Editing Estrogen (section)

==Biological function==
[[File:Estradiol during menstrual cycle.png|thumb|350px|[[Reference ranges for blood tests|Reference ranges for the blood content]] of estradiol, the primary type of estrogen, during the [[menstrual cycle]]<ref name="Häggström2014">{{cite journal|year=2014|title=Reference ranges for estradiol, progesterone, luteinizing hormone and follicle-stimulating hormone during the menstrual cycle|journal=WikiJournal of Medicine|volume=1|issue=1|doi=10.15347/wjm/2014.001|issn=2002-4436| vauthors = Häggström M |doi-access=free}}</ref>]]

The actions of estrogen are mediated by the [[estrogen receptor]] (ER), a dimeric nuclear protein that binds to DNA and controls [[gene expression]]. Like other steroid hormones, estrogen enters passively into the cell where it binds to and activates the estrogen receptor. The estrogen:ER complex binds to specific DNA sequences called a [[hormone response element]] to activate the transcription of target genes (in a study using an estrogen-dependent breast cancer cell line as model, 89 such genes were identified).<ref name="pmid15345050">{{cite journal | vauthors = Lin CY, Ström A, Vega VB, Kong SL, Yeo AL, Thomsen JS, Chan WC, Doray B, Bangarusamy DK, Ramasamy A, Vergara LA, Tang S, Chong A, Bajic VB, Miller LD, Gustafsson JA, Liu ET | title = Discovery of estrogen receptor alpha target genes and response elements in breast tumor cells | journal = Genome Biology | volume = 5 | issue = 9 | pages = R66 | year = 2004 | pmid = 15345050 | pmc = 522873 | doi = 10.1186/gb-2004-5-9-r66 | doi-access = free }}</ref> Since estrogen enters all cells, its actions are dependent on the presence of the ER in the cell. The ER is expressed in specific tissues including the ovary, uterus and breast. The metabolic effects of estrogen in postmenopausal women have been linked to the genetic polymorphism of the ER.<ref name="pmid21117950">{{cite journal | vauthors = Darabi M, Ani M, Panjehpour M, Rabbani M, Movahedian A, Zarean E | title = Effect of estrogen receptor β A1730G polymorphism on ABCA1 gene expression response to postmenopausal hormone replacement therapy | journal = Genetic Testing and Molecular Biomarkers | volume = 15 | issue = 1–2 | pages = 11–15 | year = 2011 | pmid = 21117950 | doi = 10.1089/gtmb.2010.0106 }}</ref>

While estrogens are present in both [[man|men]] and [[woman|women]], they are usually present at significantly higher levels in biological women of reproductive age. They promote the development of female [[secondary sexual characteristic]]s, such as [[breasts]], darkening and enlargement of [[nipples]],<ref name="Lauwers Shinskie 2004 p. 93">{{cite book | vauthors = Lauwers J, Shinskie D | title=Counseling the Nursing Mother: A Lactation Consultant's Guide | publisher=Jones & Bartlett Learning, LLC | year=2004 | isbn=978-0-7637-2765-9 | url=https://books.google.com/books?id=Krm2RwGEYjEC&pg=PA93 | access-date=12 October 2023 | page=93}}</ref> and thickening of the [[endometrium]] and other aspects of regulating the menstrual cycle. In males, estrogen regulates certain functions of the [[reproductive system]] important to the maturation of [[sperm]]<ref name="titleScience News Online (12/6/97): Estrogens Emerging Manly Alter Ego">{{cite magazine | url = http://www.sciencenews.org/pages/sn_arc97/12_6_97/fob1.htm | title = Science News Online (12/6/97): Estrogen's Emerging Manly Alter Ego | access-date = 4 March 2008 | vauthors = Raloff J | date = 6 December 1997 | magazine = Science News }}</ref><ref name="pmid9393999">{{cite journal | vauthors = Hess RA, Bunick D, Lee KH, Bahr J, Taylor JA, Korach KS, Lubahn DB | title = A role for oestrogens in the male reproductive system | journal = Nature | volume = 390 | issue = 6659 | pages = 509–512 | date = December 1997 | pmid = 9393999 | pmc = 5719867 | doi = 10.1038/37352 | bibcode = 1997Natur.390..509H }}</ref><ref name="Science_Blog">{{cite web | url = http://www.scienceblog.com/community/older/1997/B/199701564.html | title = Estrogen Linked To Sperm Count, Male Fertility | access-date = 4 March 2008 | publisher = Science Blog | archive-date = 7 May 2007 | archive-url = https://web.archive.org/web/20070507120938/http://www.scienceblog.com/community/older/1997/B/199701564.html | url-status = dead }}</ref> and may be necessary for a healthy [[libido]].<ref name="pmid15555924">{{cite journal | vauthors = Hill RA, Pompolo S, Jones ME, Simpson ER, Boon WC | title = Estrogen deficiency leads to apoptosis in dopaminergic neurons in the medial preoptic area and arcuate nucleus of male mice | journal = Molecular and Cellular Neurosciences | volume = 27 | issue = 4 | pages = 466–476 | date = December 2004 | pmid = 15555924 | doi = 10.1016/j.mcn.2004.04.012 | s2cid = 25280077 }}</ref>

{{Affinities of estrogen receptor ligands for the ERα and ERβ}}

{{Relative affinities of estrogens for steroid hormone receptors and blood proteins}}

