This paper forms part of a special collection produced in collaboration with the Endocrine Society of Australia. The guest editors for this section are Timothy Cole and Bu Yeap.
Polycystic ovary syndrome (PCOS) is a common endocrinopathy occurring in reproductive-age women. Hyperandrogenism, polycystic ovaries, chronic anovulation, and metabolic aberrations are the common features in PCOS. Hormonal changes are causing pathological symptoms in women with PCOS. The various hormone alterations in PCOS have been demonstrated. Hormones, such as insulin, growth hormones (GH), ghrelin, LEAP-2, gonadotropin-releasing hormone (GnRH), insulin, the luteinizing hormone/follicle-stimulating hormone (LH/FSH) ratio, androgens, and estrogens, are all abnormal in PCOS women. These hormones are related to metabolic disorders, such as diabetes and insulin resistance, overweight and obesity, infertility, and disturbed menstrual cycle in PCOS patients. The pathological changes of these hormones, such as increased insulin, reduced GH, increased ghrelin, and leptin resistance, result in an increased prevalence of diabetes and obesity in PCOS women. A reduced GH, increased LEAP-2 levels, high LH basal, increased LH/FSH ratio, high androgens, and low estrogen are demonstrated in PCOS and linked to infertility. This narrative review aims to clarify the changes of hormone profiles, such as insulin, GH, LH, FSH, androgens, estrogen, progesterone, ghrelin, LEAP-2, asprosin, and subfatin, in PCOS, which may reveal novel targets for better diagnosis and treatment of PCOS.
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Adashi EY, Resnick CE, D’Ercole AJ, Svoboda ME & & Van Wyk JJ 1985 Insulin-like growth factors as intraovarian regulators of granulosa cell growth and function. Endocrine Reviews 6 400–420. (https://doi.org/10.1210/edrv-6-3-400)
Ajmal N, Khan SZ & & Shaikh R 2019 Polycystic ovary syndrome (PCOS) and genetic predisposition: a review article. European Journal of Obstetrics and Gynecology and Reproductive Biology 3 100060. (https://doi.org/10.1016/j.eurox.2019.100060)
Alan M, Gurlek B, Yilmaz A, Aksit M, Aslanipour B, Gulhan I, Mehmet C & & Taner CE 2019 Asprosin: a novel peptide hormone related to insulin resistance in women with polycystic ovary syndrome. Gynecological Endocrinology 35 220–223. (https://doi.org/10.1080/09513590.2018.1512967)
AlKhairi I, Cherian P, Abu-Farha M, Madhoun AA, Nizam R, Melhem M, Jamal M, Al-Sabah S, Ali H, Tuomilehto J, et al.2019 Increased expression of meteorin-like hormone in Type 2 diabetes and obesity and its association with irisin. Cells 8. (https://doi.org/10.3390/cells8101283)
Amisi CA 2022 Markers of insulin resistance in polycystic ovary syndrome women: an update. World Journal of Diabetes 13 129–149. (https://doi.org/10.4239/wjd.v13.i3.129)
Aslanipour B, Alan M & & Demir I 2020 Decreased levels of liver-expressed antimicrobial peptide-2 and ghrelin are related to insulin resistance in women with polycystic ovary syndrome. Gynecological Endocrinology 36 222–225. (https://doi.org/10.1080/09513590.2019.1665646)
Azziz R 2002 Polycystic ovary syndrome, insulin resistance, and molecular defects of insulin signaling. Journal of Clinical Endocrinology and Metabolism 87 4085–4087. (https://doi.org/10.1210/jc.2002-021131)
Azziz R 2016 Introduction: determinants of polycystic ovary syndrome. Fertility and Sterility 106 4–5. (https://doi.org/10.1016/j.fertnstert.2016.05.009)
Azziz R, Woods KS, Reyna R, Key TJ, Knochenhauer ES & & Yildiz BO 2004 The prevalence and features of the polycystic ovary syndrome in an unselected population. Journal of Clinical Endocrinology and Metabolism 89 2745–2749. (https://doi.org/10.1210/jc.2003-032046)
Baptiste CG, Battista MC, Trottier A & & Baillargeon JP 2010 Insulin and hyperandrogenism in women with polycystic ovary syndrome. Journal of Steroid Biochemistry and Molecular Biology 122 42–52. (https://doi.org/10.1016/j.jsbmb.2009.12.010)
Barnes RB, Rosenfield RL, Burstein S & & Ehrmann DA 1989 Pituitary-ovarian responses to nafarelin testing in the polycystic ovary syndrome. New England Journal of Medicine 320 559–565. (https://doi.org/10.1056/NEJM198903023200904)
Blank SK, McCartney CR & & Marshall JC 2006 The origins and sequelae of abnormal neuroendocrine function in polycystic ovary syndrome. Human Reproduction Update 12 351–361. (https://doi.org/10.1093/humupd/dml017)
Bothou A, Koutlaki N, Iatrakis G, Mastorakos G, Tsikouras P, Liberis V, Galazios G, Liberis A, Lykeridou A & & Zervoudis S 2017 AntiMüllerian hormone as indicator of ovarian dysfunction. Acta Endocrinology 13 237–245. (https://doi.org/10.4183/aeb.2017.237)
Brassard M, AinMelk Y & & Baillargeon JP 2008 Basic infertility including polycystic ovary syndrome. Medical Clinics of North America 92 1163–1192. (https://doi.org/10.1016/j.mcna.2008.04.008)
