Official reprint from UpToDate®
www.uptodate.com ©2016 UpToDate®

Effect of oral contraceptives and postmenopausal hormone therapy on blood pressure

Norman M Kaplan, MD
Section Editor
George L Bakris, MD
Deputy Editor
John P Forman, MD, MSc


Women who have ever used oral contraceptives have a significantly lower mortality rate (adjusted relative risk 0.88, confidence interval 0.82 to 0.93) [1]. Nonetheless, chronic use of oral contraceptives will slightly increase the systemic blood pressure (BP) in most women and may have other adverse effects on cardiovascular risk. Early epidemiologic studies using high-dose estrogen found a mean elevation in BP of 3-6/2-5 mmHg, with approximately 5 percent of women developing overt hypertension [2]. This is more likely to occur in patients who developed hypertension during a prior pregnancy or who have a family history of hypertension. Although the rise in BP is usually mild, malignant hypertension can very rarely occur [3]. Cessation of therapy typically leads to a return to baseline BP within 2 to 12 months, but proteinuria may persist [4].

Dose dependence and mechanisms — The mechanisms responsible for the hypertensive effect of oral contraceptives are incompletely understood [2]. Both estrogen and progesterone appear to contribute in a dose-dependent fashion. The 5 percent incidence of hypertension reported in 1988 was largely derived from studies of high-dose therapy in which the estrogen dose was at least 50 mcg and the progestin dose was 1 to 4 mg. However, current preparations contain as little as 20 percent of the estrogen and progestin in previous preparations. A report from the Nurses' Health Study prospectively evaluated almost 70,000 female nurses, aged 25 to 42 years [5]. After adjustment for age, weight, smoking, family history, and other risk factors, the relative risk of hypertension compared to women who never used oral contraceptives was 1.8 for current users and 1.2 for previous users. Overall, only 41.5 cases per 10,000 person-years could be attributed to oral contraceptive use; this risk rapidly declined with cessation of therapy.

How hormone therapy might raise the BP is unclear. The renin-angiotensin system may be involved, since estrogen stimulates the hepatic production of renin substrate (angiotensinogen) [6]. However, a similar response is seen in women who do or do not develop a rise in BP and the administration of an angiotensin-converting enzyme inhibitor does not reverse the hypertension [4]. No changes in muscle sympathetic nerve activity or systemic hemodynamics were found between young women taking an oral contraceptive and women with natural menstrual cycles [7].

Cardiovascular consequences — The main concern with an oral contraceptive-induced rise in BP is the development of persistent hypertension and subsequent premature cardiovascular disease. The incidence is greatest in women over the age of 35 years and in those who have coronary risk factors, particularly smoking [8]. In a meta-analysis of 14 independent studies published from 1980 to 2003, the relative risk of stroke and heart attack was increased two-fold in current users of "low-dose" oral contraceptives (defined as less than 50 mcg of ethinyl estradiol) [9]. A statistically significant increase in risk for ischemic stroke was also seen with both second and third generation oral contraceptive formulations, while a trend toward an enhanced risk for myocardial infarction was noted among third generation low-dose oral contraceptive users.

Since these risks are higher in women who are over age 35 years and who smoke [10], current recommendations exclude such individuals from oral contraceptive use. However, some authorities have also questioned the use of oral contraceptives in younger, non-smoking women with either polycystic ovary syndrome or the metabolic syndrome since their increased baseline risk is likely to be aggravated by oral contraceptives [9].


Subscribers log in here

To continue reading this article, you must log in with your personal, hospital, or group practice subscription. For more information or to purchase a personal subscription, click below on the option that best describes you:
Literature review current through: Sep 2016. | This topic last updated: Sep 23, 2015.
The content on the UpToDate website is not intended nor recommended as a substitute for medical advice, diagnosis, or treatment. Always seek the advice of your own physician or other qualified health care professional regarding any medical questions or conditions. The use of this website is governed by the UpToDate Terms of Use ©2016 UpToDate, Inc.
  1. Hannaford PC, Iversen L, Macfarlane TV, et al. Mortality among contraceptive pill users: cohort evidence from Royal College of General Practitioners' Oral Contraception Study. BMJ 2010; 340:c927.
  2. Woods JW. Oral contraceptives and hypertension. Hypertension 1988; 11:II11.
  3. Lim KG, Isles CG, Hodsman GP, et al. Malignant hypertension in women of childbearing age and its relation to the contraceptive pill. Br Med J (Clin Res Ed) 1987; 294:1057.
  4. Ribstein J, Halimi JM, du Cailar G, Mimran A. Renal characteristics and effect of angiotensin suppression in oral contraceptive users. Hypertension 1999; 33:90.
  5. Chasan-Taber L, Willett WC, Manson JE, et al. Prospective study of oral contraceptives and hypertension among women in the United States. Circulation 1996; 94:483.
  6. Goldhaber SZ, Hennekens CH, Spark RF, et al. Plasma renin substrate, renin activity, and aldosterone levels in a sample of oral contraceptive users from a community survey. Am Heart J 1984; 107:119.
  7. Harvey RE, Hart EC, Charkoudian N, et al. Oral Contraceptive Use, Muscle Sympathetic Nerve Activity, and Systemic Hemodynamics in Young Women. Hypertension 2015; 66:590.
  8. Croft P, Hannaford PC. Risk factors for acute myocardial infarction in women: evidence from the Royal College of General Practitioners' oral contraception study. BMJ 1989; 298:165.
  9. Baillargeon JP, McClish DK, Essah PA, Nestler JE. Association between the current use of low-dose oral contraceptives and cardiovascular arterial disease: a meta-analysis. J Clin Endocrinol Metab 2005; 90:3863.
  10. Vessey M, Painter R, Yeates D. Mortality in relation to oral contraceptive use and cigarette smoking. Lancet 2003; 362:185.
  11. Rossouw JE, Anderson GL, Prentice RL, et al. Risks and benefits of estrogen plus progestin in healthy postmenopausal women: principal results From the Women's Health Initiative randomized controlled trial. JAMA 2002; 288:321.
  12. Effects of estrogen or estrogen/progestin regimens on heart disease risk factors in postmenopausal women. The Postmenopausal Estrogen/Progestin Interventions (PEPI) Trial. The Writing Group for the PEPI Trial. JAMA 1995; 273:199.
  13. Butkevich A, Abraham C, Phillips RA. Hormone replacement therapy and 24-hour blood pressure profile of postmenopausal women. Am J Hypertens 2000; 13:1039.
  14. Cagnacci A, Rovati L, Zanni A, et al. Physiological doses of estradiol decrease nocturnal blood pressure in normotensive postmenopausal women. Am J Physiol 1999; 276:H1355.
  15. Scuteri A, Bos AJ, Brant LJ, et al. Hormone replacement therapy and longitudinal changes in blood pressure in postmenopausal women. Ann Intern Med 2001; 135:229.
  16. Bath PM, Gray LJ. Association between hormone replacement therapy and subsequent stroke: a meta-analysis. BMJ 2005; 330:342.