{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,16]],"date-time":"2026-10-16T09:02:57Z","timestamp":1792141377741,"version":"4.4.0"},"reference-count":105,"publisher":"Portland Press Ltd.","issue":"11","license":[{"start":{"date-parts":[[2023,6,5]],"date-time":"2023-06-05T00:00:00Z","timestamp":1685923200000},"content-version":"vor","delay-in-days":4,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"content-domain":{"domain":["portlandpress.com"],"crossmark-restriction":true},"short-container-title":[],"published-print":{"date-parts":[[2023,6,14]]},"abstract":"<jats:title>Abstract<\/jats:title>\n               <jats:p>Reproductive conditions secondary to disorders of the hypothalamic\u2013pituitary\u2013gonadal (HPG) axis are common and are associated with important health implications and considerable psychosocial impact. Basal and dynamic tests enable interrogation of individual components of the HPG axis, facilitating diagnosis and understanding of the pathophysiology of reproductive disorders. Onset of puberty is controlled by hypothalamic gonadotrophin-releasing hormone (GnRH) neuronal function. To date, a dynamic test of hypothalamic function is not yet available. Therefore, accurate differentiation of pubertal disorders such as constitutional delay of growth and puberty (CDGP) and congenital hypogonadotrophic hypogonadism (CHH) as causes of delayed puberty is challenging due to similar clinical presentations and hormonal profiles. Likewise, although the two commonest reproductive disorders in women, polycystic ovary syndrome (PCOS) and functional hypothalamic amenorrhoea (FHA) have disparate hypothalamic function, oligo\/amenorrhoea frequently poses a diagnostic conundrum owing to the overlap in the criteria used to define both conditions. This review aims to describe pubertal and reproductive disorders secondary to pathologies affecting the HPG axis. Challenges encountered in clinical practice in differentiating pubertal and reproductive conditions are reviewed in conjunction with the utility of baseline and dynamic endocrine tests to interrogate specific components of the HPG axis. We also highlight putative hypothalamic, pituitary, and gonadal markers in development that could improve the diagnosis of patients presenting with disorders of puberty or reproduction.<\/jats:p>","DOI":"10.1042\/cs20220146","type":"journal-article","created":{"date-parts":[[2023,6,5]],"date-time":"2023-06-05T06:20:39Z","timestamp":1685946039000},"page":"863-879","update-policy":"https:\/\/doi.org\/10.1042\/crossmark_policy","source":"Crossref","is-referenced-by-count":47,"title":["Assessing hypothalamic pituitary gonadal function in reproductive disorders"],"prefix":"10.1042","volume":"137","author":[{"given":"Kanyada","family":"Koysombat","sequence":"first","affiliation":[{"name":"1Section of Investigative Medicine, Imperial College London, London, United Kingdom"},{"name":"2Department of Endocrinology, Imperial College Healthcare NHS Trust, London, United Kingdom"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Waljit\u00a0S.","family":"Dhillo","sequence":"additional","affiliation":[{"name":"1Section of Investigative Medicine, Imperial College London, London, United Kingdom"},{"name":"2Department of Endocrinology, Imperial College Healthcare NHS Trust, London, United Kingdom"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Ali","family":"Abbara","sequence":"additional","affiliation":[{"name":"1Section of Investigative Medicine, Imperial College London, London, United Kingdom"},{"name":"2Department of Endocrinology, Imperial College Healthcare NHS Trust, London, United Kingdom"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"288","published-online":{"date-parts":[[2023,6,5]]},"reference":[{"key":"2023060506202718600_B1","doi-asserted-by":"publisher","first-page":"23","DOI":"10.1055\/s-0031-1299594","article-title":"Estrogen Receptor-\u03b2 in the Gonadotropin-Releasing Hormone Neuron","volume":"30","author":"Wolfe","year":"2012","journal-title":"Semin. Reprod. Med."},{"key":"2023060506202718600_B2","doi-asserted-by":"publisher","first-page":"2302","DOI":"10.1210\/en.2011-0096","article-title":"Molecular mapping of the neural pathways linking leptin to the neuroendocrine reproductive axis","volume":"152","author":"Louis","year":"2011","journal-title":"Endocrinology"},{"key":"2023060506202718600_B3","doi-asserted-by":"publisher","first-page":"807","DOI":"10.1016\/j.molmed.2021.05.008","article-title":"Clinical potential of kisspeptin in reproductive health","volume":"27","author":"Abbara","year":"2021","journal-title":"Trends Mol. Med."