Burke MC, Letts PA, Krajewski SJ & & Rance NE 2006 Coexpression of dynorphin and neurokinin B immunoreactivity in the rat hypothalamus: morphologic evidence of interrelated function within the arcuate nucleus. Journal of Comparative Neurology 498 712–726. (https://doi.org/10.1002/cne.21086)
Casanueva FF, Villanueva L, Dieguez C, Diaz Y, Cabranes JA, Szoke B, Scanlon MF, Schally AV & & Fernandez-Cruz A 1987 Free fatty acids block growth hormone (GH) releasing hormone-stimulated GH secretion in man directly at the pituitary. Journal of Clinical Endocrinology and Metabolism 65 634–642. (https://doi.org/10.1210/jcem-65-4-634)
Cedars MI, Steingold KA, de Ziegler D, Lapolt PS, Chang RJ & & Judd HL 1992 Long-term administration of gonadotropin-releasing hormone agonist and dexamethasone: assessment of the adrenal role in ovarian dysfunction. Fertility and Sterility 57 495–500. (https://doi.org/10.1016/s0015-0282(1654890-0)
Chang CL, Huang SY, Hsu YC, Chin TH & & Soong YK 2019 The serum level of irisin, but not asprosin, is abnormal in polycystic ovary syndrome patients. Scientific Reports 9 6447. (https://doi.org/10.1038/s41598-019-42061-9)
Chen X, Huang L, Tan HY, Li H, Wan Y, Cowley M, Veldhuis JD & & Chen C 2017 Deficient melanocortin-4 receptor causes abnormal reproductive neuroendocrine profile in female mice. Reproduction 153 267–276. (https://doi.org/10.1530/REP-16-0341)
Cheng G, Coolen LM, Padmanabhan V, Goodman RL & & Lehman MN 2010 The kisspeptin/neurokinin B/dynorphin (KNDy) cell population of the arcuate nucleus: sex differences and effects of prenatal testosterone in sheep. Endocrinology 151 301–311. (https://doi.org/10.1210/en.2009-0541)
Chrousos GP, MacLusky NJ, Brandon DD, Tomita M, Renquist DM, Loriaux DL & & Lipsett MB 1986 Progesterone resistance. Advances in Experimental Medicine and Biology 196 317–328. (https://doi.org/10.1007/978-1-4684-5101-6_21)
Clasey JL, Weltman A, Patrie J, Weltman JY, Pezzoli S, Bouchard C, Thorner MO & & Hartman ML 2001 Abdominal visceral fat and fasting insulin are important predictors of 24-hour GH release independent of age, gender, and other physiological factors. Journal of Clinical Endocrinology and Metabolism 86 3845–3852. (https://doi.org/10.1210/jcem.86.8.7731)
Cui L, Tan C, Huang L, Wang W, Huang Z, Geng F, Wu M, Chen X, Cowley M, Roelfsema F, et al.2022 Dapagliflozin partially restores reproductive function in MC4R KO obese female mice. Journal of Endocrinology 254 65–76. (https://doi.org/10.1530/JOE-21-0449)
Dadmanesh M, Aghajani H, Fadaei R & & Ghorban K 2018 Lower serum levels of Meteorin-like/Subfatin in patients with coronary artery disease and type 2 diabetes mellitus are negatively associated with insulin resistance and inflammatory cytokines. PLoS One 13 e0204180. (https://doi.org/10.1371/journal.pone.0204180)
Daghestani MH, Daghestani MH & & El-Mazny A 2011 Circulating ghrelin levels and the polycystic ovary syndrome: correlation with the clinical, hormonal and metabolic features. European Journal of Obstetrics, Gynecology, and Reproductive Biology 155 65–68. (https://doi.org/10.1016/j.ejogrb.2010.11.019)
Daghestani MH, Daghestani M, Daghistani M, El-Mazny A, Bjørklund G, Chirumbolo S, Al Saggaf SH & & Warsy A 2018 A study of ghrelin and leptin levels and their relationship to metabolic profiles in obese and lean Saudi women with polycystic ovary syndrome (PCOS). Lipids in Health and Disease 17 195. (https://doi.org/10.1186/s12944-018-0839-9)
Dahan MH & & Reaven G 2019 Relationship among obesity, insulin resistance, and hyperinsulinemia in the polycystic ovary syndrome. Endocrine 64 685–689. (https://doi.org/10.1007/s12020-019-01899-9)
Deniz R, Yavuzkir S, Ugur K, Ustebay DU, Baykus Y, Ustebay S & & Aydin S 2021 Subfatin and asprosin, two new metabolic players of polycystic ovary syndrome. Journal of Obstetrics and Gynaecology 41 279–284. (https://doi.org/10.1080/01443615.2020.1758926)
Ding H, Zhang J, Zhang F, Zhang S, Chen X, Liang W & & Xie Q 2021 Resistance to the insulin and elevated level of androgen: a major cause of polycystic ovary syndrome. Frontiers in Endocrinology 12 741764. (https://doi.org/10.3389/fendo.2021.741764)
Doi SA 2008 Neuroendocrine dysfunction in PCOS: a critique of recent reviews. Clinical Medicine and Research 6 47–53. (https://doi.org/10.3121/cmr.2008.796)
Duerrschmid C, He Y, Wang C, Li C, Bournat JC, Romere C, Saha PK, Lee ME, Phillips KJ, Jain M, et al.2017 Asprosin is a centrally acting orexigenic hormone. Nature Medicine 23 1444–1453. (https://doi.org/10.1038/nm.4432)
Dumesic DA, Oberfield SE, Stener-Victorin E, Marshall JC, Laven JS & & Legro RS 2015 Scientific statement on the diagnostic criteria, epidemiology, pathophysiology, and Molecular Genetics of polycystic ovary syndrome. Endocrine Reviews 36 487–525. (https://doi.org/10.1210/er.2015-1018)
Dumitrescu R, Mehedintu C, Briceag I, Purcarea VL & & Hudita D 2015 The polycystic ovary syndrome: an update on metabolic and hormonal mechanisms. Journal of Medicine and Life 8 142–145.
