Mestranol was discovered in 1956 and was introduced for medical use in 1957.[12][13] It was the estrogen component in the first birth control pill.[12][13] In 1969, mestranol was replaced by ethinylestradiol in most birth control pills, although mestranol continues to be used in a few birth control pills even today.[14][9] Mestranol remains available only in a few countries, including theUnited States,United Kingdom,Japan, andChile.[9]
Theelimination half-life of mestranol has been reported to be 50 minutes.[2] The elimination half-life of the active form of mestranol, ethinylestradiol, is 7 to 36 hours.[3][4][5][6]
The effectiveovulation-inhibiting dosage of mestranol has been studied in women.[19][20][21] It has been reported to be about 98% effective at inhibiting ovulation at a dosage of 75 or 80 μg/day.[22][21][23] In another study, the ovulation rate was 15.4% at 50 μg/day, 5.7% at 80 μg/day, and 1.1% at 100 μg/day.[24]
In April 1956,noretynodrel was investigated, inPuerto Rico, in the first large-scaleclinical trial of aprogestogen as an oral contraceptive.[12][13] The trial was conducted in Puerto Rico due to the high birth rate in the country and concerns of moral censure in the United States.[47] It was discovered early into the study that the initialchemical syntheses of noretynodrel had been contaminated with small amounts (1–2%) of the 3-methyl ether of ethinylestradiol (noretynodrel having been synthesized from ethinylestradiol).[12][13] When this impurity was removed, higher rates ofbreakthrough bleeding occurred.[12][13] As a result, mestranol, that same year (1956),[48] was developed and serendipitously identified as a very potent synthetic estrogen (and eventually as a prodrug of ethinylestradiol), given its name, and added back to the formulation.[12][13] This resulted in Enovid byG. D. Searle & Company, the first oral contraceptive and a combination of 9.85 mg noretynodrel and 150 μg mestranol per pill.[12][13]
Around 1969, mestranol was replaced by ethinylestradiol in most combined oral contraceptives due to widespread panic about the recently uncovered increased risk ofvenous thromboembolism with estrogen-containing oral contraceptives.[14] The rationale was that ethinylestradiol was approximately twice as potent by weight as mestranol and hence that the dose could be halved, which it was thought might result in a lower incidence of venous thromboembolism.[14] Whether this actually did result in a lower incidence of venous thromboembolism has never been assessed.[14]
Mestranol is thegeneric name of the drug and itsINNTooltip International Nonproprietary Name,USANTooltip United States Adopted Name,USPTooltip United States Pharmacopeia,BANTooltip British Approved Name,DCFTooltip Dénomination Commune Française, andJANTooltip Japanese Accepted Name, whilemestranolo is itsDCITTooltip Denominazione Comune Italiana.[44][45][1][9]
Mestranol has been marketed under a variety of brand names, mostly or exclusively in combination with progestins, including Devocin, Enavid, Enovid, Femigen, Mestranol, Norbiogest, Ortho-Novin, Ortho-Novum, Ovastol, and Tranel among others.[7][44][49][45] Today, it continues to be sold in combination with progestins under brand names including Lutedion, Necon, Norinyl, Ortho-Novum, and Sophia.[9]
^abGoldzieher JW, Brody SA (December 1990). "Pharmacokinetics of ethinyl estradiol and mestranol".American Journal of Obstetrics and Gynecology.163 (6 Pt 2):2114–2119.doi:10.1016/0002-9378(90)90550-Q.PMID2256522.
^abStanczyk FZ, Archer DF, Bhavnani BR (June 2013). "Ethinyl estradiol and 17β-estradiol in combined oral contraceptives: pharmacokinetics, pharmacodynamics and risk assessment".Contraception.87 (6):706–727.doi:10.1016/j.contraception.2012.12.011.PMID23375353.
^Wittlinger H (1980). "Clinical Effects of Estrogens".Functional Morphologic Changes in Female Sex Organs Induced by Exogenous Hormones. Springer. pp. 67–71.doi:10.1007/978-3-642-67568-3_10.ISBN978-3-642-67570-6.
^Faigle JW, Schenkel L (1998). "Pharmacokinetics of estrogens and progestogens". In Fraser IS, Whitehead MI, Jansen R, Lobo RA (eds.).Estrogens and Progestogens in Clinical Practice. London: Churchill Livingstone. pp. 273–294.ISBN0-443-04706-5.