},{"key":"2023060506202718600_B4","doi-asserted-by":"publisher","first-page":"1761","DOI":"10.1073\/pnas.0409330102","article-title":"Kisspeptin directly stimulates gonadotropin-releasing hormone release via G protein-coupled receptor 54","volume":"102","author":"Messager","year":"2005","journal-title":"Proc. Natl. Acad. Sci."},{"key":"2023060506202718600_B5","doi-asserted-by":"publisher","first-page":"34631","DOI":"10.1074\/jbc.M104847200","article-title":"The Metastasis Suppressor Gene KiSS-1 Encodes Kisspeptins, the Natural Ligands of the Orphan G Protein-coupled Receptor GPR54","volume":"276","author":"Kotani","year":"2001","journal-title":"J. Biol. Chem."},{"key":"2023060506202718600_B6","doi-asserted-by":"publisher","first-page":"10972","DOI":"10.1073\/pnas.1834399100","article-title":"Hypogonadotropic hypogonadism due to loss of function of the KiSS1-derived peptide receptor GPR54","volume":"100","author":"de Roux","year":"2003","journal-title":"Proc. Natl. Acad. Sci."},{"key":"2023060506202718600_B7","doi-asserted-by":"publisher","first-page":"1614","DOI":"10.1056\/NEJMoa035322","article-title":"The GPR54 Gene as a Regulator of Puberty","volume":"349","author":"Seminara","year":"2003","journal-title":"N. Engl. J. Med."},{"key":"2023060506202718600_B8","doi-asserted-by":"publisher","first-page":"203","DOI":"10.1016\/S2213-8587(22)00339-4","article-title":"Molecular basis of normal and pathological puberty: from basic mechanisms to clinical implications","volume":"11","author":"Argente","year":"2023","journal-title":"Lancet Diab. Endocrinol."},{"key":"2023060506202718600_B9","doi-asserted-by":"publisher","first-page":"709","DOI":"10.1056\/NEJMoa073443","article-title":"A GPR54-activating mutation in a patient with central precocious puberty","volume":"358","author":"Teles","year":"2008","journal-title":"N. Engl. J. Med."},{"key":"2023060506202718600_B10","doi-asserted-by":"publisher","DOI":"10.3389\/fendo.2022.951938","article-title":"Kisspeptin-neuron control of LH pulsatility and ovulation","volume":"13","author":"Stevenson","year":"2022","journal-title":"Front Endocrinol. (Lausanne)"},{"key":"2023060506202718600_B11","doi-asserted-by":"publisher","first-page":"5752","DOI":"10.1210\/en.2007-0961","article-title":"Kisspeptin Neurons in the Arcuate Nucleus of the Ewe Express Both Dynorphin A and Neurokinin B","volume":"148","author":"Goodman","year":"2007","journal-title":"Endocrinology"},{"key":"2023060506202718600_B12","doi-asserted-by":"publisher","first-page":"631","DOI":"10.1126\/science.100883","article-title":"Hypophysial responses to continuous and intermittent delivery of hypothalamic gonadotropin-releasing hormone","volume":"202","author":"Belchetz","year":"1978","journal-title":"Science (1979)"},{"key":"2023060506202718600_B13","doi-asserted-by":"publisher","first-page":"729","DOI":"10.1507\/endocrj.K09E-185","article-title":"GnRH Pulsatility, the Pituitary Response and Reproductive Dysfunction","volume":"56","author":"Tsutsumi","year":"2009","journal-title":"Endocr. J."},{"key":"2023060506202718600_B14","doi-asserted-by":"publisher","first-page":"669","DOI":"10.1210\/er.2018-00116","article-title":"Clinical Management of Congenital Hypogonadotropic Hypogonadism","volume":"40","author":"Young","year":"2019","journal-title":"Endocr. Rev."},{"key":"2023060506202718600_B15","doi-asserted-by":"publisher","first-page":"152","DOI":"10.1016\/j.coemr.2020.08.003","article-title":"Makorin RING finger protein 3 and central precocious puberty","volume":"14","author":"Maione","year":"2020","journal-title":"Curr. Opin. Endocr. Metab. Res."},{"key":"2023060506202718600_B16","doi-asserted-by":"publisher","first-page":"443","DOI":"10.1056\/NEJMcp1109290","article-title":"Delayed Puberty","volume":"366","author":"Palmert","year":"2012","journal-title":"N. Engl. J. Med."},{"key":"2023060506202718600_B17","doi-asserted-by":"publisher","first-page":"1285","DOI":"10.1210\/er.2018-00248","article-title":"Delayed Puberty\u2014Phenotypic Diversity, Molecular Genetic Mechanisms, and Recent Discoveries","volume":"40","author":"Howard","year":"2019","journal-title":"Endocr. Rev."},{"key":"2023060506202718600_B18","doi-asserted-by":"publisher","first-page":"1739","DOI":"10.1210\/clinem\/dgac054","article-title":"An Approach to the Patient With Delayed Puberty","volume":"107","author":"Harrington","year":"2022","journal-title":"J. Clin. Endocrinol. Metab."},{"key":"2023060506202718600_B19","doi-asserted-by":"publisher","first-page":"473","DOI":"10.1111\/cen.14606","article-title":"Genetics of pubertal delay","volume":"97","author":"Saengkaew","year":"2022","journal-title":"Clin. Endocrinol. (Oxf)"},{"key":"2023060506202718600_B20","doi-asserted-by":"publisher","first-page":"3056","DOI":"10.1210\/jc.2012-1598","article-title":"Distinguishing Constitutional Delay of Growth and Puberty from Isolated Hypogonadotropic Hypogonadism: Critical Appraisal of Available Diagnostic Tests","volume":"97","author":"Harrington","year":"2012","journal-title":"J. Clin. Endocrinol. Metab."