Mestranol/noretynodrel

Medical uses

Mestranol/noretynodrel was indicated in the treatment of gynecological and menstrual disorders. Originally it was not legal to use contraception so it was marketed for menstrual relief with the side effect of inability to conceive. It has also been used to suppress lactation and to treat endometriosis in women.

Available forms

The medication contained 0.15 mg mestranol and 10 mg noretynodrel. Additional formulations containing 0.075 mg mestranol and 5 mg noretynodrel as well as 0.1 mg mestranol and 2.5 mg noretynodrel were subsequently introduced. One formulation also contained 0.075 mg mestranol and 3 mg noretynodrel.

History

Creation

Enovid was first manufactured when scientists isolated progesterone from diosgenin, then removed 19-carbon from the molecule. This new form of progesterone had higher progestational activity, which prevented pregnancy.

Social impact

Initially sold in 1957, Enovid was first marketed as a treatment for gynecological disorders. In 1960, its sale as an oral contraceptive was approved by the FDA. This was seen as a major improvement to contraceptives as a whole, being preferred over other methods such as condoms and diaphragms.

Complications and legal proceedings

The first published case report of a blood clot and pulmonary embolism in a woman using Enavid (Enovid 10 mg in the U.S.) at a dose of 20 mg/day did not appear until November 1961, four years after its approval, by which time it had been used by over one million women.

-- -- It would take almost a decade of epidemiological studies to conclusively establish an increased risk of venous thrombosis in oral contraceptive users and an increased risk of stroke and myocardial infarction in oral contraceptive users who smoke or have high blood pressure or other cardiovascular or cerebrovascular risk factors. -- These risks of oral contraceptives were dramatized in the 1969 book The Doctors' Case Against the Pill by feminist journalist Barbara Seaman who helped arrange the 1970 Nelson Pill Hearings called by Senator Gaylord Nelson. -- The hearings were conducted by senators who were all men and the witnesses in the first round of hearings were all men, leading Alice Wolfson and other feminists to protest the hearings and generate media attention. -- Their work led to mandating the inclusion of patient package inserts with oral contraceptives to explain their possible side effects and risks to help facilitate informed consent.

-- -- Today's standard dose oral contraceptives contain an estrogen dose that is one third lower than the first marketed oral contraceptive and contain lower doses of different, more potent progestins in a variety of formulations.

Enovid was discontinued in the U.S. in 1988, along with other first-generation high-estrogen COCPs.

References

References

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8. (2 December 2012). "The Breast: Morphology, Physiology, and Lactation". Elsevier Science.
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11. Hampson, Elizabeth. (2023-01-01). "Oral contraceptives in the central nervous system: Basic pharmacology, methodological considerations, and current state of the field". Frontiers in Neuroendocrinology.
12. Junod, Suzanne. (2002-04-01). "Women's Trials: The Approval of the First Oral Contraceptive Pill in the United States and Great Britain". Journal of the History of Medicine and Allied Sciences.
13. (March 1965). "The incidence of thromboembolism in Enovid users". Metabolism.
14. (November 18, 1961). "Pulmonary embolism". Lancet.
15. (1969). "The Doctors' Case Against the Pill". P. H. Wyden.
16. FDA. (June 11, 1970). "Statement of policy concerning oral contraceptive labeling directed to users". Federal Register.
17. FDA. (January 31, 1978). "Oral contraceptives; requirement for labeling directed to the patient". Federal Register.
18. FDA. (May 25, 1989). "Oral contraceptives; patient package insert requirement". Federal Register.
19. (2001). "Sexual Chemistry: A History of the Contraceptive Pill". Yale University Press.
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21. (2005). "A Clinical Guide for Contraception". Lippincott Williams & Wilkins.
22. (1988-04-15). "Searle, 2 others to stop making high-estrogen pill". St. Louis Post-Dispatch.
23. (1988-04-15). "High-estrogen 'pill' going off market". San Jose Mercury News.