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Perimenopause, body fat, metabolism and menopausal symptoms in relation to serum markers of adiposity, inflammation and digestive metabolism

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Perimenopausal women gain weight that may alter inflammatory status, endocrine equilibrium, and the intensity of vasomotor symptoms.


To measure serum levels of markers related to adiposity, inflammation/angiogenesis and digestive metabolism and correlate them with body mass index (BMI), waist-to-hip ratio (WHR), metabolic parameters and menopausal symptoms (assessed with the 10-item Cervantes Scale [CS-10]).


Serum of perimenopausal women (n = 24), STRAW stages-2 and -1, was analyzed using the Bio-Plex 200 System technology to assess 30 proposed analytes. The MetS was defined by the American Heart Association criteria and women were divided as: normal BMI (NBMI), excessive BMI (EBMI), and EBMI with MetS (EBMI–MetS).


Weight, BMI, abdominal circumference, WHR, systolic blood pressure, glucose and triglyceride levels were significantly higher and high-density lipoprotein cholesterol (HDL-C) was lower in EBMI-MetS women compared to NBMI ones. Insulin, C-peptide, resistin, adipsin, GIP, leptin, IL-6, FGF21 and PAI-1 levels were significantly higher and ghrelin and IGFBP-1 lower in EBMI–MetS women as compared to NBMI ones. Spearman’s correlation of pooled data showed a significant positive correlation between abdominal perimeter and WHR and C-peptide, insulin, adipsin, resistin, leptin, PAI-1 and FGF21 and a negative correlation with IGFBP-1 levels. Total CS-10 scores and hot flush intensity did not differ between studied groups, yet positively correlated with anthropometric values but not with studied analytes.


Perimenopausal women with EBMI and the MetS showed an altered metabolic profile, but no differences in menopausal symptoms which also did not correlate with changes in studied biomarkers.

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10-item Cervantes Scale


Body mass index


Cardiovascular disease


Excessive body mass index


Fibroblast growth factor 21


Fibroblast growth factor 23


Glucagon-like peptide-1


Glucose-dependent insulinotropic peptide


High-density lipoprotein cholesterol


Homeostatic model assessment


Insulin growth factor-binding protein 1


Interleukin 6


Interleukin 8


Low-density lipoprotein cholesterol


Metabolic syndrome


Normal body mass index


Obstructive sleep apneas






Plasminogen activator inhibitor-1


Soluble Fas ligand


Soluble form of cluster of differentiation 40 ligand


Soluble leptin receptor


Stages of Reproductive Aging Workshop


Tumor necrosis factor alpha


Urokinase-type plasminogen activator


Vascular endothelial growth factor A


Waist-to-hip ratio


World Health Organization


  1. Stevenson JC, Tsiligiannis S, Panay N (2018) Cardiovascular risk in perimenopausal women. Curr Vasc Pharmacol.

    Article  Google Scholar 

  2. Janssen I, Powell LH, Crawford S et al (2008) Menopause and the metabolic syndrome: the Study of Women’s Health Across the Nation. Arch Intern Med 168:1568–1575.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  3. Gurka MJ, Vishnu A, Santen RJ, DeBoer MD (2016) Progression of metabolic syndrome severity during the menopausal transition. J Am Hear Assoc.

    Article  Google Scholar 

  4. Davis SR, Castelo-Branco C, Chedraui P et al (2012) Understanding weight gain at menopause. Climacteric 15:419–429.

    Article  CAS  PubMed  Google Scholar 

  5. da Alexandre ST, Aubertin-Leheudre M, Carvalho LP et al (2018) Dynapenic obesity as an associated factor to lipid and glucose metabolism disorders and metabolic syndrome in older adults—findings from SABE Study. Clin Nutr 37:1360–1366.

    Article  CAS  PubMed  Google Scholar 

  6. Garcia-Alfaro P, Garcia S, Rodriguez I et al (2019) Factors related to muscle strength in postmenopausal women aged younger than 65 years with normal vitamin D status. Climacteric.