},{"key":"2023060506202718600_B21","doi-asserted-by":"publisher","first-page":"547","DOI":"10.1038\/nrendo.2015.112","article-title":"European Consensus Statement on congenital hypogonadotropic hypogonadism\u2014pathogenesis, diagnosis and treatment","volume":"11","author":"Boehm","year":"2015","journal-title":"Nat. Rev. Endocrinol."},{"key":"2023060506202718600_B22","doi-asserted-by":"publisher","first-page":"2198","DOI":"10.1210\/jc.2013-1024","article-title":"Treatment and Outcomes of Precocious Puberty: An Update","volume":"98","author":"Fuqua","year":"2013","journal-title":"J. Clin. Endocrinol. Metab."},{"key":"2023060506202718600_B23","doi-asserted-by":"publisher","first-page":"542","DOI":"10.1111\/cen.14475","article-title":"Central precocious puberty: Recent advances in understanding the aetiology and in the clinical approach","volume":"95","author":"Maione","year":"2021","journal-title":"Clin. Endocrinol. (Oxf)"},{"key":"2023060506202718600_B24","doi-asserted-by":"publisher","first-page":"S219","DOI":"10.1016\/j.fertnstert.2008.08.038","article-title":"Current evaluation of amenorrhea","volume":"90","author":"The Practice Committee of the American Society for Reproductive Medicine","year":"2008","journal-title":"Fertil. Steril."},{"key":"2023060506202718600_B25","doi-asserted-by":"publisher","first-page":"926","DOI":"10.1093\/humrep\/dew027","article-title":"ESHRE Guideline: management of women with premature ovarian insufficiency","volume":"31","year":"2016","journal-title":"Hum. Reprod."},{"key":"2023060506202718600_B26","doi-asserted-by":"publisher","first-page":"105","DOI":"10.1159\/000489264","article-title":"Interpretation of Serum Gonadotropin Levels in Hyperprolactinaemia","volume":"107","author":"Abbara","year":"2018","journal-title":"Neuroendocrinology"},{"key":"2023060506202718600_B27","doi-asserted-by":"publisher","first-page":"328","DOI":"10.1159\/000124459","article-title":"Hyperprolactinemia alters the frequency and amplitude of pulsatile luteinizing hormone secretion in the ovariectomized rat","volume":"42","author":"Cohen-Becker","year":"1986","journal-title":"Neuroendocrinology"},{"key":"2023060506202718600_B28","doi-asserted-by":"publisher","first-page":"350","DOI":"10.1159\/000124844","article-title":"Suppression of Pulsatile LH Secretion, Pituitary GnRH Receptor Content and Pituitary Responsiveness to GnRH by Hyperprolactinemia in the Male Rat","volume":"46","author":"Fox","year":"1987","journal-title":"Neuroendocrinology"},{"key":"2023060506202718600_B29","doi-asserted-by":"publisher","first-page":"1143","DOI":"10.1016\/S0015-0282(16)57176-3","article-title":"Mechanism of anovulation in hyperprolactinemic amenorrhea determined by pulsatile gonadotropin-releasing hormone injection combined with human chorionic gonadotropin","volume":"62","author":"Matsuzaki","year":"1994","journal-title":"Fertil. Steril."},{"key":"2023060506202718600_B30","doi-asserted-by":"publisher","first-page":"364","DOI":"10.1016\/j.fertnstert.2018.05.004","article-title":"Recommendations from the international evidence-based guideline for the assessment and management of polycystic ovary syndrome","volume":"110","author":"Teede","year":"2018","journal-title":"Fertil. Steril."},{"key":"2023060506202718600_B31","doi-asserted-by":"publisher","first-page":"19","DOI":"10.1016\/j.fertnstert.2003.10.004","article-title":"Revised 2003 consensus on diagnostic criteria and long-term health risks related to polycystic ovary syndrome","volume":"81","author":"Rotterdam ESHRE\/ASRM-Sponsored PCOS Consensus Workshop Group","year":"2004","journal-title":"Fertil. Steril."},{"key":"2023060506202718600_B32","doi-asserted-by":"publisher","first-page":"467","DOI":"10.1210\/er.2015-1104","article-title":"The Pathogenesis of Polycystic Ovary Syndrome (PCOS): The Hypothesis of PCOS as Functional Ovarian Hyperandrogenism Revisited","volume":"37","author":"Rosenfield","year":"2016","journal-title":"Endocr. Rev."},{"key":"2023060506202718600_B33","doi-asserted-by":"publisher","first-page":"1413","DOI":"10.1210\/jc.2017-00131","article-title":"Functional Hypothalamic Amenorrhea: An Endocrine Society Clinical Practice Guideline","volume":"102","author":"Gordon","year":"2017","journal-title":"J. Clin. Endocrinol. Metab."},{"key":"2023060506202718600_B34","doi-asserted-by":"publisher","first-page":"589","DOI":"10.1515\/JPEM.2002.15.5.589","article-title":"Basal Ultrasensitive LH Assay: A Useful Tool in the Early Diagnosis of Male Pubertal Delay?","volume":"15","author":"Sequera","year":"2002","journal-title":"J. Pediatr. Endocrinol. Metab."