Dunaif A 1997 Insulin resistance and the polycystic ovary syndrome: mechanism and implications for pathogenesis. Endocrine Reviews 18 774–800. (https://doi.org/10.1210/edrv.18.6.0318)
Ehrmann DA 2002 Insulin resistance and polycystic ovary syndrome. Current Diabetes Reports 2 71–76. (https://doi.org/10.1007/s11892-002-0061-y)
Ehrmann DA 2005 Polycystic ovary syndrome. New England Journal of Medicine 352 1223–1236. (https://doi.org/10.1056/NEJMra041536)
Ehrmann DA, Schneider DJ, Sobel BE, Cavaghan MK, Imperial J, Rosenfield RL & & Polonsky KS 1997 Troglitazone improves defects in insulin action, insulin secretion, ovarian steroidogenesis, and fibrinolysis in women with polycystic ovary syndrome. Journal of Clinical Endocrinology and Metabolism 82 2108–2116. (https://doi.org/10.1210/jcem.82.7.4069)
Fernandez-Twinn DS, Alfaradhi MZ, Martin-Gronert MS, Duque-Guimaraes DE, Piekarz A, Ferland-McCollough D, Bushell M & & Ozanne SE 2014 Downregulation of IRS-1 in adipose tissue of offspring of obese mice is programmed cell-autonomously through post-transcriptional mechanisms. Molecular Metabolism 3 325–333. (https://doi.org/10.1016/j.molmet.2014.01.007)
Ferrero S, Anserini P, Remorgida V, Bentivoglio G & & Ragni N 2006 Total and active ghrelin levels in women with polycystic ovary syndrome. Human Reproduction 21 565. (https://doi.org/10.1093/humrep/dei334)
Fortin J, Kumar V, Zhou X, Wang Y, Auwerx J, Schoonjans K, Boehm U, Boerboom D & & Bernard DJ 2013 NR5A2 regulates Lhb and Fshb transcription in gonadotrope-like cells in vitro, but is dispensable for gonadotropin synthesis and fertility in vivo. PLoS One 8 e59058. (https://doi.org/10.1371/journal.pone.0059058)
Frystyk J 2004 Free insulin-like growth factors -- measurements and relationships to growth hormone secretion and glucose homeostasis. Growth Hormone and IGF Research 14 337–375. (https://doi.org/10.1016/j.ghir.2004.06.001)
Gao T, Wu L, Chang F & & Cao G 2016 Low circulating ghrelin levels in women with polycystic ovary syndrome: a systematic review and meta-analysis. Endocrine Journal 63 93–100. (https://doi.org/10.1507/endocrj.EJ15-0318)
Garin MC, Butts SF, Sarwer DB, Allison KC, Senapati S & & Dokras A 2017 Ghrelin is independently associated with anti-Mullerian hormone levels in obese but not non-obese women with polycystic ovary syndrome. Endocrine 55 907–913. (https://doi.org/10.1007/s12020-016-1210-4)
Ge X, Yang H, Bednarek MA, Galon-Tilleman H, Chen P, Chen M, Lichtman JS, Wang Y, Dalmas O, Yin Y, et al.2018 LEAP2 is an endogenous antagonist of the ghrelin receptor. Cell Metabolism 27 461–469.e6. (https://doi.org/10.1016/j.cmet.2017.10.016)
Genazzani AD, Lanzoni C, Ricchieri F & & Jasonni VM 2008 myo-inositol administration positively affects hyperinsulinemia and hormonal parameters in overweight patients with polycystic ovary syndrome. Gynecological Endocrinology 24 139–144. (https://doi.org/10.1080/09513590801893232)
Glintborg D, Støving RK, Hagen C, Hermann AP, Frystyk J, Veldhuis JD, Flyvbjerg A & & Andersen M 2005 Pioglitazone treatment increases spontaneous growth hormone (GH) secretion and stimulated GH levels in polycystic ovary syndrome. Journal of Clinical Endocrinology and Metabolism 90 5605–5612. (https://doi.org/10.1210/jc.2005-0615)
Gong Y, Luo S, Fan P, Zhu H, Li Y & & Huang W 2020 Growth hormone activates PI3K/Akt signaling and inhibits ROS accumulation and apoptosis in granulosa cells of patients with polycystic ovary syndrome. Reproductive Biology and Endocrinology 18 121. (https://doi.org/10.1186/s12958-020-00677-x)
Goodman RL, Lehman MN, Smith JT, Coolen LM, de Oliveira CV, Jafarzadehshirazi MR, Pereira A, Iqbal J, Caraty A, Ciofi P, et al.2007 Kisspeptin neurons in the arcuate nucleus of the ewe express both dynorphin A and neurokinin B. Endocrinology 148 5752–5760. (https://doi.org/10.1210/en.2007-0961)
Goshadrou F, Kazerouni F, Mehranfard N & & Sadeghi B 2015 Chronic administration of ghrelin regulates plasma glucose and normalizes insulin levels following fasting hyperglycemia and hyperinsulinemia. General and Comparative Endocrinology 224 113–120. (https://doi.org/10.1016/j.ygcen.2015.07.001)
Gottsch ML, Cunningham MJ, Smith JT, Popa SM, Acohido BV, Crowley WF, Seminara S, Clifton DK & & Steiner RA 2004 A role for kisspeptins in the regulation of gonadotropin secretion in the mouse. Endocrinology 145 4073–4077. (https://doi.org/10.1210/en.2004-0431)
Gross KM, Matsumoto AM & & Bremner WJ 1987 Differential control of luteinizing hormone and follicle-stimulating hormone secretion by luteinizing hormone-releasing hormone pulse frequency in man. Journal of Clinical Endocrinology and Metabolism 64 675–680. (https://doi.org/10.1210/jcem-64-4-675)
