{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,14]],"date-time":"2026-10-14T02:38:13Z","timestamp":1791945493434,"version":"4.3.4"},"reference-count":70,"publisher":"Wiley","issue":"2","license":[{"start":{"date-parts":[[2021,1,11]],"date-time":"2021-01-11T00:00:00Z","timestamp":1610323200000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/onlinelibrary.wiley.com\/termsAndConditions#vor"}],"content-domain":{"domain":["onlinelibrary.wiley.com"],"crossmark-restriction":true},"short-container-title":["Clinical Endocrinology"],"published-print":{"date-parts":[[2021,8]]},"abstract":"<jats:title>Abstract<\/jats:title>\n                  <jats:sec>\n                    <jats:title>Introduction<\/jats:title>\n                    <jats:p>Functional hypothalamic amenorrhoea (FHA) is a common form of secondary amenorrhoea without an identifiable structural cause. Suppression of gonadotrophin\u2010releasing hormone (GnRH) pulsatility results in reduced luteinizing hormone (LH) levels, with subsequent reduction in oestradiol, anovulation and cessation of menstruation. GnRH pulsatility suppression is a recognized complication of psychological stress, disordered eating, low body weight, excessive exercise or a combination of these factors.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Pathophysiology of FHA<\/jats:title>\n                    <jats:p>Individuals with FHA demonstrate low energy availability (EA), body fat percentage and energy expenditure. Documented adipocytokine changes notably, raised adiponectin, ghrelin, PYY, and decreased leptin, are associated with GnRH suppression. Other endocrine responses seen in this low EA state include low insulin levels, low total T3, increased basal cortisol levels and a reduced response to corticotrophin\u2010releasing hormone (CRH) administration. FHA is associated with raised growth hormone (GH) and low insulin\u2010like growth factor (IGF\u20101), suggesting relative GH resistance. Kisspeptins are a group of polypeptides, recently discovered to play a major role in the regulation of the reproductive axis through influencing GnRH release. KNDy (kisspeptin\/neurokinin B\/dynorphin) act on GnRH neurons and a multitude of factors result in their release.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Implications for future treatment<\/jats:title>\n                    <jats:p>Management of FHA is imperative to prevent adverse outcomes in bone density, cardiovascular risk profile, psychological well\u2010being and fertility. Outwith modification of nutritional intake and exercise, limited therapeutic strategies are currently available for women with FHA. Advancements in the understanding of the pathophysiological basis of this under\u2010recognized and under\u2010treated clinical entity will aid management and may result in the development of novel therapeutic approaches.<\/jats:p>\n                  <\/jats:sec>","DOI":"10.1111\/cen.14399","type":"journal-article","created":{"date-parts":[[2020,12,21]],"date-time":"2020-12-21T07:28:54Z","timestamp":1608535734000},"page":"229-238","update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":92,"title":["A review of the pathophysiology of functional hypothalamic amenorrhoea in women subject to psychological stress, disordered eating, excessive exercise or a combination of these factors"],"prefix":"10.1111","volume":"95","author":[{"ORCID":"https:\/\/orcid.org\/0000-0003-3353-1863","authenticated-orcid":false,"given":"Amy E.","family":"Morrison","sequence":"first","affiliation":[{"name":"Department of Endocrinology University Hospitals of Leicester Leicester UK"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Suzannah","family":"Fleming","sequence":"additional","affiliation":[{"name":"Department of Endocrinology University Hospitals of Leicester Leicester UK"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-7256-7880","authenticated-orcid":false,"given":"Miles J.","family":"Levy","sequence":"additional","affiliation":[{"name":"Department of Endocrinology University Hospitals of Leicester Leicester UK"},{"name":"Department of Endocrinology University of Leicester Leicester