Mestranolのソースを表示

{{Short description|Chemical compound}}
{{cs1 config|name-list-style=vanc|display-authors=6}}
{{Drugbox
| Verifiedfields = verified
| Watchedfields = verified
| verifiedrevid = 462249106
| IUPAC_name = (8''R'',9''S'',13''S'',14''S'',17''R'')-17-ethynyl-3-methoxy-13-methyl-7,8,9,11,12,14,15,16-octahydro-6''H''-cyclopenta[''a'']phenanthren-17-ol
| image = Mestranol.svg
| width = 225px
| image2 = Mestranol molecule ball.png
| width2 = 250px

<!--Clinical data-->
| tradename = Enovid, Norinyl, Ortho-Novum, others
| Drugs.com = {{drugs.com|international|mestranol}}
| MedlinePlus = a601050
| pregnancy_AU = <!-- A / B1 / B2 / B3 / C / D / X -->
| pregnancy_US = <!-- A / B / C / D / X -->
| pregnancy_category = 
| legal_AU = <!-- Unscheduled / S2 / S4 / S8 -->
| legal_UK = <!-- GSL / P / POM / CD -->
| legal_US = <!-- OTC / Rx-only -->
| legal_status = Rx-only
| routes_of_administration = [[Oral administration|By mouth]]<ref name="MortonHall2012" />
| class = [[Estrogen (medication)|Estrogen]]; [[Estrogen ether]]

<!--Pharmacokinetic data-->
| bioavailability = 
| protein_bound = 
| metabolism = 
| metabolites = [[Ethinylestradiol]]
| elimination_half-life = Mestranol: 50 min<ref name="RunnebaumRabe2013" /><br />{{abbr|EE|Ethinylestradiol}}: 7–36 hours<ref name="HughesWaters2016" /><ref name="pmid2256522" /><ref name="pmid23375353" /><ref name="Shellenberger1986" />
| excretion = 

<!--Identifiers-->
| CAS_number_Ref = {{cascite|correct|??}}
| CAS_number = 72-33-3
| ATC_prefix = None
| ATC_suffix = 
| ATC_supplemental = 
| PubChem = 6291
| IUPHAR_ligand = 7087
| DrugBank_Ref = {{drugbankcite|correct|drugbank}}
| DrugBank = DB01357
| ChemSpiderID_Ref = {{chemspidercite|correct|chemspider}}
| ChemSpiderID = 6054
| UNII_Ref = {{fdacite|correct|FDA}}
| UNII = B2V233XGE7
| KEGG_Ref = {{keggcite|correct|kegg}}
| KEGG = D00575
| ChEBI_Ref = {{ebicite|correct|EBI}}
| ChEBI = 6784
| ChEMBL_Ref = {{ebicite|correct|EBI}}
| 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

<!--Chemical data-->
| C=21 | H=26 | O=2
| SMILES = O(c1cc4c(cc1)[C@H]3CC[C@]2([C@@H](CC[C@]2(C#C)O)[C@@H]3CC4)C)C
| StdInChI_Ref = {{stdinchicite|correct|chemspider}}
| 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 = {{stdinchicite|correct|chemspider}}
| StdInChIKey = IMSSROKUHAOUJS-MJCUULBUSA-N
}}
<!-- Definition and medical uses -->
'''Mestranol''', sold under the brand names '''Enovid''', '''Norinyl''', and '''Ortho-Novum''' among others, is an [[estrogen (medication)|estrogen]] medication which has been used in [[birth control pill]]s, [[menopausal hormone therapy]], and the treatment of [[menstrual disorder]]s.<ref name="MortonHall2012" /><ref name="Marks2010" /><ref name="Blum2013" /><ref name="Drugs.com" /> It is formulated in combination with a [[progestin]] and is not available alone.<ref name="Drugs.com" /> It is taken [[oral administration|by mouth]].<ref name="MortonHall2012" />