},{"key":"2023060506202718600_B35","doi-asserted-by":"publisher","first-page":"295","DOI":"10.1530\/EJE-11-0720","article-title":"The utility of basal serum LH in prediction of central precocious puberty in girls","volume":"166","author":"Pasternak","year":"2012","journal-title":"Eur. J. Endocrinol."},{"key":"2023060506202718600_B36","doi-asserted-by":"publisher","first-page":"851","DOI":"10.1055\/s-0032-1321905","article-title":"Utility of Basal Luteinizing Hormone Levels for Detecting Central Precocious Puberty in Girls","volume":"44","author":"Lee","year":"2012","journal-title":"Horm. Metab. Res."},{"key":"2023060506202718600_B37","doi-asserted-by":"publisher","first-page":"1393","DOI":"10.1210\/jc.2010-2745","article-title":"Diagnostic Work-Up of 449 Consecutive Girls Who Were Referred to be Evaluated for Precocious Puberty","volume":"96","author":"Mogensen","year":"2011","journal-title":"J. Clin. Endocrinol. Metab."},{"key":"2023060506202718600_B38","doi-asserted-by":"publisher","first-page":"685","DOI":"10.1016\/j.bpobgyn.2004.05.004","article-title":"The pathophysiology of polycystic ovary syndrome: trying to understand PCOS and its endocrinology","volume":"18","author":"Balen","year":"2004","journal-title":"Best Pract. Res. Clin. Obstet. Gynaecol."},{"key":"2023060506202718600_B39","doi-asserted-by":"publisher","first-page":"2248","DOI":"10.1210\/jcem.82.7.4105","article-title":"Determinants of Abnormal Gonadotropin Secretion in Clinically Defined Women with Polycystic Ovary Syndrome1","volume":"82","author":"Taylor","year":"1997","journal-title":"J. Clin. Endocrinol. Metab."},{"key":"2023060506202718600_B40","doi-asserted-by":"publisher","first-page":"165","DOI":"10.1210\/jcem-66-1-165","article-title":"Hyperfunction of the Hypothalamic-Pituitary Axis in Women with Polycystic Ovarian Disease: Indirect Evidence for Partial Gonadotroph Desensitization*","volume":"66","author":"Waldstreicher","year":"1988","journal-title":"J. Clin. Endocrinol. Metab."},{"key":"2023060506202718600_B41","doi-asserted-by":"publisher","first-page":"145","DOI":"10.1530\/EJE-12-0655","article-title":"Association between menstrual cycle irregularities and endocrine and metabolic characteristics of the polycystic ovary syndrome","volume":"168","author":"Panidis","year":"2013","journal-title":"Eur. J. Endocrinol."},{"key":"2023060506202718600_B42","doi-asserted-by":"publisher","first-page":"e2008","DOI":"10.1210\/clinem\/dgaa116","article-title":"Anti-M\u00fcllerian Hormone and Ovarian Morphology in Women With Hypothalamic Hypogonadism","volume":"105","author":"Alemyar","year":"2020","journal-title":"J. Clin. Endocrinol. Metab."},{"key":"2023060506202718600_B43","doi-asserted-by":"publisher","first-page":"e92","DOI":"10.1007\/BF03327602","article-title":"Disturbances in gonadal axis in women with anorexia nervosa","volume":"12","author":"Tomova","year":"2007","journal-title":"Eat. Weight Dis."},{"key":"2023060506202718600_B44","doi-asserted-by":"publisher","first-page":"579","DOI":"10.1111\/cen.13934","article-title":"Exploration of the role of anti-Mullerian hormone and LH\/FSH ratio in diagnosis of polycystic ovary syndrome","volume":"90","author":"Le","year":"2019","journal-title":"Clin. Endocrinol. (Oxf)"},{"key":"2023060506202718600_B45","first-page":"35","article-title":"Polycystic ovarian syndrome: the correlation between the LH\/FSH ratio and disease manifestations","volume":"12","author":"Alnakash","year":"2007","journal-title":"Middle East Fertil. Soc. J."},{"key":"2023060506202718600_B46","doi-asserted-by":"publisher","first-page":"289","DOI":"10.5455\/medarh.2020.74.289-293","article-title":"Follicle Stimulating Hormone (LH: FSH) Ratio in Polycystic Ovary Syndrome (PCOS) - Obese vs. Non- Obese Women","volume":"74","author":"Saadia","year":"2020","journal-title":"Medical Archives"},{"key":"2023060506202718600_B47","doi-asserted-by":"publisher","first-page":"1229","DOI":"10.1210\/jcem-72-6-1229","article-title":"Patterns of Pulsatile luteinizing hormone and follicle-stimulating hormone secretion in prepubertal (midchildhood) boys and girls and patients with idiopathic hypogonadotropic hypogonadism (Kallmann's syndrome): a study using an ultrasensitive time-resolved immunofluorometric assay","volume":"72","author":"Wu","year":"1991","journal-title":"J. Clin. Endocrinol. Metab."},{"key":"2023060506202718600_B48","doi-asserted-by":"publisher","first-page":"1251","DOI":"10.1210\/jcem-71-5-1251","article-title":"Gonadotropin secretory dynamics during puberty in normal girls and boys","volume":"71","author":"Oerter","year":"1990","journal-title":"J. Clin. Endocrinol. Metab."},{"key":"2023060506202718600_B49","doi-asserted-by":"publisher","first-page":"282","DOI":"10.1056\/NEJM197308092890602","article-title":"Twenty-four hour patterns of plasma luteinizing hormone and follicle-stimulating hormone in sexual precocity","volume":"289","author":"Boyar","year":"1973","journal-title":"N. Engl. J. Med."