Association of Hormonal imbalance in menopausal women with cardiovascular disease in Erbil city

Halala H. Mohammed; Leweza B. Abbas

doi:10.21271/ZJPAS.34.6.22

Authors

Halala H. Mohammed Department of Basic Science, College of Medicine, Hawler Medical University, Kurdistan Region, Iraq
Leweza B. Abbas Department of Basic Science, College of Medicine, Hawler Medical University, Kurdistan Region, Iraq

DOI:

https://doi.org/10.21271/ZJPAS.34.6.22

Keywords:

: Sex hormone, Estradiol, Sex hormone-binding globulin, Total testosterone, Menopausal women, and, Cardiovascular disease.

Abstract

Menopausal women have a higher risk of cardiovascular disease (CVD), which is thought to be due to an imbalance in serum estradiol and total testosterone level. To find out the effect of menopause on sex hormone levels such as estrogen, testosterone, and progesterone in serum menopausal women and to elevate the relationship between these hormones and CVD. This case-control study included (224) participants (menopausal women with CVD and non-CVD) in the age range (of 40-69 years) who visited (The surgical specialty hospital cardiac center and Hawler teaching hospital). A self-administered questionnaire was used for data collection. Fasting serum metabolic parameters and hormones were measured which included (E2, TT, P, SHBG) and (Total Cholesterol, Triglycerides, HDL, LDL, and VLDL). Women with CVD represented 60.7%., who had previously been diagnosed by specializes in the cardiac center, and healthy menopausal women represented 39.3%. The mean value of E2 was significantly lower in menopausal women with CVD (20.066±1.773 Pg/ml vs 29.455±3.807 Pg/ml) along with serum progesterone level (0.234±0.0102 ng/ml vs 0.452±0.137 ng/ml) and SHBG level (31.705±1.085 nmol/L vs 37.191±1.804 nmol/L) compared to healthy menopausal women (for all, p<0.05). On the other hand, a significantly elevated level of total testosterone (17.970±1.28 nmol/L vs 10.552±.99nmol/L) was observed in menopausal women with CVD compared with healthy women (p<0.001). Multiple linear regression analysis showed the E2 negative correlation with LDL-C (p<0.01), and TT negative correlation with HDL-C (P<0.01). Low serum levels in terms of sex hormones, (E2, P, and SHBG) with high-level serum TT might be contributed to cardiovascular disease.

References

Anagnostis, P., Lambrinoudaki, I., Stevenson, J.C., Goulis, D.G., 2022. Menopause-associated risk of cardiovascular disease. Endocr. Connect. 11. https://doi.org/10.1530/EC-21-0537

Bales, A.C., 2000. In search of lipid balance in older women. New studies raise questions about what works best. Postgrad. Med. 108, 57–60, 66, 69–72. https://doi.org/10.3810/pgm.2000.12.1312

Bogers, R.P., Bemelmans, W.J.E., Hoogenveen, R.T., Boshuizen, H.C., Woodward, M., Knekt, P., van Dam, R.M., Hu, F.B., Visscher, T.L.S., Menotti, A., Thorpe, R.J., Jr, Jamrozik, K., Calling, S., Strand, B.H., Shipley, M.J., BMI-CHD Collaboration Investigators, 2007. Association of Overweight With Increased Risk of Coronary Heart Disease Partly Independent of Blood Pressure and Cholesterol Levels: A Meta-analysis of 21 Cohort Studies Including More Than 300 000 Persons. Arch. Intern. Med. 167, 1720–1728. https://doi.org/10.1001/archinte.167.16.1720

Bolognese, M., Krege, J.H., Utian, W.H., Feldman, R., Broy, S., Meats, D.L., Alam, J., Lakshmanan, M., Omizo, M., 2009. Effects of arzoxifene on bone mineral density and endometrium in postmenopausal women with normal or low bone mass. J. Clin. Endocrinol. Metab. 94, 2284–2289. https://doi.org/10.1210/jc.2008-2143

Brown, J.C., Gerhardt, T.E., Kwon, E., 2021. Risk Factors For Coronary Artery Diseas.