    Article  PubMed  Google Scholar 

  7. Perez-Lopez FR, Chedraui P (2017) The metabolic syndrome in mid-aged women. In: Cano A (ed) Menopause: a comprehensive approach. Springer Nature, Cham, pp 141–151

    Chapter  Google Scholar 

  8. Pérez-López FR, Larrad-Mur L, Kallen A et al (2010) Gender differences in cardiovascular disease: hormonal and biochemical influences. Reprod Sci 17:511–531.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  9. Chedraui P, Perez-Lopez FR (2019) Metabolic syndrome during female midlife: what are the risks? Climacteric 22:127–132.

    Article  CAS  PubMed  Google Scholar 

  10. Tilg H, Moschen AR (2006) Adipocytokines: mediators linking adipose tissue, inflammation and immunity. Nat Rev Immunol 6:772–783.

    Article  CAS  PubMed  Google Scholar 

  11. Chedraui P, Escobar GS, Pérez-López FR et al (2014) Angiogenesis, inflammation and endothelial function in postmenopausal women screened for the metabolic syndrome. Maturitas.

    Article  PubMed  Google Scholar 

  12. Chedraui P, Pérez-López FR, Escobar GS et al (2014) Circulating leptin, resistin, adiponectin, visfatin, adipsin and ghrelin levels and insulin resistance in postmenopausal women with and without the metabolic syndrome. Maturitas.

    Article  PubMed  Google Scholar 

  13. Hameed S, Dhillo WS, Bloom SR (2009) Gut hormones and appetite control. Oral Dis 15:18–26.

    Article  CAS  PubMed  Google Scholar 

  14. El-Salhy M, Mazzawi T, Hausken T, Hatlebakk JG (2016) Interaction between diet and gastrointestinal endocrine cells. Biomed Rep 4:651–656.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  15. Cagnacci A, Palma F, Romani C et al (2015) Are climacteric complaints associated with risk factors of cardiovascular disease in peri-menopausal women? Gynecol Endocrinol 31:359–362.

    Article  PubMed  Google Scholar 

  16. Franco OH, Muka T, Colpani V et al (2015) Vasomotor symptoms in women and cardiovascular risk markers: systematic review and meta-analysis. Maturitas 81:353–361.

    Article  PubMed  Google Scholar 

  17. Tuomikoski P, Savolainen-Peltonen H (2017) Vasomotor symptoms and metabolic syndrome. Maturitas 97:61–65.

    Article  CAS  PubMed  Google Scholar 

  18. Thurston RC, El Khoudary SR, Sutton-Tyrrell K et al (2012) Vasomotor symptoms and insulin resistance in the study of women’s health across the nation. J Clin Endocrinol Metab 97:3487–3494.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  19. van Dijk GM, Maneva M, Colpani V et al (2015) The association between vasomotor symptoms and metabolic health in peri- and postmenopausal women: a systematic review. Maturitas 80:140–147.

    Article  PubMed  Google Scholar 

  20. Harlow SD, Gass M, Hall JE et al (2012) Executive summary of the stages of reproductive aging workshop + 10: addressing the unfinished agenda of staging reproductive aging. J Clin Endocrinol Metab 97:1159–1168.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  21. World Health Organization (2019) BMI classification. Accessed Nov 2019

  22. Perez-Lopez FR, Fernandez-Alonso AM, Perez-Roncero G et al (2013) Assessment of menopause-related symptoms in mid-aged women with the 10-item Cervantes Scale. Maturitas 76:151–154.

    Article  PubMed  Google Scholar 

  23. Chedraui P, Perez-Lopez FR, Sanchez H et al (2014) Application of the 10-item Cervantes Scale among mid-aged Ecuadorian women for the assessment of menopausal symptoms. Maturitas 79:100–105.

