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Current Vascular Pharmacology

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ISSN (Print): 1570-1611
ISSN (Online): 1875-6212

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Review Article

Non-Hormonal Replacement Therapy Regimens: Do they have an Effect on Cardiovascular Risk?

Author(s): Evangelia Mareti*, Christina Ampatzi, Stavroula A. Paschou, Evangelia Voziki and Dimitrios G. Goulis

Volume 17, Issue 6, 2019

Page: [573 - 578] Pages: 6

DOI: 10.2174/1570161116666180911104942

Price: $65

Abstract

Introduction: Menopause is associated with adverse effects on quality of life of perimenopausal and post-menopausal women. It also has an impact on the development of cardiovascular disease (CVD). Hormonal treatments are the most effective medications for menopausal symptoms relief. Given the fact that hormonal treatments are contraindicated for many women, non-hormonal treatment, such as Selective Serotonin Reuptake Inhibitors (SSRIs), Serotonin and Norepinephrine Reuptake Inhibitors (SNRIs), gabapentin, pregabalin, clonidine and phytoestrogens, constitute alternative treatments. Nevertheless, little is known about their effects on CVD risk.

Methods: PubMed, EMBASE and Cochrane Library were searched for the effects of non-hormonal treatment on CVD risk, blood pressure, heart rate, lipids and glucose concentrations, weight gain, cardiovascular events, stroke, mortality and morbidity.

Results: Phytoestrogens, pregabalin and gabapentin seem to have no adverse effects on the cardiovascular system. Phytoestrogens, in particular, seem to reduce CVD risk through many pathways. On the other hand, SSRIs and SNRIs, although effective in reducing menopausal vasomotor symptoms, should be cautiously administered to women with known CVD (e.g. with cardiac arrhythmias, atherosclerotic disease or stroke). As clonidine has been associated with cardiovascular adverse effects, it should be administered only in cases where blood pressure regulation is mandatory.

Conclusion: Further research is needed to produce definite conclusions regarding the cardiovascular safety of non-hormonal medications for menopausal symptoms relief.

Keywords: Menopause, non-hormonal therapy, cardiovascular disease, adverse effects, safety, women's health.

