The DOI matches its Crossref record; 91 of the 92 references it cites were found in a registry or an index.
Contraceptive Hormone Use and Cardiovascular Disease
Open accessAbstract
Contraceptive hormones, most commonly prescribed as oral contraceptives (OCs), are a widely utilized method to prevent ovulation, implantation, and, therefore, pregnancy. The Women's Health Initiative demonstrated cardiovascular risk linked to menopausal hormone therapy among women without pre-existing cardiovascular disease, prompting a review of the safety, efficacy, and side effects of other forms of hormone therapy. A variety of basic science, animal, and human data suggests that contraceptive hormones have antiatheromatous effects; however, relatively less is known regarding the impact on atherosclerosis, thrombosis, vasomotion, and arrhythmogenesis. Newer generation OC formulations in use indicate no increased myocardial infarction risk for current users, but a persistent increased risk of venous thromboembolism. There are no cardiovascular data available for the newest generation contraceptive hormone formulations, including those that contain newer progestins that lower blood pressure, as well as the nonoral routes (transdermal and vaginal). Current guidelines indicate that, as with all medication, contraceptive hormones should be selected and initiated by weighing risks and benefits for the individual patient. Women 35 years and older should be assessed for cardiovascular risk factors including hypertension, smoking, diabetes, nephropathy, and other vascular diseases, including migraines, prior to use. Existing data are mixed with regard to possible protection from OCs for atherosclerosis and cardiovascular events; longer-term cardiovascular follow-up of menopausal women with regard to prior OC use, including subgroup information regarding adequacy of ovulatory cycling, the presence of hyperandrogenic conditions, and the presence of prothrombotic genetic disorders is needed to address this important issue.
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“Although there have been no placebo-controlled trials in children, observational studies have suggested that early treatment can reduce LDL-C burden, improve endothelial function, substantially attenuate the development of atherosclerosis, and improve coronary outcomes [369-371].”
From 2019 ESC/EAS guidelines for the management of dyslipidaemias: lipid modification to reduce cardiovascular risk (2019) · cites this paper as [370]
In the citing paper
“Although there have been no placebo-controlled trials in children, observational studies have suggested that early treatment can reduce LDL-C burden, improve endothelial function, substantially attenuate the development of atherosclerosis, and improve coronary outcomes [369-371].”
From 2019 ESC/EAS guidelines for the management of dyslipidaemias: lipid modification to reduce cardiovascular risk (2019) · cites this paper as [370]
In the citing paper
“Although there have been no placebo-controlled trials in children, observational studies have suggested that early treatment can reduce LDL-C burden, improve endothelial function, substantially attenuate the development of atherosclerosis, and improve coronary outcomes [369-371].”
From 2019 ESC/EAS guidelines for the management of dyslipidaemias: lipid modification to reduce cardiovascular risk (2019) · cites this paper as [370]
In the citing paper
“Although there have been no placebo-controlled trials in children, observational studies have suggested that early treatment can reduce LDL-C burden, improve endothelial function, substantially attenuate the development of atherosclerosis, and improve coronary outcomes [369-371].”
From 2019 ESC/EAS guidelines for the management of dyslipidaemias: lipid modification to reduce cardiovascular risk (2019) · cites this paper as [370]
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Citations
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“Existing observational data with earlier first- and second generation, higher-dosage formulations consistently demonstrate small but significantly elevated risks of MI and venous thromboembolism (VTE), while the newer-generation formulations currently in use indicate no increasedMI risk, but a persistent increased ris…”
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“In the United States, it is estimated that nearly 20% of women are currently prescribed oral contraceptives; additionally, since their introduction in the 1960s, 80% of women have used oral contraceptives at some point in their life (16).”
BackgroundIschemic stroke and cerebral venous sinus thrombosis in pregnancy
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Greater Beta-Adrenergic Receptor Mediated Vasodilation in Women Using Oral Contraceptives
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“Consistent with this, changes in lipid profile have been shown previously with oral contraceptive use (Sitruk-Ware, 2006; Shufelt and Bairey Merz, 2009).”
