{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,8,28]],"date-time":"2026-08-28T23:30:47Z","timestamp":1787959847641,"version":"build-2784847793"},"reference-count":80,"publisher":"Springer Science and Business Media LLC","issue":"2","license":[{"start":{"date-parts":[[2019,1,30]],"date-time":"2019-01-30T00:00:00Z","timestamp":1548806400000},"content-version":"tdm","delay-in-days":0,"URL":"http:\/\/www.springer.com\/tdm"}],"content-domain":{"domain":["link.springer.com"],"crossmark-restriction":false},"short-container-title":["Endocrine"],"published-print":{"date-parts":[[2019,5]]},"DOI":"10.1007\/s12020-019-01850-y","type":"journal-article","created":{"date-parts":[[2019,1,30]],"date-time":"2019-01-30T05:52:42Z","timestamp":1548827562000},"page":"209-219","update-policy":"https:\/\/doi.org\/10.1007\/springer_crossmark_policy","source":"Crossref","is-referenced-by-count":15,"title":["Relative hyperestrogenism in Klinefelter Syndrome: results from a meta-analysis"],"prefix":"10.1007","volume":"64","author":[{"given":"Daniele","family":"Santi","sequence":"first","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Sara","family":"De Vincentis","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Sara","family":"Scaltriti","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-8169-0696","authenticated-orcid":false,"given":"Vincenzo","family":"Rochira","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"297","published-online":{"date-parts":[[2019,1,30]]},"reference":[{"key":"1850_CR1","doi-asserted-by":"publisher","first-page":"615","DOI":"10.1210\/jcem-2-11-615","volume":"2","author":"HF Klinefelter","year":"1942","unstructured":"H.F. Klinefelter, E.C. Reifenstein, F. Albright, Syndrome characterized by gynecomastia, aspermatogenesis without Leydigism, increased excretion of follicle stimulating hormone. J. Clin. Endocrinol. 2, 615\u2013627 (1942)","journal-title":"J. Clin. Endocrinol."},{"issue":"12","key":"1850_CR2","doi-asserted-by":"publisher","first-page":"1309","DOI":"10.1001\/archinte.158.12.1309","volume":"158","author":"CM Smyth","year":"1998","unstructured":"C.M. Smyth, W.J. Bremner, Klinefelter syndrome. Arch. Intern. Med. 158(12), 1309\u20131314 (1998)","journal-title":"Arch. Intern. Med."},{"issue":"2","key":"1850_CR3","doi-asserted-by":"publisher","first-page":"123","DOI":"10.1007\/s40618-016-0541-6","volume":"40","author":"M Bonomi","year":"2017","unstructured":"M. Bonomi, V. Rochira, D. Pasquali, G. Balercia, E.A. Jannini, A. Ferlin, Klinefelter syndrome (KS): genetics, clinical phenotype and hypogonadism. J. Endocrinol. Invest. 40(2), 123\u2013134 (2017). https:\/\/doi.org\/10.1007\/s40618-016-0541-6","journal-title":"J. Endocrinol. Invest."},{"key":"1850_CR4","doi-asserted-by":"publisher","unstructured":"C.H. Gravholt, S. Chang, M. Wallentin, J. Fedder, P. Moore, A. Skakkebaek, Klinefelter syndrome\u2014integrating genetics, neuropsychology and endocrinology. Endocr. Rev. (2018). https:\/\/doi.org\/10.1210\/er.2017-00212","DOI":"10.1210\/er.2017-00212"},{"issue":"4","key":"1850_CR5","doi-asserted-by":"publisher","first-page":"314","DOI":"10.1001\/archinte.1966.00290160014004","volume":"118","author":"KL Becker","year":"1966","unstructured":"K.L. Becker, D.L. Hoffman, L.O. Underdahl, H.L. Mason, Klinefelter\u2019s syndrome. Clinical and laboratory findings in 50 patients. Arch. Intern. Med. 118(4), 314\u2013321 (1966)","journal-title":"Arch. Intern. Med."},{"issue":"4","key":"1850_CR6","doi-asserted-by":"publisher","first-page":"399","DOI":"10.1111\/j.1365-2265.1975.tb01547.x","volume":"4","author":"C Wang","year":"1975","unstructured":"C. Wang, H.W. Baker, H.G. Burger, D.M. De Kretser, B. Hudson, Hormonal studies in Klinefelter\u2019s syndrome. Clin. Endocrinol. 4(4), 399\u2013411 (1975)","journal-title":"Clin. Endocrinol."},{"issue":"5","key":"1850_CR7","doi-asserted-by":"publisher","first-page":"447","DOI":"10.1097\/00005792-197809000-00004","volume":"57","author":"WA Hsueh","year":"1978","unstructured":"W.A. Hsueh, T.H. Hsu, D.D. Federman, Endocrine features of Klinefelter\u2019s syndrome. Medicine 57(5), 447\u2013461 (1978)","journal-title":"Medicine"},{"key":"1850_CR8","first-page":"561","volume":"28","author":"JS Stewart","year":"1959","unstructured":"J.S. Stewart, W.S. Mack, A.D. Govan, M.A. Ferguson-Smith, B. Lennox, Klinefelter\u2019s syndrome: clinical and hormonal aspects. Q. J. Med. 28, 561\u2013571 (1959)","journal-title":"Q. J. Med."},{"issue":"2","key":"1850_CR9","first-page":"179","volume":"22","author":"G Concolino","year":"1969","unstructured":"G. Concolino, A. Marocchi, F. Sciarra, Plasma estrogens in bilateral gynecomastia. Folia Endocrinol. 