The Effect of Reproductive Factors on Coronary Artery Disease in Women

Soodabeh Darvish, Saeed Sadeghian, Azizeh Ghaseminejad, Reza Mohebi



Abstract Introduction: There is a sex discrepancy in cardiovascular physiology. In this study, we aimed to investigate the effect of female reproductive factors on coronary artery disease (CAD) beyond the known CAD risk factors. Methods: In a case-control study, women referred to Tehran Heart Center for coronary artery angiography from 2012 to 2014 were enrolled. Of these, 80 premenopausal and 100 postmenopausal females with CAD in angiography were randomly selected as cases and 80 premenopausal and 100 postmenopausal females without CAD in angiography were selected as controls. A questionnaire including reproductive history and known CAD risk factors was filled for every subject. Analysis was performed separately for pre and postmenopausal women and a final adjustment for coronary artery disease risk factors was done. Results: Among reproductive factors, oligomenorrhea (OR= 6.72) was a significant risk factor for CAD in premenopausal women and history of oral contraceptive (OCP) use had a protective effect on CAD in pre and postmenopausal woman (OR= 0.24 and 0.20, respectively). Conclusions: Since oligomenorrhea has a strong association with insulin resistance and diabetes, a conventional risk factor of CAD, women with oligomenorrhea should be treated not only for cyclic irregularity but also for prevention of CAD.

Coronary Artery Disease, Contraceptives, Oral, Oligomenorrhea


women health

Full Text:




Mendelsohn ME, Karas RH. Molecular and cellular basis of cardiovascular gender differences. Science. 2005; 308: 1583 – 7

Ness RB, Harris T, Cobb J, Flegal KM, Kelsey JL, Balanger A, et al. Number of pregnancies and the subsequent risk of cardiovascular disease. N Engl J Med. 1993; 328:1528-33.

Sattar N, Greer IA. Pregnancy complications and maternal cardiovascular risk: opportunities for intervention and screening? BMJ. 2002; 325:157-60.

Solomon CG, Hu FB, Dunaif A, Rich-Edwards JE, Stampfer MJ, Willett WC, et al. Menstrual cycle irregularity and risk for future cardiovascular disease. J Clin Endocrinol Metab. 2002; 87: 2013-7.

Talbott E, Guzick D, Clerici A, Berga S, Detre K, Weimer K, et al .Coronary heart disease risk factors in women with polycystic ovary syndrome. Arterioscler Thromb Vasc Biol. 1995; 15:821–6.

Bairey Merz CN, Johnson BD, Sharaf BL, Bittner V, Berga SL, Braunstein GD, et al. Hypoestrogenemia of hypothalamic origin and coronary artery disease in premenopausal women: a report from the NHLBI-sponsored WISE study. J Am Coll Cardiol. 2003; 41: 413-9.

- Colditz GA, Willett WC, Stampfer MJ, et al. A prospective study of age at menarche, parity, age at first birth, and coronary heart disease in women. Am J Epidemiol 1987;126:861–70

- Kharazmi E, Fallah M, Luoto R. Maternal Age at First Delivery and Risk of Cardiovascular Disease Later in Life. ISRN Epidemiology. 2013; Article ID 876724, 6 pages

-Cooper GS, Ephross SA, Weinberg CR, Baird DD, Whelan EA, Sandler DP. Menstrual and reproductive risk factors for ischemic heart disease. Epidemiology 1999;10:255–9.

-Hardy R, Lawlor DA, Black S, Mishra GD, Kuh D. Age at birth of first child and coronary heart disease risk factors at age 53 years in men and women: British birth cohort study. J Epidemiol Community Health. 2009; 63: 99–105.

-Pirkle CM, de Albuquerque Sousa AC, Alvarado B, Zunzunegui MV; IMIAS Research Group. Early maternal age at first birth is associated with chronic diseases and poor physical performance in older age: cross-sectional analysis from the International Mobility in Aging Study. BMC Public Health. 2014;14:293.

-Hardy R, Lawlor DA, Black S, Wadsworth ME, Kuh D. Number of children and coronary heart disease risk factors in men and women from a British birth cohort. BJOG 2007;114:721–30

- Parikh NI, Cnattingius S, Dickman PW, Mittleman MA, Ludvigsson JF, Ingelsson E. Parity and risk of later-life maternal cardiovascular disease. Am Heart J. 2010; 159: 215-21. e6.

-Jacobsen BK, Knutsen SF, Oda K, Fraser GE. Parity and total, ischemic heart disease and stroke mortality. The Adventist Health Study, 1976-1988. Eur J Epidemiol. 2011; 26: 711-8.

- Wang ET, Cirillo PM, Vittinghoff E, Bibbins-Domingo K, Cohn BA, Cedars MI. Menstrual irregularity and cardiovascular mortality. J Clin Endocrinol Metab. 2011; 96: E114-8.

- He L, Tang X, Li N, Wu YQ, Wang JW, Li JR, et al. Menopause with cardiovascular disease and its risk factors among rural Chinese women in Beijing: a population-based study. Maturitas. 2012; 72: 132-8.

- Mueller NT, Odegaard AO, Gross MD, Koh WP, Yuan JM, Pereira MA. Age at menarche and cardiovascular disease mortality in Singaporean Chinese women: the Singapore Chinese Health Study. Ann Epidemiol. 2012; 22: 717-22

- Wu X, Cai H1, Kallianpur A1, Gao YT2, Yang G1, Chow WH3, et al. Age at menarche and natural menopause and number of reproductive years in association with mortality: results from a median follow-up of 11.2 years among 31,955 naturally menopausal Chinese women. PLoS One. 2014 ; 9: e103673.

-Canoy D, Beral V, Balkwill A, Wright FL, Kroll ME, Reeves GK, Green J, Cairns BJ. Age at Menarche and Risks of Coronary Heart and Other Vascular Diseases in a Large UK Cohort. Circulation. 2014 Dec 15. pii: CIRCULATIONAHA.114.010070. [Epub ahead of print].

- Qiu C, Chen H, Wen J, Zhu P, Lin F, Huang B, et al. Associations Between Age at Menarche and Menopause With Cardiovascular Disease, Diabetes, and Osteoporosis in Chinese Women. J Clin Endocrinol Metab. 2013; 98: 1612-21.

Kaplan JR, Adams MR, Anthony MS, Morgan TM, Manuck SB, Clarkson TB. Dominant social status and contraceptive hormone treatment inhibit atherogenesis in premenopausal monkeys. Arterioscler Thromb Vasc Biol.1995; 15: 2094–100

Merz CN , Johnson BD, Berga S, Braunstein G, Reis SE, Bittner V; WISE Study Group. Past oral contraceptive use and angiographic coronary artery disease in postmenopausal women: data from the National Heart, Lung, and Blood Institute-sponsored Women's Ischemia Syndrome Evaluation. Fertil Steril. 2006; 85:1425-31.

Stampfer MJ, Willett WC, Colditz GA, Speizer FE, Hennekens CH. Past use of oral contraceptives and cardiovascular disease: a meta-analysis in the context of the Nurses’ Health Study. Am J Obstet Gynecol. 1990; 163:285–91.

- Friedman J, Cremer M, Jelani QU, Huang X, Jian J, Shah S, Katz SD. Oral contraceptive use, iron stores and vascular endothelial function in healthy women. Contraception. 2011; 84:285-90.


Creative Commons License
This work is licensed under a Creative Commons Attribution-NonCommercial 4.0 International License.

Print ISSN: 2383-3750
Electronic ISSN: 2538-399x