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

{{Selected biological properties of endogenous estrogens in rats}}

===Overview of actions===
{{Prose|section|date=October 2019}}
* Musculoskeletal
** [[Anabolic]]: Increases [[muscle mass]] and strength, speed of muscle regeneration, and [[bone density]], increased sensitivity to exercise, protection against muscle damage, stronger [[collagen]] synthesis, increases the collagen content of [[connective tissues]], [[tendon]]s, and [[ligament]]s, but also decreases stiffness of [[tendon]]s and [[ligament]]s (especially during [[menstruation]]). Decreased stiffness of tendons gives women much lower predisposition to muscle strains but soft ligaments are much more prone to injuries ([[Anterior cruciate ligament injury|ACL]] tears are 2-8x more common among women than men).<ref name="urlFrontiers | Effect of Estrogen on Musculoskeletal Performance and Injury Risk | Physiology">{{cite journal | vauthors = Chidi-Ogbolu N, Baar K | title = Effect of Estrogen on Musculoskeletal Performance and Injury Risk | journal = Frontiers in Physiology | volume = 9 | pages = 1834 | year = 2018 | pmid = 30697162 | pmc = 6341375 | doi = 10.3389/fphys.2018.01834 | doi-access = free }}</ref><ref name="urlMechanisms behind Estrogens' Beneficial Effect on Muscle Strength in Females">{{cite journal | vauthors = Lowe DA, Baltgalvis KA, Greising SM | title = Mechanisms behind estrogen's beneficial effect on muscle strength in females | journal = Exercise and Sport Sciences Reviews | volume = 38 | issue = 2 | pages = 61–67 | date = April 2010 | pmid = 20335737 | pmc = 2873087 | doi = 10.1097/JES.0b013e3181d496bc }}</ref><ref name="Max_1984">{{cite journal | vauthors = Max SR | title = Androgen-estrogen synergy in rat levator ani muscle: glucose-6-phosphate dehydrogenase | journal = Molecular and Cellular Endocrinology | volume = 38 | issue = 2–3 | pages = 103–107 | date = December 1984 | pmid = 6510548 | doi = 10.1016/0303-7207(84)90108-4 | s2cid = 24198956 }}</ref><ref name="pmid1958566">{{cite journal | vauthors = Koot RW, Amelink GJ, Blankenstein MA, Bär PR | title = Tamoxifen and oestrogen both protect the rat muscle against physiological damage | journal = The Journal of Steroid Biochemistry and Molecular Biology | volume = 40 | issue = 4–6 | pages = 689–695 | date = 1991 | pmid = 1958566 | doi = 10.1016/0960-0760(91)90292-d | s2cid = 44446541 }}</ref>
** Reduce [[bone resorption]], increase bone formation
** In mice, estrogen has been shown to increase the proportion of the fastest-twitch (type IIX) muscle fibers by over 40%.<ref>{{cite journal | vauthors = Haizlip KM, Harrison BC, Leinwand LA | title = Sex-based differences in skeletal muscle kinetics and fiber-type composition | journal = Physiology | volume = 30 | issue = 1 | pages = 30–39 | date = January 2015 | pmid = 25559153 | pmc = 4285578 | doi = 10.1152/physiol.00024.2014 }} "Supplementation with estrogen increases the type-IIX percentage composition in the plantaris back to 42%. (70)"</ref>
* Metabolic
** Anti-inflammatory properties
** Accelerate [[metabolism]]
** [[Gynoid fat distribution]]: increased [[fat distribution|fat storage]] or [[estrogenic fat]] in some body parts such as breasts, buttocks, and legs but decreased abdominal and [[visceral fat]] (androgenic obesity).<ref name="pmid30097511">{{cite journal | vauthors = Frank AP, de Souza Santos R, Palmer BF, Clegg DJ | title = Determinants of body fat distribution in humans may provide insight about obesity-related health risks | journal = Journal of Lipid Research | volume = 60 | issue = 10 | pages = 1710–1719 | date = October 2019 | pmid = 30097511 | pmc = 6795075 | doi = 10.1194/jlr.R086975  |doi-access=free }}</ref><ref name="urlMetabolic impact of sex hormones on obesity - PubMed">{{cite journal | vauthors = Brown LM, Gent L, Davis K, Clegg DJ | title = Metabolic impact of sex hormones on obesity | journal = Brain Research | volume = 1350 | pages = 77–85 | date = September 2010 | pmid = 20441773 | pmc = 2924463 | doi = 10.1016/j.brainres.2010.04.056 }}</ref><ref name="urlTestosterone and Visceral Fat in Midlife Women: The Study of Women's Health Across the Nation (SWAN) Fat Patterning Study">{{cite journal | vauthors = Janssen I, Powell LH, Kazlauskaite R, Dugan SA | title = Testosterone and visceral fat in midlife women: the Study of Women's Health Across the Nation (SWAN) fat patterning study | journal = Obesity | volume = 18 | issue = 3 | pages = 604–610 | date = March 2010 | pmid = 19696765 | pmc = 2866448 | doi = 10.1038/oby.2009.251 }}</ref>
** [[Estradiol]] also regulates energy expenditure, body weight [[homeostasis]], and seems to have much stronger anti-obesity effects than testosterone in general.<ref name="urlChapter 24: Estrogens and Body Weight Regulation in Men">{{cite book | vauthors = Rubinow KB | title = Sex and Gender Factors Affecting Metabolic Homeostasis, Diabetes and Obesity | chapter = Estrogens and Body Weight Regulation in Men | series = Advances in Experimental Medicine and Biology | volume = 1043 | pages = 285–313 | year = 2017 | publisher = Springer | pmid = 29224100 | pmc = 5835337 | doi = 10.1007/978-3-319-70178-3_14 | isbn = 978-3-319-70177-6 }}</ref>
* Other structural
** Maintenance of vessels and skin
* [[Protein]] synthesis
** Increase [[hepatic production]] of [[binding protein]]s
** Increase production of the hepatokine [[adropin]].<ref name="Hepatic adropin is regulated by est">{{cite journal | vauthors = Stokar J, Gurt I, Cohen-Kfir E, Yakubovsky O, Hallak N, Benyamini H, Lishinsky N, Offir N, Tam J, Dresner-Pollak R | title = Hepatic adropin is regulated by estrogen and contributes to adverse metabolic phenotypes in ovariectomized mice | journal = Molecular Metabolism | volume = 60 | pages = 101482 | date = June 2022 | pmid = 35364299 | pmc = 9044006 | doi = 10.1016/j.molmet.2022.101482 }}</ref>
* [[Coagulation]]
** Increase circulating level of [[coagulation factor|factors]] [[factor II|2]], [[factor VII|7]], [[factor IX|9]], [[factor X|10]], [[plasminogen]]
** Decrease [[antithrombin]] III
** Increase [[platelet]] adhesiveness
** Increase [[Von Willebrand factor|vWF]] (estrogen -> [[Angiotensin|Angiotensin II]] -> [[Vasopressin]])
** Increase [[PAI-1]] and [[Plasminogen activator inhibitor-2|PAI-2]] also through Angiotensin II
* [[Lipid]]
** Increase [[high density lipoprotein|HDL]], [[triglyceride]]
** Decrease [[low density lipoprotein|LDL]], fat deposition
* Fluid balance