22(2), 179\u2013189 (1969)","journal-title":"Folia Endocrinol."},{"issue":"3","key":"1850_CR10","doi-asserted-by":"publisher","first-page":"499","DOI":"10.1530\/acta.0.0630499","volume":"63","author":"JL Gabrilove","year":"1970","unstructured":"J.L. Gabrilove, G.L. Nicolis, R.U. Hausknecht, Urinary testosterone, oestrogen production rate and urinary oestrogen in chromatin positive Klinefelter\u2019s syndrome. Acta Endocrinol. 63(3), 499\u2013504 (1970)","journal-title":"Acta Endocrinol."},{"issue":"4","key":"1850_CR11","doi-asserted-by":"publisher","first-page":"737","DOI":"10.1530\/acta.0.0660737","volume":"66","author":"DC Sharma","year":"1971","unstructured":"D.C. Sharma, J.L. Gabrilove, Biosynthesis of testosterone and oestrogens in vitro by the testicular tissue from patients with Klinefelter\u2019s syndrome. Acta Endocrinol. 66(4), 737\u2013744 (1971)","journal-title":"Acta Endocrinol."},{"issue":"6","key":"1850_CR12","doi-asserted-by":"publisher","first-page":"621","DOI":"10.1097\/MOU.0b013e32831367c7","volume":"18","author":"DA Paduch","year":"2008","unstructured":"D.A. Paduch, R.G. Fine, A. Bolyakov, J. Kiper, New concepts in Klinefelter syndrome. Curr. Opin. Urol. 18(6), 621\u2013627 (2008). https:\/\/doi.org\/10.1097\/MOU.0b013e32831367c7","journal-title":"Curr. Opin. Urol."},{"issue":"2","key":"1850_CR13","doi-asserted-by":"publisher","first-page":"137","DOI":"10.1055\/s-0029-1202302","volume":"27","author":"DA Paduch","year":"2009","unstructured":"D.A. Paduch, A. Bolyakov, P. Cohen, A. Travis, Reproduction in men with Klinefelter syndrome: the past, the present, and the future. Semin. Reprod. Med. 27(2), 137\u2013148 (2009). https:\/\/doi.org\/10.1055\/s-0029-1202302","journal-title":"Semin. Reprod. Med."},{"issue":"9430","key":"1850_CR14","doi-asserted-by":"publisher","first-page":"273","DOI":"10.1016\/s0140-6736(04)16678-6","volume":"364","author":"F Lanfranco","year":"2004","unstructured":"F. Lanfranco, A. Kamischke, M. Zitzmann, E. Nieschlag, Klinefelter\u2019s syndrome. Lancet 364(9430), 273\u2013283 (2004). https:\/\/doi.org\/10.1016\/s0140-6736(04)16678-6","journal-title":"Lancet"},{"issue":"4","key":"1850_CR15","doi-asserted-by":"publisher","first-page":"192","DOI":"10.1038\/ncpuro0775","volume":"4","author":"A Bojesen","year":"2007","unstructured":"A. Bojesen, C.H. Gravholt, Klinefelter syndrome in clinical practice. Nat. Clin. Pract. Urol. 4(4), 192\u2013204 (2007). https:\/\/doi.org\/10.1038\/ncpuro0775","journal-title":"Nat. Clin. Pract. Urol."},{"issue":"1","key":"1850_CR16","doi-asserted-by":"crossref","first-page":"41","DOI":"10.1002\/j.1939-4640.2003.tb02638.x","volume":"24","author":"A Kamischke","year":"2003","unstructured":"A. Kamischke, A. Baumgardt, J. Horst, E. Nieschlag, Clinical and diagnostic features of patients with suspected Klinefelter syndrome. J. Androl. 24(1), 41\u201348 (2003)","journal-title":"J. Androl."},{"issue":"7","key":"1850_CR17","doi-asserted-by":"publisher","first-page":"1591","DOI":"10.2337\/dc06-0145","volume":"29","author":"A Bojesen","year":"2006","unstructured":"A. Bojesen, K. Kristensen, N.H. Birkebaek, J. Fedder, L. Mosekilde, P. Bennett, P. Laurberg, J. Frystyk, A. Flyvbjerg, J.S. Christiansen, C.H. Gravholt, The metabolic syndrome is frequent in Klinefelter\u2019s syndrome and is associated with abdominal obesity and hypogonadism. Diabetes Care 29(7), 1591\u20131598 (2006). https:\/\/doi.org\/10.2337\/dc06-0145","journal-title":"Diabetes Care"},{"issue":"6 Part 2","key":"1850_CR18","doi-asserted-by":"publisher","first-page":"e642","DOI":"10.1111\/j.1365-2605.2011.01223.x","volume":"34","author":"A Bojesen","year":"2011","unstructured":"A. Bojesen, J.M. Hertz, C.H. Gravholt, Genotype and phenotype in Klinefelter syndrome\u2014impact of androgen receptor polymorphism and skewed X inactivation. Int. J. Androl. 34(6 Part 2), e642\u2013e648 (2011). https:\/\/doi.org\/10.1111\/j.1365-2605.2011.01223.x","journal-title":"Int. J. Androl."