Editing Estrogen (section)

===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>