Önemi. 1. Baskı. Ankara: Türkiye Klinikleri; 2022. p.7-13.
17. Fournier C, Karagounis LG, Sacco SM, Horcajada MN, Decaens T, Offord E, et al. Impact of moderate dietary protein restriction on glucose homeostasis in a model of estrogen deficiency. J Nutr Biochem. 2022; 102: 108952. DOI: 10.1016/j.jnutbio.2022.108952.
18. Boutot ME, Purdue-Smithe A, Whitcomb BW, Szegda KL, Manson JE, Hankinson SE, et al. Dietary Protein Intake and Early Menopause in the Nurses' Health Study II. Am J Epidemiol. 2018; 187(2):270–277. DOI: 10.1093/ aje/kwx256.
19. Macdonald HM, Yang T. Dietary Protein Intake and Early Menopause In The Nurses' Health Study II. Am J Epidemiol. 2018; 187(6):1341–1342. DOI: 10.1093/aje/kwy058.
20. Bach-Faig A, Berry EM, Lairon D, Reguant J, Trichopoulou A, Dernini S, et al. Mediterranean Diet Foundation Expert Group. Mediterranean diet pyramid today. Science and cultural updates. Public Health Nutr. 2011, 14, 2274–2284. DOI: 10.1017/S1368980011002515.
21. Leone A, De Amicis R, Battezzati A and Bertoli S. Adherence to the Mediterranean Diet and Risk of Metabolically Unhealthy Obesity in Women: A Cross-Sectional Study. Front. Nutr. 2022; 9:858206. DOI: 10.3389/ fnut.2022.858206.
22. Hidalgo-Mora JJ, Cortés-Sierra L, García-Pérez MÁ, Tarín JJ, Cano A. Diet to Reduce the Metabolic Syndrome Associated with Menopause. The Logic for Olive Oil. Nutrients. 2020; 18;12(10):3184. DOI: 10.3390/nu12103184.
23. Ly TTG, Yun J, Lee D-H, Chung J-S, Kwon S-M. Protective Effects and Benefits of Olive Oil and Its Extracts on Women’s Health. Nutrients. 2021; 13(12):4279. DOI: 10.3390/nu13124279.
24. Cole RM, Puchala S, Ke JY, Abdel-Rasoul M, Harlow K, O'Donnell B, et al. Linoleic Acid-Rich Oil Supplementation Increases Total and High-Molecular- Weight Adiponectin and Alters Plasma Oxylipins in Postmenopausal Women with Metabolic Syndrome. Curr Dev Nutr. 2020; 21;4(9):nzaa136. DOI: 10.1093/cdn/nzaa136.
25. Bauset C, Martínez-Aspas A, Smith-Ballester S, García-Vigara A, Monllor- Tormos A, Kadi F, Nilsson A, Cano A. Nuts and Metabolic Syndrome: Reducing the Burden of Metabolic Syndrome in Menopause. Nutrients. 2022; 14(8):1677. DOI: 10.3390/nu14081677.
26. Toth MJ, Poehlman ET, Matthews DE, Tchernof A, MacCoss MJ. Effects of estradiol and progesterone on body composition, protein synthesis, and lipoprotein lipase in rats. Am J Physiol Endocrinol Metab. 2001; 280:3, E496-E501. DOI: 10.1152/ajpendo.2001.280.3.E496.
27. Nelson LR, Bulun SE. Estrogen production and action. J Am Acad Dermatol. 2001; 45 (3):S116-S124. DOI: 10.1067/mjd.2001.117432.
28. Shen ZY, Saloniemi T, Rönnblad A, Järvensivu P, Pakarinen P, Poutanen M. Sex Steroid-Dependent and -Independent Action of Hydroxysteroid (17β) Dehydrogenase 2: Evidence from Transgenic Female Mice. Endocrinology. 2009; 150 (11):4941–4949. DOI: 10.1210/en.2009-0670.
29. Tessier S, Riesco E, Lacaille M, Pérusse F, Weisnagel J, Doré J, et al. Impact of walking on adipose tissue lipoprotein lipase activity and expression in pre- and postmenopausal women. Obes Facts. 2010;3(3):191-9. DOI: 10.1159/000314611.