},{"key":"1850_CR19","doi-asserted-by":"publisher","unstructured":"S. Chang, A. Skakkebaek, C. Trolle, A. Bojesen, J.M. Hertz, A. Cohen, D.M. Hougaard, M. Wallentin, A.D. Pedersen, J.R. Ostergaard, C.H. Gravholt, Anthropometry in Klinefelter syndrome\u2014multifactorial influences due to CAG length, testosterone treatment and possibly intrauterine hypogonadism. J. Clin. Endocrinol. Metab., jc20142834 (2014). https:\/\/doi.org\/10.1210\/jc.2014-2834","DOI":"10.1210\/jc.2014-2834"},{"issue":"6","key":"1850_CR20","doi-asserted-by":"publisher","first-page":"801","DOI":"10.1530\/eje-15-1224","volume":"174","author":"S Belli","year":"2016","unstructured":"S. Belli, D. Santi, E. Leoni, E. Dall\u2019Olio, F. Fanelli, M. Mezzullo, C. Pelusi, L. Roli, S. Tagliavini, T. Trenti, A.R. Granata, U. Pagotto, R. Pasquali, V. Rochira, C. Carani, M. Simoni, Human chorionic gonadotropin stimulation gives evidence of differences in testicular steroidogenesis in Klinefelter syndrome, as assessed by liquid chromatography-tandem mass spectrometry. Eur. J. Endocrinol.\/Eur. Fed. Endocr. Soc. 174(6), 801\u2013811 (2016). https:\/\/doi.org\/10.1530\/eje-15-1224","journal-title":"Eur. J. Endocrinol.\/Eur. Fed. Endocr. Soc."},{"key":"1850_CR21","doi-asserted-by":"publisher","unstructured":"A. Ferlin, R. Selice, S. Angelini, M. Di Grazia, N. Caretta, F. Cavalieri, A. Di Mambro, C. Foresta, Endocrine and psychological aspects of sexual dysfunction in Klinefelter patients. Andrology (2018). https:\/\/doi.org\/10.1111\/andr.12474","DOI":"10.1111\/andr.12474"},{"issue":"2","key":"1850_CR22","doi-asserted-by":"publisher","first-page":"149","DOI":"10.1007\/BF03350363","volume":"1","author":"G Forti","year":"1978","unstructured":"G. Forti, G. Giusti, A. Borghi, M. Pazzagli, G. Fiorelli, E. Cabresi, M. Mannelli, F. Bassi, P. Giannotti, S. Fusi, M. Serio, Klinefelter\u2019s syndrome: a study of its hormonal plasma pattern. J. Endocrinol. Invest. 1(2), 149\u2013154 (1978)","journal-title":"J. Endocrinol. Invest."},{"issue":"6","key":"1850_CR23","first-page":"438","volume":"25","author":"M Wielgos","year":"2004","unstructured":"M. Wielgos, L. Bablok, S. Fracki, M. Czaplicki, L. Marianowski, The naloxone test in Klinefelter syndrome. Neuro. Endocrinol. Lett. 25(6), 438\u2013442 (2004)","journal-title":"Neuro. Endocrinol. Lett."},{"issue":"5","key":"1850_CR24","doi-asserted-by":"publisher","first-page":"1278","DOI":"10.1016\/j.fertnstert.2003.11.029","volume":"81","author":"Z Yesilova","year":"2004","unstructured":"Z. Yesilova, M. Ozata, C. Oktenli, S.Y. Sanisoglu, M.K. Erbil, K. Dagalp, Effect of supraphysiologic doses of testosterone on fasting plasma total homocysteine concentrations in men with Klinefelter\u2019s syndrome. Fertil. Steril. 81(5), 1278\u20131282 (2004). https:\/\/doi.org\/10.1016\/j.fertnstert.2003.11.029","journal-title":"Fertil. Steril."},{"issue":"1","key":"1850_CR25","doi-asserted-by":"publisher","first-page":"11","DOI":"10.1385\/endo:27:1:011","volume":"27","author":"Z Yesilova","year":"2005","unstructured":"Z. Yesilova, C. Oktenli, S.Y. Sanisoglu, U. Musabak, E. Cakir, M. Ozata, K. Dagalp, Evaluation of insulin sensitivity in patients with Klinefelter\u2019s syndrome: a hyperinsulinemic euglycemic clamp study. Endocrine 27(1), 11\u201315 (2005). https:\/\/doi.org\/10.1385\/endo:27:1:011","journal-title":"Endocrine"},{"issue":"6","key":"1850_CR26","doi-asserted-by":"publisher","first-page":"743","DOI":"10.1530\/eje-13-0488","volume":"169","author":"R Selice","year":"2013","unstructured":"R. Selice, N. Caretta, A. Di Mambro, M. Torino, P. Palego, A. Ferlin, C. Foresta, Prostate volume and growth during testosterone replacement therapy is related to visceral obesity in Klinefelter syndrome. Eur. J. Endocrinol.\/Eur. Fed. Endocr. Soc. 169(6), 743\u2013749 (2013). https:\/\/doi.org\/10.1530\/eje-13-0488","journal-title":"Eur. J. Endocrinol.\/Eur. Fed. Endocr. Soc."},{"issue":"Suppl.","key":"1850_CR27","first-page":"225","volume":"22","author":"DA Smith","year":"1977","unstructured":"D.A. Smith, M.S. Walker, Changes in plasma steroids and bone density in Klinefelter\u2019s syndrome. Calcif. Tissue Res. 22(Suppl.), 225\u2013228 (1977)","journal-title":"Calcif. Tissue Res."},{"issue":"1","key":"1850_CR28","doi-asserted-by":"publisher","first-page":"62","DOI":"10.1210\/jcem-66-1-62","volume":"66","author":"VA Giagulli","year":"1988","unstructured":"V.A. Giagulli, A. Vermeulen, Leydig cell function in infertile men with idiopathic oligospermic infertility. J. Clin. Endocrinol. Metab. 66(1), 62\u201367 (1988). https:\/\/doi.org\/10.1210\/jcem-66-1-62","journal-title":"J. Clin. Endocrinol. Metab."},{"issue":"9","key":"1850_CR29","doi-asserted-by":"publisher","first-page":"3372","DOI":"10.1210\/jcem.81.9.8784099","volume":"81","author":"M Ozata","year":"1996","unstructured":"M. Ozata, M. Yildirimkaya, M. Bulur, K. Yilmaz, E. Bolu, A. Corakci, M.A. Gundogan, Effects of gonadotropin and testosterone treatments on Lipoprotein(a), high density lipoprotein particles, and other lipoprotein levels in male hypogonadism. J. Clin. Endocrinol. Metab. 