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[1]
Roger VL, Go AS, Lloyd-Jones DM, et al. Heart disease and stroke statistics--2011 update: A report from the American Heart Association. Circulation 2011; 123: 18-209.
[2]
Malik S, Wong ND, Franklin SS, et al. Impact of the metabolic syndrome on mortality from coronary heart disease, cardiovascular disease, and all causes in United States adults. Circulation 2004; 110: 1245-50.
[3]
Kannel WB, Hjortland MC, McNamara PM, et al. Menopause and risk of cardiovascular disease: The Framingham study. Ann Intern Med 1976; 85: 447-52.
[4]
Gordon T, Kannel WB, Hjortland MC, et al. Menopause and coronary heart disease. The Framingham study. Ann Intern Med 1978; 89: 157-61.
[5]
Muka T, Oliver-Williams C, Kunutsor S, et al. Association of age at onset of menopause and time since onset of menopause with cardiovascular outcomes, intermediate vascular traits, and all-cause mortality: A systematic review and meta-analysis. JAMA Cardiol 2016; 1: 767-76.
[6]
Newson L. Menopause and cardiovascular disease. Post Reprod Health 2018; 24: 44-9.
[7]
Mendelsohn ME, Karas RH. Molecular and cellular basis of cardiovascular gender differences. Science 2005; 308: 1583-7.
[8]
Allison MA, Manson JE, Langer RD, et al. Oophorectomy, hormone therapy, and subclinical coronary artery disease in women with hysterectomy: The women’s health initiative coronary artery calcium study. Menopause 2008; 15: 639-47.
[9]
Atsma F, Bartelink M-LEL, Grobbee DE, et al. Postmenopausal status and early menopause as independent risk factors for cardiovascular disease: A meta-analysis. Menopause 2006; 13: 265-79.
[10]
Franco OH, Muka T, Colpani V, et al. Vasomotor symptoms in women and cardiovascular risk markers: Systematic review and meta-analysis. Maturitas 2015; 81: 353-61.
[11]
Biglia N, Cagnacci A, Gambacciani M, et al. Vasomotor symptoms in menopause: A biomarker of cardiovascular disease risk and other chronic diseases? Climacteric 2017; 20: 306-12.
[12]
Traianos A, Vavilis D, Makedos A, et al. Effect of short-term tibolone treatment on risk markers for cardiovascular disease in healthy postmenopausal women: A randomized controlled study. Clin Exp Obstet Gynecol 2013; 40: 542-5.
[13]
Vassalle C, Cicinelli E, Lello S, et al. Effects of menopause and tibolone on different cardiovascular biomarkers in healthy women. Gynecol Endocrinol 2011; 27: 163-9.
[14]
Boardman HMP, Hartley L, Eisinga A, et al. Hormone therapy for preventing cardiovascular disease in post-menopausal women. Cochrane Database Syst Rev 2015; 3CD002229
[15]
Pinkerton JV, Sánchez Aguirre F, Blake J, et al. The 2017 hormone therapy position statement of the north American menopause society. Menopause 2017; 24: 728-53.
[16]
Hall WL, Vafeiadou K, Hallund J, et al. Soy-isoflavone-enriched foods and markers of lipid and glucose metabolism in postmenopausal women: Interactions with genotype and equol production. Am J Clin Nutr 2006; 83: 592-600.
[17]
Cobin RH, Goodman NF. American association of clinical endocrinologists and American college of endocrinology position statement on menopause-2017 update. Endocr Pract 2017; 23: 869-80.
[18]
Mintziori G, Lambrinoudaki I, Goulis DG, et al. EMAS position statement: Non-hormonal management of menopausal vasomotor symptoms. Maturitas 2015; 81: 410-3.
[19]
Nezafati MH, Eshraghi A, Vojdanparast M, et al. Selective serotonin reuptake inhibitors and cardiovascular events: A systematic review. J Res Med Sci 2016; 21: 66.
[20]
Coupland C, Hill T, Morriss R, et al. Antidepressant use and risk of cardiovascular outcomes in people aged 20 to 64: Cohort study using primary care database. BMJ 2016; 352: 1350.
[21]
Whiskey E, Taylor D. A review of the adverse effects and safety of noradrenergic antidepressants. J Psychopharmacol 2013; 27: 732-9.
[22]
Serebruany VL, Suckow RF, Cooper TB, et al. Relationship between release of platelet/endothelial biomarkers and plasma levels of sertraline and N-desmethylsertraline in acute coronary syndrome patients receiving SSRI treatment for depression. Am J Psychiatry 2005; 162: 1165-70.
[23]
Zhong Z, Wang L, Wen X, et al. A meta-analysis of effects of selective serotonin reuptake inhibitors on blood pressure in depression treatment: Outcomes from placebo and serotonin and noradrenaline reuptake inhibitor controlled trials. Neuropsychiatr Dis Treat 2017; 13: 2781-96.
[24]
Serebruany VL, Glassman AH, Malinin AI, et al. Platelet/endothelial biomarkers in depressed patients treated with the selective serotonin reuptake inhibitor sertraline after acute coronary events: The sertraline antidepressant heart attack randomized trial (SADHART) platelet substudy. Circulation 2003; 108: 939-44.
[25]