},{"key":"2023060506202718600_B50","doi-asserted-by":"publisher","first-page":"190","DOI":"10.1007\/BF00446063","article-title":"Studies of gonadotrophin pulsatility and pelvic ultrasound examinations distinguish between isolated premature thelarche and central precocious puberty","volume":"145","author":"Stanhope","year":"1986","journal-title":"Eur. J. Pediatr."},{"key":"2023060506202718600_B51","doi-asserted-by":"publisher","first-page":"1905","DOI":"10.1210\/jc.84.6.1905","article-title":"Neuroendocrine abnormalities in hypothalamic amenorrhea: spectrum, stability, and response to neurotransmitter modulation 1","volume":"84","author":"Perkins","year":"1999","journal-title":"J. Clin. Endocrinol. Metab."},{"key":"2023060506202718600_B52","doi-asserted-by":"publisher","first-page":"755","DOI":"10.1210\/jcem-64-4-755","article-title":"Diurnal patterns of pulsatile luteinizing hormone secretion in hypothalamic amenorrhea: reproducibility and responses to opiate blockade and an \u03b12 -adrenergic agonist*","volume":"64","author":"Khoury","year":"1987","journal-title":"J. Clin. Endocrinol. Metab."},{"key":"2023060506202718600_B53","doi-asserted-by":"publisher","first-page":"1156","DOI":"10.1093\/humrep\/12.6.1156","article-title":"Pulsatile gonadotrophin secretion in women with polycystic ovary syndrome after gonadotrophin-releasing hormone agonist treatment","volume":"12","author":"Cheung","year":"1997","journal-title":"Hum. Reprod."},{"key":"2023060506202718600_B54","first-page":"2854","article-title":"Insulin, somatotropic, and luteinizing hormone axes in lean and obese women with polycystic ovary syndrome: common and distinct features","volume":"81","author":"Morales","year":"1996","journal-title":"J. Clin. Endocrinol. Metab."},{"key":"2023060506202718600_B55","doi-asserted-by":"publisher","first-page":"239","DOI":"10.1111\/cen.14402","article-title":"Clinical and biochemical discriminants between functional hypothalamic amenorrhoea (FHA) and polycystic ovary syndrome (PCOS)","volume":"95","author":"Phylactou","year":"2021","journal-title":"Clin. Endocrinol. (Oxf)"},{"key":"2023060506202718600_B56","doi-asserted-by":"publisher","first-page":"941","DOI":"10.1210\/jcem-59-5-941","article-title":"Abnormal Patterns of Pulsatile Luteinizing Hormone Secretion in Women with Hyperprolactinemia and Amenorrhea: Responses to Bromocriptine*","volume":"59","author":"Sauder","year":"1984","journal-title":"J. Clin. Endocrinol. Metab."},{"key":"2023060506202718600_B57","doi-asserted-by":"publisher","first-page":"494","DOI":"10.1001\/archpedi.1985.02140070068036","article-title":"GnRH and HCG Tests Are Both Necessary in Differential Diagnosis of Male Delayed Puberty","volume":"139","author":"Dunkel","year":"1985","journal-title":"Arch. Pediatr. Adolesc. Med."},{"key":"2023060506202718600_B58","doi-asserted-by":"publisher","first-page":"95","DOI":"10.1210\/edrv-7-1-95","article-title":"Pharmacokinetics of gonadotropin-releasing hormone and its analogs","volume":"7","author":"Handelsman","year":"1986","journal-title":"Endocr. Rev."},{"key":"2023060506202718600_B59","doi-asserted-by":"publisher","first-page":"391","DOI":"10.1146\/annurev.med.45.1.391","article-title":"Gonadotropin-releasing hormone and its analogs","volume":"45","author":"Conn","year":"1994","journal-title":"Annu. Rev. Med."},{"key":"2023060506202718600_B60","first-page":"2980","article-title":"Gonadotropin releasing hormone agonist (nafarelin) test to differentiate gonadotropin deficiency from constitutionally delayed puberty in teen-age boys\u2013a clinical research center study","volume":"80","author":"Ghai","year":"1995","journal-title":"J. Clin. Endocrinol. Metab."},{"key":"2023060506202718600_B61","doi-asserted-by":"publisher","first-page":"100","DOI":"10.1111\/cen.12613","article-title":"Inhibin B plus LH vs GnRH agonist test for distinguishing constitutional delay of growth and puberty from isolated hypogonadotropic hypogonadism in boys","volume":"82","author":"Binder","year":"2015","journal-title":"Clin. Endocrinol. (Oxf)"},{"key":"2023060506202718600_B62","doi-asserted-by":"publisher","first-page":"89","DOI":"10.1016\/j.jpeds.2005.08.045","article-title":"Evaluation of the buserelin stimulation test in diagnosing gonadotropin deficiency in males with delayed puberty","volume":"148","author":"Wilson","year":"2006","journal-title":"J. Pediatr."},{"key":"2023060506202718600_B63","doi-asserted-by":"publisher","first-page":"1","DOI":"10.1159\/000185421","article-title":"Effectiveness and limitations of the use of the gonadotropin-releasing hormone agonist leuprolide acetate in the diagnosis of delayed puberty in males","volume":"48","author":"Lanes","year":"1997","journal-title":"Horm. Res."