Hahn S, Backhaus M, Broecker-Preuss M, Tan S, Dietz T, Kimmig R, Schmidt M, Mann K & & Janssen OE 2007 Retinol-binding protein 4 levels are elevated in polycystic ovary syndrome women with obesity and impaired glucose metabolism. European Journal of Endocrinology 157 201–207. (https://doi.org/10.1530/EJE-07-0143)
Hall JE, Taylor AE, Hayes FJ & & Crowley WF Jr 1998 Insights into hypothalamic-pituitary dysfunction in polycystic ovary syndrome. Journal of Endocrinological Investigation 21 602–611. (https://doi.org/10.1007/BF03350785)
Hanna F, Wu P, Heald A & & Fryer A 2023 Diabetes detection in women with gestational diabetes and polycystic ovarian syndrome. BMJ 382 e071675. (https://doi.org/10.1136/bmj-2022-071675)
Harter CJL, Kavanagh GS & & Smith JT 2018 The role of kisspeptin neurons in reproduction and metabolism. Journal of Endocrinology 238 R173–R183. (https://doi.org/10.1530/JOE-18-0108)
Herman R, Sikonja J, Jensterle M, Janez A & & Dolzan V 2023 Insulin metabolism in polycystic ovary syndrome: secretion, signaling, and clearance. International Journal of Molecular Sciences 24 3140. (https://doi.org/10.3390/ijms24043140)
Homburg R 1996 Growth hormone and fertility--clinical studies. Hormone Research 45 81–85. (https://doi.org/10.1159/000184764)
Houjeghani S, Pourghassem Gargari B & & Farzadi L 2012 Serum leptin and ghrelin levels in women with polycystic ovary syndrome: correlation with anthropometric, metabolic, and endocrine parameters. International Journal of Fertility and Sterility 6 117–126.
Hu Y & & Yang Y 2016 Clinical significance of serum FSH, LH, and testosterone detection in patients with polycystic ovary syndrome. Journal of Baotou Medical College 32 92–93.
Huang Z, Huang L, Waters MJ & & Chen C 2020 Insulin and growth hormone balance: implications for obesity. Trends in Endocrinology and Metabolism 31 642–654. (https://doi.org/10.1016/j.tem.2020.04.005)
Ibrahim RO, Omer SH & & Fattah CN 2020 The correlation between hormonal disturbance in PCOS women and serum level of kisspeptin. International Journal of Endocrinology 2020 6237141. (https://doi.org/10.1155/2020/6237141)
Islam MN, Mita Y, Maruyama K, Tanida R, Zhang W, Sakoda H & & Nakazato M 2020 Liver-expressed antimicrobial peptide 2 antagonizes the effect of ghrelin in rodents. Journal of Endocrinology 244 13–23. (https://doi.org/10.1530/JOE-19-0102)
Iwata K, Kunimura Y, Matsumoto K & & Ozawa H 2017 Effect of androgen on Kiss1 expression and luteinizing hormone release in female rats. Journal of Endocrinology 233 281–292. (https://doi.org/10.1530/JOE-16-0568)
Joham AE, Norman RJ, Stener-Victorin E, Legro RS, Franks S, Moran LJ, Boyle J & & Teede HJ 2022 Polycystic ovary syndrome. Lancet Diabetes and Endocrinology 10 668–680. (https://doi.org/10.1016/S2213-8587(2200163-2)
Joham AE & & Teede HJ 2022 PCOS - a metabolic condition with health impacts on women and men. Nature Reviews Endocrinology 18 197–198. (https://doi.org/10.1038/s41574-022-00636-z)
Johnson JE, Daley D, Tarta C & & Stanciu PI 2023 Risk of endometrial cancer in patients with polycystic ovarian syndrome: a metaanalysis. Oncology Letters 25 168. (https://doi.org/10.3892/ol.2023.13754)
Joshi B, Mukherjee S, Patil A, Purandare A, Chauhan S & & Vaidya R 2014 A cross-sectional study of polycystic ovarian syndrome among adolescent and young girls in Mumbai, India. Indian Journal of Endocrinology and Metabolism 18 317–324. (https://doi.org/10.4103/2230-8210.131162)
Kakoly NS, Khomami MB, Joham AE, Cooray SD, Misso ML, Norman RJ, Harrison CL, Ranasinha S, Teede HJ & & Moran LJ 2018 Ethnicity, obesity and the prevalence of impaired glucose tolerance and type 2 diabetes in PCOS: a systematic review and meta-regression. Human Reproduction Update 24 455–467. (https://doi.org/10.1093/humupd/dmy007)
Kale-Gurbuz T, Akhan SE, Bastu E, Telci A, Iyibozkurt AC & & Topuz S 2013 Adiponectin, leptin and ghrelin levels in obese adolescent girls with polycystic ovary syndrome. Journal of Pediatric and Adolescent Gynecology 26 27–30. (https://doi.org/10.1016/j.jpag.2012.09.002)
Kaltsas T, Pontikides N, Krassas GE, Seferiadis K, Lolis D & & Messinis IE 1999 Growth hormone response to thyrotrophin releasing hormone in women with polycystic ovarian syndrome. Human Reproduction 14 2704–2708. (https://doi.org/10.1093/humrep/14.11.2704)
Katz E, Ricciarelli E & & Adashi EY 1993 The potential relevance of growth hormone to female reproductive physiology and pathophysiology. Fertility and Sterility 59 8–34. (https://doi.org/10.1016/s0015-0282(1655610-6)
Krause A, Sillard R, Kleemeier B, Klüver E, Maronde E, Conejo-García JR, Forssmann WG, Schulz-Knappe P, Nehls MC, Wattler F, et al.2003 Isolation and biochemical characterization of LEAP-2, a novel blood peptide expressed in the liver. Protein Science 12 143–152. (https://doi.org/10.1110/ps.0213603)