Buttari, B., Riganò, R., Palmieri, L., Lo Noce, C., Blankenberg, S., Zeller, T., Vannucchi, S., Di Lonardo, A., Gabbianelli, M., Donfrancesco, C., 2022. Sex Hormone-Binding Globulin and Its Association to Cardiovascular Risk Factors in an Italian Adult Population Cohort. Y Rep. 5, 5. https://doi.org/10.3390/reports5010005

Chen, Y., Zeleniuch-Jacquotte, A., Arslan, A.A., Wojcik, O., Toniolo, P., Shore, R., Levitz, M., Koenig, K., 2011. Endogenous Hormones and Coronary Heart Disease in Postmenopausal Women. Atherosclerosis 216, 414–419. https://doi.org/10.1016/j.atherosclerosis.2011.01.053

Chrysohoou, C., Aggeli, C., Avgeropoulou, C., et al., 2020. Cardiovascular disease in women: Executive summary of the expert panel statement of women in cardiology of the hellenic cardiological society. Hellenic J. Cardiol. 61, 362–377. https://doi.org/10.1016/j.hjc.2020.09.015

Dai, W., Li, Y., Zheng, H., 2012. Estradiol/Testosterone imbalance: impact on coronary heart disease risk factors in postmenopausal women. Cardiology 121, 249–254. https://doi.org/10.1159/000337274

Das, D.V., Saikia, U.K., Sarma, D., 2019. Sex Hormone Levels - Estradiol, Testosterone, and Sex Hormone Binding Globulin as a Risk Marker for Atherosclerotic Coronary Artery Disease in Post-menopausal Women. Indian J. Endocrinol. Metab. 23, 60–66. https://doi.org/10.4103/ijem.IJEM_505_18

Dobiásová, M., 2006. [AIP--atherogenic index of plasma as a significant predictor of cardiovascular risk: from research to practice]. Vnitr. Lek. 52, 64–71.

Dobiás̆ová, M., Frohlich, J., 2001. The plasma parameter log (TG/HDL-C) as an atherogenic index: correlation with lipoprotein particle size and esterification rate inapob-lipoprotein-depleted plasma (FERHDL). Clin. Biochem. 34, 583–588. https://doi.org/10.1016/S0009-9120(01)00263-6

Greiling, H., Gressner, A.M., 1995. Lehrbuch der Klinischen Chemie und der Pathobiochemie. Schattauer, F.K. Verlag, Stuttgart New York.

Haring, R., Travison, T., Bhasin, S., Vasan, R., Wallaschofski, H., Davda, M., Coviello, A., Murabito, J., 2011. Relation between Sex Hormone Concentrations, Peripheral Arterial Disease, and Change in Ankle-Brachial Index: Findings from the Framingham Heart Study. J. Clin. Endocrinol. Metab. 96, 3724–32. https://doi.org/10.1210/jc.2011-1068

He, H., Yang, F., Liu, X., Zeng, X., Hu, Q., Zhu, Q., Tu, B., 2007. Sex hormone ratio changes in men and postmenopausal women with coronary artery disease. Menopause N. Y. N 14, 385–390. https://doi.org/10.1097/01.gme.0000235369.24479.dd

Islam, R.M., Bell, R.J., Handelsman, D.J., McNeil, J.J., Nelson, M.R., Reid, C.M., Tonkin, A.M., Wolfe, R.S., Woods, R.L., Davis, S.R., 2022. Associations between blood sex steroid concentrations and risk of major adverse cardiovascular events in healthy older women in Australia: a prospective cohort substudy of the ASPREE trial. Lancet Healthy Longev. 3, e109–e118. https://doi.org/10.1016/S2666-7568(22)00001-0

Johnson, M.R., Carter, G., Grint, C., Lightman, S.L., 1993. Relationship between ovarian steroids, gonadotrophins and relaxin during the menstrual cycle. Acta Endocrinol. (Copenh.) 129, 121–125. https://doi.org/10.1530/acta.0.1290121

Khanna, R., Bansal, A., Kumar, S., Garg, N., Tewari, S., Kapoor, A., Goel, P., 2021. Association between Endogenous Sex Hormones and Coronary Artery Disease in Postmenopausal Women. Indian J. Cardiovasc. Dis. Women - WINCARS 06. https://doi.org/10.1055/s-0041-1736250

Khazaál, M.S., 2013. Atherogenic Index of Plasma (AIP) As a Parameter in Predicting Cardiovascular Risk in Males Compared To the Conventional Dyslipidemic Indices (Cholesterol Ratios) 8.