** Salt ([[Sodium in biology|sodium]]) and water retention, including facial swelling and [[edema]]<ref>{{cite web | vauthors = Frysh P |title=Reasons Why Your Face Looks Swollen |url=https://www.webmd.com/allergies/ss/slideshow-swollen-face |website=WebMD |language=en}}</ref><ref>{{cite journal | vauthors = Stachenfeld NS | title = Sex hormone effects on body fluid regulation | journal = Exercise and Sport Sciences Reviews | volume = 36 | issue = 3 | pages = 152–159 | date = July 2008 | pmid = 18580296 | pmc = 2849969 | doi = 10.1097/JES.0b013e31817be928 }}</ref>
** Estrogen is associated with [[edema]], including facial and abdominal swelling.
* [[Melanin]]
** Estrogen is known to cause darkening of skin, especially in the face and [[areolae]].<ref name="Pawlina 2023 p. 1481">{{cite book | vauthors = Pawlina W | title=Histology: A Text and Atlas: With Correlated Cell and Molecular Biology | publisher=Wolters Kluwer Health | year=2023 | isbn=978-1-9751-8152-9 | url=https://books.google.com/books?id=dCrKEAAAQBAJ&pg=PT1481 | access-date=12 October 2023 | page=1481}}</ref> Pale skinned women will develop browner and yellower skin during pregnancy, as a result of the increase of estrogen, known as the [[Melasma|"mask of pregnancy"]].<ref name="Greenberg Bruess Oswalt 2014 p. 248">{{cite book | vauthors = Greenberg J, Bruess C, Oswalt S | chapter = Conception, Pregnancy, and Birth | title=Exploring the Dimensions of Human Sexuality | publisher=Jones & Bartlett Learning | year=2014 | isbn=978-1-4496-4851-0 | chapter-url=https://books.google.com/books?id=hm3aTuANFroC&pg=PA248 | access-date=12 October 2023 | page=248}}</ref> Estrogen may explain why women have darker eyes than men, and also a lower risk of skin cancer than men; a European study found that women generally have darker skin than men.<ref>{{cite news |title=Researchers discover genetic causes of higher melanoma risk in men |url=https://www.sciencedaily.com/releases/2016/07/160721072753.htm |work=ScienceDaily |language=en}}</ref><ref>{{cite journal | vauthors = Hernando B, Ibarrola-Villava M, Fernandez LP, Peña-Chilet M, Llorca-Cardeñosa M, Oltra SS, Alonso S, Boyano MD, Martinez-Cadenas C, Ribas G | title = Sex-specific genetic effects associated with pigmentation, sensitivity to sunlight, and melanoma in a population of Spanish origin | journal = Biology of Sex Differences | volume = 7 | issue = 1 | pages = 17 | date = 18 March 2016 | pmid = 26998216 | doi = 10.1186/s13293-016-0070-1 | doi-access = free | pmc = 4797181 }} "The results of this study suggest that there are indeed sex-specific genetic effects in human pigmentation, with larger effects for darker pigmentation in females compared to males. A plausible cause might be the differentially expressed melanogenic genes in females due to higher oestrogen levels. These sex-specific genetic effects would help explain the presence of darker eye and skin pigmentation in females, as well as the well-known higher melanoma risk displayed by males."</ref>
* [[Lung function]]
** Promotes lung function by supporting [[Pulmonary alveolus|alveoli]] (in rodents but probably in humans).<ref name="pmid15298854">{{cite journal | vauthors = Massaro D, Massaro GD | title = Estrogen regulates pulmonary alveolar formation, loss, and regeneration in mice | journal = American Journal of Physiology. Lung Cellular and Molecular Physiology | volume = 287 | issue = 6 | pages = L1154–L1159 | date = December 2004 | pmid = 15298854 | doi = 10.1152/ajplung.00228.2004 | url = http://pdfs.semanticscholar.org/65aa/5f698c0b57e4d3746dace1af255260ebeae5.pdf | url-status = dead | s2cid = 24642944 | archive-url = https://web.archive.org/web/20190225225427/http://pdfs.semanticscholar.org/65aa/5f698c0b57e4d3746dace1af255260ebeae5.pdf | archive-date = 25 February 2019 }}</ref>
* Sexual
** Mediate formation of female [[secondary sex characteristics]]
** Stimulate [[endometrium|endometrial]] growth
** Increase [[uterus|uterine]] growth
** Increase [[vaginal lubrication]]
** Thicken the [[vagina]]l wall
* [[Uterus]] lining
** Estrogen together with [[progesterone]] promotes and maintains the uterus lining in preparation for implantation of fertilized egg and maintenance of uterus function during gestation period, also upregulates [[oxytocin]] receptor in myometrium
* [[Ovulation]]
** Surge in estrogen level induces the release of [[luteinizing hormone]], which then triggers ovulation by releasing the egg from the [[Graafian follicle]] in the [[ovary]].
* [[Sexual behavior]]
** Estrogen is required for female mammals to engage in [[lordosis behavior]] during [[estrus]] (when animals are "in heat").<ref>{{cite journal | vauthors = Christensen A, Bentley GE, Cabrera R, Ortega HH, Perfito N, Wu TJ, Micevych P | title = Hormonal regulation of female reproduction | journal = Hormone and Metabolic Research | volume = 44 | issue = 8 | pages = 587–591 | date = July 2012 | pmid = 22438212 | pmc = 3647363 | doi = 10.1055/s-0032-1306301 }}</ref><ref name="pmid21851428">{{cite journal | vauthors = Handa RJ, Ogawa S, Wang JM, Herbison AE | title = Roles for oestrogen receptor β in adult brain function | journal = Journal of Neuroendocrinology | volume = 24 | issue = 1 | pages = 160–173 | date = January 2012 | pmid = 21851428 | pmc = 3348521 | doi = 10.1111/j.1365-2826.2011.02206.x }}</ref> This behavior is required for sexual receptivity in these mammals and is regulated by the [[ventromedial nucleus]] of the [[hypothalamus]].<ref name="pmid9638959">{{cite journal | vauthors = Kow LM, Pfaff DW | title = Mapping of neural and signal transduction pathways for lordosis in the search for estrogen actions on the central nervous system | journal = Behavioural Brain Research | volume = 92 | issue = 2 | pages = 169–180 | date = May 1998 | pmid = 9638959 | doi = 10.1016/S0166-4328(97)00189-7 | s2cid = 28276218 }}</ref>
** [[Sex drive]] is dependent on [[androgen]] levels<ref name="pmid16037752">{{cite journal | vauthors = Warnock JK, Swanson SG, Borel RW, Zipfel LM, Brennan JJ | title = Combined esterified estrogens and methyltestosterone versus esterified estrogens alone in the treatment of loss of sexual interest in surgically menopausal women | journal = Menopause | volume = 12 | issue = 4 | pages = 374–384 | year = 2005 | pmid = 16037752 | doi = 10.1097/01.GME.0000153933.50860.FD | s2cid = 24557071 }}</ref> only in the presence of estrogen, but without estrogen, free testosterone level actually decreases sexual desire (instead of increasing sex drive), as demonstrated for those women who have [[hypoactive sexual desire disorder]], and the sexual desire in these women can be restored by administration of estrogen (using oral contraceptive).<ref name="pmid21514299">{{cite journal | vauthors = Heiman JR, Rupp H, Janssen E, Newhouse SK, Brauer M, Laan E | title = Sexual desire, sexual arousal and hormonal differences in premenopausal US and Dutch women with and without low sexual desire | journal = Hormones and Behavior | volume = 59 | issue = 5 | pages = 772–779 | date = May 2011 | pmid = 21514299 | doi = 10.1016/j.yhbeh.2011.03.013 | s2cid = 20807391 }}</ref>