Taylor D, Lenox-Smith A, Bradley A. A review of the suitability of duloxetine and venlafaxine for use in patients with depression in primary care with a focus on cardiovascular safety, suicide and mortality due to antidepressant overdose. Ther Adv Psychopharmacol 2013; 3: 151-61.
[26]
Oh SW, Kim J, Myung SK, et al. Antidepressant use and risk of coronary heart disease: Meta-analysis of observational studies. Br J Clin Pharmacol 2014; 78: 727-37.
[27]
Siepmann T, Penzlin AI, Kepplinger J, et al. Selective serotonin reuptake inhibitors to improve outcome in acute ischemic stroke: Possible mechanisms and clinical evidence. Brain Behav 2015; 5e00373
[28]
Nezafati MH, Vojdanparast M, Nezafati P. Antidepressants and cardiovascular adverse events: A narrative review. ARYA Atheroscler 2015; 11: 295-304.
[29]
Funk KA, Bostwick JR. A comparison of the risk of QT prolongation among SSRIs. Ann Pharmacother 2013; 47: 1330-41.
[30]
Pacher P, Ungvari Z. Selective serotonin-reuptake inhibitor antidepressants increase the risk of falls and hip fractures in elderly people by inhibiting cardiovascular ion channels. Med Hypotheses 2001; 57: 469-71.
[31]
Ventetuolo CE, Barr RG, Bluemke DA, et al. Selective serotonin reuptake inhibitor use is associated with right ventricular structure and function: The MESA-right ventricle study. PLoS One 2012; 7e30480
[32]
Marechaux S, Jeu A, Jobic Y, et al. Impact of selective serotonin reuptake inhibitor therapy on heart valves in patients exposed to benfluorex: A multicentre study. Arch Cardiovasc Dis 2013; 106: 349-56.
[33]
Shin D, Oh YH, Eom CS, et al. Use of selective serotonin reuptake inhibitors and risk of stroke: A systematic review and meta-analysis. J Neurol 2014; 261: 686-95.
[34]
Shah SJ, Gomberg-Maitland M, Thenappan T, et al. Selective serotonin reuptake inhibitors and the incidence and outcome of pulmonary hypertension. Chest 2009; 136: 694-700.
[35]
Rieckmann N, Kronish IM, Shapiro PA, et al. SSRI use, depression and long-term outcomes after an acute coronary syndrome - a prospective cohort study. JAMA Intern Med 2013; 173: 1150-1.
[36]
Narita K, Murata T, Takahashi T, et al. Plasma levels of adiponectin and tumor necrosis factor-alpha in patients with remitted major depression receiving long-term maintenance antidepressant therapy. Prog Neuropsychopharmacol Biol Psychiatry 2006; 30: 1159-62.
[37]
Shively CA, Silverstein-Metzler M, Justice J, et al. The impact of treatment with selective serotonin reuptake inhibitors on primate cardiovascular disease, behavior, and neuroanatomy. Neurosci Biobehav Rev 2017; 74: 433-43.
[38]
Shively CA, Register TC, Appt SE, et al. Effects of long-term sertraline treatment and depression on coronary artery atherosclerosis in premenopausal female primates. Psychosom Med 2015; 77: 267-78.
[39]
Sun Z, Hao Y, Zhang M. Efficacy and safety of desvenlafaxine treatment for hot flashes associated with menopause: A meta-analysis of randomized controlled trials. Gynecol Obstet Invest 2013; 75: 255-62.
[40]
Spindelegger CJ, Papageorgiou K, Grohmann R, et al. Cardiovascular adverse reactions during antidepressant treatment: A drug surveillance report of German-speaking countries between 1993 and 2010. Int J Neuropsychopharmacol 2014; 18 pii: pyu080.
[41]
Hudson JI, Wohlreich MM, Kajdasz DK, et al. Safety and tolerability of duloxetine in the treatment of major depressive disorder: Analysis of pooled data from eight placebo-controlled clinical trials. Hum Psychopharmacol 2005; 20: 327-41.
[42]
Mago R, Tripathi N, Andrade C. Cardiovascular adverse effects of newer antidepressants. Expert Rev Neurother 2014; 14: 539-51.
[43]
Carvalho AF, Sharma MS, Brunoni AR, et al. The Safety, tolerability and risks associated with the use of newer generation antidepressant drugs: A critical review of the literature. Psychother Psychosom 2016; 85: 270-88.
[44]
Wernicke J, Lledo A, Raskin J, et al. An evaluation of the cardiovascular safety profile of duloxetine: Findings from 42 placebo-controlled studies. Drug Saf 2007; 30: 437-55.
[45]
Archer DF, Pinkerton JV, Guico-Pabia CJ, et al. Cardiovascular, cerebrovascular, and hepatic safety of desvenlafaxine for 1 year in women with vasomotor symptoms associated with menopause. Menopause 2013; 20: 47-56.
[46]
Martinez JM, Ferguson MB, Pangallo BA, et al. Safety and tolerability of edivoxetine as adjunctive treatment to selective serotonin reuptake inhibitor antidepressants for patients with major depressive disorder. Drugs Context 2015; 4212279
[47]
Lima SMRR, Bernardo BFA, Yamada SS, et al. Effects of Glycine max (L.) Merr. soy isoflavone vaginal gel on epithelium morphology and estrogen receptor expression in postmenopausal women: A 12-week, randomized, double-blind, placebo-controlled trial. Maturitas 2014; 78: 205-11.