30. Jeong S, Yoon M. 17β-Estradiol inhibition of PPARγ-induced adipogenesis and adipocyte-specific gene expression. Acta Pharmacol Sin. 2011; 32: 230– 238. DOI: 10.1038/aps.2010.198.
31. Abeles ED, Cordeiro LM, Martins AS, Pesquero JL, Reis AM, Andrade SP, Botion LM. Estrogen therapy attenuates adiposity markers in spontaneously hypertensive rats. Metabolism. 2012;61(8):1100-7. DOI: 10.1016/j. metabol.2011.12.015.
32. Beckett T, Tchernof A, Toth MJ. Effect of ovariectomy and estradiol replacement on skeletal muscle enzyme activity in female rats. Metabolism. 2002; 51 (11):1397-1401. DOI: 10.1053/meta.2002.35592.
33. Stirone C, Boroujerdi A, Duckles SP, Krause DN. Estrogen Receptor Activation of Phosphoinositide-3 Kinase, Akt, and Nitric Oxide Signaling in Cerebral Blood Vessels: Rapid and Long-Term Effects. Mol Pharmacol.2005; 67 (1):105-113. DOI: 10.1124/mol.104.004465.
34. Oosthuyse T, Bosch AN. Oestrogen's regulation of fat metabolism during exercise and gender specific effects. Curr Opin Pharmacol.2012; 12 (3):363- 371. DOI: 10.1016/j.coph.2012.02.008.
35. Mauvais-Jarvis F, Clegg DJ, Hevener AL. The Role of Estrogens in Control of Energy Balance and Glucose Homeostasis. Endocr Rev. 2013; 34 (3):309– 338. DOI: 10.1210/er.2012-1055.
36. Alaynick WA. Nuclear receptors, mitochondria and lipid metabolism. Mitochondrion. 2008; 8(4):329-337. DOI: 10.1016/j.mito.2008.02.001.
37. Razmara A, Sunday L, Stirone C, Wang XB, Diana N. DN, Duckles SP et al. Mitochondrial Effects of Estrogen Are Mediated by Estrogen Receptor α in Brain Endothelial Cells. J Pharmacol Exp Ther. 2008; 325 (3): 782-790. DOI: 10.1124/jpet.107.134072.
38. Prokai L, Nguyen V, Urbanski HF. Effect of estradiol replacement on hippocampal concentrations of estrogens in aged rhesus macaques maintained on an obesogenic diet. Biochem Biophys Rep. 2023; 16;35:101548. DOI: 10.1016/j.bbrep.2023.101548.
39. Rodríguez-Cuenca S, Monjo M, Gianotti M, Proenza AM, Roca P. Expression of mitochondrial biogenesis-signaling factors in brown adipocytes is influenced specifically by 17β-estradiol, testosterone, and progesterone. Am J Physiol Endocrinol Metab.2007; 292(1):E340-6. DOI: 10.1152/ajpendo.00175.2006.
40. Leclère R, Torregrosa-Muñumer R, Kireev R, García C, Vara E, Tresguerres JA, et al. Effect of estrogens on base excision repair in brain and liver mitochondria of aged female rats. Biogerontology. 2013; 14(4):383-94. DOI: 10.1007/s10522-013-9431-x.
41. Rodriguez-Cuenca S, Monjo M, Frontera M, Gianotti M, Proenza AM, Roca P. Sex steroid receptor expression profile in brown adipose tissue. Effects of hormonal status. Cell Physiol Biochem. 2007;20(6):877-86. DOI: 10.1159/000110448.
42. Pedersen SB, Bruun JM, Kristensen K, Richelsen B. Regulation of UCP1, UCP2, and UCP3 mRNA Expression in Brown Adipose Tissue, White Adipose Tissue, and Skeletal Muscle in Rats by Estrogen. Biochem Biophys Res Commun. 2001; 288 (1):191-197. DOI: 10.1006/bbrc.2001.5763.
43. Sakurai K, Kawazuma M, Adachi T, Harigaya T, Saito Y, Hashimoto N, et al. Bisphenol A affects glucose transport in mouse 3T3-F442A adipocytes. Br J Pharmacol. 2004; 141(2):209-14. DOI: 10.1038/sj.bjp.0705520.