===Female pubertal development===
Estrogens are responsible for the development of female [[secondary sexual characteristic]]s during [[puberty]], including [[breast development]], widening of the [[hip]]s, and female [[fat distribution]]. Conversely, [[androgen]]s are responsible for [[pubic hair|pubic]] and [[body hair]] [[hair growth|growth]], as well as [[acne]] and [[body odor|axillary odor]].

====Breast development====
{{See also|Breast development#Biochemistry}}

Estrogen, in conjunction with [[growth hormone]] (GH) and its secretory product [[insulin-like growth factor 1]] (IGF-1), is critical in mediating breast development during [[puberty]], as well as breast maturation during [[pregnancy]] in preparation of [[lactation]] and [[breastfeeding]].<ref name="Malley2010">{{cite journal | vauthors = Brisken C, O'Malley B | title = Hormone action in the mammary gland | journal = Cold Spring Harbor Perspectives in Biology | volume = 2 | issue = 12 | pages = a003178 | date = December 2010 | pmid = 20739412 | pmc = 2982168 | doi = 10.1101/cshperspect.a003178 }}</ref><ref name="pmid9516076">{{cite journal | vauthors = Kleinberg DL | title = Role of IGF-I in normal mammary development | journal = Breast Cancer Research and Treatment | volume = 47 | issue = 3 | pages = 201–208 | date = February 1998 | pmid = 9516076 | doi = 10.1023/a:1005998832636 | s2cid = 30440069 }}</ref> Estrogen is primarily and directly responsible for inducing the ductal component of breast development,<ref name="Johnson2003">{{cite book | vauthors = Johnson LR | title = Essential Medical Physiology | url = https://books.google.com/books?id=j9e-tkdHeUoC&pg=PA770 | year = 2003 | publisher = Academic Press | isbn = 978-0-12-387584-6 | pages = 770 }}</ref><ref name="NormanHenry2014">{{cite book | vauthors = Norman AW, Henry HL | title = Hormones | url = https://books.google.com/books?id=_renonjXq68C&pg=PA311 | date = 30 July 2014|publisher=Academic Press | isbn = 978-0-08-091906-5 | pages = 311 }}</ref><ref name="CoadDunstall2011">{{cite book | vauthors = Coad J, Dunstall M | title = Anatomy and Physiology for Midwives, with Pageburst online access,3: Anatomy and Physiology for Midwives | url = https://books.google.com/books?id=OmSKoYD-iW0C&pg=PA413 | year = 2011 | publisher = Elsevier Health Sciences | isbn = 978-0-7020-3489-3 | pages = 413 }}</ref> as well as for causing [[fat deposition]] and [[connective tissue]] growth.<ref name="Johnson2003" /><ref name="NormanHenry2014" /> It is also indirectly involved in the lobuloalveolar component, by increasing [[progesterone receptor]] expression in the breasts<ref name="Johnson2003" /><ref name="CoadDunstall2011" /><ref name="HaslamOsuch2006">{{cite book | vauthors = Haslam SZ, Osuch JR | title = Hormones and Breast Cancer in Post-Menopausal Women | url = https://books.google.com/books?id=wGaKtDw50K0C&pg=PA69 | date = 1 January 2006 | publisher=IOS Press | isbn = 978-1-58603-653-9 | pages = 69 }}</ref> and by inducing the secretion of [[prolactin]].<ref name="SilbernaglDespopoulos2011">{{cite book | vauthors = Silbernagl S, Despopoulos A | title = Color Atlas of Physiology | url = https://books.google.com/books?id=WyuCGhv4kvwC&pg=PA305 | date = 1 January 2011 | publisher = Thieme | isbn = 978-3-13-149521-1 | pages = 305– }}</ref><ref name="Fadem2007">{{cite book| vauthors = Fadem B | title = High-yield Comprehensive USMLE Step 1 Review | url = https://books.google.com/books?id=d-MxROzDPgcC&pg=PA445 | year = 2007 | publisher = Lippincott Williams & Wilkins | isbn = 978-0-7817-7427-7 | pages = 445– }}</ref> Allowed for by estrogen, [[progesterone]] and prolactin work together to complete lobuloalveolar development during pregnancy.<ref name="NormanHenry2014" /><ref name="Blackburn2014">{{cite book | vauthors = Blackburn S | title = Maternal, Fetal, & Neonatal Physiology | url = https://books.google.com/books?id=RNLsAwAAQBAJ&pg=PA146 | date = 14 April 2014 | publisher = Elsevier Health Sciences | isbn = 978-0-323-29296-2 | pages = 146– }}</ref>

[[Androgen]]s such as testosterone powerfully oppose estrogen action in the breasts, such as by reducing [[estrogen receptor]] expression in them.<ref name="IIIBarbieri2013">{{cite book | vauthors = Strauss JF, Barbieri RL | title = Yen and Jaffe's Reproductive Endocrinology | url = https://books.google.com/books?id=KZ95AAAAQBAJ&pg=PA236 | date = 13 September 2013 | publisher=Elsevier Health Sciences | isbn = 978-1-4557-2758-2 | pages = 236– }}</ref><ref name="WilsonNizet2015">{{cite book | vauthors = Wilson CB, Nizet V, Maldonado Y, Remington JS, Klein JO | title = Remington and Klein's Infectious Diseases of the Fetus and Newborn Infant | url = https://books.google.com/books?id=VuZ1BwAAQBAJ&pg=PA190 | date = 24 February 2015 | publisher = Elsevier Health Sciences | isbn = 978-0-323-24147-2 | pages = 190– }}</ref>