81(9), 3372\u20133378 (1996). https:\/\/doi.org\/10.1210\/jcem.81.9.8784099","journal-title":"J. Clin. Endocrinol. Metab."},{"issue":"4","key":"1850_CR30","doi-asserted-by":"publisher","first-page":"1376","DOI":"10.1210\/jc.2012-3780","volume":"98","author":"W Rosner","year":"2013","unstructured":"W. Rosner, S.E. Hankinson, P.M. Sluss, H.W. Vesper, M.E. Wierman, Challenges to the measurement of estradiol: an endocrine society position statement. J. Clin. Endocrinol. Metab. 98(4), 1376\u20131387 (2013). https:\/\/doi.org\/10.1210\/jc.2012-3780","journal-title":"J. Clin. Endocrinol. Metab."},{"issue":"3","key":"1850_CR31","doi-asserted-by":"publisher","first-page":"510","DOI":"10.1373\/clinchem.2013.213363","volume":"60","author":"DJ Handelsman","year":"2014","unstructured":"D.J. Handelsman, J.D. Newman, M. Jimenez, R. McLachlan, G. Sartorius, G.R. Jones, Performance of direct estradiol immunoassays with human male serum samples. Clin. Chem. 60(3), 510\u2013517 (2014). https:\/\/doi.org\/10.1373\/clinchem.2013.213363","journal-title":"Clin. Chem."},{"issue":"Part A","key":"1850_CR32","doi-asserted-by":"publisher","first-page":"1","DOI":"10.1016\/j.steroids.2014.12.012","volume":"99","author":"RJ Santen","year":"2015","unstructured":"R.J. Santen, L.M. Demers, R.G. Ziegler, Workshop on measuring estrogen exposure and metabolism: summary of the presentations. Steroids 99(Part A), 1\u20137 (2015). https:\/\/doi.org\/10.1016\/j.steroids.2014.12.012","journal-title":"Steroids"},{"issue":"2","key":"1850_CR33","doi-asserted-by":"publisher","first-page":"D1","DOI":"10.1530\/eje-15-0338","volume":"173","author":"AE Taylor","year":"2015","unstructured":"A.E. Taylor, B. Keevil, I.T. Huhtaniemi, Mass spectrometry and immunoassay: how to measure steroid hormones today and tomorrow. Eur. J. Endocrinol.\/Eur. Fed. Endocr. Soc. 173(2), D1\u201312 (2015). https:\/\/doi.org\/10.1530\/eje-15-0338","journal-title":"Eur. J. Endocrinol.\/Eur. Fed. Endocr. Soc."},{"issue":"3","key":"1850_CR34","doi-asserted-by":"publisher","first-page":"343","DOI":"10.1111\/j.1365-2265.1979.tb03083.x","volume":"11","author":"JL Gabrilove","year":"1979","unstructured":"J.L. Gabrilove, E.K. Freiberg, J.C. Thornton, G.L. Nicolis, Effect of age on testicular function in patients with Klinefelter\u2019s syndrome. Clin. Endocrinol. 11(3), 343\u2013347 (1979)","journal-title":"Clin. Endocrinol."},{"key":"1850_CR35","unstructured":"D. Meschede, J. Horst, Klinefelter Syndrome. In: J.H. Wass, S.M. Shalet (ed.), Oxford Textbook of Endocrinology and Diabetes, pp. 1292\u20131294 (Oxford University Press, Oxford, UK, 2002)"},{"issue":"1","key":"1850_CR36","doi-asserted-by":"publisher","first-page":"128","DOI":"10.1097\/EDE.0b013e3181fe7825","volume":"22","author":"D Moher","year":"2011","unstructured":"D. Moher, D.G. Altman, A. Liberati, J. Tetzlaff, PRISMA statement. Epidemiology 22(1), 128 (2011). https:\/\/doi.org\/10.1097\/EDE.0b013e3181fe7825 . author reply 128","journal-title":"Epidemiology"},{"issue":"5","key":"1850_CR37","doi-asserted-by":"publisher","first-page":"336","DOI":"10.1016\/j.ijsu.2010.02.007","volume":"8","author":"D Moher","year":"2010","unstructured":"D. Moher, A. Liberati, J. Tetzlaff, D.G. Altman, Preferred reporting items for systematic reviews and meta-analyses: the PRISMA statement. Int. J. Surg. 8(5), 336\u2013341 (2010). https:\/\/doi.org\/10.1016\/j.ijsu.2010.02.007","journal-title":"Int. J. Surg."},{"key":"1850_CR38","doi-asserted-by":"publisher","unstructured":"D. Santi, S. De Vincentis, S. Scaltriti, V. Rochira, Data from: Is serum estradiol really increased in Klinefelter Syndrome? Evidence of relative hyperestrogenism from a meta-analysis. Figshare (2018. Deposited 7 July 2018 https:\/\/doi.org\/10.6084\/m9.figshare.6790007.v1 ). https:\/\/doi.org\/10.6084\/m9.figshare.6790007.v1","DOI":"10.6084\/m9.figshare.6790007.v1 10.6084\/m9.figshare.6790007.v1"},{"key":"1850_CR39","volume-title":"Cochrane Methods","author":"J Chandler","year":"2012","unstructured":"J. Chandler, M. Clarke, J. Higgins. The Cochrane Collaboration. Cochrane Methods. (John Wiley & Sons Ltd, UK), 2012)"},{"issue":"4","key":"1850_CR40","first-page":"287","volume":"60","author":"F Eulry","year":"1993","unstructured":"F. Eulry, B. Bauduceau, D. Lechevalier, J. Magnin, J. Flageat, D. Gautier, [Early spinal bone loss in Klinefelter syndrome. X-ray computed tomographic evaluation in 16 cases]. Rev. Rhum. (Ed. francaise: 1993) 60(4), 287\u2013291 (1993)","journal-title":"Rev. Rhum. (Ed. francaise: 