Krause, D.N., Duckles, S.P., Gonzales, R.J., 2011. Local oestrogenic/androgenic balance in the cerebral vasculature. Acta Physiol. Oxf. Engl. 203, 181–186. https://doi.org/10.1111/j.1748-1716.2011.02323.x

Lambrinoudaki, Christodoulakos, G., Rizos, D., Economou, E., Argeitis, J., Vlachou, S., Creatsa, M., Kouskouni, E., Botsis, D., 2006. Endogenous sex hormones and risk factors atherosclerosis in healthy Greek postmenopausal women. Eur. J. Endocrinol. 154, 907–916.

Lozano, R., Naghavi, M., Foreman, K., et al., 2012. Global and regional mortality from 235 causes of death for 20 age groups in 1990 and 2010: a systematic analysis for the Global Burden of Disease Study 2010. Lancet Lond. Engl. 380, 2095–2128. https://doi.org/10.1016/S0140-6736(12)61728-0

Mack, M., Gopal, A., 2016. Epidemiology, Traditional and Novel Risk Factors in Coronary Artery Disease. Heart Fail. Clin. 12, 1–10. https://doi.org/10.1016/j.hfc.2015.08.002

Masood, D.-N., Roach, E.C., Beauregard, K.G., Khalil, R.A., 2010. Impact of Sex Hormone Metabolism on the Vascular Effects of Menopausal Hormone Therapy in Cardiovascular Disease. Curr. Drug Metab. 11, 693–714.

Maturana, M.A., Breda, V., Lhullier, F., Spritzer, P.M., 2008. Relationship between endogenous testosterone and cardiovascular risk in early postmenopausal women. Metabolism 57, 961–965. https://doi.org/10.1016/j.metabol.2008.02.012

Maturana, M.A., Moreira, R.M.C., Spritzer, P.M., 2011. Lipid accumulation product (LAP) is related to androgenicity and cardiovascular risk factors in postmenopausal women. Maturitas 70, 395–399. https://doi.org/10.1016/j.maturitas.2011.09.012

Mendelsohn, M.E., Karas, R.H., 1999. The protective effects of estrogen on the cardiovascular system. N. Engl. J. Med. 340, 1801–1811. https://doi.org/10.1056/NEJM199906103402306

Mikhael, S., Punjala-Patel, A., Gavrilova-Jordan, L., 2019. Hypothalamic-Pituitary-Ovarian Axis Disorders Impacting Female Fertility. Biomedicines 7, 5. https://doi.org/10.3390/biomedicines7010005

Miller, V.M., Duckles, S.P., 2008. Vascular Actions of Estrogens: Functional Implications. Pharmacol. Rev. 60, 210–241. https://doi.org/10.1124/pr.107.08002

Mirza, F.S., Padhi, I.D., Raisz, L.G., Lorenzo, J.A., 2010. Serum Sclerostin Levels Negatively Correlate with Parathyroid Hormone Levels and Free Estrogen Index in Postmenopausal Women. J. Clin. Endocrinol. Metab. 95, 1991–1997. https://doi.org/10.1210/jc.2009-2283

Mudali, S., Dobs, A.S., Ding, J., Cauley, J.A., Szklo, M., Golden, S.H., atherosclerosis risk in communities study, 2005. Endogenous postmenopausal hormones and serum lipids: the atherosclerosis risk in communities study. J. Clin. Endocrinol. Metab. 90, 1202–1209. https://doi.org/10.1210/jc.2004-0744

Nauck, M., März, W., Jarausch, J., Cobbaert, C., Sägers, A., Bernard, D., Delanghe, J., Honauer, G., Lehmann, P., Oestrich, E., von Eckardstein, A., Walch, S., Wieland, H., Assmann, G., 1997. Multicenter evaluation of a homogeneous assay for HDL-cholesterol without sample pretreatment. Clin. Chem. 43, 1622–1629.

Nickenig, G., Strehlow, K., Wassmann, S., Bäumer, A.T., Albory, K., Sauer, H., Böhm, M., 2000. Differential effects of estrogen and progesterone on AT(1) receptor gene expression in vascular smooth muscle cells. Circulation 102, 1828–1833. https://doi.org/10.1161/01.cir.102.15.1828

Njajou, O.T., Kanaya, A.M., Holvoet, P., Connelly, S., Strotmeyer, E.S., Harris, T.B., Cummings, S.R., Hsueh, W.-C., 2009. Association between oxidized LDL, obesity and type 2 diabetes in a population-based cohort, the Health Aging and Body Composition study. Diabetes Metab. Res. Rev. 25, 733–739. https://doi.org/10.1002/dmrr.1011

Noyan, V., Yucel, A., Sagsoz, N., 2004. The association of androgenic sex steroids with serum lipid levels in postmenopausal women. Acta Obstet. Gynecol. Scand. 83, 487–490. https://doi.org/10.1111/j.0001-6349.2004.00417.x

Olvera Lopez, E., Ballard, B.D., Jan, A., 2022. Cardiovascular Disease, in: StatPearls. StatPearls Publishing, Treasure Island (FL).