    Article  PubMed  Google Scholar 

  24. Grundy SM, Cleeman JI, Daniels SR et al (2005) Diagnosis and management of the metabolic syndrome: an American Heart Association/National Heart, Lung, and Blood Institute scientific statement. Circulation 112:2735–2752.

    Article  PubMed  Google Scholar 

  25. Chedraui P, San Miguel G, Villacreses D et al (2013) Assessment of insomnia and related risk factors in postmenopausal women screened for the metabolic syndrome. Maturitas 74:154–159.

    Article  PubMed  Google Scholar 

  26. Houser B (2012) Bio-Rad’s Bio-Plex(R) suspension array system, xMAP technology overview. Arch Physiol Biochem 118:192–196.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  27. Dodds RM, Syddall HE, Cooper R et al (2014) Grip strength across the life course: normative data from twelve British studies. PLoS One 9:e113637.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  28. Lovejoy JC, Champagne CM, de Jonge L et al (2008) Increased visceral fat and decreased energy expenditure during the menopausal transition. Int J Obes (Lond) 32:949–958.

    Article  CAS  Google Scholar 

  29. Marlatt KL, Redman LM, Beyl RA et al (2019) Racial differences in body composition and cardiometabolic risk during the menopause transition: a prospective, observational cohort study. Am J Obstet Gynecol.

    Article  PubMed  Google Scholar 

  30. Abildgaard J, Danielsen ER, Dorph E et al (2018) Ectopic lipid deposition is associated with insulin resistance in postmenopausal women. J Clin Endocrinol Metab 103:3394–3404.

    Article  PubMed  Google Scholar 

  31. Bueno-Notivol J, Calvo-Latorre J, Alonso-Ventura V et al (2017) Effect of programmed exercise on insulin sensitivity in postmenopausal women: a systematic review and meta-analysis of randomized controlled trials. Menopause 24:1404–1413.

    Article  PubMed  Google Scholar 

  32. Lee CG, Carr MC, Murdoch SJ et al (2009) Adipokines, inflammation, and visceral adiposity across the menopausal transition: a prospective study. J Clin Endocrinol Metab 94:1104–1110.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  33. Tamakoshi K, Yatsuya H, Wada K et al (2007) The transition to menopause reinforces adiponectin production and its contribution to improvement of insulin-resistant state. Clin Endocrinol 66:65–71.

    Article  CAS  Google Scholar 

  34. Ben Ali S, Jemaa R, Ftouhi B et al (2011) Relationship of plasma leptin and adiponectin concentrations with menopausal status in Tunisian women. Cytokine 56:338–342.

    Article  CAS  PubMed  Google Scholar 

  35. Mostafazadeh M, Haiaty S, Rastqar A, Keshvari M (2018) Correlation between resistin level and metabolic syndrome component: a review. Horm Metab Res 50:521–536.

    Article  CAS  PubMed  Google Scholar 

  36. Park HT, Cho SH, Cho GJ et al (2009) Relationship between serum adipocytokine levels and metabolic syndrome in menopausal women. Gynecol Endocrinol 25:27–31.

    Article  CAS  PubMed  Google Scholar 

  37. Sowers MR, Wildman RP, Mancuso P et al (2008) Change in adipocytokines and ghrelin with menopause. Maturitas 59:149–157.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  38. Chu S, Ding W, Li K et al (2008) Plasma resistin associated with myocardium injury in patients with acute coronary syndrome. Circ J 72:1249–1253.