===Female reproductive system===
Estrogens are responsible for maturation and maintenance of the [[vagina]] and [[uterus]], and are also involved in [[ovary|ovarian]] function, such as maturation of [[ovarian follicle]]s. In addition, estrogens play an important role in regulation of [[gonadotropin]] [[secretion]]. For these reasons, estrogens are required for female [[fertility]].{{cn|date=January 2025}}

===Neuroprotection and DNA repair===

Estrogen regulated [[DNA repair]] mechanisms in the [[brain]] have neuroprotective effects.<ref>{{cite journal | vauthors = Zárate S, Stevnsner T, Gredilla R | title = Role of Estrogen and Other Sex Hormones in Brain Aging. Neuroprotection and DNA Repair | journal = Frontiers in Aging Neuroscience | volume = 9 | pages = 430 | year = 2017 | pmid = 29311911 | pmc = 5743731 | doi = 10.3389/fnagi.2017.00430 | doi-access = free }}</ref>  Estrogen regulates the [[transcription (biology)|transcription]] of DNA [[base excision repair]] genes as well as the translocation of the base excision repair enzymes between different subcellular compartments.

===Brain and behavior===

====Sex drive====
{{See also|Sexual motivation and hormones}}

Estrogens are involved in [[libido]] (sex drive) in both women and men.

====Cognition====
[[Verbal memory]] scores are frequently used as one measure of higher level [[cognition]]. These scores vary in direct proportion to estrogen levels throughout the menstrual cycle, pregnancy, and menopause. Furthermore, estrogens when administered shortly after natural or surgical menopause prevents decreases in verbal memory. In contrast, estrogens have little effect on verbal memory if first administered years after menopause.<ref name="pmid22004260">{{cite journal | vauthors = Sherwin BB | title = Estrogen and cognitive functioning in women: lessons we have learned | journal = Behavioral Neuroscience | volume = 126 | issue = 1 | pages = 123–127 | date = February 2012 | pmid = 22004260 | pmc = 4838456 | doi = 10.1037/a0025539 }}</ref> Estrogens also have positive influences on other measures of cognitive function.<ref name="pmid26109339">{{cite journal | vauthors = Hara Y, Waters EM, McEwen BS, Morrison JH | title = Estrogen Effects on Cognitive and Synaptic Health Over the Lifecourse | journal = Physiological Reviews | volume = 95 | issue = 3 | pages = 785–807 | date = July 2015 | pmid = 26109339 | pmc = 4491541 | doi = 10.1152/physrev.00036.2014 }}</ref> However the effect of estrogens on cognition is not uniformly favorable and is dependent on the timing of the dose and the type of cognitive skill being measured.<ref name="pmid26149525">{{cite journal | vauthors = Korol DL, Pisani SL | title = Estrogens and cognition: Friends or foes?: An evaluation of the opposing effects of estrogens on learning and memory | journal = Hormones and Behavior | volume = 74 | pages = 105–115 | date = August 2015 | pmid = 26149525 | pmc = 4573330 | doi = 10.1016/j.yhbeh.2015.06.017 }}</ref>

The protective effects of estrogens on cognition may be mediated by estrogen's anti-inflammatory effects in the brain.<ref name="pmid26774208">{{cite journal | vauthors = Au A, Feher A, McPhee L, Jessa A, Oh S, Einstein G | title = Estrogens, inflammation and cognition | journal = Frontiers in Neuroendocrinology | volume = 40 | pages = 87–100 | date = January 2016 | pmid = 26774208 | doi = 10.1016/j.yfrne.2016.01.002 | doi-access = free }}</ref> Studies have also shown that the Met allele gene and level of estrogen mediates the efficiency of [[prefrontal cortex]] dependent working memory tasks.<ref>{{cite journal | vauthors = Jacobs E, D'Esposito M | title = Estrogen shapes dopamine-dependent cognitive processes: implications for women's health | journal = The Journal of Neuroscience | volume = 31 | issue = 14 | pages = 5286–5293 | date = April 2011 | pmid = 21471363 | pmc = 3089976 | doi = 10.1523/JNEUROSCI.6394-10.2011 }}</ref><ref>{{cite journal | vauthors = Colzato LS, Hommel B | title = Effects of estrogen on higher-order cognitive functions in unstressed human females may depend on individual variation in dopamine baseline levels | journal = Frontiers in Neuroscience | volume = 8 | pages = 65 | date = 1 January 2014 | pmid = 24778605 | pmc = 3985021 | doi = 10.3389/fnins.2014.00065 | doi-access = free }}</ref> Researchers have urged for further research to illuminate the role of estrogen and its potential for improvement on cognitive function.<ref>{{cite journal | vauthors = Hogervorst E | title = Estrogen and the brain: does estrogen treatment improve cognitive function? | journal = Menopause International | volume = 19 | issue = 1 | pages = 6–19 | date = March 2013 | pmid = 27951525 | doi = 10.1177/1754045312473873 | s2cid = 10122688 }}</ref>