<!-- Side effects and mechanism -->
[[Side effect]]s of mestranol include [[nausea]], [[breast tension]], [[edema]], and [[breakthrough bleeding]] among others.<ref name="Wittlinger1980">{{Cite book | vauthors = Wittlinger H |title=Functional Morphologic Changes in Female Sex Organs Induced by Exogenous Hormones |year=1980 |isbn=978-3-642-67570-6 |pages=67–71 |chapter=Clinical Effects of Estrogens |publisher=Springer |doi=10.1007/978-3-642-67568-3_10}}</ref> It is an [[estrogen (medication)|estrogen]], or an [[agonist]] of the [[estrogen receptor]]s, the [[biological target]] of estrogens like [[estradiol]].<ref name="Shoupe2007">{{Cite book | vauthors = Shoupe D |url=https://books.google.com/books?id=sczb0Tk_2IwC&pg=PA23 |title=The Handbook of Contraception: A Guide for Practical Management |date=7 November 2007 |publisher=Springer Science & Business Media |isbn=978-1-59745-150-5 |pages=23– |quote=EE is about 1.7 times as potent as the same weight of mestranol.}}</ref> Mestranol is a [[prodrug]] of [[ethinylestradiol]] in the body.<ref name="Shoupe2007" />

<!-- History, society, and culture -->
Mestranol was discovered in 1956 and was introduced for medical use in 1957.<ref name="Sneader2005" /><ref name="LentzLobo2012" /> It was the estrogen component in the first birth control pill.<ref name="Sneader2005" /><ref name="LentzLobo2012" /> 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.<ref name="Aronson2009" /><ref name="Drugs.com" /> Mestranol remains available only in a few countries, including the [[United States]], [[United Kingdom]], [[Japan]], and [[Chile]].<ref name="Drugs.com" />

==Medical uses==
Mestranol was employed as the estrogen component in many of the first [[combined oral contraceptive pill|oral contraceptive]]s, such as [[mestranol/noretynodrel]] (brand name ''Enovid'') and [[mestranol/norethisterone]] (brand names ''Ortho-Novum'', ''Norinyl''), and is still in use today.<ref name="Marks2010">{{Cite book | vauthors = Marks L |url=https://books.google.com/books?id=_i-s4biQs7MC&pg=PA75 |title=Sexual Chemistry: A History of the Contraceptive Pill |publisher=Yale University Press |year=2010 |isbn=978-0-300-16791-7 |pages=75–}}</ref><ref name="Blum2013">{{Cite book | vauthors = Blum RW |url=https://books.google.com/books?id=36PpAgAAQBAJ&pg=PA216 |title=Adolescent Health Care: Clinical Issues |date=22 October 2013 |publisher=Elsevier Science |isbn=978-1-4832-7738-7 |pages=216–}}</ref><ref name="Drugs.com" /> In addition to its use as an oral contraceptive, mestranol has been used as a component of [[menopausal hormone therapy]] for the treatment of [[menopause|menopausal]] [[symptom]]s.<ref name="MortonHall2012" />

==Side effects==
{{See also|Ethinylestradiol#Side effects|Estrogen (medication)#Side effects}}
{{empty section|date=December 2023}}

==Pharmacology==
[[File:Ethinylestradiol.svg|thumb|right|225px|[[Ethinylestradiol]] (EE), the [[active metabolite|active form]] of mestranol.]]