BackgroundInfluentialNisenbaum, M. G., Melo, N. R. D., Giribela, C. R. G., Morais, T. L. D., Guerra, G. M., de Angelis, K., Mostarda, C., Baracat, E. C., & Consolim-Colombo, F. M. (2014) · European Journal of Obstetrics & Gynecology and Reproductive Biology · doi:10.1016/j.ejogrb.2014.01.006 · Cited by 37
“006 Many studies have demonstrated increases in blood pressure in women after chronic use of COCs [2,3].”
BackgroundInfluentialEffect of a new oral contraceptive with estradiol valerate/dienogest on carbohydrate metabolism
Leo, V. D., Fruzzetti, F., Musacchio, M. C., Scolaro, V., Sabatino, A. D., & Morgante, G. (2013) · Contraception · doi:10.1016/j.contraception.2012.09.003 · Cited by 37
“The metabolic changes induced by the synthetic steroid used in contraception, such as changes in lipoproteins, insulin response to glucose, and coagulation, have been considered as potential markers of cardiovascular and venous risk [1,2].”
BackgroundHow I treat unexplained arterial thrombosis
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Oral Contraceptive Use Among Women in the Military and the General U.S. Population
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“4 With respect to cancer, the direction of the association between OC use and risk is site dependent.”
Meendering, J. R., Torgrimson, B. N., Miller, N. P., Kaplan, P., & Minson, C. T. (2010) · Contraception · doi:10.1016/j.contraception.2010.03.009 · Cited by 36
“This may be due to the relatively low incidence of acute cardiovascular events in young women using newer generation oral contraceptives [32].”
Improving clinical outcomes through attention to sex and hormones in research
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Primary and Secondary Prevention of Coronary Heart Disease
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Comprehensive primary prevention of cardiovascular disease in women
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“The risks did not differ significantly between the types of progestin.7 However, as MI is extremely rare in healthy, premenopausal women, doubling the risk results in an extremely low population attributable risk.7 On the other hand, OC should not be prescribed for women who are over the age of 35 years and smoke, per…”
BackgroundResultInfluentialSex Influence on Heart Failure Prognosis
Postigo, A., & Martínez‐Sellés, M. (2020) · Frontiers in Cardiovascular Medicine · doi:10.3389/fcvm.2020.616273 · Cited by 35
“Regarding premenopausal women, oral contraceptive use could explain a certain trend to higher blood pressure, being associated with an increase in around 7–8 mmHg from baseline and almost double risk of hypertension compared with neverusers (32, 33).”
BackgroundOkoth, K., Parry‐Smith, W., Thomas, G. N., Nirantharakumar, K., & Adderley, N. J. (2023) · BMC Medicine · doi:10.1186/s12916-023-02794-x · Cited by 33
“Attenuation of the effect size on exclusion of women on current prescription for combined oral contraceptive (COC) suggests that increased CVD risk may be partly mediated by COC use [48].”
BackgroundFranconi, F., Carru, C., Spoletini, I., Malorni, W., Vella, S., Mercuro, G., Deidda, M., & Rosano, G. M. C. (2011) · Therapeutic Delivery · doi:10.4155/tde.11.117 · Cited by 32
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“While both positive and negative effects on hypertension, CVD and arterial function have been shown in postmenopausal women, overall, postmenopausal HRT in women did not meet the expectations of a positive effect on cardiovascular mortality [14,15].”
BackgroundThe Egyptian Hypertension Society
(2014) · The Egyptian Heart Journal · doi:10.1016/j.ehj.2014.03.001 · Cited by 33
“Newer progestins such as drospirenone contain a spironolactone-like moiety [141] with mild mineralocorticoid antagonist action; as a result, drospirenone-estrogen combinations generally cause a small decrease in BP.”
BackgroundAdverse pregnancy outcomes and cardiovascular risk factor management
Mehta, P. K., Minissian, M., & Merz, C. N. B. (2015) · Seminars in Perinatology · doi:10.1053/j.semperi.2015.05.005 · Cited by 32
Gender Differences in Ischemic Cardiomyopathy
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Is Extra Virgin Olive Oil an Ally for Women’s and Men’s Cardiovascular Health?
