Mestranol/noretynodrel

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Mestranol/noretynodrel
Bottle of Enovid 10 mg Oral Contraceptive - DPLA - 0cc9d42b69b6fd3d586205f5831cade0.jpg
A 10 mg bottle of Enovid, the first mestranol/noretynodrel medication
Combination of
Mestranol Estrogen
Norethynodrel Progestogen
Clinical data
Trade names Enavid, Enovid
Routes of
administration 		By mouth
ATC code
Legal status
Legal status
  • Discontinued
Identifiers
CAS Number
PubChem CID
CompTox Dashboard (EPA)

Mestranol/norethynodrel was the first combined oral contraceptive pill (COCP) being mestranol and norethynodrel. It sold as Enovid in the United States and as Enavid in the United Kingdom. Developed by Gregory Pincus at G. D. Searle & Company, it was first approved on June 10, 1957, by the U.S. Food and Drug Administration for treatment of menstrual disorders. [1] The FDA approved an additional indication for use as a contraceptive on June 23, 1960, though it only became legally prescribable nationwide and regardless of the woman's marital status after Eisenstadt v. Baird in 1972. [2] [3] [4] [5] In 1961, it was approved as a contraceptive in the UK and in Canada. [6] [7]

Contents

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. [8] It has also been used to suppress lactation and to treat endometriosis in women. [9] [10]

Available forms

The medication contained 0.15 mg mestranol and 10 mg noretynodrel. [8] 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. [8] One formulation also contained 0.075 mg mestranol and 3 mg noretynodrel. [8]

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. [11]

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. [12]

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. [3] [13] [14] 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. [15] 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. [16] 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. [17] 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. [18] [19] [20] 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. [15] [17] [21]

Enovid was discontinued in the U.S. in 1988, along with other first-generation high-estrogen COCPs. [22] [23]

See also

Related Research Articles

<span class="mw-page-title-main">Emergency contraception</span> Birth control measures taken after sexual intercourse

Emergency contraception (EC) is a birth control measure, used after sexual intercourse to prevent pregnancy.

<span class="mw-page-title-main">Combined oral contraceptive pill</span> Birth control method which is taken orally

The combined oral contraceptive pill (COCP), often referred to as the birth control pill or colloquially as "the pill", is a type of birth control that is designed to be taken orally by women. It is the oral form of combined hormonal contraception. The pill contains two important hormones: a progestin and estrogen. When taken correctly, it alters the menstrual cycle to eliminate ovulation and prevent pregnancy.

<span class="mw-page-title-main">Progestogen (medication)</span> Medication producing effects similar to progesterone

A progestogen, also referred to as a progestagen, gestagen, or gestogen, is a type of medication which produces effects similar to those of the natural female sex hormone progesterone in the body. A progestin is a synthetic progestogen. Progestogens are used most commonly in hormonal birth control and menopausal hormone therapy. They can also be used in the treatment of gynecological conditions, to support fertility and pregnancy, to lower sex hormone levels for various purposes, and for other indications. Progestogens are used alone or in combination with estrogens. They are available in a wide variety of formulations and for use by many different routes of administration. Examples of progestogens include natural or bioidentical progesterone as well as progestins such as medroxyprogesterone acetate and norethisterone.

Progestogen-only pills (POPs), colloquially known as "mini pills", are a type of oral contraceptive that contain synthetic progestogens (progestins) and do not contain estrogens. They are primarily used for the prevention of undesired pregnancy, although additional medical uses also exist.

<span class="mw-page-title-main">Ethinylestradiol</span> Estrogen medication

Ethinylestradiol (EE) is an estrogen medication which is used widely in birth control pills in combination with progestins. In the past, EE was widely used for various indications such as the treatment of menopausal symptoms, gynecological disorders, and certain hormone-sensitive cancers. It is usually taken by mouth but is also used as a patch and vaginal ring.

Extended or continuous cycle combined oral contraceptive pills are a packaging of combined oral contraceptive pills (COCPs) that reduce or eliminate the withdrawal bleeding that would occur once every 28 days in traditionally packaged COCPs. It works by reducing the frequency of the pill-free or placebo days. Extended cycle use of COCPs may also be called menstrual suppression, although other hormonal medications or medication delivery systems may also be used to suppress menses. Any brand of combined oral contraceptive pills can be used in an extended or continuous manner by simply discarding the placebo pills; this is most commonly done with monophasic pills in which all of the pills in a package contain the same fixed dosing of a synthetic estrogen and a progestin in each active pill.