    Article  CAS  PubMed  Google Scholar 

  39. White RT, Damm D, Hancock N et al (1992) Human adipsin is identical to complement factor D and is expressed at high levels in adipose tissue. J Biol Chem 267:9210–9213

    CAS  PubMed  Google Scholar 

  40. Lo JC, Ljubicic S, Leibiger B et al (2014) Adipsin is an adipokine that improves beta cell function in diabetes. Cell 158:41–53.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  41. Napolitano A, Lowell BB, Damm D et al (1994) Concentrations of adipsin in blood and rates of adipsin secretion by adipose tissue in humans with normal, elevated and diminished adipose tissue mass. Int J Obes Relat Metab Disord 18:213–218

    CAS  PubMed  Google Scholar 

  42. Schrover IM, van der Graaf Y, Spiering W et al (2018) The relation between body fat distribution, plasma concentrations of adipokines and the metabolic syndrome in patients with clinically manifest vascular disease. Eur J Prev Cardiol 25:1548–1557.

    Article  PubMed  PubMed Central  Google Scholar 

  43. Nieuwdorp M, Stroes ES, Meijers JC, Buller H (2005) Hypercoagulability in the metabolic syndrome. Curr Opin Pharmacol 5:155–159.

    Article  CAS  PubMed  Google Scholar 

  44. Mertens I, Verrijken A, Michiels JJ et al (2006) Among inflammation and coagulation markers, PAI-1 is a true component of the metabolic syndrome. Int J Obes 30:1308–1314.

    Article  CAS  Google Scholar 

  45. Dandona P, Aljada A, Bandyopadhyay A (2004) Inflammation: the link between insulin resistance, obesity and diabetes. Trends Immunol 25:4–7

    Article  CAS  Google Scholar 

  46. Zhang X, Yeung DC, Karpisek M et al (2008) Serum FGF21 levels are increased in obesity and are independently associated with the metabolic syndrome in humans. Diabetes 57:1246–1253.

    Article  CAS  PubMed  Google Scholar 

  47. Muller TD, Nogueiras R, Andermann ML et al (2015) Ghrelin. Mol Metab 4:437–460.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  48. Poykko SM, Kellokoski E, Horkko S et al (2003) Low plasma ghrelin is associated with insulin resistance, hypertension, and the prevalence of type 2 diabetes. Diabetes 52:2546–2553.

    Article  PubMed  Google Scholar 

  49. Barazzoni R, Zanetti M, Ferreira C et al (2007) Relationships between desacylated and acylated ghrelin and insulin sensitivity in the metabolic syndrome. J Clin Endocrinol Metab 92:3935–3940.

    Article  CAS  PubMed  Google Scholar 

  50. Tschop M, Weyer C, Tataranni PA et al (2001) Circulating ghrelin levels are decreased in human obesity. Diabetes 50:707–709

    Article  CAS  Google Scholar 

  51. Shiiya T, Nakazato M, Mizuta M et al (2002) Plasma ghrelin levels in lean and obese humans and the effect of glucose on ghrelin secretion. J Clin Endocrinol Metab 87:240–244.

    Article  CAS  PubMed  Google Scholar 

  52. Ukkola O (2005) Ghrelin and the metabolic balance. J Endocrinol Investig 28:849–852

    Article  CAS  Google Scholar 

  53. Reinehr T, Kleber M, Toschke AM et al (2011) Longitudinal association between IGFBP-1 levels and parameters of the metabolic syndrome in obese children before and after weight loss. Int J Pediatr Obes 6:236–243.

    Article  PubMed  Google Scholar 

  54. Lewitt MS, Hilding A, Brismar K et al (2010) IGF-binding protein 1 and abdominal obesity in the development of type 2 diabetes in women. Eur J Endocrinol 163:233–242.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  55. Muka T, Oliver-Williams C, Colpani V et al (2016) Association of vasomotor and other menopausal symptoms with risk of cardiovascular disease: a systematic review and meta-analysis. PLoS One 11:e0157417.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  56. Biglia N, Cagnacci A, Gambacciani M et al (2017) Vasomotor symptoms in menopause: a biomarker of cardiovascular disease risk and other chronic diseases? Climacteric 20:306–312.

    Article  CAS  PubMed  Google Scholar 

  57. Yasui T, Uemura H, Tomita J et al (2006) Association of interleukin-8 with hot flashes in premenopausal, perimenopausal, and postmenopausal women and bilateral oophorectomized women. J Clin Endocrinol Metab 91:4805–4808.

