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Overview of the use of estrogen-progestin contraceptives

Kathryn A Martin, MD
Robert L Barbieri, MD
Section Editor
William F Crowley, Jr, MD
Deputy Editor
Kathryn A Martin, MD


Oral contraceptives (OCs) are a reliable form of contraception and have noncontraceptive benefits, as well. Furthermore, the decrease in both estrogen and progestin content in the last decade has led to a reduction in both side effects and cardiovascular complications [1]. As a result, these preparations are a safe contraceptive option for many women. While the US Food and Drug Administration (FDA) had previously set upper age limits for OC use as 35 years for smokers and 40 years for nonsmokers, all references to age limits were removed in 1989 for healthy, nonsmoking women. Thus, OCs can be given until menopause in such women.

This topic will review the general principles of the use of combined estrogen-progestin OCs, including pharmacology, mechanisms of action, indications, contraindications, efficacy, and the different preparations that are available. Progestin-only OCs, the side effects that may be associated with OCs, other forms of estrogen-progestin contraception, and the topic of contraception in general are discussed separately. (See "Progestin-only pills (POPs) for contraception" and "Risks and side effects associated with estrogen-progestin contraceptives" and "Transdermal contraceptive patch" and "Contraceptive counseling and selection".)


The discovery in 1938 that addition of an ethinyl group to estradiol resulted in both an orally active estrogen compound and a dramatic increase in estrogenic potency was a major advance in steroid biochemistry. This compound, known as ethinyl estradiol, is the estrogen in nearly all oral contraceptives (OCs) currently used.

Soon thereafter, ethinyl substitution of testosterone also was found to result in an orally active compound (ethisterone). Removal of the carbon at the C-19 position of ethisterone changed it from an androgen to a progestin. This finding resulted in the development of a class of progestins referred to as 19-nortestosterone derivatives. Included in this class are commonly used progestins such as norethindrone, norethindrone acetate, and levonorgestrel. Ethynodiol diacetate, another progestin in this category, also has significant estrogenic activity (table 1).

All of these testosterone-derived progestins bind to the androgen receptor and have some residual androgenic activity. The adverse metabolic effects of OCs, such as the reduction in serum high-density lipoprotein (HDL) cholesterol concentrations, are the result of the androgenic activity of the progestin. New progestins have been developed with less androgenic activity (table 1). (See 'Progestin component' below.)

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Literature review current through: Nov 2017. | This topic last updated: Aug 17, 2016.
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