Krishnan A & & Muthusami S 2017 Hormonal alterations in PCOS and its influence on bone metabolism. Journal of Endocrinology 232 R99–R113. (https://doi.org/10.1530/JOE-16-0405)
Kuliczkowska-Płaksej J, Mierzwicka A, Jończyk M, Stachowska B, Urbanovych A & & Bolanowski M 2019 Adropin in women with polycystic ovary syndrome. Endokrynologia Polska 70 151–156. (https://doi.org/10.5603/EP.a2018.0092)
Kumar N & & Agarwal H 2022 Early clinical, biochemical and radiological features in obese and non-obese young women with polycystic ovarian syndrome: a comparative study. Hormone and Metabolic Research 54 620–624. (https://doi.org/10.1055/a-1880-1264)
Kumbak B, Oral E & & Bukulmez O 2012 Female obesity and assisted reproductive technologies. Seminars in Reproductive Medicine 30 507–516. (https://doi.org/10.1055/s-0032-1328879)
Lanzi R, Manzoni MF, Andreotti AC, Malighetti ME, Bianchi E, Sereni LP, Caumo A, Luzi L & & Pontiroli AE 1997 Evidence for an inhibitory effect of physiological levels of insulin on the growth hormone (GH) response to GH-releasing hormone in healthy subjects. Journal of Clinical Endocrinology and Metabolism 82 2239–2243. (https://doi.org/10.1210/jcem.82.7.4071)
Lanzi R, Luzi L, Caumo A, Andreotti AC, Manzoni MF, Malighetti ME, Sereni LP & & Pontiroli AE 1999 Elevated insulin levels contribute to the reduced growth hormone (GH) response to GH-releasing hormone in obese subjects. Metabolism 48 1152–1156. (https://doi.org/10.1016/s0026-0495(9990130-0)
Lanzone A, Villa P, Fulghesu AM, Pavone V, Caruso A & & Mancuso S 1995 The growth hormone response to growth hormone-releasing hormone is blunted in polycystic ovary syndrome: relationship with obesity and hyperinsulinaemia. Human Reproduction 10 1653–1657. (https://doi.org/10.1093/oxfordjournals.humrep.a136150)
Layacha SY & & Biswas DA 2023 Women with polycystic ovary syndrome: a review of susceptibility to type 2 diabetes. Cureus 15 e33390. (https://doi.org/10.7759/cureus.33390)
Lazaridou S, Dinas K & & Tziomalos K 2017 Prevalence, pathogenesis and management of prediabetes and type 2 diabetes mellitus in patients with polycystic ovary syndrome. Hormones 16 373–380. (https://doi.org/10.14310/horm.2002.1757)
Lee EJ, Lee BS, Lee HC, Park KH, Song CH & & Huh KB 1993 Growth hormone response to L-dopa and pyridostigmine in women with polycystic ovarian syndrome. Fertility and Sterility 60 53–57. (https://doi.org/10.1016/s0015-0282(1656035-x)
Lee JH, Kang YE, Kim JM, Choung S, Joung KH, Kim HJ & & Ku BJ 2018 Serum Meteorin-like protein levels decreased in patients newly diagnosed with type 2 diabetes. Diabetes Research and Clinical Practice 135 7–10. (https://doi.org/10.1016/j.diabres.2017.10.005)
Li R, Zhang Q, Yang D, Li S, Lu S, Wu X, Wei Z, Song X, Wang X, Fu S, et al.2013 Prevalence of polycystic ovary syndrome in women in China: a large community-based study. Human Reproduction 28 2562–2569. (https://doi.org/10.1093/humrep/det262)
Li ZY, Zheng SL, Wang P, Xu TY, Guan YF, Zhang YJ & & Miao CY 2014 Subfatin is a novel adipokine and unlike Meteorin in adipose and brain expression. CNS Neuroscience and Therapeutics 20 344–354. (https://doi.org/10.1111/cns.12219)
Li ZY, Song J, Zheng SL, Fan MB, Guan YF, Qu Y, Xu J, Wang P & & Miao CY 2015 Adipocyte Metrnl antagonizes insulin resistance through PPARγ signaling. Diabetes 64 4011–4022. (https://doi.org/10.2337/db15-0274)
Li X, Liao M, Shen R, Zhang L, Hu H, Wu J, Wang X, Qu H, Guo S, Long M, et al.2018 Plasma asprosin levels are associated with glucose metabolism, lipid, and sex hormone profiles in females with metabolic-related diseases. Mediators of Inflammation 2018 7375294. (https://doi.org/10.1155/2018/7375294)
Li X, Yang D, Pan P, Azziz R, Yang D, Cheng Y & & Zhao X 2022 The degree of menstrual disturbance is associated with the severity of insulin resistance in PCOS. Frontiers in Endocrinology 13 873726. (https://doi.org/10.3389/fendo.2022.873726)
Lihn AS, Pedersen SB & & Richelsen B 2005 Adiponectin: action, regulation and association to insulin sensitivity. Obesity Reviews 6 13–21. (https://doi.org/10.1111/j.1467-789X.2005.00159.x)
Lim SS, Davies MJ, Norman RJ & & Moran LJ 2012 Overweight, obesity and central obesity in women with polycystic ovary syndrome: a systematic review and meta-analysis. Human Reproduction Update 18 618–637. (https://doi.org/10.1093/humupd/dms030)
Lim SS, Norman RJ, Davies MJ & & Moran LJ 2013 The effect of obesity on polycystic ovary syndrome: a systematic review and meta-analysis. Obesity Reviews 14 95–109. (https://doi.org/10.1111/j.1467-789X.2012.01053.x)
Liu H 2016 Analysis of the diagnostic value of LH/FSH ratio in polycystic ovary syndrome. Shenzhen Journal of Integrated Traditional Chinese and Western Medicine 26 60–61.
