Mestranol

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title: "Mestranol" type: doc version: 1 created: 2026-02-28 author: "Wikipedia contributors" status: active scope: public tags: ["ethynyl-compounds", "estranes", "estrogen-ethers", "hormonal-contraception", "prodrugs", "synthetic-estrogens"] topic_path: "general/ethynyl-compounds" source: "https://en.wikipedia.org/wiki/Mestranol" license: "CC BY-SA 4.0" wikipedia_page_id: 0 wikipedia_revision_id: 0

::data[format=table title="Infobox drug"]

Field	Value
Verifiedfields	verified
Watchedfields	verified
verifiedrevid	462249106
IUPAC_name	(8R,9S,13S,14S,17R)-17-ethynyl-3-methoxy-13-methyl-7,8,9,11,12,14,15,16-octahydro-6H-cyclopenta[a]phenanthren-17-ol
image	Mestranol.svg
image_class	skin-invert-image
width	225px
image2	Mestranol molecule ball.png
image_class2	bg-transparent
width2	250px
tradename	Enovid, Norinyl, Ortho-Novum, others
Drugs.com
MedlinePlus	a601050
pregnancy_AU
pregnancy_US
legal_AU
legal_UK
legal_US
legal_status	Rx-only
routes_of_administration	By mouth
class	Estrogen; Estrogen ether
metabolites	Ethinylestradiol
elimination_half-life	Mestranol: 50 min
EE: 7–36 hours
CAS_number_Ref
CAS_number	72-33-3
ATC_prefix	None
PubChem	6291
IUPHAR_ligand	7087
DrugBank_Ref
DrugBank	DB01357
ChemSpiderID_Ref
ChemSpiderID	6054
UNII_Ref
UNII	B2V233XGE7
KEGG_Ref
KEGG	D00575
ChEBI_Ref
ChEBI	6784
ChEMBL_Ref
ChEMBL	1201151
synonyms	Ethinylestradiol 3-methyl ether; EEME; EE3ME; CB-8027; L-33355; RS-1044; 17α-Ethynylestradiol 3-methyl ether; 17α-Ethynyl-3-methoxyestra-1,3,5(10)-trien-17β-ol; 3-Methoxy-19-norpregna-1,3,5(10)-trien-20-yn-17β-ol
C	21
SMILES	O(c1cc4c(cc1)[C@H]3CC[C@]2(C@@H[C@@H]3CC4)C)C
StdInChI_Ref
StdInChI	1S/C21H26O2/c1-4-21(22)12-10-19-18-7-5-14-13-15(23-3)6-8-16(14)17(18)9-11-20(19,21)2/h1,6,8,13,17-19,22H,5,7,9-12H2,2-3H3/t17-,18-,19+,20+,21+/m1/s1
StdInChIKey_Ref
StdInChIKey	IMSSROKUHAOUJS-MJCUULBUSA-N
::

| C=21 | H=26 | O=2 | SMILES = O(c1cc4c(cc1)[C@H]3CC[C@]2(C@@H[C@@H]3CC4)C)C | StdInChI_Ref = | StdInChI = 1S/C21H26O2/c1-4-21(22)12-10-19-18-7-5-14-13-15(23-3)6-8-16(14)17(18)9-11-20(19,21)2/h1,6,8,13,17-19,22H,5,7,9-12H2,2-3H3/t17-,18-,19+,20+,21+/m1/s1 | StdInChIKey_Ref = | StdInChIKey = IMSSROKUHAOUJS-MJCUULBUSA-N 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.

Side effects of mestranol include nausea, breast tension, edema, and breakthrough bleeding among others. It is an estrogen, or an agonist of the estrogen receptors, the biological target of estrogens like estradiol. Mestranol is a prodrug of ethinylestradiol in the body.

Mestranol was discovered in 1956 and was introduced for medical use in 1957. It was the estrogen component in the first birth control pill. 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. Mestranol remains available only in a few countries, including the United States, United Kingdom, Japan, and Chile.

Medical uses

Mestranol was employed as the estrogen component in many of the first oral contraceptives, such as mestranol/noretynodrel (brand name Enovid) and mestranol/norethisterone (brand names Ortho-Novum, Norinyl), and is still in use today. In addition to its use as an oral contraceptive, mestranol has been used as a component of menopausal hormone therapy for the treatment of menopausal symptoms.

Side effects

Pharmacology

::figure[src="https://upload.wikimedia.org/wikipedia/commons/6/6d/Ethinylestradiol.svg" caption="active form]] of mestranol"] ::

Mestranol is a biologically inactive prodrug of ethinylestradiol to which it is demethylated in the liver (via O-Dealkylation) with a conversion efficiency of 70% (50 μg of mestranol is pharmacokinetically bioequivalent to 35 μg of ethinylestradiol). It has been found to possess 0.1–2.3% of the relative binding affinity of estradiol (100%) for the estrogen receptor, compared to 75–190% for ethinylestradiol.

The elimination half-life of mestranol has been reported to be 50 minutes. The elimination half-life of the active form of mestranol, ethinylestradiol, is 7 to 36 hours.

The effective ovulation-inhibiting dosage of mestranol has been studied in women. It has been reported to be about 98% effective at inhibiting ovulation at a dosage of 75 or 80 μg/day. 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.

Chemistry

Mestranol, also known as ethinylestradiol 3-methyl ether (EEME) or as 17α-ethynyl-3-methoxyestra-1,3,5(10)-trien-17β-ol, is a synthetic estrane steroid and a derivative of estradiol. It is specifically a derivative of ethinylestradiol (17α-ethynylestradiol) with a methyl ether at the C3 position.