Mestranol is a biologically inactive [[prodrug]] of ethinylestradiol to which it is [[demethylation|demethylated]] in the [[liver]] (via O-Dealkylation) with a conversion efficiency of 70% (50&nbsp;μg of mestranol is [[pharmacokinetic]]ally [[bioequivalent]] to 35&nbsp;μg of ethinylestradiol).<ref name="FaigleSchenkel1998">{{Cite book | vauthors = Faigle JW, Schenkel L |chapter=Pharmacokinetics of estrogens and progestogens | veditors = Fraser IS, Whitehead MI, Jansen R, Lobo RA  |title=Estrogens and Progestogens in Clinical Practice |publisher=Churchill Livingstone |year=1998 |isbn=0-443-04706-5 |location=London |pages=273–294 }}</ref><ref name="FalconeHurd2007">{{Cite book | vauthors = Falcone T, Hurd WW |url= https://books.google.com/books?id=fOPtaEIKvcIC&pg=PA388 |title=Clinical Reproductive Medicine and Surgery |publisher= Elsevier Health Sciences |year=2007 |isbn=978-0-323-03309-1 |pages=388–}}</ref><ref name="Shoupe2007" /> It has been found to possess 0.1 to 2.3% of the [[relative binding affinity]] of [[estradiol (medication)|estradiol]] (100%) for the [[estrogen receptor]], compared to 75 to 190% for [[ethinylestradiol]].<ref name="pmid10746941">{{cite journal | vauthors = Blair RM, Fang H, Branham WS, Hass BS, Dial SL, Moland CL, Tong W, Shi L, Perkins R, Sheehan DM | title = The estrogen receptor relative binding affinities of 188 natural and xenochemicals: structural diversity of ligands | journal = Toxicological Sciences | volume = 54 | issue = 1 | pages = 138–153 | date = March 2000 | pmid = 10746941 | doi = 10.1093/toxsci/54.1.138 | doi-access = free }}</ref><ref name="Ruenitz2010">{{Cite book | vauthors = Ruenitz PC |title=Burger's Medicinal Chemistry and Drug Discovery |year=2010 |isbn=978-0-471-26694-5 |pages=219–264 |chapter=Female Sex Hormones, Contraceptives, And Fertility Drugs |publisher=Wiley |doi=10.1002/0471266949.bmc054}}</ref>

The [[elimination half-life]] of mestranol has been reported to be 50&nbsp;minutes.<ref name="RunnebaumRabe2013">{{Cite book | vauthors = Runnebaum B, Rabe T |url=https://books.google.com/books?id=mBF9BwAAQBAJ&pg=PA88 |title=Gynäkologische Endokrinologie und Fortpflanzungsmedizin: Band 1: Gynäkologische Endokrinologie |date=17 April 2013 |publisher=Springer-Verlag |isbn=978-3-662-07635-4 |pages=88–}}</ref> The elimination half-life of the active form of mestranol, ethinylestradiol, is 7 to 36&nbsp;hours.<ref name="HughesWaters2016">{{Cite book | vauthors = Hughes CL, Waters MD |url= https://books.google.com/books?id=5qPWCwAAQBAJ&pg=PA73 |title=Translational Toxicology: Defining a New Therapeutic Discipline |date=23 March 2016 |publisher=Humana Press |isbn=978-3-319-27449-2 |pages=73–}}</ref><ref name="pmid2256522">{{cite journal | vauthors = Goldzieher JW, Brody SA | title = Pharmacokinetics of ethinyl estradiol and mestranol | journal = American Journal of Obstetrics and Gynecology | volume = 163 | issue = 6 Pt 2 | pages = 2114–2119 | date = December 1990 | pmid = 2256522 | doi = 10.1016/0002-9378(90)90550-Q }}</ref><ref name="pmid23375353">{{cite journal | vauthors = Stanczyk FZ, Archer DF, Bhavnani BR | title = Ethinyl estradiol and 17β-estradiol in combined oral contraceptives: pharmacokinetics, pharmacodynamics and risk assessment | journal = Contraception | volume = 87 | issue = 6 | pages = 706–727 | date = June 2013 | pmid = 23375353 | doi = 10.1016/j.contraception.2012.12.011 }}</ref><ref name="Shellenberger1986">{{Cite book | vauthors = Shellenberger TE |title=The Climacteric in Perspective |year=1986 |isbn=978-94-010-8339-3 |pages=393–410 |chapter=Pharmacology of estrogens |publisher=Springer |doi=10.1007/978-94-009-4145-8_36}}</ref>