Liu Q, Xie YJ, Qu LH, Zhang MX & & Mo ZC 2019 Dyslipidemia involvement in the development of polycystic ovary syndrome. Taiwanese Journal of Obstetrics and Gynecology 58 447–453. (https://doi.org/10.1016/j.tjog.2019.05.003)
Liu J, Qu T, Li Z, Yu L, Zhang S, Yuan D & & Wu H 2021 Serum kisspeptin levels in polycystic ovary syndrome: a meta-analysis. Journal of Obstetrics and Gynaecology Research 47 2157–2165. (https://doi.org/10.1111/jog.14767)
Liu X 2011 The clinical significance of detecting plasma leptin and serum T, E2, FSH, LH, PRL levels in patients with polycystic ovary syndrome. Medical Information 24 3912–3913.
Liu YX & & Hsueh AJ 1986 Synergism between granulosa and theca-interstitial cells in estrogen biosynthesis by gonadotropin-treated rat ovaries: studies on the two-cell, two-gonadotropin hypothesis using steroid antisera. Biology of Reproduction 35 27–36. (https://doi.org/10.1095/biolreprod35.1.27)
Livadas S, Paparodis R, Anagnostis P, Gambineri A, Bjekić-Macut J, Petrović T, Yildiz BO, Micić D, Mastorakos G & & Macut D 2023 Assessment of Type 2 diabetes risk in young women with polycystic ovary syndrome. Diagnostics 13 2067. (https://doi.org/10.3390/diagnostics13122067)
Longcope C, Pratt JH, Schneider SH & & Fineberg SE 1976 The in vivo metabolism of androgens by muscle and adipose tissue of normal men. Steroids 28 521–533. (https://doi.org/10.1016/0039-128x(7690021-0)
Lord J & & Wilkin T 2002 Polycystic ovary syndrome and fat distribution: the central issue? Human Fertility 5 67–71. (https://doi.org/10.1080/1464727022000198952)
Lu X, Huang L, Huang Z, Feng D, Clark RJ & & Chen C 2021 LEAP-2: an emerging endogenous ghrelin receptor antagonist in the pathophysiology of obesity. Frontiers in Endocrinology 12 717544. (https://doi.org/10.3389/fendo.2021.717544)
Ma N, Chen Z & & Gao CY 2023 Research progress of polycystic ovary syndrome and metabolic syndrome. Medical and Health 13 381–387. (https://doi.org/10.12677/MD.2023.133058)
March WA, Moore VM, Willson KJ, Phillips DI, Norman RJ & & Davies MJ 2010 The prevalence of polycystic ovary syndrome in a community sample assessed under contrasting diagnostic criteria. Human Reproduction 25 544–551. (https://doi.org/10.1093/humrep/dep399)
Marcondes JA, Yamashita SA, Maciel GA, Baracat EC & & Halpern A 2007 Metformin in normal-weight hirsute women with polycystic ovary syndrome with normal insulin sensitivity. Gynecological Endocrinology 23 273–278. (https://doi.org/10.1080/09513590701192529)
Mei Y, Peng X & & Zhang X 2010 Observation of metabolic characteristics in 94 patients with polycystic ovary syndrome. Journal of Nanchang University 50 55–57.
Mendelson CR & & Kamat A 2007 Mechanisms in the regulation of aromatase in developing ovary and placenta. Journal of Steroid Biochemistry and Molecular Biology 106 62–70. (https://doi.org/10.1016/j.jsbmb.2007.05.001)
Metwally M, Li TC & & Ledger WL 2007 The impact of obesity on female reproductive function. Obesity Reviews 8 515–523. (https://doi.org/10.1111/j.1467-789X.2007.00406.x)
Miller WL 2002 Androgen biosynthesis from cholesterol to DHEA. Molecular and Cellular Endocrinology 198 7–14. (https://doi.org/10.1016/s0303-7207(0200363-5)
Mitkov M, Pehlivanov B & & Orbetzova M 2008 Serum ghrelin level in women with polycystic ovary syndrome and its relationship with endocrine and metabolic parameters. Gynecological Endocrinology 24 625–630. (https://doi.org/10.1080/09513590802302233)
Möhlig M, Weickert MO, Ghadamgahi E, Arafat AM, Spranger J, Pfeiffer AF & & Schöfl C 2008 Retinol-binding protein 4 is associated with insulin resistance, but appears unsuited for metabolic screening in women with polycystic ovary syndrome. European Journal of Endocrinology 158 517–523. (https://doi.org/10.1530/EJE-07-0833)
Morales AJ, Laughlin GA, Bützow T, Maheshwari H, Baumann G & & Yen SS 1996 Insulin, somatotropic, and luteinizing hormone axes in lean and obese women with polycystic ovary syndrome: common and distinct features. Journal of Clinical Endocrinology and Metabolism 81 2854–2864. (https://doi.org/10.1210/jcem.81.8.8768842)