History

In April 1956, noretynodrel was investigated, in Puerto Rico, in the first large-scale clinical trial of a progestogen as an oral contraceptive. 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. It was discovered early into the study that the initial chemical syntheses of noretynodrel had been contaminated with small amounts (1–2%) of the 3-methyl ether of ethinylestradiol (noretynodrel having been synthesized from ethinylestradiol). When this impurity was removed, higher rates of breakthrough bleeding occurred. As a result, mestranol, that same year (1956), 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. This resulted in Enovid by G. D. Searle & Company, the first oral contraceptive and a combination of 9.85 mg noretynodrel and 150 μg mestranol per pill.

Around 1969, mestranol was replaced by ethinylestradiol in most combined oral contraceptives due to widespread panic about the recently uncovered increased risk of venous thromboembolism with estrogen-containing oral contraceptives. 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. Whether this actually did result in a lower incidence of venous thromboembolism has never been assessed.

Society and culture

Generic names

Mestranol is the generic name of the drug and its , , , , , and , while mestranolo is its .

Brand names

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. Today, it continues to be sold in combination with progestins under brand names including Lutedion, Necon, Norinyl, Ortho-Novum, and Sophia.

Availability

Mestranol remains available only in the United States, the United Kingdom, Japan, and Chile. It is only marketed in combination with progestins, such as norethisterone.

Research

Mestranol has been studied as a male contraceptive and was found to be highly effective. At a dosage of 0.45 mg/day, it suppressed gonadotropin levels, reduced sperm count to zero within 4 to 6 weeks, and decreased libido, erectile function, and testicular size. Gynecomastia occurred in all of the men. These findings contributed to the conclusion that estrogens would be unacceptable as contraceptives for men.

Environmental presence

In 2021, mestranol was one of the 12 compounds identified in sludge samples taken from 12 wastewater treatment plants in California that were collectively associated with estrogenic activity in in vitro.

References

(1980). "Functional Morphologic Changes in Female Sex Organs Induced by Exogenous Hormones". Springer.
(7 November 2007). "The Handbook of Contraception: A Guide for Practical Management". Springer Science & Business Media.
(2010). "Sexual Chemistry: A History of the Contraceptive Pill". Yale University Press.
(22 October 2013). "Adolescent Health Care: Clinical Issues". Elsevier Science.
(1998). "Estrogens and Progestogens in Clinical Practice". Churchill Livingstone.
(2007). "Clinical Reproductive Medicine and Surgery". Elsevier Health Sciences.
(March 2000). "The estrogen receptor relative binding affinities of 188 natural and xenochemicals: structural diversity of ligands". Toxicological Sciences.
(2010). "Burger's Medicinal Chemistry and Drug Discovery". Wiley.
(17 April 2013). "Gynäkologische Endokrinologie und Fortpflanzungsmedizin: Band 1: Gynäkologische Endokrinologie". Springer-Verlag.
(23 March 2016). "Translational Toxicology: Defining a New Therapeutic Discipline". Humana Press.
(December 1990). "Pharmacokinetics of ethinyl estradiol and mestranol". American Journal of Obstetrics and Gynecology.
(June 2013). "Ethinyl estradiol and 17β-estradiol in combined oral contraceptives: pharmacokinetics, pharmacodynamics and risk assessment". Contraception.
(1986). "The Climacteric in Perspective". Springer.
(February 1973). "Oral contraceptives: therapeutics versus adverse reactions, with an outlook for the future I". Journal of Pharmaceutical Sciences.
(3 September 2013). "The Control of Fertility". Elsevier.
(1966). "Ovulation: Stimulation, Suppression, and Detection". Lippincott.
(1972). "Reviews of Physiology Biochemistry and Experimental Pharmacology, Volume 67".
(1970). "Chemical and Biological Aspects of Steroid Conjugation". Springer.
(July 1975). "Comparative studies of the ethynyl estrogens used in oral contraceptives. II. Antiovulatory potency". American Journal of Obstetrics and Gynecology.
(6 December 2012). "Clinical Endocrinology: Theory and Practice". Springer Science & Business Media.
(23 June 2005). "Drug Discovery: A History". John Wiley & Sons.
(2012). "Comprehensive Gynecology". Elsevier Health Sciences.
(22 October 2013). "Contraception: Science and Practice". Elsevier Science.
(February 1969). "Lactation suppression utilizing norethynodrel with mestranol". The Journal of the Florida Medical Association.
(21 February 2009). "Meyler's Side Effects of Endocrine and Metabolic Drugs". Elsevier.
(14 November 2014). "The Dictionary of Drugs: Chemical Data: Chemical Data, Structures and Bibliographies". Springer.
(2000). "Index Nominum 2000: International Drug Directory". Taylor & Francis.
(6 December 2012). "Concise Dictionary of Pharmacological Agents: Properties and Synonyms". Springer Science & Business Media.
"Mestranol and norethindrone Uses, Side Effects & Warnings".
(22 October 2013). "Pharmaceutical Manufacturing Encyclopedia". Elsevier.
(1980). "Pharmacology of estrogens-general". Pharmacology & Therapeutics.
(November 1975). "Progress towards a male oral contraceptive". Clinics in Endocrinology and Metabolism.
(1999). "Estrogens and Antiestrogens II: Pharmacology and Clinical Application of Estrogens and Antiestrogen". Springer Science & Business Media.
(December 1959). "Effects of progesterone and synthetic progestins on the reproductive physiology of normal men". Federation Proceedings.
(May 2021). "Using Estrogenic Activity and Nontargeted Chemical Analysis to Identify Contaminants in Sewage Sludge". Environmental Science & Technology.

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