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“OC should not be prescribed for women over the age of 35 years and smokers (American College of Obstetricians and Gynecologists) and should be prescribed with caution in case of CV risk factors such as hypertension, diabetes, and dyslipidemia [54]”
BackgroundMaas, A. H. E. M., von Euler, M., Bongers, M. Y., Rolden, H. J. A., Grutters, J. P. C., Ulrich, L. G., & Schenck-Gustafsson, K. G. (2015) · Maturitas · doi:10.1016/j.maturitas.2015.08.014 · Cited by 30
Coronary Artery Disease in Women: A Comprehensive Appraisal
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“APOs are associated with microvascular dysfunction and a higher risk of cardiovascular events later in life [19]”
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The influence of sex on neuroimmune communication, pain, and physiology
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“These contraceptive pills are the most commonly prescribed contraceptive pills in the United States, however, individuals who experience migraines are not recommended to take them due to the increased risk of migraines [296].”
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“The risk of developing SLE increases with greater concentrations of ethinyloestradiol in the pill formulation and is higher in women using first- or second-generation contraceptives that are known to have higher oestrogen doses compared to more modern drug formulations [99,100].”
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“The first generation of COCs consisted of norethindrone and ≥50 mcg mestranol or ethinylestradiol (EE), whereas subsequent generations consisted of b50 mcg EE and other progestins, including levonorgestrel (LNG) in the second generation; gestodene and desogestrel, with lower androgen activity than LNG, in the third ge…”
BackgroundPijuan‐Domenech, A., Mariné, F. B., Rojas-Torrijos, M., Dos, L., Moral, V. P.-D., Domenech, M. T. S., Goya, M., Cabero, L., David Garcia-dorado, A., & Casaldáliga, J. (2013) · The American Journal of Cardiology · doi:10.1016/j.amjcard.2013.04.027 · Cited by 24
Estrogen-Free Oral Hormonal Contraception: Benefits of the Progestin-Only Pill
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“, hypertension, dyslipidemia, diabetes, smoking and/or obesity) (Table 2) [13,21,32–34].”
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How Does Mental Health Impact Women's Heart Health?
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Molecular screening of Chinese medicinal plants for progestogenic and anti-progestogenic activity
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InfluentialStatins in High Cardiovascular Risk Patients: Do Comorbidities and Characteristics Matter?
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“In the event of an unintended pregnancy, women should discontinue statins despite the cardiovascular risk [115].”
BackgroundThe Impact of Estradiol and 1,25(OH)2D3 on Metabolic Syndrome in Middle-Aged Taiwanese Males
Cheng, K., Huang, S., Huang, C., Lee, Y., Chu, C., Chang, C., Lai, W., & Liu, C. (2013) · PLoS ONE · doi:10.1371/journal.pone.0060295 · Cited by 22
“However, hormone replacement therapy (HRT) during menopause has turned out to be a harmful risk factor in that it increases the risk of stroke, venous thromboembolism, and coronary heart disease [49,50].”
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Agarwal, M., SHUFELT, C. L., Mehta, P. K., Gill, E. B., Berman, D. S., Li, D., Sharif, B., Li, N., Merz, C. N. B., & Thomson, L. (2013) · Europe PMC (PubMed Central) · doi:10.3978/j.issn.2223-3652.2013.08.01 · Cited by 22
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“However, for young women with no other risk factors there may not be any increase risk of arterial thrombotic events [2].”