},{"key":"2023060506202718600_B64","doi-asserted-by":"publisher","first-page":"2366","DOI":"10.1056\/NEJMcp0800459","article-title":"Precocious puberty","volume":"358","author":"Carel","year":"2008","journal-title":"N. Engl. J. Med."},{"key":"2023060506202718600_B65","doi-asserted-by":"publisher","first-page":"398","DOI":"10.1111\/j.1365-2265.2012.04517.x","article-title":"High diagnostic accuracy of subcutaneous Triptorelin test compared with GnRH test for diagnosing central precocious puberty in girls","volume":"78","author":"Freire","year":"2013","journal-title":"Clin. Endocrinol. (Oxf)"},{"key":"2023060506202718600_B66","article-title":"Guideline: GnRH analogue stimulation testing to investigate precocious puberty","author":"Alvi","year":"2021"},{"key":"2023060506202718600_B67","doi-asserted-by":"publisher","first-page":"159","DOI":"10.1210\/jcem-43-1-159","article-title":"Secretion Rates of LH and FSH During Infusion of LH-FSH\/RH in Normal Women and in Patients with Secondary Amenorrhea: Suggestive Evidence for Two Pools of LH and FSH","volume":"43","author":"Koninckx","year":"1976","journal-title":"J. Clin. Endocrinol. Metab."},{"key":"2023060506202718600_B68","doi-asserted-by":"publisher","first-page":"67","DOI":"10.1111\/j.1365-2265.2004.01945.x","article-title":"Relationship of GnRH-stimulated LH release to episodic LH secretion and baseline endocrine-metabolic measures in women with polycystic ovary syndrome","volume":"60","author":"Patel","year":"2004","journal-title":"Clin. Endocrinol. (Oxf)"},{"key":"2023060506202718600_B69","first-page":"120","article-title":"The utility of the gonadotrophin releasing hormone (GnRH) test in the diagnosis of polycystic ovary syndrome (PCOS)","volume":"62","author":"Lewandowski","year":"2011","journal-title":"Endokrynol. Pol."},{"key":"2023060506202718600_B70","doi-asserted-by":"publisher","DOI":"10.1210\/clinem\/dgad026","article-title":"Endocrine Responses to Triptorelin in Healthy Women, Women With Polycystic Ovary Syndrome, and Women With Hypothalamic Amenorrhea","author":"Abbara","year":"2023","journal-title":"J. Clin. Endocrinol. Metab."},{"key":"2023060506202718600_B71","doi-asserted-by":"publisher","first-page":"559","DOI":"10.1056\/NEJM198903023200904","article-title":"Pituitary-ovarian responses to nafarelin testing in the polycystic ovary syndrome","volume":"320","author":"Barnes","year":"2010","journal-title":"N. Engl. J. Med."},{"key":"2023060506202718600_B72","doi-asserted-by":"publisher","first-page":"1416","DOI":"10.1093\/humrep\/12.7.1416","article-title":"A pilot study of the human chorionic gonadotrophin test for ovarian hyperandrogenism","volume":"12","author":"Levrant","year":"1997","journal-title":"Hum. Reprod."},{"key":"2023060506202718600_B73","doi-asserted-by":"publisher","first-page":"E902","DOI":"10.1152\/ajpendo.00415.2003","article-title":"Exaggerated 17-hydroxyprogesterone response to intravenous infusions of recombinant human LH in women with polycystic ovary syndrome","volume":"286","author":"McCartney","year":"2004","journal-title":"Am. J. Physiol.-Endocrinol. Metab."},{"key":"2023060506202718600_B74","doi-asserted-by":"publisher","first-page":"3138","DOI":"10.1093\/humrep\/der291","article-title":"Determination of the source of androgen excess in functionally atypical polycystic ovary syndrome by a short dexamethasone androgen-suppression test and a low-dose ACTH test","volume":"26","author":"Rosenfield","year":"2011","journal-title":"Hum. Reprod."},{"key":"2023060506202718600_B75","doi-asserted-by":"publisher","DOI":"10.3389\/fendo.2022.1076984","article-title":"Insulin-like peptide 3 (INSL3) in congenital hypogonadotrophic hypogonadism (CHH) in boys with delayed puberty and adult men","volume":"13","author":"Abbara","year":"2022","journal-title":"Front Endocrinol. (Lausanne)"},{"key":"2023060506202718600_B76","doi-asserted-by":"publisher","first-page":"882","DOI":"10.1111\/andr.12088","article-title":"Inhibin B, AMH, but not INSL3, IGF1 or DHEAS support differentiation between constitutional delay of growth and puberty and hypogonadotropic hypogonadism","volume":"3","author":"Rohayem","year":"2015","journal-title":"Andrology"},{"key":"2023060506202718600_B77","first-page":"1401","article-title":"Measurement of dimeric inhibin B throughout the human menstrual cycle","volume":"81","author":"Groome","year":"1996","journal-title":"J. Clin. Endocrinol. Metab."},{"key":"2023060506202718600_B78","doi-asserted-by":"publisher","first-page":"101","DOI":"10.1093\/humrep\/deh560","article-title":"The ovarian markers of the FSH insufficiency in functional hypothalamic amenorrhoea","volume":"20","author":"Jonard","year":"2005","journal-title":"Hum. Reprod."