The effective [[ovulation]]-inhibiting dosage of mestranol has been studied in women.<ref name="pmid4568621">{{cite journal | vauthors = Bingel AS, Benoit PS | title = Oral contraceptives: therapeutics versus adverse reactions, with an outlook for the future I | journal = Journal of Pharmaceutical Sciences | volume = 62 | issue = 2 | pages = 179–200 | date = February 1973 | pmid = 4568621 | doi = 10.1002/jps.2600620202 }}</ref><ref name="Pincus2013">{{Cite book | vauthors =  Pincus G |url=https://books.google.com/books?id=ehQlBQAAQBAJ&pg=PA222 |title=The Control of Fertility |date=3 September 2013 |publisher=Elsevier |isbn=978-1-4832-7088-3 |pages=222–}}</ref><ref name="Greenblatt1966a">{{Cite book | vauthors = Martinez-Manautou J, Rudel HW  |url=https://books.google.com/books?id=le1qAAAAMAAJ |title=Ovulation: Stimulation, Suppression, and Detection |publisher=Lippincott |year=1966 |isbn=978-0-397-59010-0 | veditors = Greenblatt BR |pages=243–253 |chapter=Antiovulatory Activity of Several Synthetic and Natural Estrogens}}</ref> It has been reported to be about 98% effective at inhibiting ovulation at a dosage of 75 or 80&nbsp;μg/day.<ref name="Elger1972">{{Cite book | vauthors = Elger W |title=Reviews of Physiology Biochemistry and Experimental Pharmacology, Volume 67 |year=1972 |isbn=3-540-05959-8 |series=Ergebnisse der Physiologie Reviews of Physiology |volume=67 |pages=69–168 |chapter=Physiology and pharmacology of female reproduction under the aspect of fertility control |doi=10.1007/BFb0036328 |pmid=4574573}}</ref><ref name="Greenblatt1966a" /><ref name="HerrRevesz1970a">{{Cite book | vauthors = Herr F, Revesz C, Manson AJ, Jewell JB |title=Chemical and Biological Aspects of Steroid Conjugation |year= 1970 |isbn=978-3-642-49506-9 |pages=368–408 |chapter=Biological Properties of Estrogen Sulfates |publisher=Springer |doi=10.1007/978-3-642-49793-3_8|doi-broken-date=2024-11-02 }}</ref> In another study, the ovulation rate was 15.4% at 50&nbsp;μg/day, 5.7% at 80&nbsp;μg/day, and 1.1% at 100&nbsp;μg/day.<ref name="pmid1146927">{{cite journal | vauthors = Goldzieher JW, Pena A, Chenault CB, Woutersz TB | title = Comparative studies of the ethynyl estrogens used in oral contraceptives. II. Antiovulatory potency | journal = American Journal of Obstetrics and Gynecology | volume = 122 | issue = 5 | pages = 619–624 | date = July 1975 | pmid = 1146927 | doi = 10.1016/0002-9378(75)90061-7 }}</ref>

{{Affinities and estrogenic potencies of estrogen esters and ethers at the estrogen receptors}}

{{Oral potencies of estrogens}}

==Chemistry==
{{See also|List of estrogens|List of estrogen esters#Ethers of steroidal estrogens}}

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 compound|synthetic]] [[estrane]] [[steroid]] and a [[chemical derivative|derivative]] of [[estradiol]].<ref name="Elks2014" /><ref name="IndexNominum2000" /><ref name="Labhart2012">{{Cite book | vauthors = Labhart A |url=https://books.google.com/books?id=DAgJCAAAQBAJ&pg=PA575 |title=Clinical Endocrinology: Theory and Practice |date=6 December 2012 |publisher=Springer Science & Business Media |isbn=978-3-642-96158-8 |pages=575–}}</ref> It is specifically a derivative of [[ethinylestradiol]] (17α-ethynylestradiol) with a [[methyl group|methyl]] [[ether]] at the C3 position.<ref name="Elks2014" /><ref name="IndexNominum2000" />