1993)"},{"issue":"4","key":"1850_CR41","doi-asserted-by":"publisher","first-page":"903","DOI":"10.1158\/1055-9965.epi-10-0081","volume":"19","author":"FZ Stanczyk","year":"2010","unstructured":"F.Z. Stanczyk, J. Jurow, A.W. Hsing, Limitations of direct immunoassays for measuring circulating estradiol levels in postmenopausal women and men in epidemiologic studies. Cancer epidemiology, biomarkers & prevention: a publication of the American Association for Cancer Research, cosponsored by the American Society of Preventive. Oncology 19(4), 903\u2013906 (2010). https:\/\/doi.org\/10.1158\/1055-9965.epi-10-0081","journal-title":"Oncology"},{"key":"1850_CR42","doi-asserted-by":"publisher","unstructured":"H. Ketha, A. Girtman, R. Singh, Estradiol assays\u2014the path ahead. Steroids (2014). https:\/\/doi.org\/10.1016\/j.steroids.2014.08.009","DOI":"10.1016\/j.steroids.2014.08.009"},{"key":"1850_CR43","doi-asserted-by":"publisher","first-page":"7","DOI":"10.1016\/j.steroids.2013.12.005","volume":"82","author":"HW Vesper","year":"2014","unstructured":"H.W. Vesper, J.C. Botelho, M.L. Vidal, Y. Rahmani, L.M. Thienpont, S.P. Caudill, High variability in serum estradiol measurements in men and women. Steroids 82, 7\u201313 (2014). https:\/\/doi.org\/10.1016\/j.steroids.2013.12.005","journal-title":"Steroids"},{"issue":"1","key":"1850_CR44","doi-asserted-by":"publisher","first-page":"56","DOI":"10.1210\/jc.2013-2905","volume":"99","author":"FZ Stanczyk","year":"2014","unstructured":"F.Z. Stanczyk, N.J. Clarke, Measurement of estradiol\u2014challenges ahead. J. Clin. Endocrinol. Metab. 99(1), 56\u201358 (2014). https:\/\/doi.org\/10.1210\/jc.2013-2905","journal-title":"J. Clin. Endocrinol. Metab."},{"issue":"10","key":"1850_CR45","doi-asserted-by":"publisher","first-page":"3791","DOI":"10.1210\/jc.2005-2378","volume":"91","author":"JS Lee","year":"2006","unstructured":"J.S. Lee, B. Ettinger, F.Z. Stanczyk, E. Vittinghoff, V. Hanes, J.A. Cauley, W. Chandler, J. Settlage, M.S. Beattie, E. Folkerd, M. Dowsett, D. Grady, S.R. Cummings, Comparison of methods to measure low serum estradiol levels in postmenopausal women. J. Clin. Endocrinol. Metab. 91(10), 3791\u20133797 (2006). https:\/\/doi.org\/10.1210\/jc.2005-2378","journal-title":"J. Clin. Endocrinol. Metab."},{"issue":"5","key":"1850_CR46","doi-asserted-by":"publisher","first-page":"1004","DOI":"10.1158\/1055-9965.epi-06-0792","volume":"16","author":"AW Hsing","year":"2007","unstructured":"A.W. Hsing, F.Z. Stanczyk, A. Belanger, P. Schroeder, L. Chang, R.T. Falk, T.R. Fears, Reproducibility of serum sex steroid assays in men by RIA and mass spectrometry. Cancer epidemiology, biomarkers & prevention: a publication of the American Association for Cancer Research, cosponsored by the American Society of Preventive. Oncology 16(5), 1004\u20131008 (2007). https:\/\/doi.org\/10.1158\/1055-9965.epi-06-0792","journal-title":"Oncology"},{"issue":"5-6","key":"1850_CR47","first-page":"201","volume":"55","author":"J Reinsberg","year":"2009","unstructured":"J. Reinsberg, O. Batz, T. Bertsch, N. Bewarder, W. Deschner, V. Drescher, M. Dronsek, M. Emami, R. Keller, M. Klemm, H.U. Koch, J. Meissner, T. Plecko, I. Schauer, A.M. Schweiger, A. Ullrich, H.M. van de Loo, M. Zwirner, Precision and long-term stability of different estradiol immunoassays assessed in a multi-center quality control study. Clin. Lab. 55(5-6), 201\u2013206 (2009)","journal-title":"Clin. Lab."},{"issue":"3","key":"1850_CR48","doi-asserted-by":"publisher","first-page":"332","DOI":"10.1309\/5n2r-4ht4-gm0a-gpby","volume":"122","author":"DT Yang","year":"2004","unstructured":"D.T. Yang, W.E. Owen, C.S. Ramsay, H. Xie, W.L. Roberts, Performance characteristics of eight estradiol immunoassays. Am. J. Clin. Pathol. 122(3), 332\u2013337 (2004). https:\/\/doi.org\/10.1309\/5n2r-4ht4-gm0a-gpby","journal-title":"Am. J. Clin. Pathol."},{"issue":"1\u20132","key":"1850_CR49","doi-asserted-by":"publisher","first-page":"99","DOI":"10.1016\/j.cca.2007.10.020","volume":"388","author":"PM Sluss","year":"2008","unstructured":"P.M. Sluss, F.J. Hayes, J.M. Adams, W. Barnes, G. Williams, S. Frost, J. Ramp, D. Pacenti, D.C. Lehotay, S. George, C. Ramsay, R.C. Doss, W.F. Crowley Jr., Mass spectrometric and physiological validation of a sensitive, automated, direct immunoassay for serum estradiol using the Architect. Clin. Chim. Acta; Int. J. Clin. Chem. 388(1\u20132), 99\u2013105 (2008). https:\/\/doi.org\/10.1016\/j.cca.2007.10.020","journal-title":"Clin. Chim. Acta; Int. J. Clin. Chem."