    Article  CAS  PubMed  Google Scholar 

  58. Alexander C, Cochran CJ, Gallicchio L et al (2010) Serum leptin levels, hormone levels, and hot flashes in midlife women. Fertil Steril 94:1037–1043.

    Article  CAS  PubMed  Google Scholar 

  59. Thurston RC, Chang Y, Mancuso P, Matthews KA (2013) Adipokines, adiposity, and vasomotor symptoms during the menopause transition: findings from the Study of Women’s Health Across the Nation. Fertil Steril 100:793–800.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  60. Huang WY, Chang CC, Chen DR et al (2017) Circulating leptin and adiponectin are associated with insulin resistance in healthy postmenopausal women with hot flashes. PLoS One 12:e0176430.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  61. Jequier E (2002) Leptin signaling, adiposity, and energy balance. Ann N Y Acad Sci 967:379–388.

    Article  CAS  PubMed  Google Scholar 

  62. Almabrouk TA, Ewart MA, Salt IP, Kennedy S (2014) Perivascular fat, AMP-activated protein kinase and vascular diseases. Br J Pharmacol 171:595–617.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  63. Gao CC, Kapoor E, Lipford MC et al (2018) Association of vasomotor symptoms and sleep apnea risk in midlife women. Menopause 25:391–398.

    Article  PubMed  PubMed Central  Google Scholar 

  64. Hitchcock CL, Elliott TG, Norman EG et al (2012) Hot flushes and night sweats differ in associations with cardiovascular markers in healthy early postmenopausal women. Menopause 19:1208–1214.

    Article  PubMed  Google Scholar 

  65. Tuomikoski P, Haapalahti P, Ylikorkala O, Mikkola TS (2010) Vasomotor hot flushes and 24-hour ambulatory blood pressure in recently post-menopausal women. Ann Med 42:216–222.

    Article  PubMed  Google Scholar 

  66. Yiannikouris F, Gupte M, Putnam K, Cassis L (2010) Adipokines and blood pressure control. Curr Opin Nephrol Hypertens 19:195–200.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

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We thank women who participated in the “The Omega II, Women’s Health Project: Evaluación de severidad de síntomas menopaúsicos, estado metabólico y depresión en mujeres de mediana edad”.


This research was partially supported by the Sistema de Investigación y Desarrollo and the Vice-Rectorado de Investigación & Postgrado of the Universidad Católica de Santiago de Guayaquil, Guayaquil, Ecuador, through Grant no. SIU-318-853-2014 (The Omega II, Women’s Health Project 2014) provided to Peter Chedraui and Grant no. SIU-411-11-2017 provided to Isabel Grijalva-Grijalva; and also by VitaNova project, Grant CUP D18C15000130008, University of Pisa, Pisa Italy provided to Tommaso Simoncini.

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PC, TS and FRPL conceived and designed the research; CRM, IGG and DSP recruited participants; GP, CRM, MMG and JS performed biochemical assays; GP and MMG analyzed the data and wrote the original draft; PC, TS and FRPL performed data interpretation and contributed to the final editing of the manuscript. All authors reviewed and approved the final version.

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Correspondence to T. Simoncini or P. Chedraui.

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All the authors declare that there are no conflicts of interest regarding the publication of this paper.

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The research protocol was reviewed and approved by the Ethics and Bioethics Committee of the Enrique C. Sotomayor Hospital. All procedures performed in the present study involving humans were in accordance with the ethical standards of the institution or practice at which the studies were conducted. This article does not contain any studies with animals performed by any of the authors.

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Palla, G., Ramírez-Morán, C., Montt-Guevara, M.M. et al. Perimenopause, body fat, metabolism and menopausal symptoms in relation to serum markers of adiposity, inflammation and digestive metabolism. J Endocrinol Invest 43, 809–820 (2020).

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