<span class="mw-page-title-main">Norethisterone acetate</span> Chemical compound

Norethisterone acetate (NETA), also known as norethindrone acetate and sold under the brand name Primolut-Nor among others, is a progestin medication which is used in birth control pills, menopausal hormone therapy, and for the treatment of gynecological disorders. The medication available in low-dose and high-dose formulations and is used alone or in combination with an estrogen. It is ingested orally.

Intermenstrual bleeding (IMB) is vaginal bleeding at irregular intervals between expected menstrual periods. It may be associated with bleeding with sexual intercourse.

<span class="mw-page-title-main">Hormonal contraception</span> Birth control methods that act on the endocrine system

Hormonal contraception refers to birth control methods that act on the endocrine system. Almost all methods are composed of steroid hormones, although in India one selective estrogen receptor modulator is marketed as a contraceptive. The original hormonal method—the combined oral contraceptive pill—was first marketed as a contraceptive in 1960. In the ensuing decades many other delivery methods have been developed, although the oral and injectable methods are by far the most popular. Hormonal contraception is highly effective: when taken on the prescribed schedule, users of steroid hormone methods experience pregnancy rates of less than 1% per year. Perfect-use pregnancy rates for most hormonal contraceptives are usually around the 0.3% rate or less. Currently available methods can only be used by women; the development of a male hormonal contraceptive is an active research area.

<span class="mw-page-title-main">Norethisterone</span> Progestin medication

Norethisterone, also known as norethindrone and sold under many brand names, is a progestin medication used in birth control pills, menopausal hormone therapy, and for the treatment of gynecological disorders. The medication is available in both low-dose and high-dose formulations and both alone and in combination with an estrogen. It is used by mouth or, as norethisterone enanthate, by injection into muscle.

<span class="mw-page-title-main">Mestranol</span> Chemical compound

Mestranol, sold under the brand names Enovid, Norinyl, and Ortho-Novum among others, is an estrogen medication which has been used in birth control pills, menopausal hormone therapy, and the treatment of menstrual disorders. It is formulated in combination with a progestin and is not available alone. It is taken by mouth.

Frank Benjamin Colton, American chemist who first synthesized noretynodrel, the progestin used in Enovid, the first oral contraceptive, at G. D. Searle & Company in Skokie, Illinois in 1952.

<span class="mw-page-title-main">Dienogest</span> Chemical compound

Dienogest, sold under the brand name Visanne among others, is a progestin medication which is used in birth control pills and in the treatment of endometriosis. It is also used in menopausal hormone therapy and to treat heavy periods. Dienogest is available both alone and in combination with estrogens. It is taken by mouth.

Combined injectable contraceptives (CICs) are a form of hormonal birth control for women. They consist of monthly injections of combined formulations containing an estrogen and a progestin to prevent pregnancy.

Birth control pills come in a variety of formulations. The main division is between combined oral contraceptive pills, containing both estrogens and synthetic progestogens (progestins), and progestogen only pills. Combined oral contraceptive pills also come in varying types, including varying doses of estrogen, and whether the dose of estrogen or progestogen changes from week to week.

<span class="mw-page-title-main">Medroxyprogesterone acetate</span> Injectible form of birth control

Medroxyprogesterone acetate (MPA), also known as depot medroxyprogesterone acetate (DMPA) in injectable form and sold under the brand name Depo-Provera among others, is a hormonal medication of the progestin type. It is used as a method of birth control and as a part of menopausal hormone therapy. It is also used to treat endometriosis, abnormal uterine bleeding, paraphilia, and certain types of cancer. The medication is available both alone and in combination with an estrogen. It is taken by mouth, used under the tongue, or by injection into a muscle or fat.

<span class="mw-page-title-main">Noretynodrel</span> Chemical compound

Noretynodrel, or norethynodrel, sold under the brand name Enovid among others, is a progestin medication which was previously used in birth control pills and in the treatment of gynecological disorders but is now no longer marketed. It was available both alone and in combination with an estrogen. The medication is taken by mouth.

The first large-scale human trial of the birth control pill was conducted by Gregory Pincus and John Rock in 1955 in Puerto Rico. Before the drug was approved as safe in the mainland U.S., many Puerto Rican women were used as test subjects. These trials are a major component in the history of the development of female oral contraceptives, occurring in between initial small trial testing on the east coast and the release of the drug for public consumption. As a result, women gained more independence as they were able to delay pregnancies. The trials are controversial because the Puerto Rican women were uninformed of the potential health and safety risks of the drug. There was a large amount of criticism coming from feminist circles surrounding the trial.

Mestranol/norethisterone is a combination of the estrogen ethinylestradiol and the progestin norethisterone (norethindrone) which was introduced in 1963 and was the second combined oral contraceptive to be marketed, following mestranol/noretynodrel in 1960. Although most mestranol-containing oral contraceptive formulations have been discontinued, the combination remains available today in the United States in a single formulation under the brand name Norinyl 1+50 28-Day. It has largely been superseded by ethinylestradiol/norethisterone, which has been marketed under many of the same brand names.