},{"issue":"2","key":"1850_CR50","doi-asserted-by":"publisher","first-page":"347","DOI":"10.1530\/acta.0.0920347","volume":"92","author":"A Barbarino","year":"1979","unstructured":"A. Barbarino, L. De Marinis, Klinefelter\u2019s syndrome: effects of oestrogen on growth hormone, prolactin and thyrotrophin release, and on thyrotrophin and prolactin responses to thyrotrophin-releasing hormone. Acta Endocrinol. 92(2), 347\u2013357 (1979)","journal-title":"Acta Endocrinol."},{"issue":"3","key":"1850_CR51","doi-asserted-by":"publisher","first-page":"645","DOI":"10.1210\/jcem-57-3-645","volume":"57","author":"SR Plymate","year":"1983","unstructured":"S.R. Plymate, J.M. Leonard, C.A. Paulsen, B.L. Fariss, A.E. Karpas, Sex hormone-binding globulin changes with androgen replacement. J. Clin. Endocrinol. Metab. 57(3), 645\u2013648 (1983). https:\/\/doi.org\/10.1210\/jcem-57-3-645","journal-title":"J. Clin. Endocrinol. Metab."},{"issue":"4","key":"1850_CR52","doi-asserted-by":"publisher","first-page":"463","DOI":"10.1046\/j.1365-2265.1997.2881089.x","volume":"47","author":"R Luboshitzky","year":"1997","unstructured":"R. Luboshitzky, O. Wagner, S. Lavi, P. Herer, P. Lavie, Abnormal melatonin secretion in hypogonadal men: the effect of testosterone treatment. Clin. Endocrinol. 47(4), 463\u2013469 (1997)","journal-title":"Clin. Endocrinol."},{"issue":"6","key":"1850_CR53","doi-asserted-by":"publisher","first-page":"455","DOI":"10.1007\/BF01626608","volume":"5","author":"G Luisetto","year":"1995","unstructured":"G. Luisetto, I. Mastrogiacomo, G. Bonanni, G. Pozzan, S. Botteon, L. Tizian, P. Galuppo, Bone mass and mineral metabolism in Klinefelter\u2019s syndrome. Osteoporos. Int. 5(6), 455\u2013461 (1995)","journal-title":"Osteoporos. Int."},{"issue":"3","key":"1850_CR54","doi-asserted-by":"publisher","first-page":"137","DOI":"10.1023\/A:1015467912592","volume":"22","author":"C Oktenli","year":"2002","unstructured":"C. Oktenli, Z. Yesilova, I.H. Kocar, U. Musabak, M. Ozata, A. Inal, D. Gul, Y. Sanisoglu, Study of autoimmunity in Klinefelter\u2019s syndrome and idiopathic hypogonadotropic hypogonadism. J. Clin. Immunol. 22(3), 137\u2013143 (2002)","journal-title":"J. Clin. Immunol."},{"issue":"2","key":"1850_CR55","doi-asserted-by":"publisher","first-page":"214","DOI":"10.1046\/j.1365-2265.2003.01828.x","volume":"59","author":"PA Tomasi","year":"2003","unstructured":"P.A. Tomasi, R. Oates, L. Brown, G. Delitala, D.C. Page, The pituitary-testicular axis in Klinefelter\u2019s syndrome and in oligo-azoospermic patients with and without deletions of the Y chromosome long arm. Clin. Endocrinol. 59(2), 214\u2013222 (2003)","journal-title":"Clin. Endocrinol."},{"key":"1850_CR56","doi-asserted-by":"publisher","first-page":"1","DOI":"10.1530\/EJE-15-1224","volume":"174","author":"S Belli","year":"2016","unstructured":"S. Belli, D. Santi, E. Leoni, E. Dall\u2019Olio, F. Fanelli, M. Mezzullo, C. Pelusi, L. Roli, S. Tagliavini, T. Trenti, A.R.M. Granata, U. Pagotto, R. Pasquali, V. Rochira, C. Carani, M. Simoni, Human chorionic gonadotropin stimulation gives evidence of differences in testicular steroidogenesis in Klinefelter syndrome, as assessed by liquid chromatography\u2013tandem mass spectrometry. Eur. J. Endocrinol. 174, 1\u201311 (2016). https:\/\/doi.org\/10.1530\/EJE-15-1224","journal-title":"Eur. J. Endocrinol."},{"issue":"5","key":"1850_CR57","doi-asserted-by":"publisher","first-page":"1441","DOI":"10.1007\/s00198-010-1354-7","volume":"22","author":"A Bojesen","year":"2011","unstructured":"A. Bojesen, N. Birkebaek, K. Kristensen, L. Heickendorff, L. Mosekilde, J.S. Christiansen, C.H. Gravholt, Bone mineral density in Klinefelter syndrome is reduced and primarily determined by muscle strength and resorptive markers, but not directly by testosterone. Osteoporos. Int. 22(5), 1441\u20131450 (2011). https:\/\/doi.org\/10.1007\/s00198-010-1354-7","journal-title":"Osteoporos. Int."},{"issue":"3","key":"1850_CR58","doi-asserted-by":"publisher","first-page":"211","DOI":"10.1111\/j.1365-2362.2009.02250.x","volume":"40","author":"C Host","year":"2010","unstructured":"C. Host, A. Bojesen, J. Frystyk, A. Flyvbjerg, J.S. Christiansen, C.H. Gravholt, Effect of sex hormone treatment on circulating adiponectin and subforms in Turner and Klinefelter syndrome. Eur. J. Clin. Invest. 40(3), 211\u2013219 (2010). https:\/\/doi.org\/10.1111\/j.1365-2362.2009.02250.x","journal-title":"Eur. J. Clin. Invest."},{"issue":"1","key":"1850_CR59","first-page":"50","volume":"32","author":"G Bleau","year":"1987","unstructured":"G. Bleau, C.L. Richer, A. Chapdelaine, K.D. Roberts, Hormone study in a case of Klinefelter syndrome with an isochromosome Xq. Int. J. Fertil. 