[48]
Weeke P, Jensen A, Folke F, et al. Antidepressant use and risk of out-of-hospital cardiac arrest: A nationwide case-time-control study. Clin Pharmacol Ther 2012; 92: 72-9.
[49]
Klein-Schwartz W, Shepherd JG, Gorman S, et al. Characterization of gabapentin overdose using a poison center case series. J Toxicol Clin Toxicol 2003; 41: 11-5.
[50]
Ucak A, Onan B, Sen H, et al. The effects of gabapentin on acute and chronic postoperative pain after coronary artery bypass graft surgery. J Cardiothorac Vasc Anesth 2011; 25: 824-9.
[51]
Schiavo A, Stagnaro FM, Salzano A, et al. Pregabalin-induced first degree atrioventricular block in a young patient treated for pain from extrapulmonary tuberculosis. Monaldi Arch Chest Dis Arch Monaldi per Le Mal Del Torace 2017; 87: 838.
[52]
Diaper A, Rich AS, Wilson SJ, et al. Changes in cardiovascular function after venlafaxine but not pregabalin in healthy volunteers: a double-blind, placebo-controlled study of orthostatic challenge, blood pressure and heart rate. Hum Psychopharmacol 2013; 28: 562-75.
[53]
Joshi SS, Jagadeesh AM. Efficacy of perioperative pregabalin in acute and chronic post-operative pain after off-pump coronary artery bypass surgery: A randomized, double-blind placebo controlled trial. Ann Card Anaesth 2013; 16: 180-5.
[54]
Del Rio G, Menozzi R, Della Casa L, et al. Alpha-2 adrenergic activity in perimenopausal women. J Endocrinol Invest 1997; 20: 603-10.
[55]
Thacker HL. Assessing risks and benefits of nonhormonal treatments for vasomotor symptoms in perimenopausal and postmenopausal women. J Womens Health (Larchmt) 2011; 20: 1007-16.
[56]
Lethaby A, Marjoribanks J, Kronenberg F, et al. Phytoestrogens for menopausal vasomotor symptoms. Cochrane Database Syst Rev 2013; 3CD001395
[57]
Bolego C, Poli A, Cignarella A, et al. Phytoestrogens: pharmacological and therapeutic perspectives. Curr Drug Targets 2003; 4: 77-87.
[58]
Irace C, Marini H, Bitto A, et al. Genistein and endothelial function in postmenopausal women with metabolic syndrome. Eur J Clin Invest 2013; 43: 1025-31.
[59]
Vitale DC, Piazza C, Melilli B, et al. Isoflavones: Estrogenic activity, biological effect and bioavailability. Eur J Drug Metab Pharmacokinet 2013; 38: 15-25.
[60]
Gil-Izquierdo A, Penalvo JL, Gil JI, et al. Soy isoflavones and cardiovascular disease epidemiological, clinical and -omics perspectives. Curr Pharm Biotechnol 2012; 13: 624-31.
[61]
Andres S, Hansen U, Niemann B, et al. Determination of the isoflavone composition and estrogenic activity of commercial dietary supplements based on soy or red clover. Food Funct 2015; 6: 2017-25.
[62]
Mainini G, Torella M, Di Donna MC, et al. Nonhormonal management of postmenopausal women: Effects of a red clover based isoflavones supplementation on climacteric syndrome and cardiovascular risk serum profile. Clin Exp Obstet Gynecol 2013; 40: 337-41.
[63]
Barentsen R. Red clover isoflavones and menopausal health. J Br Menopause Soc 2004; 10: 4-7.
[64]
Jackman KA, Woodman OL, Sobey CG. Isoflavones, equol and cardiovascular disease: Pharmacological and therapeutic insights. Curr Med Chem 2007; 14: 2824-30.
[65]
Acharjee S, Zhou J-R, Elajami TK, et al. Effect of soy nuts and equol status on blood pressure, lipids and inflammation in postmenopausal women stratified by metabolic syndrome status. Metabolism 2015; 64: 236-43.
[66]
De Kleijn MJJ, van der Schouw YT, Wilson PWF, et al. Dietary intake of phytoestrogens is associated with a favorable metabolic cardiovascular risk profile in postmenopausal U.S. women: The Framingham study. J Nutr 2002; 132: 276-82.
[67]
Villa P, Costantini B, Suriano R, et al. The differential effect of the phytoestrogen genistein on cardiovascular risk factors in postmenopausal women: Relationship with the metabolic status. J Clin Endocrinol Metab 2009; 94: 552-8.
[68]
Atteritano M, Marini H, Minutoli L, et al. Effects of the phytoestrogen genistein on some predictors of cardiovascular risk in osteopenic, postmenopausal women: A two-year randomized, double-blind, placebo-controlled study. J Clin Endocrinol Metab 2007; 92: 3068-75.
[69]
Husain D, Khanna K, Puri S, et al. Supplementation of soy isoflavones improved sex hormones, blood pressure, and postmenopausal symptoms. J Am Coll Nutr 2015; 34: 42-8.
[70]
Liu Z-M, Ho SC, Chen Y-M, et al. The effects of isoflavones combined with soy protein on lipid profiles, C-reactive protein and cardiovascular risk among postmenopausal Chinese women. Nutr Metab Cardiovasc Dis 2012; 22: 712-9.
[71]
Clarkson TB. Soy, Soy phytoestrogens and cardiovascular disease. J Nutr 2002; 132: 566-9.

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