==History==
In April 1956, [[noretynodrel]] was investigated, in [[Puerto Rico]], in the first large-scale [[clinical trial]] of a [[progestogen]] as an oral contraceptive.<ref name="Sneader2005">{{Cite book | vauthors = Sneader W |url= https://books.google.com/books?id=Cb6BOkj9fK4C&pg=PA202 |title=Drug Discovery: A History |date=23 June 2005 |publisher=John Wiley & Sons |isbn=978-0-471-89979-2 |pages=202–}}</ref><ref name="LentzLobo2012">{{Cite book | vauthors = Lentz GM, Lobo RA, Gershenson DM, Katz VL |url=https://books.google.com/books?id=OmpULog7A_QC&pg=PA224 |title=Comprehensive Gynecology |publisher=Elsevier Health Sciences |year=2012 |isbn=978-0-323-06986-1 |pages=224–}}</ref> 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.<ref name="FilshieGuillebaud2013">{{Cite book | vauthors = Filshie M, Guillebaud J |url= https://books.google.com/books?id=Ug3-BAAAQBAJ&pg=PA12 |title=Contraception: Science and Practice  |date=22 October 2013 |publisher=Elsevier Science |isbn=978-1-4831-6366-6 |pages=12–}}</ref> It was discovered early into the study that the initial [[chemical synthesis|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).<ref name="Sneader2005" /><ref name="LentzLobo2012" /> When this impurity was removed, higher rates of [[breakthrough bleeding]] occurred.<ref name="Sneader2005" /><ref name="LentzLobo2012" /> As a result, mestranol, that same year (1956),<ref name="pmid4884828">{{cite journal | vauthors = Billingsley FS | title = Lactation suppression utilizing norethynodrel with mestranol | journal = The Journal of the Florida Medical Association | volume = 56 | issue = 2 | pages = 95–97 | date = February 1969 | pmid = 4884828 }}</ref> 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.<ref name="Sneader2005" /><ref name="LentzLobo2012" /> This resulted in Enovid by [[G.D. Searle, LLC|G. D. Searle & Company]], the first oral contraceptive and a combination of 9.85&nbsp;mg noretynodrel and 150&nbsp;μg mestranol per pill.<ref name="Sneader2005" /><ref name="LentzLobo2012" />

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.<ref name="Aronson2009">{{Cite book | vauthors = Aronson JK |url=https://books.google.com/books?id=BWMeSwVwfTkC&pg=PA224 |title=Meyler's Side Effects of Endocrine and Metabolic Drugs |date=21 February 2009 |publisher=Elsevier |isbn=978-0-08-093292-7 |pages=224–}}</ref> 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.<ref name="Aronson2009" /> Whether this actually did result in a lower incidence of venous thromboembolism has never been assessed.<ref name="Aronson2009" />

==Society and culture==

===Generic names===
''Mestranol'' is the [[generic term|generic name]] of the drug and its {{abbrlink|INN|International Nonproprietary Name}}, {{abbrlink|USAN|United States Adopted Name}}, {{abbrlink|USP|United States Pharmacopeia}}, {{abbrlink|BAN|British Approved Name}}, {{abbrlink|DCF|Dénomination Commune Française}}, and {{abbrlink|JAN|Japanese Accepted Name}}, while ''mestranolo'' is its {{abbrlink|DCIT|Denominazione Comune Italiana}}.<ref name="Elks2014">{{Cite book | vauthors = Elks J |url= https://books.google.com/books?id=0vXTBwAAQBAJ&pg=PA775 |title=The Dictionary of Drugs: Chemical Data: Chemical Data, Structures and Bibliographies |date=14 November 2014 |publisher=Springer |isbn=978-1-4757-2085-3 |pages=775–}}</ref><ref name="IndexNominum2000">{{Cite book |url=https://books.google.com/books?id=5GpcTQD_L2oC&pg=PA656 |title=Index Nominum 2000: International Drug Directory |publisher=Taylor & Francis |year=2000 |isbn=978-3-88763-075-1 |pages=656–}}</ref><ref name="MortonHall2012">{{Cite book | vauthors = Morton IK, Hall JM |url=https://books.google.com/books?id=tsjrCAAAQBAJ&pg=PA177 |title=Concise Dictionary of Pharmacological Agents: Properties and Synonyms |date=6 December 2012 |publisher=Springer Science & Business Media |isbn=978-94-011-4439-1 |pages=177–}}</ref><ref name="Drugs.com">{{Cite web |title=Mestranol and norethindrone Uses, Side Effects & Warnings |url=https://www.drugs.com/international/mestranol.html |access-date=2017-11-24 |archive-date=2017-12-01 |archive-url=https://web.archive.org/web/20171201042946/https://www.drugs.com/international/mestranol.html |url-status=dead }}</ref>