^Bingel AS, Benoit PS (February 1973). "Oral contraceptives: therapeutics versus adverse reactions, with an outlook for the future I".Journal of Pharmaceutical Sciences.62 (2):179–200.doi:10.1002/jps.2600620202.PMID4568621.
^Elger W (1972). "Physiology and pharmacology of female reproduction under the aspect of fertility control".Reviews of Physiology Biochemistry and Experimental Pharmacology, Volume 67. Ergebnisse der Physiologie Reviews of Physiology. Vol. 67. pp. 69–168.doi:10.1007/BFb0036328.ISBN3-540-05959-8.PMID4574573.
^Herr F, Revesz C, Manson AJ, Jewell JB (1970). "Biological Properties of Estrogen Sulfates".Chemical and Biological Aspects of Steroid Conjugation. Springer. pp. 368–408.doi:10.1007/978-3-642-49793-3_8 (inactive 12 July 2025).ISBN978-3-642-49506-9.{{cite book}}: CS1 maint: DOI inactive as of July 2025 (link)
^Goldzieher JW, Pena A, Chenault CB, Woutersz TB (July 1975). "Comparative studies of the ethynyl estrogens used in oral contraceptives. II. Antiovulatory potency".American Journal of Obstetrics and Gynecology.122 (5):619–624.doi:10.1016/0002-9378(75)90061-7.PMID1146927.
^Lauritzen C (June 1977). "[Estrogen thearpy in practice. 3. Estrogen preparations and combination preparations]" [Estrogen therapy in practice. 3. Estrogen preparations and combination preparations].Fortschritte Der Medizin (in German).95 (21):1388–92.PMID559617.
^Lauritzen CH (January 1976). "The female climacteric syndrome: significance, problems, treatment".Acta Obstetricia Et Gynecologica Scandinavica. Supplement.51:47–61.doi:10.3109/00016347509156433.PMID779393.
^Lauritzen C (1975). "The Female Climacteric Syndrome: Significance, Problems, Treatment".Acta Obstetricia et Gynecologica Scandinavica.54 (s51):48–61.doi:10.3109/00016347509156433.ISSN0001-6349.
^Ryden AB (1950). "Natural and synthetic oestrogenic substances; their relative effectiveness when administered orally".Acta Endocrinologica.4 (2):121–39.doi:10.1530/acta.0.0040121.PMID15432047.
^Ryden AB (1951). "The effectiveness of natural and synthetic oestrogenic substances in women".Acta Endocrinologica.8 (2):175–91.doi:10.1530/acta.0.0080175.PMID14902290.
^Kottmeier HL (1947). "Ueber blutungen in der menopause: Speziell der klinischen bedeutung eines endometriums mit zeichen hormonaler beeinflussung: Part I".Acta Obstetricia et Gynecologica Scandinavica.27 (s6):1–121.doi:10.3109/00016344709154486.ISSN0001-6349.There is no doubt that the conversion of the endometrium with injections of both synthetic and native estrogenic hormone preparations succeeds, but the opinion whether native, orally administered preparations can produce a proliferation mucosa changes with different authors. PEDERSEN-BJERGAARD (1939) was able to show that 90% of the folliculin taken up in the blood of the vena portae is inactivated in the liver. Neither KAUFMANN (1933, 1935), RAUSCHER (1939, 1942) nor HERRNBERGER (1941) succeeded in bringing a castration endometrium into proliferation using large doses of orally administered preparations of estrone or estradiol. Other results are reported by NEUSTAEDTER (1939), LAUTERWEIN (1940) and FERIN (1941); they succeeded in converting an atrophic castration endometrium into an unambiguous proliferation mucosa with 120–300 oestradiol or with 380 oestrone.
^Martinez-Manautou J, Rudel HW (1966). "Antiovulatory Activity of Several Synthetic and Natural Estrogens". In Robert Benjamin Greenblatt (ed.).Ovulation: Stimulation, Suppression, and Detection. Lippincott. pp. 243–253.
^Herr F, Revesz C, Manson AJ, Jewell JB (1970). "Biological Properties of Estrogen Sulfates".Chemical and Biological Aspects of Steroid Conjugation. pp. 368–408.doi:10.1007/978-3-642-49793-3_8.ISBN978-3-642-49506-9.
^Billingsley FS (February 1969). "Lactation suppression utilizing norethynodrel with mestranol".The Journal of the Florida Medical Association.56 (2):95–97.PMID4884828.
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