UK"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"311","published-online":{"date-parts":[[2021,1,11]]},"reference":[{"key":"e_1_2_7_2_1","doi-asserted-by":"publisher","DOI":"10.1210\/jc.2017-00131"},{"key":"e_1_2_7_3_1","doi-asserted-by":"publisher","DOI":"10.1097\/00005768-199705000-00037"},{"issue":"5","key":"e_1_2_7_4_1","doi-asserted-by":"crossref","first-page":"S219","DOI":"10.1016\/j.fertnstert.2008.08.038","article-title":"Current evaluation of amenorrhea","volume":"90","year":"2008","journal-title":"Fertil Steril"},{"key":"e_1_2_7_5_1","doi-asserted-by":"publisher","DOI":"10.1055\/s-0037-1603581"},{"key":"e_1_2_7_6_1","doi-asserted-by":"publisher","DOI":"10.1210\/jcem-68-2-301"},{"key":"e_1_2_7_7_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.mce.2019.110579"},{"key":"e_1_2_7_8_1","doi-asserted-by":"publisher","DOI":"10.1016\/S0015-0282(99)00601-9"},{"key":"e_1_2_7_9_1","doi-asserted-by":"publisher","DOI":"10.1093\/bfgp\/elw037"},{"key":"e_1_2_7_10_1","doi-asserted-by":"publisher","DOI":"10.1056\/NEJMoa0911064"},{"key":"e_1_2_7_11_1","doi-asserted-by":"publisher","DOI":"10.1016\/S0015-0282(16)56165-2"},{"key":"e_1_2_7_12_1","doi-asserted-by":"publisher","DOI":"10.1210\/endo-127-2-849"},{"key":"e_1_2_7_13_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.ijdevneu.2018.08.003"},{"key":"e_1_2_7_14_1","doi-asserted-by":"publisher","DOI":"10.1210\/jcem-68-3-523"},{"key":"e_1_2_7_15_1","doi-asserted-by":"publisher","DOI":"10.1111\/j.1365-2826.2006.01450.x"},{"key":"e_1_2_7_16_1","doi-asserted-by":"publisher","DOI":"10.1210\/jcem-70-2-311"},{"key":"e_1_2_7_17_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.cell.2019.05.048"},{"key":"e_1_2_7_18_1","doi-asserted-by":"publisher","DOI":"10.1152\/ajpregu.2001.280.2.R563"},{"key":"e_1_2_7_19_1","doi-asserted-by":"publisher","DOI":"10.1016\/S0091-3057(83)80003-3"},{"key":"e_1_2_7_20_1","doi-asserted-by":"publisher","DOI":"10.1097\/JSM.0000000000000085"},{"key":"e_1_2_7_21_1","doi-asserted-by":"publisher","DOI":"10.2165\/00007256-200535090-00002"},{"key":"e_1_2_7_22_1","doi-asserted-by":"publisher","DOI":"10.4085\/1062-6050-43.1.80"},{"key":"e_1_2_7_23_1","doi-asserted-by":"publisher","DOI":"10.1056\/NEJMoa040388"},{"key":"e_1_2_7_24_1","doi-asserted-by":"publisher","DOI":"10.1371\/journal.pone.0058698"},{"key":"e_1_2_7_25_1","doi-asserted-by":"publisher","DOI":"10.1093\/humrep\/deq375"},{"key":"e_1_2_7_26_1","doi-asserted-by":"publisher","DOI":"10.1016\/S2213-8587(13)70180-3"},{"key":"e_1_2_7_27_1","doi-asserted-by":"publisher","DOI":"10.1155\/2018\/7965071"},{"key":"e_1_2_7_28_1","doi-asserted-by":"publisher","DOI":"10.1186\/1550-2783-10-34"},{"key":"e_1_2_7_29_1","doi-asserted-by":"publisher","DOI":"10.1210\/jc.2011-2607"},{"key":"e_1_2_7_30_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.bone.2009.03.668"},{"key":"e_1_2_7_31_1","doi-asserted-by":"publisher","DOI":"10.1210\/clinem\/dgz103"},{"issue":"1","key":"e_1_2_7_32_1","first-page":"25","article-title":"Nutritional and endocrine\u2010metabolic aberrations in women with functional hypothalamic amenorrhea","volume":"83","author":"Laughlin GA","year":"1998","journal-title":"J Clin Endocrinol Metab"},{"key":"e_1_2_7_33_1","doi-asserted-by":"publisher","DOI":"10.1210\/jcem.86.3.7361"},{"key":"e_1_2_7_34_1","doi-asserted-by":"publisher","DOI":"10.1249\/00005768-199410000-00007"},{"issue":"3","key":"e_1_2_7_35_1","first-page":"95","article-title":"Influence of intensive exercise on insulin\u2010like growth factor I, thyroid and steroid hormones in female gymnasts","volume":"1","author":"Jahreis G","year":"1991","journal-title":"Growth Regul"},{"key":"e_1_2_7_36_1","doi-asserted-by":"publisher","DOI":"10.1016\/S0015-0282(97)00393-2"},{"key":"e_1_2_7_37_1","doi-asserted-by":"publisher","DOI":"10.1016\/1054-139X(95)00229-L"},{"key":"e_1_2_7_38_1","doi-asserted-by":"publisher","DOI":"10.1136\/bjsports-2015-095735"},{"key":"e_1_2_7_39_1","doi-asserted-by":"publisher","DOI":"10.1210\/jc.2002-020369"},{"key":"e_1_2_7_40_1","doi-asserted-by":"publisher","DOI":"10.1126\/science.185.4155.949"},{"key":"e_1_2_7_41_1","doi-asserted-by":"publisher","DOI":"10.1210\/jc.2004-0723"},{"key":"e_1_2_7_42_1","doi-asserted-by":"publisher","DOI":"10.1073\/pnas.1834399100"},{"key":"e_1_2_7_43_1","doi-asserted-by":"publisher","DOI":"10.1056\/NEJMoa035322"},{"key":"e_1_2_7_44_1","doi-asserted-by":"publisher","DOI":"10.1111\/j.1460-9568.2010.07239.x"},{"key":"e_1_2_7_45_1","doi-asserted-by":"publisher","DOI":"10.1159\/000356903"},{"key":"e_1_2_7_46_1","doi-asserted-by":"publisher","DOI":"10.1172\/JCI139681"},{"key":"e_1_2_7_47_1","doi-asserted-by":"publisher","DOI":"10.1210\/en.2005-0337"},{"key":"e_1_2_7_48_1","doi-asserted-by":"publisher","DOI":"10.1210\/en.2013-1331"},{"key":"e_1_2_7_49_1","doi-asserted-by":"publisher","DOI":"10.1210\/en.2013-1268"},{"key":"e_1_2_7_50_1","article-title":"The