},{"key":"2023060506202718600_B79","doi-asserted-by":"publisher","first-page":"5559","DOI":"10.1210\/jc.2002-020546","article-title":"Serum Inhibin B in polycystic ovary syndrome: regulation by insulin and luteinizing hormone","volume":"87","author":"Welt","year":"2002","journal-title":"J. Clin. Endocrinol. Metab."},{"key":"2023060506202718600_B80","doi-asserted-by":"publisher","first-page":"147","DOI":"10.1095\/biolreprod.113.108969","article-title":"INSL3 as a Biomarker of Leydig Cell Functionality","volume":"88","author":"Ivell","year":"2013","journal-title":"Biol. Reprod."},{"key":"2023060506202718600_B81","doi-asserted-by":"publisher","DOI":"10.3389\/fendo.2014.00006","article-title":"Insulin-Like Factor 3 and the HPG Axis in the Male","volume":"5","author":"Ivell","year":"2014","journal-title":"Front. Endocrinol. (Lausanne)"},{"key":"2023060506202718600_B82","doi-asserted-by":"publisher","first-page":"639","DOI":"10.1093\/humupd\/dmy029","article-title":"Insulin-like peptide 3 (INSL3) is a major regulator of female reproductive physiology","volume":"24","author":"Ivell","year":"2018","journal-title":"Hum. Reprod. Update"},{"key":"2023060506202718600_B83","doi-asserted-by":"publisher","first-page":"3093","DOI":"10.1093\/humrep\/det349","article-title":"Circulating insulin-like factor 3 (INSL3) in healthy and infertile women","volume":"28","author":"Anand-Ivell","year":"2013","journal-title":"Hum. Reprod."},{"key":"2023060506202718600_B84","doi-asserted-by":"publisher","first-page":"2066","DOI":"10.1210\/jc.2006-1678","article-title":"Insulin-Like Factor 3: A New Circulating Hormone Related to Luteinizing Hormone-Dependent Ovarian Hyperandrogenism in the Polycystic Ovary Syndrome","volume":"92","author":"Gambineri","year":"2007","journal-title":"J. Clin. Endocrinol. Metab."},{"key":"2023060506202718600_B85","doi-asserted-by":"publisher","DOI":"10.3389\/fendo.2019.00656","article-title":"Anti-M\u00fcllerian hormone (AMH) in the Diagnosis of Menstrual Disturbance Due to Polycystic Ovarian Syndrome","volume":"10","author":"Abbara","year":"2019","journal-title":"Front Endocrinol. (Lausanne)"},{"key":"2023060506202718600_B86","doi-asserted-by":"publisher","first-page":"161","DOI":"10.1016\/j.maturitas.2009.08.003","article-title":"Premature menopause or early menopause: Long-term health consequences","volume":"65","author":"Shuster","year":"2010","journal-title":"Maturitas"},{"key":"2023060506202718600_B87","doi-asserted-by":"publisher","first-page":"327","DOI":"10.1093\/humupd\/dmac045","article-title":"Anti-M\u00fcllerian hormone for the diagnosis and prediction of menopause: a systematic review","volume":"29","author":"Nelson","year":"2023","journal-title":"Hum. Reprod. Update"},{"key":"2023060506202718600_B88","doi-asserted-by":"publisher","first-page":"729","DOI":"10.1210\/jc.2012-3176","article-title":"Modeling Age at Menopause Using Serum Concentration of Anti-Mullerian Hormone","volume":"98","author":"Tehrani","year":"2013","journal-title":"J. Clin. Endocrinol. Metab."},{"key":"2023060506202718600_B89","doi-asserted-by":"publisher","DOI":"10.3389\/fendo.2021.601752","article-title":"Ovarian reserve markers in premature ovarian insufficiency: within different clinical stages and different etiologies","volume":"12","author":"Jiao","year":"2021","journal-title":"Front Endocrinol. (Lausanne)"},{"key":"2023060506202718600_B90","doi-asserted-by":"publisher","first-page":"1587","DOI":"10.1210\/jc.2008-2248","article-title":"Characterization of functionally typical and atypical types of polycystic ovary syndrome","volume":"94","author":"Hirshfeld-Cytron","year":"2009","journal-title":"J. Clin. Endocrinol. Metab."},{"key":"2023060506202718600_B91","doi-asserted-by":"publisher","first-page":"98","DOI":"10.1016\/S0167-4889(97)00019-0","article-title":"The rotational diffusion of LH receptors differs when receptors are occupied by hCG versus LH and is increased by cytochalasin D","volume":"1357","author":"Roess","year":"1997","journal-title":"Biochim. Biophys. Acta."},{"key":"2023060506202718600_B92","doi-asserted-by":"publisher","first-page":"549","DOI":"10.1210\/er.2018-00065","article-title":"Two hormones for one receptor: evolution, biochemistry, actions, and pathophysiology of LH and hCG","volume":"39","author":"Casarini","year":"2018","journal-title":"Endocr. Rev."