<span class="mw-page-title-main">Combined hormonal contraception</span> Form of hormonal contraception combining both an estrogen and a progestogen

Combined hormonal contraception (CHC), or combined birth control, is a form of hormonal contraception which combines both an estrogen and a progestogen in varying formulations.

References

  1. ↑ Junod SW (1998). "FDA's Approval of the First Oral Contraceptive, Enovid". Histories of Product Regulation. Update (bimonthly publication of the Food and Drug Law Institute). U.S. Food and Drug Administration. Archived from the original on 14 January 2012.
  2. ↑ "FDA Approved Drug Products". FDA.
  3. 1 2 Junod SW, Marks L (April 2002). "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. 57 (2): 117–160. doi: 10.1093/jhmas/57.2.117 . PMID   11995593.
  4. ↑ Tone A (2001). Devices & Desires: A History of Contraceptives in America. New York: Hill and Wang. ISBN   0-8090-3817-X.
  5. ↑ Watkins ES (1998). On the Pill: A Social History of Oral Contraceptives, 1950–1970. Baltimore: Johns Hopkins University Press. ISBN   0-8018-5876-3.
  6. ↑ "ANNOTATIONS". British Medical Journal. 2 (5258): 1007–1009. October 1961. doi:10.1136/bmj.2.3490.1009. PMC   1970146 . PMID   20789252.
  7. ↑ "Medical News". Br Med J . 2 (5258): 1032–1034. October 14, 1961. doi:10.1136/bmj.2.5258.1032. PMC   1970195 .
  8. 1 2 3 4 Marks L (2010). Sexual Chemistry: A History of the Contraceptive Pill. Yale University Press. pp. 75, 77–78. ISBN   978-0-300-16791-7.
  9. ↑ Vorherr H (2 December 2012). "Suppression of Laction". The Breast: Morphology, Physiology, and Lactation. Elsevier Science. pp. 202–. ISBN   978-0-323-15726-1.
  10. ↑ Olive DL (29 November 2004). "Medical therapy of endometriosis". In Olive D (ed.). Endometriosis in Clinical Practice. CRC Press. pp. 246–. ISBN   978-0-203-31939-0.
  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. 68: 101040. doi: 10.1016/j.yfrne.2022.101040 . ISSN   0091-3022. PMID   36243109.
  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. 57 (2): 117–160. doi: 10.1093/jhmas/57.2.117 . PMID   11995593 . Retrieved 2023-11-29.
  13. ↑ Winter IC (March 1965). "The incidence of thromboembolism in Enovid users". Metabolism. 14 (Supplement): 422–428. doi:10.1016/0026-0495(65)90029-6. PMID   14261427.
  14. ↑ Jordan WM, Anand JK (November 18, 1961). "Pulmonary embolism". Lancet. 278 (7212): 1146–1147. doi:10.1016/S0140-6736(61)91061-3.
  15. 1 2 Marks L (2001). Sexual Chemistry: A History of the Contraceptive Pill. New Haven: Yale University Press. ISBN   0-300-08943-0.
  16. ↑ Seaman B (1969). The Doctors' Case Against the Pill. New York: P. H. Wyden. ISBN   0-385-14575-6.
  17. 1 2 Watkins ES (1998). On the Pill: A Social History of Oral Contraceptives, 1950–1970. Baltimore: Johns Hopkins University Press. ISBN   0-8018-5876-3.
  18. ↑ FDA (June 11, 1970). "Statement of policy concerning oral contraceptive labeling directed to users". Federal Register. 35 (113): 9001–9003.
  19. ↑ FDA (January 31, 1978). "Oral contraceptives; requirement for labeling directed to the patient". Federal Register. 43 (21): 4313–4334.
  20. ↑ FDA (May 25, 1989). "Oral contraceptives; patient package insert requirement". Federal Register. 54 (100): 22585–22588.
  21. ↑ Speroff L, Darney OD (2005). "Oral Contraception". A Clinical Guide for Contraception (4th ed.). Philadelphia: Lippincott Williams & Wilkins. pp. 21–138. ISBN   0-7817-6488-2.
  22. ↑ "Searle, 2 others to stop making high-estrogen pill". St. Louis Post-Dispatch. Reuters News Service. 1988-04-15. pp. 7D. Retrieved 2009-08-29.
  23. ↑ "High-estrogen 'pill' going off market". San Jose Mercury News. 1988-04-15. Retrieved 2009-08-29.

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