32(1), 50\u201355 (1987)","journal-title":"Int. J. Fertil."},{"issue":"6","key":"1850_CR60","doi-asserted-by":"publisher","first-page":"244","DOI":"10.1159\/000181526","volume":"33","author":"C Boucekkine","year":"1990","unstructured":"C. Boucekkine, M. Semrouni, Presence of positive feedback in males with Klinefelter\u2019s syndrome. Horm. Res. 33(6), 244\u2013247 (1990)","journal-title":"Horm. Res."},{"issue":"3","key":"1850_CR61","first-page":"160","volume":"50","author":"VH Goh","year":"1998","unstructured":"V.H. Goh, K.O. Lee, Does a positive oestrogen feedback on the hypothalamic-pituitary axis exist concurrently with a defective testosterone feedback in Klinefelter\u2019s syndrome? Horm. Res. 50(3), 160\u2013165 (1998)","journal-title":"Horm. Res."},{"issue":"4","key":"1850_CR62","doi-asserted-by":"publisher","first-page":"589","DOI":"10.1016\/S8756-3282(03)00205-9","volume":"33","author":"JJ Stepan","year":"2003","unstructured":"J.J. Stepan, P. Burckhardt, V. Hana, The effects of three-month intravenous ibandronate on bone mineral density and bone remodeling in Klinefelter\u2019s syndrome: the influence of vitamin D deficiency and hormonal status. Bone 33(4), 589\u2013596 (2003)","journal-title":"Bone"},{"issue":"12","key":"1850_CR63","doi-asserted-by":"publisher","first-page":"6208","DOI":"10.1210\/jc.2004-1424","volume":"89","author":"M Zitzmann","year":"2004","unstructured":"M. Zitzmann, M. Depenbusch, J. Gromoll, E. Nieschlag, X-chromosome inactivation patterns and androgen receptor functionality influence phenotype and social characteristics as well as pharmacogenetics of testosterone therapy in Klinefelter patients. J. Clin. Endocrinol. Metab. 89(12), 6208\u20136217 (2004). https:\/\/doi.org\/10.1210\/jc.2004-1424","journal-title":"J. Clin. Endocrinol. Metab."},{"issue":"9","key":"1850_CR64","doi-asserted-by":"publisher","first-page":"5041","DOI":"10.1210\/jc.2005-0432","volume":"90","author":"AR Zinn","year":"2005","unstructured":"A.R. Zinn, P. Ramos, F.F. Elder, K. Kowal, C. Samango-Sprouse, J.L. Ross, Androgen receptor CAGn repeat length influences phenotype of 47,XXY (Klinefelter) syndrome. J. Clin. Endocrinol. Metab. 90(9), 5041\u20135046 (2005). https:\/\/doi.org\/10.1210\/jc.2005-0432","journal-title":"J. Clin. Endocrinol. Metab."},{"issue":"11","key":"1850_CR65","doi-asserted-by":"publisher","first-page":"789","DOI":"10.3275\/6935","volume":"33","author":"R Selice","year":"2010","unstructured":"R. Selice, A. Di Mambro, A. Garolla, V. Ficarra, M. Iafrate, A. Ferlin, C. Foresta, Spermatogenesis in Klinefelter syndrome. J. Endocrinol. Invest. 33(11), 789\u2013793 (2010). https:\/\/doi.org\/10.3275\/6935","journal-title":"J. Endocrinol. Invest."},{"key":"1850_CR66","doi-asserted-by":"publisher","first-page":"324835","DOI":"10.1155\/2012\/324835","volume":"2012","author":"N Pacenza","year":"2012","unstructured":"N. Pacenza, T. Pasqualini, S. Gottlieb, P. Knoblovits, P.R. Costanzo, J. Stewart Usher, R.A. Rey, M.P. Martinez, S. Aszpis, Clinical presentation of Klinefelter\u2019s Syndrome: differences according to age. Int. J. Endocrinol. 2012, 324835 (2012). https:\/\/doi.org\/10.1155\/2012\/324835","journal-title":"Int. J. Endocrinol."},{"issue":"3","key":"1850_CR67","doi-asserted-by":"publisher","first-page":"441","DOI":"10.2164\/jandrol.110.011536","volume":"33","author":"MM Abdel-Razic","year":"2012","unstructured":"M.M. Abdel-Razic, I.A. Abdel-Hamid, E. Elsobky, F. El-Dahtory, Further evidence of the clinical, hormonal, and genetic heterogeneity of Klinefelter syndrome: a study of 216 infertile Egyptian patients. J. Androl. 33(3), 441\u2013448 (2012). https:\/\/doi.org\/10.2164\/jandrol.110.011536","journal-title":"J. Androl."},{"issue":"1","key":"1850_CR68","doi-asserted-by":"publisher","first-page":"54","DOI":"10.1177\/1557988312458449","volume":"7","author":"M Inci","year":"2013","unstructured":"M. Inci, O. Akgul, N. Baydilli, O. Ekmekcioglu, S. Ozgocmen, Increased femoral cartilage thickness in patients with Klinefelter syndrome. Am. J. Men\u2019s Health 7(1), 54\u201357 (2013). https:\/\/doi.org\/10.1177\/1557988312458449","journal-title":"Am. J. Men\u2019s Health"},{"issue":"4","key":"1850_CR69","doi-asserted-by":"publisher","first-page":"950","DOI":"10.1016\/j.fertnstert.2013.12.051","volume":"101","author":"MK Samplaski","year":"2014","unstructured":"M.K. Samplaski, K.C. Lo, E.D. Grober, A. Millar, A. Dimitromanolakis, K.A. Jarvi, Phenotypic differences in mosaic Klinefelter patients as compared with non-mosaic Klinefelter patients. Fertil. Steril. 