Cochrane Briefs

Lower- vs. Higher-Dose Estrogen for Contraception


Am Fam Physician. 2005 Oct 1;72(7):1224-1225.

Clinical Question

Compared with higher-dose pills, are combination oral contraceptives with 20 mcg of estrogen (ethinyl estradiol) equally effective and well tolerated?

Evidence-Based Answer

Although no difference in effectiveness has been demonstrated in existing trials, too few patients have been studied to detect small but clinically important differences in pregnancy rates. Low-dose estrogen pills have higher rates of discontinuation and bleeding disturbances.

Practice Pointers

Although complications are rare with these pills, combination oral contraceptives have been linked to breast cancer, cerebral vascular complications, thrombosis, and myocardial infarction. Therefore, many physicians and patients prefer to use the lowest-dose pill that will provide adequate cycle control and effectiveness.

Gallo and colleagues reviewed the literature to determine how pills containing 20 mcg of ethinyl estradiol compare with higher-dose pills. They found 69 randomized controlled trials. Most trials followed patients for six to 12 cycles. The trials varied in dose of estrogen and in type and dose of progesterone; therefore, meta-analysis was not possible. No trial found a difference in contraceptive effectiveness; however, because pregnancy in women who take oral contraceptives is uncommon, the studies were insufficiently powered to show such a difference. In many of the lower-dose groups, early discontinuation occurred because of amenorrhea, adverse events, or bleeding irregularities. More specific information about which pills are most effective or which estrogen-progestin combinations have the fewest bleeding problems could not be determined. Furthermore, it could not be determined whether lower-dose estrogen pills have the same advantages as higher-dose pills for prevention of ovarian and endometrial cancer and reduction of acne.

Current data indicate disadvantages, but no clear advantages, to combined contraceptive pills with 20 mcg of estrogen. Therefore, it is reasonable to prescribe pills with more than 20 mcg of ethinyl estradiol for most women. The American College of Obstetricians and Gynecologists (ACOG) finds little or no increased risk of oral contraceptives for women with fibroadenoma, benign breast disease with epithelial hyperplasia with or without atypia, or a family history of breast cancer.1 ACOG recommends progesterone-only pills for lactating women and those with increased risk of thromboembolism. Caution should be used when prescribing combination pills for women older than 35 years who smoke. ACOG recommends pills with less than 35 mcg of estrogen for women younger than 35 years who have hypertension.1

For all women, the best form of birth control is the one that will be used consistently. For women who wish to reduce side effects and have regular periods, pills with 30 to 35 mcg of ethinyl estradiol may be a better choice than those with only 20 mcg.

Gallo MF, et al. 20 mcg versus >20 mcg estrogen combined oral contraceptives for contraception. Cochrane Database Syst Rev. 2004;(4):CD003989.


1. ACOG Practice Bulletin no. 18, July 2000. The use of hormonal contraception in women with coexisting medical conditions. Washington, D.C.: American College of Obstetricians and Gynecologists, 2000.



Copyright © 2005 by the American Academy of Family Physicians.
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