44. Obici S. Molecular Targets for Obesity Therapy in the Brain. Endocrinology. 2009; 150, (6):2512–2517. DOI: 10.1210/en.2009-0409.
45. Hart-Unger S, Korach KS. Estrogens and Obesity: Is It All in Our Heads?. Cell Metab. 2011; 14(4):435-436. DOI: 10.1016/j.cmet.2011.09.003.
46. Combs TP, Pajvani UB, Berg AH, Lin Y, Jelicks LA, Laplante M, et al. A Transgenic Mouse with a Deletion in the Collagenous Domain of Adiponectin Displays Elevated Circulating Adiponectin and Improved Insulin Sensitivity. Endocrinology. 2004;145 (1):367–383. DOI: 10.1210/en.2003-1068.
47. Combs TP, Berg AH, Rajala MW, Klebanov S, Iyengar P, Jimenez-Chillaron JC, et al. Sexual Differentiation, Pregnancy, Calorie Restriction, and Aging Affect the Adipocyte-Specific Secretory Protein Adiponectin. Diabetes. 2003; 52 (2):268–276. DOI: 10.2337/diabetes.52.2.268.
48. Rose DP, Komninou D, Stephenson GD. Obesity, adipocytokines, and insulin resistance in breast cancer. Obes Rev. 2004; 5(3):153-65. DOI: 10.1111/j.1467-789X.2004.00142.x.
49. Yonezawa R, Wada T, Matsumoto N, Morita M, Sawakawa K, Ishii Y, et al. Central versus peripheral impact of estradiol on the impaired glucose metabolism in ovariectomized mice on a high-fat diet. Am J Physiol Endocrinol Metab. 2012; 303(4):E445-56. DOI: 10.1152/ajpendo.00638.2011.
50. Stubbins RE, Najjar K, Holcomb VB, Hong J, Núñez NP. Oestrogen alters adipocyte biology and protects female mice from adipocyte inflammation and insulin resistance. Diabetes Obes Metab. 2012; 14(1):58-66. DOI: 10.1111/j.1463-1326.2011.01488.x.
51. Andrea G, Marta C, Andrea R, Tommaso S. Menopause, Hormone Replacement Therapy (HRT) and Obesity. Curre Res Diabetes & Obes J. 2018; 7(1): 555704. DOI: 10.19080/CRDOJ.2018.07.555704.
52. “The 2022 Hormone Therapy Position Statement of The North American Menopause Society” Advisory Panel. The 2022 hormone therapy position statement of The North American Menopause Society. Menopause. 2022;29(7):767-794. DOI: 10.1097/GME.0000000000002028.
53. Opoku AA, Abushama M, Konje JC. Obesity and menopause. Best Pract Res Clin Obstet Gynaecol. 2023;88:102348. DOI: 10.1016/j. bpobgyn.2023.102348.
54. Kamińska MS, Schneider-Matyka D, Rachubińska K, Panczyk M, Grochans E, Cybulska AM. Menopause Predisposes Women to Increased Risk of Cardiovascular Disease. J Clin Med. 2023; 12(22):7058. DOI: 10.3390/ jcm12227058.
55. Bontempo S, Yeganeh L, Giri R, Vincent AJ. Use of MHT in women with cardiovascular disease: a systematic review and meta-analysis. Climacteric. 2024 Feb;27(1):93-103. doi: 10.1080/13697137.2023.2273524.
56. Ou YJ, Lee JI, Huang SP, Chen SC, Geng JH, Su CH. Association between Menopause, Postmenopausal Hormone Therapy and Metabolic Syndrome. J Clin Med. 2023; 30;12(13):4435. DOI: 10.3390/jcm12134435.
57. Mendoza N, Ramírez I, de la Viuda E, Coronado P, Baquedano L, Llaneza P, et al. Eligibility criteria for Menopausal Hormone Therapy (MHT): a position statement from a consortium of scientific societies for the use of MHT in women with medical conditions. MHT Eligibility Criteria Group. Maturitas. 2022;166:65-85. DOI: 10.1016/j.maturitas.2022.08.008.