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  • Title: Estrogens: why harmless as menopausal therapy but hazardous in the "Pill"?
    Author: Edwards CC, Drill VA.
    Journal: JAMA; 1971 Jan 18; 215(3):(3): 492-493. PubMed ID: 12332746.
    Abstract:
    An inquiry as to why the use of estrogens in large doses has been sanctioned in a variety of therapeutic situations and condemned when used in smaller doses as contraceptives is answered by 2 consultants. Dr. C.C. Edwards of the U.S. Food and Drug Administration answers that there is considerable difference between the conjugated equine estrogens used in therapy and the synthetic estrogens, ethinyl estradiol and mestranol, used in contraceptive medications. The same menopausal symptoms relieved by 1.25 mg of conjugated equine estrogens daily require only .02 mg of ethinyl estradiol. .05 mg ethinyl estradiol daily has a potent ovulation inhibiting effect while 3.75 mg of conjugated equine estrogens daily is ineffective in inhibiting ovulation consistently. Oral contraceptives with .02 mg of ethinyl estradiol might be virtually without serious estrogenic adverse reactions, but studies to date have shown .02 mg daily to be ineffective as an ovulation inhibitor. Dr. V.A. Drill of G.D. Searle and Company contends that the British investigators who reported an increased incidence of thromboembolism in oral contraceptive users compared the estrogens taken simply on a milligram basis rather than in relationship to their estrogenic potency. Errors were also made statistically. Dr. Drill asserts that the controversy regarding thromboembolic disease which followed the British announcement is not based on established facts. Early appraisals of the possible role of different doses of mestranol and ethinyl estradiol in the British study are premature.
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