},{"key":"2023060506202718600_B93","doi-asserted-by":"publisher","first-page":"635","DOI":"10.1007\/s12020-020-02481-4","article-title":"Kisspeptin and LH pulsatility in patients with functional hypothalamic amenorrhea","volume":"70","author":"Podfigurna","year":"2020","journal-title":"Endocrine"},{"key":"2023060506202718600_B94","doi-asserted-by":"publisher","first-page":"141","DOI":"10.1016\/j.appet.2016.09.032","article-title":"Plasma kisspeptin and ghrelin levels are independently correlated with physical activity in patients with anorexia nervosa","volume":"108","author":"Hofmann","year":"2017","journal-title":"Appetite"},{"key":"2023060506202718600_B95","doi-asserted-by":"publisher","DOI":"10.3389\/fendo.2019.00298","article-title":"Kisspeptin and polycystic ovary syndrome","volume":"10","author":"Tang","year":"2019","journal-title":"Front Endocrinol. (Lausanne)"},{"key":"2023060506202718600_B96","doi-asserted-by":"publisher","first-page":"685","DOI":"10.1016\/j.rbmo.2019.04.018","article-title":"Circulatory metastin\/kisspeptin-1 in polycystic ovary syndrome: a systematic review and meta-analysis with diagnostic test accuracy","volume":"39","author":"Varikasuvu","year":"2019","journal-title":"Reprod. Biomed. Online"},{"key":"2023060506202718600_B97","doi-asserted-by":"publisher","first-page":"149","DOI":"10.1007\/s12020-018-1609-1","article-title":"Kisspeptin and LH pulsatile temporal coupling in PCOS patients","volume":"61","author":"Katulski","year":"2018","journal-title":"Endocrine"},{"key":"2023060506202718600_B98","doi-asserted-by":"publisher","first-page":"1","DOI":"10.1155\/2020\/6237141","article-title":"The Correlation between Hormonal Disturbance in PCOS Women and Serum Level of Kisspeptin","volume":"2020","author":"Ibrahim","year":"2020","journal-title":"Int. J. Endocrinol."},{"key":"2023060506202718600_B99","doi-asserted-by":"publisher","first-page":"524","DOI":"10.1111\/j.1365-2265.2009.03575.x","article-title":"Kisspeptin serum levels in girls with central precocious puberty","volume":"71","author":"de Vries","year":"2009","journal-title":"Clin. Endocrinol. (Oxf)"},{"key":"2023060506202718600_B100","doi-asserted-by":"publisher","first-page":"589","DOI":"10.1159\/000515660","article-title":"Kisspeptin Levels in Girls with Precocious Puberty: A Systematic Review and Meta-Analysis","volume":"93","author":"Cintra","year":"2020","journal-title":"Horm. Res. Paediatr."},{"key":"2023060506202718600_B101","doi-asserted-by":"publisher","first-page":"e99109","DOI":"10.1172\/jci.insight.99109","article-title":"Divergent responses to kisspeptin in children with delayed puberty","volume":"3","author":"Chan","year":"2018","journal-title":"JCI Insight"},{"key":"2023060506202718600_B102","doi-asserted-by":"publisher","first-page":"e2717","DOI":"10.1210\/clinem\/dgaa162","article-title":"Using kisspeptin to predict pubertal outcomes for youth with pubertal delay","volume":"105","author":"Chan","year":"2020","journal-title":"J. Clin. Endocrinol. Metab."},{"key":"2023060506202718600_B103","doi-asserted-by":"publisher","first-page":"1176","DOI":"10.1159\/000513248","article-title":"Kisspeptin-54 accurately identifies hypothalamic gonadotropin-releasing hormone neuronal dysfunction in men with congenital hypogonadotropic hypogonadism","volume":"111","author":"Abbara","year":"2021","journal-title":"Neuroendocrinology"},{"key":"2023060506202718600_B104","doi-asserted-by":"publisher","first-page":"8804","DOI":"10.1021\/acs.jmedchem.6b00379","article-title":"Design and Synthesis of an Investigational Nonapeptide KISS1 Receptor (KISS1R) Agonist, Ac-d-Tyr-Hydroxyproline (Hyp)-Asn-Thr-Phe-azaGly-Leu-Arg(Me)-Trp-NH 2 (TAK-448), with Highly Potent Testosterone-Suppressive Activity and Excellent Water Solubility","volume":"59","author":"Nishizawa","year":"2016","journal-title":"J. Med. Chem."},{"key":"2023060506202718600_B105","doi-asserted-by":"publisher","first-page":"6739","DOI":"10.1172\/JCI139681","article-title":"Kisspeptin receptor agonist has therapeutic potential for female reproductive disorders","volume":"130","author":"Abbara","year":"2020","journal-title":"J. Clin. Invest."}],"container-title":["Clinical Science"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/portlandpress.com\/clinsci\/article-pdf\/137\/11\/863\/947004\/cs-2022-0146c.pdf","content-type":"application\/pdf","content-version":"vor","intended-application":"syndication"},{"URL":"https:\/\/portlandpress.com\/clinsci\/article-pdf\/137\/11\/863\/947004\/cs-2022-0146c.pdf","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2023,6,5]],"date-time":"2023-06-05T06:20:47Z","timestamp":1685946047000},"score":1,"resource":{"primary":{"URL":"https:\/\/portlandpress.com\/clinsci\/article\/137\/11\/863\/233116\/Assessing-hypothalamic-pituitary-gonadal-function"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2023,6]]},"references-count":105,"journal-issue":{"issue":"11","published-print":{"date-parts":[[2023,6,14]]}},"URL":"https:\/\/doi.org\/10.1042\/cs20220146","relation":{},"ISSN":["0143-5221","1470-8736"],"issn-type":[{"value":"0143-5221","type":"print"},{"value":"1470-8736","type":"electronic"}],"subject":[],"published-other":{"date-parts":[[2023,6]]},"published":{"date-parts":[[2023,6]]}}}