====Mental health====
Estrogen is considered to play a significant role in women's [[mental health]]. Sudden estrogen withdrawal, fluctuating estrogen, and [[Period of time|periods]] of sustained low estrogen levels correlate with a significant lowering of mood. Clinical recovery from [[postnatal|postpartum]], [[perimenopause]], and [[postmenopause]] depression has been shown to be effective after levels of estrogen were stabilized and/or restored.<ref name="pmid16292022">{{cite journal | vauthors = Douma SL, Husband C, O'Donnell ME, Barwin BN, Woodend AK | title = Estrogen-related mood disorders: reproductive life cycle factors | journal = ANS. Advances in Nursing Science | volume = 28 | issue = 4 | pages = 364–375 | year = 2005 | pmid = 16292022 | doi = 10.1097/00012272-200510000-00008 | s2cid = 9172877 }}</ref><ref name="pmid16388113">{{cite journal | vauthors = Osterlund MK, Witt MR, Gustafsson JA | title = Estrogen action in mood and neurodegenerative disorders: estrogenic compounds with selective properties-the next generation of therapeutics | journal = Endocrine | volume = 28 | issue = 3 | pages = 235–242 | date = December 2005 | pmid = 16388113 | doi = 10.1385/ENDO:28:3:235 | s2cid = 8205014 }}</ref><ref name="pmid17909167">{{cite journal | vauthors = Lasiuk GC, Hegadoren KM | title = The effects of estradiol on central serotonergic systems and its relationship to mood in women | journal = Biological Research for Nursing | volume = 9 | issue = 2 | pages = 147–160 | date = October 2007 | pmid = 17909167 | doi = 10.1177/1099800407305600 | s2cid = 37965502 }}</ref> [[menstrual psychosis|Menstrual exacerbation (including menstrual psychosis)]] is typically triggered by low estrogen levels,<ref>{{cite journal | vauthors = Grigoriadis S, Seeman MV | title = The role of estrogen in schizophrenia: implications for schizophrenia practice guidelines for women | journal = Canadian Journal of Psychiatry | volume = 47 | issue = 5 | pages = 437–442 | date = June 2002 | pmid = 12085678 | doi = 10.1177/070674370204700504 | doi-access = free }}</ref> and is often mistaken for [[premenstrual dysphoric disorder]].<ref>{{cite web |title=PMDD/PMS |url=https://womensmentalhealth.org/specialty-clinics/pms-and-pmdd/ |website=The Massachusetts General Hospital Center for Women's Mental Health |access-date=12 January 2019}}</ref>

Compulsions in male lab mice, such as those in obsessive-compulsive disorder (OCD), may be caused by low estrogen levels. When estrogen levels were raised through the increased activity of the enzyme [[aromatase]] in male lab mice, OCD rituals were dramatically decreased. [[Hypothalamus|Hypothalamic]] protein levels in the gene [[catechol-O-methyl transferase|COMT]] are enhanced by increasing estrogen levels which are believed to return mice that displayed OCD rituals to normal activity. Aromatase deficiency is ultimately suspected which is involved in the synthesis of estrogen in humans and has therapeutic implications in humans having obsessive-compulsive disorder.<ref name="pmid16566897">{{cite journal | vauthors = Hill RA, McInnes KJ, Gong EC, Jones ME, Simpson ER, Boon WC | title = Estrogen deficient male mice develop compulsive behavior | journal = Biological Psychiatry | volume = 61 | issue = 3 | pages = 359–366 | date = February 2007 | pmid = 16566897 | doi = 10.1016/j.biopsych.2006.01.012 | s2cid = 22669945 }}</ref>

Local application of estrogen in the rat hippocampus has been shown to inhibit the re-uptake of [[serotonin]]. Contrarily, local application of estrogen has been shown to block the ability of [[fluvoxamine]] to slow serotonin clearance, suggesting that the same pathways which are involved in SSRI efficacy may also be affected by components of local estrogen signaling pathways.<ref name="pmid22225849">{{cite journal | vauthors = Benmansour S, Weaver RS, Barton AK, Adeniji OS, Frazer A | title = Comparison of the effects of estradiol and progesterone on serotonergic function | journal = Biological Psychiatry | volume = 71 | issue = 7 | pages = 633–641 | date = April 2012 | pmid = 22225849 | pmc = 3307822 | doi = 10.1016/j.biopsych.2011.11.023 }}</ref>

====Parenthood====
Studies have also found that fathers had lower levels of cortisol and testosterone but higher levels of estrogen (estradiol) than did non-fathers.<ref>{{cite journal | vauthors = Berg SJ, Wynne-Edwards KE | title = Changes in testosterone, cortisol, and estradiol levels in men becoming fathers | journal = Mayo Clinic Proceedings | volume = 76 | issue = 6 | pages = 582–592 | date = June 2001 | pmid = 11393496 | doi = 10.4065/76.6.582 }}</ref>

====Binge eating====
Estrogen may play a role in suppressing [[binge eating]]. Hormone replacement therapy using estrogen may be a possible treatment for binge eating behaviors in females. Estrogen replacement has been shown to suppress binge eating behaviors in female mice.<ref name=Cao>{{cite journal | vauthors = Cao X, Xu P, Oyola MG, Xia Y, Yan X, Saito K, Zou F, Wang C, Yang Y, Hinton A, Yan C, Ding H, Zhu L, Yu L, Yang B, Feng Y, Clegg DJ, Khan S, DiMarchi R, Mani SK, Tong Q, Xu Y | title = Estrogens stimulate serotonin neurons to inhibit binge-like eating in mice | journal = The Journal of Clinical Investigation | volume = 124 | issue = 10 | pages = 4351–4362 | date = October 2014 | pmid = 25157819 | pmc = 4191033 | doi = 10.1172/JCI74726 }}</ref> The mechanism by which estrogen replacement inhibits binge-like eating involves the replacement of [[serotonin]] (5-HT) neurons. Women exhibiting binge eating behaviors are found to have increased brain uptake of neuron 5-HT, and therefore less of the neurotransmitter serotonin in the cerebrospinal fluid.<ref name=Jimerson>{{cite journal | vauthors = Jimerson DC, Lesem MD, Kaye WH, Hegg AP, Brewerton TD | title = Eating disorders and depression: is there a serotonin connection? | journal = Biological Psychiatry | volume = 28 | issue = 5 | pages = 443–454 | date = September 1990 | pmid = 2207221 | doi = 10.1016/0006-3223(90)90412-u | s2cid = 31058047 }}</ref> Estrogen works to activate 5-HT neurons, leading to suppression of binge like eating behaviors.<ref name=Cao />

It is also suggested that there is an interaction between hormone levels and eating at different points in the female [[menstrual cycle]]. Research has predicted increased emotional eating during hormonal flux, which is characterized by high [[progesterone]] and [[estradiol]] levels that occur during the mid-[[luteal phase]]. It is hypothesized that these changes occur due to brain changes across the menstrual cycle that are likely a genomic effect of hormones. These effects produce menstrual cycle changes, which result in hormone release leading to behavioral changes, notably binge and emotional eating. These occur especially prominently among women who are genetically vulnerable to binge eating phenotypes.<ref name=Klump2013>{{cite journal | vauthors = Klump KL, Keel PK, Racine SE, Burt SA, Burt AS, Neale M, Sisk CL, Boker S, Hu JY | title = The interactive effects of estrogen and progesterone on changes in emotional eating across the menstrual cycle | journal = Journal of Abnormal Psychology | volume = 122 | issue = 1 | pages = 131–137 | date = February 2013 | pmid = 22889242 | pmc = 3570621 | doi = 10.1037/a0029524 }}</ref>