===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.<ref name="Marks2010" /><ref name="Elks2014" /><ref name="Publishing2013">{{Cite book |url=https://books.google.com/books?id=_J2ti4EkYpkC&pg=PA2109-IA88 |title=Pharmaceutical Manufacturing Encyclopedia |date=22 October 2013 |publisher=Elsevier |isbn=978-0-8155-1856-3 |pages=2109– |edition=3rd}}</ref><ref name="IndexNominum2000" /> Today, it continues to be sold in combination with progestins under brand names including Lutedion, Necon, Norinyl, Ortho-Novum, and Sophia.<ref name="Drugs.com" />

===Availability===
Mestranol remains available only in the [[United States]], the [[United Kingdom]], [[Japan]], and [[Chile]].<ref name="Drugs.com" /> It is only marketed in combination with [[progestin]]s, such as [[norethisterone]].<ref name="Drugs.com" />

==Research==
Mestranol has been studied as a [[male contraceptive]] and was found to be highly effective.<ref name="pmid6771777">{{cite journal | vauthors = Dorfman RI | title = Pharmacology of estrogens-general | journal = Pharmacology & Therapeutics | volume = 9 | issue = 1 | pages = 107–119 | date = 1980 | pmid = 6771777 | doi = 10.1016/0163-7258(80)90018-2 }}</ref><ref name="pmid776453">{{cite journal | vauthors = Jackson H | title = Progress towards a male oral contraceptive | journal = Clinics in Endocrinology and Metabolism | volume = 4 | issue = 3 | pages = 643–663 | date = November 1975 | pmid = 776453 | doi = 10.1016/S0300-595X(75)80051-X }}</ref><ref name="Oettel1999">{{Cite book | vauthors = Oettel M |title=Estrogens and Antiestrogens II: Pharmacology and Clinical Application of Estrogens and Antiestrogen |date=1999 |publisher=Springer Science & Business Media |isbn=978-3-642-60107-1 | veditors = Oettel M, Schillinger E |series=Handbook of Experimental Pharmacology |volume=135 / 2 |pages=505–571 |chapter=Estrogens and Antiestrogens in the Male |doi=10.1007/978-3-642-60107-1_25 |issn=0171-2004  |chapter-url=https://books.google.com/books?id=wBvyCAAAQBAJ&pg=PA538}}</ref><ref name="pmid14400846">{{cite journal | vauthors = Heller CG, Moore DJ, Paulsen CA, Nelson WO, Laidlaw WM | title = Effects of progesterone and synthetic progestins on the reproductive physiology of normal men | journal = Federation Proceedings | volume = 18 | pages = 1057–1065 | date = December 1959 | pmid = 14400846 | url = https://www.popline.org/node/472874 }}</ref> At a dosage of 0.45&nbsp;mg/day, it suppressed [[gonadotropin]] levels, reduced [[sperm count]] to zero within 4 to 6&nbsp;weeks, and decreased [[libido]], [[erectile function]], and [[testicular size]].<ref name="pmid6771777" /><ref name="pmid776453" /><ref name="pmid14400846" /><ref name="Oettel1999" /> [[Gynecomastia]] occurred in all of the men.<ref name="pmid6771777" /><ref name="pmid776453" /><ref name="pmid14400846" /><ref name="Oettel1999" /> These findings contributed to the conclusion that estrogens would be unacceptable as contraceptives for men.<ref name="pmid776453" />

==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]]. <ref name="Black2021">{{cite journal | vauthors = Black GP, He G, Denison MS, Young TM | title = Using Estrogenic Activity and Nontargeted Chemical Analysis to Identify Contaminants in Sewage Sludge | journal = Environmental Science & Technology | volume = 55 | issue = 10 | pages = 6729–6739 | date = May 2021 | pmid = 33909413 | pmc = 8378343 | doi = 10.1021/acs.est.0c07846 | bibcode = 2021EnST...55.6729B }}</ref> 

== References ==
{{Reflist}}

{{Estrogens and antiestrogens}}
{{Estrogen receptor modulators}}

[[Category:Ethynyl compounds]]
[[Category:Estranes]]
[[Category:Estrogen ethers]]
[[Category:Hormonal contraception]]
[[Category:Prodrugs]]
[[Category:Synthetic estrogens]]