Effects of Kisspeptin on Brain Response to Food Images and Psychometric Parameters of Appetite in Healthy Men","author":"Yang L","year":"2020","journal-title":"J Clin Endocrinol Metab"},{"key":"e_1_2_7_51_1","doi-asserted-by":"publisher","DOI":"10.1262\/jrd.18146"},{"key":"e_1_2_7_52_1","doi-asserted-by":"publisher","DOI":"10.1007\/s12020-020-02481-4"},{"key":"e_1_2_7_53_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.neulet.2009.05.060"},{"key":"e_1_2_7_54_1","doi-asserted-by":"publisher","DOI":"10.1530\/JOE-12-0054"},{"key":"e_1_2_7_55_1","doi-asserted-by":"publisher","DOI":"10.1530\/EC-20-0068"},{"key":"e_1_2_7_56_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.physbeh.2014.05.021"},{"key":"e_1_2_7_57_1","doi-asserted-by":"publisher","DOI":"10.1073\/pnas.0901176106"},{"key":"e_1_2_7_58_1","doi-asserted-by":"publisher","DOI":"10.1093\/humrep\/des326"},{"key":"e_1_2_7_59_1","unstructured":"Recommendations | Fertility problems: assessment and treatment | Guidance | NICE."},{"key":"e_1_2_7_60_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.fertnstert.2020.08.064"},{"key":"e_1_2_7_61_1","doi-asserted-by":"publisher","DOI":"10.1111\/j.1749-6632.2010.05663.x"},{"issue":"1","key":"e_1_2_7_62_1","first-page":"45","article-title":"The diagnosis and treatment of stress\u2010induced anovulation","volume":"57","author":"Berga SL","year":"2005","journal-title":"Minerva Ginecol"},{"key":"e_1_2_7_63_1","doi-asserted-by":"publisher","DOI":"10.1074\/jbc.M104847200"},{"key":"e_1_2_7_64_1","doi-asserted-by":"publisher","DOI":"10.1210\/jc.2011-1408"},{"key":"e_1_2_7_65_1","doi-asserted-by":"publisher","DOI":"10.1016\/S1359-6349(10)71058-2"},{"key":"e_1_2_7_66_1","doi-asserted-by":"publisher","DOI":"10.1074\/jbc.M102743200"},{"key":"e_1_2_7_67_1","doi-asserted-by":"publisher","DOI":"10.1210\/jc.2012-1282"},{"key":"e_1_2_7_68_1","doi-asserted-by":"publisher","DOI":"10.1210\/jc.2009-0406"},{"key":"e_1_2_7_69_1","doi-asserted-by":"publisher","DOI":"10.1210\/jc.2013-1569"},{"key":"e_1_2_7_70_1","doi-asserted-by":"publisher","DOI":"10.1038\/clpt.2010.204"},{"key":"e_1_2_7_71_1","doi-asserted-by":"publisher","DOI":"10.1073\/pnas.1015674108"}],"container-title":["Clinical Endocrinology"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/onlinelibrary.wiley.com\/doi\/pdf\/10.1111\/cen.14399","content-type":"application\/pdf","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/onlinelibrary.wiley.com\/doi\/full-xml\/10.1111\/cen.14399","content-type":"application\/xml","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/onlinelibrary.wiley.com\/doi\/pdf\/10.1111\/cen.14399","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2023,8,28]],"date-time":"2023-08-28T00:23:15Z","timestamp":1693182195000},"score":1,"resource":{"primary":{"URL":"https:\/\/onlinelibrary.wiley.com\/doi\/10.1111\/cen.14399"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2021,1,11]]},"references-count":70,"journal-issue":{"issue":"2","published-print":{"date-parts":[[2021,8]]}},"alternative-id":["10.1111\/cen.14399"],"URL":"https:\/\/doi.org\/10.1111\/cen.14399","archive":["Portico"],"relation":{},"ISSN":["0300-0664","1365-2265"],"issn-type":[{"value":"0300-0664","type":"print"},{"value":"1365-2265","type":"electronic"}],"subject":[],"published":{"date-parts":[[2021,1,11]]},"assertion":[{"value":"2020-09-21","order":0,"name":"received","label":"Received","group":{"name":"publication_history","label":"Publication History"}},{"value":"2020-12-15","order":1,"name":"accepted","label":"Accepted","group":{"name":"publication_history","label":"Publication History"}},{"value":"2021-01-11","order":2,"name":"published","label":"Published","group":{"name":"publication_history","label":"Publication History"}}]}}