Binge eating is associated with decreased estradiol and increased progesterone.<ref name=Edler>{{cite journal | vauthors = Edler C, Lipson SF, Keel PK | title = Ovarian hormones and binge eating in bulimia nervosa | journal = Psychological Medicine | volume = 37 | issue = 1 | pages = 131–141 | date = January 2007 | pmid = 17038206 | doi = 10.1017/S0033291706008956 | s2cid = 36609028 }}</ref> Klump et al.<ref name=Klump2014 /> Progesterone may moderate the effects of low estradiol (such as during dysregulated eating behavior), but that this may only be true in women who have had clinically diagnosed binge episodes (BEs). Dysregulated eating is more strongly associated with such ovarian hormones in women with BEs than in women without BEs.<ref name=Klump2014>{{cite journal | vauthors = Klump KL, Racine SE, Hildebrandt B, Burt SA, Neale M, Sisk CL, Boker S, Keel PK | title = Ovarian Hormone Influences on Dysregulated Eating: A Comparison of Associations in Women with versus without Binge Episodes | journal = Clinical Psychological Science | volume = 2 | issue = 4 | pages = 545–559 | date = September 2014 | pmid = 25343062 | pmc = 4203460 | doi = 10.1177/2167702614521794 }}</ref>

The implantation of 17β-estradiol pellets in ovariectomized mice significantly reduced binge eating behaviors and injections of GLP-1 in ovariectomized mice decreased binge-eating behaviors.<ref name=Cao />

The associations between binge eating, menstrual-cycle phase and ovarian hormones correlated.<ref name=Edler /><ref name=Klump2008>{{cite journal | vauthors = Klump KL, Keel PK, Culbert KM, Edler C | title = Ovarian hormones and binge eating: exploring associations in community samples | journal = Psychological Medicine | volume = 38 | issue = 12 | pages = 1749–1757 | date = December 2008 | pmid = 18307829 | pmc = 2885896 | doi = 10.1017/S0033291708002997 }}</ref><ref name=Lester>{{cite journal | vauthors = Lester NA, Keel PK, Lipson SF | title = Symptom fluctuation in bulimia nervosa: relation to menstrual-cycle phase and cortisol levels | journal = Psychological Medicine | volume = 33 | issue = 1 | pages = 51–60 | date = January 2003 | pmid = 12537036 | doi = 10.1017/s0033291702006815 | s2cid = 21497515 }}</ref>

====Masculinization in rodents====
In rodents, estrogens (which are locally aromatized from androgens in the brain) play an important role in psychosexual differentiation, for example, by masculinizing territorial behavior;<ref name="pmid19804754">{{cite journal | vauthors = Wu MV, Manoli DS, Fraser EJ, Coats JK, Tollkuhn J, Honda S, Harada N, Shah NM | title = Estrogen masculinizes neural pathways and sex-specific behaviors | journal = Cell | volume = 139 | issue = 1 | pages = 61–72 | date = October 2009 | pmid = 19804754 | pmc = 2851224 | doi = 10.1016/j.cell.2009.07.036 }}</ref> the same is not true in humans.<ref name="pmid19707181">{{cite journal | vauthors = Rochira V, Carani C | title = Aromatase deficiency in men: a clinical perspective | journal = Nature Reviews. Endocrinology | volume = 5 | issue = 10 | pages = 559–568 | date = October 2009 | pmid = 19707181 | doi = 10.1038/nrendo.2009.176 | s2cid = 22116130 | url = https://zenodo.org/record/890683 }}</ref> In humans, the masculinizing effects of prenatal androgens on behavior (and other tissues, with the possible exception of effects on bone) appear to act exclusively through the androgen receptor.<ref name="pmid11534997">{{cite journal | vauthors = Wilson JD | title = Androgens, androgen receptors, and male gender role behavior | journal = Hormones and Behavior | volume = 40 | issue = 2 | pages = 358–366 | date = September 2001 | pmid = 11534997 | doi = 10.1006/hbeh.2001.1684 | url = http://pdfs.semanticscholar.org/75bb/071beb950f66cd032b9d5a9633c255f80660.pdf | url-status = dead | s2cid = 20480423 | archive-url = https://web.archive.org/web/20190226183821/http://pdfs.semanticscholar.org/75bb/071beb950f66cd032b9d5a9633c255f80660.pdf | archive-date = 26 February 2019 }}</ref> Consequently, the utility of rodent models for studying human psychosexual differentiation has been questioned.<ref name="pmid16876166">{{cite journal | vauthors = Baum MJ | title = Mammalian animal models of psychosexual differentiation: when is 'translation' to the human situation possible? | journal = Hormones and Behavior | volume = 50 | issue = 4 | pages = 579–588 | date = November 2006 | pmid = 16876166 | doi = 10.1016/j.yhbeh.2006.06.003 | s2cid = 7465192 }}</ref>

===Skeletal system===
Estrogens are responsible for both the pubertal growth spurt, which causes an acceleration in linear growth, and [[epiphyseal closure]], which limits [[human height|height]] and [[limb (anatomy)|limb]] length, in both females and males. In addition, estrogens are responsible for bone maturation and maintenance of [[bone mineral density]] throughout life. Due to hypoestrogenism, the risk of [[osteoporosis]] increases during [[menopause]].{{cn|date=January 2025}}

===Cardiovascular system===
Women are less impacted by heart disease due to vasculo-protective action of estrogen which helps in preventing atherosclerosis.<ref name="pmid10500455">{{cite journal | vauthors = Rosano GM, Panina G | title = Oestrogens and the heart | journal = Therapie | volume = 54 | issue = 3 | pages = 381–385 | year = 1999 | pmid = 10500455 }}</ref><!-- Read full text or at least abstract and expand this article --> It also helps in maintaining the delicate balance between fighting infections and protecting arteries from damage thus lowering the risk of cardiovascular disease.<ref name="pmid21836070">{{cite journal | vauthors = Nadkarni S, Cooper D, Brancaleone V, Bena S, Perretti M | title = Activation of the annexin A1 pathway underlies the protective effects exerted by estrogen in polymorphonuclear leukocytes | journal = Arteriosclerosis, Thrombosis, and Vascular Biology | volume = 31 | issue = 11 | pages = 2749–2759 | date = November 2011 | pmid = 21836070 | pmc = 3357483 | doi = 10.1161/ATVBAHA.111.235176 }}</ref> During [[pregnancy]], high levels of estrogens increase [[coagulation]] and the risk of [[venous thromboembolism]]. Estrogen has been shown to upregulate the [[peptide hormone]] [[adropin]].<ref name="Hepatic adropin is regulated by est"/>