Moran LJ, Pasquali R, Teede HJ, Hoeger KM & & Norman RJ 2009 Treatment of obesity in polycystic ovary syndrome: a position statement of the androgen excess and polycystic ovary syndrome society. Fertility and Sterility 92 1966–1982. (https://doi.org/10.1016/j.fertnstert.2008.09.018)
Müller EE, Locatelli V & & Cocchi D 1999 Neuroendocrine control of growth hormone secretion. Physiological Reviews 79 511–607. (https://doi.org/10.1152/physrev.1999.79.2.511)
Müller TD, Nogueiras R, Andermann ML, Andrews ZB, Anker SD, Argente J, Batterham RL, Benoit SC, Bowers CY, Broglio F, et al.2015 Ghrelin. Molecular Metabolism 4 437–460. (https://doi.org/10.1016/j.molmet.2015.03.005)
Murphy KG 2005 Kisspeptins: regulators of metastasis and the hypothalamic-pituitary-gonadal axis. Journal of Neuroendocrinology 17 519–525. (https://doi.org/10.1111/j.1365-2826.2005.01328.x)
Nass R, Gaylinn BD & & Thorner MO 2011 The role of ghrelin in GH secretion and GH disorders. Molecular and Cellular Endocrinology 340 10–14. (https://doi.org/10.1016/j.mce.2011.03.021)
Navarro VM, Gottsch ML, Chavkin C, Okamura H, Clifton DK & & Steiner RA 2009 Regulation of gonadotropin-releasing hormone secretion by kisspeptin/dynorphin/neurokinin B neurons in the arcuate nucleus of the mouse. Journal of Neuroscience 29 11859–11866. (https://doi.org/10.1523/JNEUROSCI.1569-09.2009)
Nelson VL, Legro RS, Strauss JF 3rd & McAllister JM 1999 Augmented androgen production is a stable steroidogenic phenotype of propagated theca cells from polycystic ovaries. Molecular Endocrinology 13 946–957. (https://doi.org/10.1210/mend.13.6.0311)
Obara-Moszyńska M, Kedzia A, Korman E & & Niedziela M 2008 Usefulness of growth hormone (GH) stimulation tests and IGF-I concentration measurement in GH deficiency diagnosis. Journal of Pediatric Endocrinology and Metabolism 21 569–579. (https://doi.org/10.1515/jpem-2008-210611)
Ollila MM, Arffman RK, Korhonen E, Morin-Papunen L, Franks S, Junttila J & & Piltonen TT 2023 Women with PCOS have an increased risk for cardiovascular disease regardless of diagnostic criteria-a prospective population-based cohort study. European Journal of Endocrinology 189 96–105. (https://doi.org/10.1093/ejendo/lvad077)
Orio F Jr, Palomba S, Colao A, Russo T, Dentico C, Tauchmanovà L, Savastano S, Nappi C, Sultan C, Zullo F, et al.2003 GH release after GHRH plus arginine administration in obese and overweight women with polycystic ovary syndrome. Journal of Endocrinological Investigation 26 117–122. (https://doi.org/10.1007/BF03345138)
Owens LA, Abbara A, Lerner A, O’Floinn S, Christopoulos G, Khanjani S, Islam R, Hardy K, Hanyaloglu AC, Lavery SA, et al.2018 The direct and indirect effects of kisspeptin-54 on granulosa lutein cell function. Human Reproduction 33 292–302. (https://doi.org/10.1093/humrep/dex357)
Panidis D, Kourtis A, Kukuvitis A, Farmakiotis D, Xita N, Georgiou I & & Tsatsoulis A 2004 Association of the T45G polymorphism in exon 2 of the adiponectin gene with polycystic ovary syndrome: role of Delta4-androstenedione. Human Reproduction 19 1728–1733. (https://doi.org/10.1093/humrep/deh336)
Paoli A, Mancin L, Giacona MC, Bianco A & & Caprio M 2020 Effects of a ketogenic diet in overweight women with polycystic ovary syndrome. Journal of Translational Medicine 18 104. (https://doi.org/10.1186/s12967-020-02277-0)
Paradisi R, Grossi G, Venturoli S, Capelli M, Porcu E, Fabbri R, Pasquali R & & Flamigni C 1988 Evidence for a hypothalamic alteration of catecholamine metabolism in polycystic ovary syndrome. Clinical Endocrinology 29 317–326. (https://doi.org/10.1111/j.1365-2265.1988.tb01230.x)
Pei X & & Ai H 2007 The relationship between ghrelin and food intake and obesity. Health Research 36 124–127.
Pekhlivanov B, Mitkov M, Orbtsova M & & Terzieva D 2008 Serum levels of ghrelin and leptin in women with polycystic ovary syndrome. Akusherstvo i Ginekologiia 47 15–19.