BackgroundERICA: cardiovascular risks associated with oral contraceptive use among Brazilian adolescents
Barros, B. D. S., Kuschnir, M. C. C., Kuschnir, F. C., & Jordão, É. A. D. O. C. (2021) · Jornal de Pediatria · doi:10.1016/j.jped.2021.03.006 · Cited by 21
Fabunmi, O. A., Dludla, P. V., & Nkambule, B. B. (2023) · Frontiers in Cardiovascular Medicine · doi:10.3389/fcvm.2023.1127104 · Cited by 21
“Despite the known health benefits of OCPs that include preventing pregnancy and treating reproductive disorders among others (8–10), their physiological impact on women’s health, combined with the risk of cardiovascular events (2, 11) such as arterial and venous thrombosis (ATE and VTE), ischemic and hemorrhagic strok…”
BackgroundMittal, S. (2019) · Annals of the National Academy of Medical Sciences (India) · doi:10.1055/s-0039-1694071 · Cited by 20
de Morais, T. L., Giribela, C. R. G., Nisenbaum, M. G., Guerra, G. M., de Mello, N. R., Baracat, E. C., & Consolim‐Colombo, F. M. (2014) · European Journal of Obstetrics & Gynecology and Reproductive Biology · doi:10.1016/j.ejogrb.2014.09.006 · Cited by 20
“Combined oral contraceptive (OC) is one of the most commonly prescribed birth control methods, used by millions of women in many countries [3].”
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“Given the risk of breast cancer and venous thrombosis from estrogen administration, further major RCTs of estrogen are unlikely, but the role of estrogen in cardiovascular disease remains an important topic relevant to the widespread use of oral contraceptives including estrogen.”
BackgroundInfluentialUnique cardiometabolic factors in women that contribute to modified cardiovascular disease risk
Hetherington, K., Thomas, J., Nicholls, S. J., Barsha, G., & Bubb, K. J. (2024) · European Journal of Pharmacology · doi:10.1016/j.ejphar.2024.177031 · Cited by 21
Metadata
- Authors
- Shufelt, C. L., & Bairey Merz, C. N.
- Affiliations
- Cedars-Sinai Medical Center (US)
- Venue
- Journal of the American College of Cardiology
- Publisher
- Elsevier BV
- Published
- 2009-01
- Volume
- 53
- Issue
- 3
- Pages
- 221-231
- ISSN
- 0735-1097 (ISSN-L)
- PMC
- PMC2660203
- OpenAlex
- W2128055881
- Cited by
- 287
- References
- 92
- Citations by year
- 2026: 14 · 2025: 10 · 2024: 15 · 2023: 17 · 2022: 12 · 2021: 16 · 2020: 24 · 2019: 17 · 2018: 10 · 2017: 11 · 2016: 18 · 2015: 16 · 2014: 17 · 2013: 22 · 2012: 18
- FWCI
- 3.06
- Type
- journal article
- Language
- en
- Open access
- bronze
- doi.org
- Licence
- Locations
- Journal of the American College of Cardiology (publishedVersion)
- PubMed (publishedVersion)
- PubMed Central (acceptedVersion)
- Funders
- National Institutes of Health (n01hv068164-006, n01hv068162-009, n01hv068161-005, n01hv068163-006)
- National Heart, Lung, and Blood Institute (N01-HV68162, N01 HV068162, N01HV68163, N01 HV068164, N01- HV-068161, N01 HV068163)
- National Center for Research Resources (MO1-RR00425, M01RR000425)
- Topics
- Health Sciences › Medicine › Public Health, Environmental and Occupational Health › Reproductive Health and Contraception
- Health Sciences › Medicine › Endocrinology, Diabetes and Metabolism › Menopause: Health Impacts and Treatments
- Health Sciences › Medicine › Cardiology and Cardiovascular Medicine › Lipoproteins and Cardiovascular Health
- Keywords
- oral contraceptives, cardiovascular risk, hormone replacement therapy, atherosclerosis, thrombosis, venous thromboembolism, myocardial infarction, progestins, vaginal ring, cardiovascular risk assessment, Women's Health Initiative
- MeSH terms
- Adult, Age Factors, Animals, Cardiovascular Diseases, Contraceptives, Oral, Hormonal, Disease Models, Animal, Female, Humans, Middle Aged, Thromboembolism, United States, Cohort Studies, Incidence, Practice Guidelines as Topic, Premenopause, Postmenopause, Risk Assessment, Hormone Replacement Therapy
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