{{Venous thromboembolism incidence during pregnancy and the postpartum period}}

===Immune system===
The effect of estrogen on the [[immune system]] is in general described as [[Th2]] favoring, rather than suppressive, as is the case of the effect of male sex hormone – testosterone.<ref name="Foo_et_al_2016">{{cite journal | vauthors = Foo YZ, Nakagawa S, Rhodes G, Simmons LW | title = The effects of sex hormones on immune function: a meta-analysis | journal = Biological Reviews of the Cambridge Philosophical Society | volume = 92 | issue = 1 | pages = 551–571 | date = February 2017 | pmid = 26800512 | doi = 10.1111/brv.12243 | s2cid = 37931012 | url = https://api.research-repository.uwa.edu.au/ws/files/21601252/Foo_et_al_2017_The_effects_of_sex_hormones_on_immune_function_a_meta_analysis.pdf }}</ref> Indeed, women respond better to [[vaccine]]s, [[infection]]s and are generally less likely to develop [[cancer]], the tradeoff of this is that they are more likely to develop an [[autoimmune disease]].<ref name="Taneja_2018">{{cite journal | vauthors = Taneja V | title = Sex Hormones Determine Immune Response | journal = Frontiers in Immunology | volume = 9 | pages = 1931 | date = 27 August 2018 | pmid = 30210492 | doi = 10.3389/fimmu.2018.01931 | pmc = 6119719 | doi-access = free }}</ref> The [[Th2]] shift manifests itself in a decrease of cellular immunity and increase in humoral immunity ([[antibody]] production) shifts it from cellular to humoral by downregulating cell-mediated immunity and enhancing Th2 immune response by stimulating IL-4 production and Th2 differentiation.<ref name="Foo_et_al_2016"/><ref name="Roved_et_al_2017">{{cite journal | vauthors = Roved J, Westerdahl H, Hasselquist D | title = Sex differences in immune responses: Hormonal effects, antagonistic selection, and evolutionary consequences | journal = Hormones and Behavior | volume = 88 | pages = 95–105 | date = February 2017 | pmid = 27956226 | doi = 10.1016/j.yhbeh.2016.11.017 | s2cid = 9137227 }}</ref> [[Th1 cell|Type 1]] and [[Th17|type 17]] immune responses are downregulated, likely to be at least partially due to [[Interleukin 4|IL-4]], which inhibits Th1. Effect of estrogen on different immune cells' cell types is in line with its Th2 bias. Activity of [[basophil]]s, [[eosinophil]]s, M2 [[macrophage]]s and is enhanced, whereas activity of [[NK cell]]s is downregulated. Conventional [[dendritic cell]]s are biased towards Th2 under the influence of estrogen, whereas plasmacytoid dendritic cells, key players in antiviral defence, have increased [[IFN-g]] secretion.<ref name="Roved_et_al_2017"/> Estrogen also influences [[B cell]]s by increasing their survival, proliferation, differentiation and function, which corresponds with higher antibody and B cell count generally detected in women.<ref name="Khan_Ansar_2016">{{cite journal | vauthors = Khan D, Ansar Ahmed S | title = The Immune System Is a Natural Target for Estrogen Action: Opposing Effects of Estrogen in Two Prototypical Autoimmune Diseases | journal = Frontiers in Immunology | volume = 6 | pages = 635 | date = 6 January 2016 | pmid = 26779182 | doi = 10.3389/fimmu.2015.00635 | pmc = 4701921 | doi-access = free }}</ref>

On a molecular level estrogen induces the above-mentioned effects on cell via acting on intracellular [[Receptor (biochemistry)|receptors]] termed ER α and ER β, which upon ligation form either homo or heterodimers. The genetic and nongenetic targets of the receptors differ between homo and heterodimers.<ref name="Kovats_2015">{{cite journal | vauthors = Kovats S | title = Estrogen receptors regulate innate immune cells and signaling pathways | journal = Cellular Immunology | volume = 294 | issue = 2 | pages = 63–69 | date = April 2015 | pmid = 25682174 | doi = 10.1016/j.cellimm.2015.01.018 | pmc = 4380804 }}</ref> Ligation of these receptors allows them to translocate to the [[Cell nucleus|nucleus]] and act as [[transcription factor]]s either by binding estrogen response elements (ERE) on [[DNA]] or binding DNA together with other transcriptional factors e.g. [[Nf-kB]] or [[Activator protein 1|AP-1]], both of which result in [[RNA polymerase]] recruitment and further [[chromatin remodelation]].<ref name="Kovats_2015"/> A non-transcriptional response to oestrogen stimulation was also documented (termed membrane-initiated steroid signalling, MISS). This pathway stimulates the ERK and PI3K/AKT pathways, which are known to increase cellular proliferation and affect chromatin remodelation.<ref name="Kovats_2015"/>

===Associated conditions===
Researchers have implicated estrogens in various [[estrogen-dependent condition]]s, such as ER-positive [[breast cancer]], as well as a number of [[genetic condition]]s involving estrogen signaling or metabolism, such as [[estrogen insensitivity syndrome]], [[aromatase deficiency]], and [[aromatase excess syndrome]].{{cn|date=January 2025}}

High estrogen can amplify [[stress hormone|stress-hormone]] responses in stressful situations.<ref>
{{cite book | vauthors = Prior JC | author-link1 = Jerilynn Prior | title = Estrogen's Storm Season: stories of perimenopause | url = https://books.google.com/books?id=2hFFDwAAQBAJ | location = Vancouver, British Columbia | publisher = CeMCOR (Centre for Menstrual Cycle and Ovulation Research) | publication-date = 2018 | isbn = 9780973827521 | access-date = 24 July 2021 | quote = [...] high estrogen amplifies your stress hormone responses to stressful things [...] }}
</ref>