Pellitero S, Piquer-Garcia I, Ferrer-Curriu G, Puig R, Martínez E, Moreno P, Tarascó J, Balibrea J, Lerin C, Puig-Domingo M, et al.2018 Opposite changes in meteorin-like and oncostatin M levels are associated with metabolic improvements after bariatric surgery. International Journal of Obesity 42 919–922. (https://doi.org/10.1038/ijo.2017.268)
Piaditis GP, Kounadi TG, Rangou DB, Trovas GP, Kaklas NA, Tzonou AJ & & Chlouverakis CS 1995 Dysfunction of the growth hormone/insulin-like growth factor-I axis in women with polycystic ovarian syndrome. Clinical Endocrinology 42 635–640. (https://doi.org/10.1111/j.1365-2265.1995.tb02691.x)
Pradhan G, Samson SL & & Sun Y 2013 Ghrelin: much more than a hunger hormone. Current Opinion in Clinical Nutrition and Metabolic Care 16 619–624. (https://doi.org/10.1097/MCO.0b013e328365b9be)
Puttabyatappa M, Sargis RM & & Padmanabhan V 2020 Developmental programming of insulin resistance: are androgens the culprits? Journal of Endocrinology 245 R23–R48. (https://doi.org/10.1530/JOE-20-0044)
Rajkhowa M, Brett S, Cuthbertson DJ, Lipina C, Ruiz-Alcaraz AJ, Thomas GE, Logie L, Petrie JR & & Sutherland C 2009 Insulin resistance in polycystic ovary syndrome is associated with defective regulation of ERK1/2 by insulin in skeletal muscle in vivo. Biochemical Journal 418 665–671. (https://doi.org/10.1042/BJ20082176)
Rasmussen MH, Hvidberg A, Juul A, Main KM, Gotfredsen A, Skakkebaek NE, Hilsted J & & Skakkebae NE 1995 Massive weight loss restores 24-hour growth hormone release profiles and serum insulin-like growth factor-I levels in obese subjects. Journal of Clinical Endocrinology and Metabolism 80 1407–1415. (https://doi.org/10.1210/jcem.80.4.7536210)
Richards JS & & Pangas SA 2010 The ovary: basic biology and clinical implications. Journal of Clinical Investigation 120 963–972. (https://doi.org/10.1172/JCI41350)
Rojas J, Chávez M, Olivar L, Rojas M, Morillo J, Mejías J, Calvo M & & Bermúdez V 2014 Polycystic ovary syndrome, insulin resistance, and obesity: navigating the pathophysiologic labyrinth. International Journal of Reproductive Medicine 2014 719050. (https://doi.org/10.1155/2014/719050)
Romere C, Duerrschmid C, Bournat J, Constable P, Jain M, Xia F, Saha PK, Del Solar M, Zhu B, York B, et al.2016 Asprosin, a fasting-induced glucogenic protein hormone. Cell 165 566–579. (https://doi.org/10.1016/j.cell.2016.02.063)
Rudnicka E, Suchta K, Grymowicz M, Calik-Ksepka A, Smolarczyk K, Duszewska AM, Smolarczyk R & & Meczekalski B 2021 Chronic low grade inflammation in pathogenesis of PCOS. International Journal of Molecular Sciences 22. (https://doi.org/10.3390/ijms22073789)
Sandrock M, Schulz A, Merkwitz C, Schöneberg T, Spanel-Borowski K & & Ricken A 2009 Reduction in corpora lutea number in obese melanocortin-4-receptor-deficient mice. Reproductive Biology and Endocrinology 7 24. (https://doi.org/10.1186/1477-7827-7-24)
Sato T, Ida T, Nakamura Y, Shiimura Y, Kangawa K & & Kojima M 2014 Physiological roles of ghrelin on obesity. Obesity Research and Clinical Practice 8 e405–e413. (https://doi.org/10.1016/j.orcp.2013.10.002)
Savaris RF, Groll JM, Young SL, DeMayo FJ, Jeong JW, Hamilton AE, Giudice LC & & Lessey BA 2011 Progesterone resistance in PCOS endometrium: a microarray analysis in clomiphene citrate-treated and artificial menstrual cycles. Journal of Clinical Endocrinology and Metabolism 96 1737–1746. (https://doi.org/10.1210/jc.2010-2600)
Seoane LM, Tovar S, Baldelli R, Arvat E, Ghigo E, Casanueva FF & & Dieguez C 2000 Ghrelin elicits a marked stimulatory effect on GH secretion in freely-moving rats. European Journal of Endocrinology 143 R7–R9. (https://doi.org/10.1530/eje.0.143r007)
Sepilian V & & Nagamani M 2005 Adiponectin levels in women with polycystic ovary syndrome and severe insulin resistance. Journal of the Society for Gynecologic Investigation 12 129–134. (https://doi.org/10.1016/j.jsgi.2004.09.003)
Shen ZQ, Zhu HT & & Lin JF 2008 Reverse of progestin-resistant atypical endometrial hyperplasia by metformin and oral contraceptives. Obstetrics and Gynecology 112 465–467. (https://doi.org/10.1097/AOG.0b013e3181719b92)
Shi Y, Guo M, Yan J, Sun W, Zhang X, Geng L, Xu L & & Chen Z 2007 Analysis of clinical characteristics in large-scale Chinese women with polycystic ovary syndrome. Neuro Endocrinology Letters 28 807–810.
Skorupskaite K, George JT & & Anderson RA 2014 The kisspeptin-GnRH pathway in human reproductive health and disease. Human Reproduction Update 20 485–500. (https://doi.org/10.1093/humupd/dmu009)
Snider AP & & Wood JR 2019 Obesity induces ovarian inflammation and reduces oocyte quality. Reproduction 158 R79–R90. (https://doi.org/10.1530/REP-18-0583)
Sonne DP & & Hemmingsen B 2017 Comment on American Diabetes Association. Standards of medical care in Diabetes-2017. Diabetes Care 2017;40(Suppl. 1):S1-S135. Diabetes Care 40 e92–e93. (https://doi.org/10.2337/dc17-0299)
Souza Dos Santos AC, Soares NP, Costa EC, de Sá JC, Azevedo GD & & Lemos TM 2015 The impact of body mass on inflammatory markers and insulin resistance in polycystic ovary syndrome. Gynecological Endocrinology 31 225–228. (https://doi.org/10.3109/09513590.2014.976546)
Stark R, Feehan J, Mousa A, Andrews ZB & & de Courten B 2023 Liver-expressed antimicrobial peptide 2 is associated with improved pancreatic insulin secretion in adults with overweight and obesity. Diabetes, Obesity and Metabolism 25 1213–1220. (https://doi.org/10.1111/dom.14968)
Stepto NK, Cassar S, Joham AE, Hutchison SK, Harrison CL, Goldstein RF & & Teede HJ 2013 Women with polycystic ovary syndrome have intrinsic insulin resistance on euglycaemic-hyperinsulaemic clamp. Human Reproduction 28