Editing Polycystic ovary syndrome (section)

== Pathogenesis ==
Polycystic ovaries develop when the ovaries are stimulated to produce excessive amounts of androgenic hormones, in particular testosterone, by either one or a combination of the following (almost certainly combined with genetic susceptibility):<ref name="AnnNYAS_thoughts" />
* The release of excessive [[luteinizing hormone]] (LH) by the [[anterior pituitary]] gland
* through high levels of insulin in the blood ([[hyperinsulinaemia]]) in women whose ovaries are sensitive to this stimulus

A majority of women with PCOS have [[insulin resistance]] and/or are [[obese]], which is a strong risk factor for insulin resistance, although insulin resistance is a common finding among women with PCOS in normal-weight women as well.<ref name="Mor2015" /><ref name="BMC2010" /><ref name="FertSter_insulin" /> Elevated insulin levels contribute to or cause the abnormalities seen in the [[Hypothalamic–pituitary–gonadal axis|hypothalamic–pituitary–ovarian axis]] that lead to PCOS. Hyperinsulinemia increases [[GnRH]] pulse frequency,<ref name=DimantiDunaif2012>{{cite journal | vauthors = Diamanti-Kandarakis E, Dunaif A | title = Insulin resistance and the polycystic ovary syndrome revisited: an update on mechanisms and implications | journal = Endocrine Reviews | volume = 33 | issue = 6 | pages = 981–1030 | date = December 2012 | pmid = 23065822 | pmc = 5393155 | doi = 10.1210/er.2011-1034 }}</ref> which in turn results in an increase in the LH/FSH ratio<ref name="DimantiDunaif2012" /><ref>{{cite journal | vauthors = Lewandowski KC, Cajdler-Łuba A, Salata I, Bieńkiewicz M, Lewiński A | title = The utility of the gonadotrophin-releasing hormone (GnRH) test in the diagnosis of polycystic ovary syndrome (PCOS) | journal = Endokrynologia Polska | volume = 62 | issue = 2 | pages = 120–8 |date= 2011 | pmid = 21528473 | url = https://journals.viamedica.pl/endokrynologia_polska/article/view/25282 | id = {{ProQuest|2464206947}} | access-date = 13 October 2021 | archive-date = 27 October 2021 | archive-url = https://web.archive.org/web/20211027181115/https://journals.viamedica.pl/endokrynologia_polska/article/view/25282 | url-status = live }}</ref> increased ovarian androgen production; decreased follicular maturation; and decreased [[SHBG]] binding.<ref name=DimantiDunaif2012/> Furthermore, excessive insulin increases the activity of [[17α-hydroxylase]], which catalyzes the conversion of [[progesterone]] to [[androstenedione]], which is in turn converted to testosterone. The combined effects of [[hyperinsulinemia]] contribute to an increased risk of PCOS.<ref name=DimantiDunaif2012/>

[[Adipose tissue|Adipose (fat) tissue]] possesses [[aromatase]], an enzyme that converts androstenedione to [[estrone]] and testosterone to [[estradiol]]. The excess of adipose tissue in obese women creates the paradox of having both excess androgens (which are responsible for hirsutism and [[virilization]]) and excess estrogens (which inhibit FSH via [[negative feedback]]).<ref name="Rojas2014">{{cite journal |vauthors=Rojas J, Chávez M, Olivar L, Rojas M, Morillo J, Mejías J, Calvo M, Bermúdez V |title=Polycystic ovary syndrome, insulin resistance, and obesity: navigating the pathophysiologic labyrinth |journal=Int J Reprod Med |date=2014 |volume=2014 |page=71905 |doi=10.1155/2014/719050 |pmid=25763405 |pmc=4334071|doi-access=free }}</ref>

The syndrome acquired its most widely used name due to the common sign on ultrasound examination of multiple (poly) ovarian [[cyst]]s. These "cysts" are in fact immature [[ovarian follicles]]. The follicles have developed from primordial follicles, but this development has stopped ("arrested") at an early stage, due to the disturbed ovarian function. The follicles may be oriented along the ovarian periphery, appearing as a 'string of pearls' on ultrasound examination.<ref>{{Cite journal | vauthors = Ali HI, Elsadawy ME, Khater NH |date= March 2016 |title=Ultrasound assessment of polycystic ovaries: Ovarian volume and morphology; which is more accurate in making the diagnosis?! |journal=The Egyptian Journal of Radiology and Nuclear Medicine |language=en |volume=47 |issue=1 |pages=347–350 |doi=10.1016/j.ejrnm.2015.10.002 |doi-access=free }}</ref>

PCOS may be associated with [[chronic inflammation]],<ref name=Mediators_Inflammation>{{cite journal | vauthors = Sathyapalan T, Atkin SL | title = Mediators of inflammation in polycystic ovary syndrome in relation to adiposity | journal = Mediators of Inflammation | volume = 2010 | page = 758656 |date= 2010 | pmid = 20396393 | pmc = 2852606 | doi = 10.1155/2010/758656 | doi-access = free }}</ref> with several investigators correlating inflammatory mediators with anovulation and other PCOS symptoms.<ref>{{cite journal | vauthors = Fukuoka M, Yasuda K, Fujiwara H, Kanzaki H, Mori T | title = Interactions between interferon gamma, tumour necrosis factor alpha, and interleukin-1 in modulating progesterone and oestradiol production by human luteinized granulosa cells in culture | journal = Human Reproduction | volume = 7 | issue = 10 | pages = 1361–64 | date = November 1992 | pmid = 1291559 | doi = 10.1093/oxfordjournals.humrep.a137574 }}</ref><ref>{{cite journal | vauthors = González F, Rote NS, Minium J, Kirwan JP | title = Reactive oxygen species-induced oxidative stress in the development of insulin resistance and hyperandrogenism in polycystic ovary syndrome | journal = The Journal of Clinical Endocrinology and Metabolism | volume = 91 | issue = 1 | pages = 336–340 | date = January 2006 | pmid = 16249279 | doi = 10.1210/jc.2005-1696 | doi-access = free }}</ref> Similarly, there seems to be a relation between PCOS and an increased level of [[oxidative stress]].<ref name="pmid23303572">{{cite journal | vauthors = Murri M, Luque-Ramírez M, Insenser M, Ojeda-Ojeda M, Escobar-Morreale HF | title = Circulating markers of oxidative stress and polycystic ovary syndrome (PCOS): a systematic review and meta-analysis | journal = Human Reproduction Update | volume = 19 | issue = 3 | pages = 268–288 |date= 2013 | pmid = 23303572 | doi = 10.1093/humupd/dms059 | doi-access = free }}</ref>