Petra, P.H., 1991. The plasma sex steroid binding protein (SBP or SHBG). A critical review of recent developments on the structure, molecular biology and function. J. Steroid Biochem. Mol. Biol. 40, 735–753. https://doi.org/10.1016/0960-0760(91)90299-k

Rastrelli, G., Corona, G., Cipriani, S., Mannucci, E., Maggi, M., 2018. Sex hormone-binding globulin is associated with androgen deficiency features independently of total testosterone. Clin. Endocrinol. (Oxf.) 88, 556–564. https://doi.org/10.1111/cen.13530

Reddy Kilim, S., Chandala, S.R., 2013. A Comparative Study of Lipid Profile and Oestradiol in Pre- and Post-Menopausal Women. J. Clin. Diagn. Res. JCDR 7, 1596–1598. https://doi.org/10.7860/JCDR/2013/6162.3234

Reinecke, H., Bogdanski, J., Woltering, A., Breithardt, G., Assmann, G., Kerber, S., von Eckardstein, A., 2002. Relation of serum levels of sex hormone binding globulin to coronary heart disease in postmenopausal women. Am. J. Cardiol. 90, 364–368. https://doi.org/10.1016/s0002-9149(02)02490-6

Rexrode, K.M., Manson, J.E., Lee, I.-M., Ridker, P.M., Sluss, P.M., Cook, N.R., Buring, J.E., 2003. Sex Hormone Levels and Risk of Cardiovascular Events in Postmenopausal Women. Circulation 108, 1688–1693. https://doi.org/10.1161/01.CIR.0000091114.36254.F3

Rifai, N., Warnick, G.R., McNamara, J.R., Belcher, J.D., Grinstead, G.F., Frantz, I.D., 1992. Measurement of low-density-lipoprotein cholesterol in serum: a status report. Clin. Chem. 38, 150–160.

Sidney, S., Quesenberry, C.P., Jr, Jaffe, M.G., Sorel, M., Nguyen-Huynh, M.N., Kushi, L.H., Go, A.S., Rana, J.S., 2016. Recent Trends in Cardiovascular Mortality in the United States and Public Health Goals. JAMA Cardiol. 1, 594–599. https://doi.org/10.1001/jamacardio.2016.1326

Sievers, C., Klotsche, J., Pieper, L., Schneider, H.J., März, W., Wittchen, H.U., Stalla, G.K., Mantzoros, C., 2010. Low testosterone levels predict all-cause mortality and cardiovascular events in women: a prospective cohort study in German primary care patients. Eur. J. Endocrinol. 163, 699–708. https://doi.org/10.1530/EJE-10-0307

Sowers, M., Derby, C., Jannausch, M.L., Torrens, J.I., Pasternak, R., 2003. Insulin resistance, hemostatic factors, and hormone interactions in pre- and perimenopausal women: SWAN. J. Clin. Endocrinol. Metab. 88, 4904–4910. https://doi.org/10.1210/jc.2003-030350

Thienpont, L., Siekmann, L., Lawson, A., Colinet, E., De Leenheer, A., 1991. Development, validation, and certification by isotope dilution gas chromatography-mass spectrometry of lyophilized human serum reference materials for cortisol (CRM 192 and 193) and progesterone (CRM 347 and 348). Clin. Chem. 37, 540–546.

Thienpont, L.M., De Brabandere, V.I., Stöckl, D., De Leenheer, A.P., 1994. Use of cyclodextrins for prepurification of progesterone and testosterone from human serum prior to determination with isotope dilution gas chromatography/mass spectrometry. Anal. Chem. 66, 4116–4119. https://doi.org/10.1021/ac00094a041

Wehr, E., Pilz, S., Boehm, B.O., Grammer, T.B., März, W., Obermayer-Pietsch, B., 2011. Low Free Testosterone Levels Are Associated With All-Cause and Cardiovascular Mortality in Postmenopausal Diabetic Women. Diabetes Care 34, 1771–1777. https://doi.org/10.2337/dc11-0596

Zhu, X., Bonet, B., Gillenwater, H., Knopp, R.H., 1999. Opposing effects of estrogen and progestins