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  • Title: The formulation of oral contraceptives: does the amount of estrogen make any clinical difference?
    Author: Speroff L.
    Journal: Johns Hopkins Med J; 1982 May; 150(5):170-6. PubMed ID: 7043035.
    Abstract:
    The question of whether the formulation of the oral contraceptive (OC) pill makes any clinically significant difference is often raised because both physicians and patients are faced with the problem of selecting from a bewildering array of available pills. The answer involves examining the contribution of estrogen and progestin separately. The estrogen component of the combination birth control pill serves 3 important functions: it exerts negative feedback action on the secretion of gonadotropins; it provides stability to the endometrium, preventing irregular shedding and unwanted breakthrough bleeding; and it increases the potency of the progestational component in its inhibitory action on gonadotropin secretion and its antifertility effects on cervical mucus, endometrium, and possibly the Fallopian tube. The presence of estrogen may eliminate a need for higher progestin doses in OCs. This effect is mediated by estrogen induced increase in the concentration of intracellular progestin receptors. A minimal pharmacologic level of estrogen is needed to achieve effective contraception, and the new low dose pills are most likely at the limit of the ability to reduce dosage. Thrombosis is the most serious side effect of the OC; it plays a key role in the increased risk of death from a variety of circulatory problems such as myocardial infarction, pulmonary embolism, and stroke. A convincing argument can be made for a dose related response between the incidence of thrombosis and the estrogen content of the pill. Only the 19-nortestosterone family of progestins is approved for contraceptive use in the U.S. The progestin component exerts its principal contraceptive effect by suppressing luteinizing hormone (LH) secretion. In 1978 an early report from the Walnut Creek study suggested that HDL-cholesterol levels were positively associated with estrogen levels in OCs and negatively with progestin. The implication was that high dose progestins would be associated with a greater risk of cardiovascular diseases. A recent report suggests that the estrogen and progestin components could be balanced to produce minimal effects on lipid metabolism. Current evidence supports the view that there is greater safety with pills containing less than 50 mcg of estrogen. The side effects of amenorrhea and breakthrough bleeding are reviewed. It is cautioned that if an older woman chooses to use OC, she should be aware of the higher risk involved with increasing age.
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