101(4), 950\u2013955 (2014). https:\/\/doi.org\/10.1016\/j.fertnstert.2013.12.051","journal-title":"Fertil. Steril."},{"key":"1850_CR70","doi-asserted-by":"publisher","unstructured":"V.V. Shanbhogue, S. Hansen, N.R. Jorgensen, K. Brixen, C.H. Gravholt, Bone geometry, volumetric density, microarchitecture and estimated bone strength assessed by HR-pQCT in Klinefelter Syndrome. J. Bone Miner. Res. (2014). https:\/\/doi.org\/10.1002\/jbmr.2272","DOI":"10.1002\/jbmr.2272"},{"issue":"11","key":"1850_CR71","doi-asserted-by":"publisher","first-page":"839","DOI":"10.1007\/bf03350351","volume":"33","author":"AF Radicioni","year":"2010","unstructured":"A.F. Radicioni, A. Ferlin, G. Balercia, D. Pasquali, L. Vignozzi, M. Maggi, C. Foresta, A. Lenzi, Consensus statement on diagnosis and clinical management of Klinefelter syndrome. J. Endocrinol. Invest. 33(11), 839\u2013850 (2010). https:\/\/doi.org\/10.1007\/bf03350351","journal-title":"J. Endocrinol. Invest."},{"issue":"1","key":"1850_CR72","doi-asserted-by":"publisher","first-page":"20","DOI":"10.1210\/jc.2012-2382","volume":"98","author":"KA Groth","year":"2013","unstructured":"K.A. Groth, A. Skakkebaek, C. Host, C.H. Gravholt, A. Bojesen, Clinical review: Klinefelter syndrome\u2014a clinical update. J. Clin. Endocrinol. Metab. 98(1), 20\u201330 (2013). https:\/\/doi.org\/10.1210\/jc.2012-2382","journal-title":"J. Clin. Endocrinol. Metab."},{"issue":"2","key":"1850_CR73","doi-asserted-by":"publisher","first-page":"185","DOI":"10.4103\/1008-682x.122201","volume":"16","author":"C Host","year":"2014","unstructured":"C. Host, A. Skakkebaek, K.A. Groth, A. Bojesen, The role of hypogonadism in Klinefelter syndrome. Asian J. Androl. 16(2), 185\u2013191 (2014). https:\/\/doi.org\/10.4103\/1008-682x.122201","journal-title":"Asian J. Androl."},{"issue":"4","key":"1850_CR74","doi-asserted-by":"publisher","first-page":"565","DOI":"10.1002\/ajhb.22548","volume":"26","author":"L Xu","year":"2014","unstructured":"L. Xu, S.L. Yeung, S. Kavikondala, C.M. Schooling, Estradiol concentrations in young healthy US versus Chinese men. Am. J. Hum. Biol. 26(4), 565\u2013569 (2014). https:\/\/doi.org\/10.1002\/ajhb.22548","journal-title":"Am. J. Hum. Biol."},{"issue":"5","key":"1850_CR75","doi-asserted-by":"publisher","first-page":"720","DOI":"10.1111\/j.1365-2605.2012.01269.x","volume":"35","author":"C Foresta","year":"2012","unstructured":"C. Foresta, N. Caretta, P. Palego, A. Ferlin, D. Zuccarello, A. Lenzi, R. Selice, Reduced artery diameters in Klinefelter syndrome. Int. J. Androl. 35(5), 720\u2013725 (2012). https:\/\/doi.org\/10.1111\/j.1365-2605.2012.01269.x","journal-title":"Int. J. Androl."},{"issue":"2","key":"1850_CR76","doi-asserted-by":"publisher","first-page":"284","DOI":"10.1210\/jcem-49-2-284","volume":"49","author":"MG Forest","year":"1979","unstructured":"M.G. Forest, A. Lecoq, J.M. Saez, Kinetics of human chorionic gonadotropin-induced steroidogenic response of the human testis. II. Plasma 17 alpha-hydroxyprogesterone, delta4-androstenedione, estrone, and 17 beta-estradiol: evidence for the action of human chorionic gonadotropin on intermediate enzymes implicated in steroid biosynthesis. J. Clin. Endocrinol. Metab. 49(2), 284\u2013291 (1979). https:\/\/doi.org\/10.1210\/jcem-49-2-284","journal-title":"J. Clin. Endocrinol. Metab."},{"key":"1850_CR77","doi-asserted-by":"publisher","unstructured":"G.A. Kanakis, E. Nieschlag, Klinefelter syndrome: more than hypogonadism. Metabolism (2018). https:\/\/doi.org\/10.1016\/j.metabol.2017.09.017","DOI":"10.1016\/j.metabol.2017.09.017"},{"issue":"1","key":"1850_CR78","doi-asserted-by":"publisher","first-page":"37","DOI":"10.1007\/s12020-016-0975-9","volume":"55","author":"A Sansone","year":"2017","unstructured":"A. Sansone, F. Romanelli, M. Sansone, A. Lenzi, L. Di Luigi, Gynecomastia and hormones. Endocrine 55(1), 37\u201344 (2017). https:\/\/doi.org\/10.1007\/s12020-016-0975-9","journal-title":"Endocrine"},{"key":"1850_CR79","unstructured":"V. Rochira, B. Madeo, C. Diazzi, L. Zirilli, S. Daniele, C. Carani, Estrogens and male reproduction. In: L.J. De Groot, G. Chrousos, K. Dungan, K.R. Feingold, A. Grossman, J.M. Hershman, C. Koch, M. Korbonits, R. McLachlan, M. New, J. Purnell, R. Rebar, F. Singer, A. Vinik (eds.), Endotext (MDText.com, Inc., South Dartmouth, MA, 2000)"},{"issue":"4","key":"1850_CR80","doi-asserted-by":"publisher","first-page":"397","DOI":"10.1586\/17446651.2014.926810","volume":"9","author":"M Shozu","year":"2014","unstructured":"M. Shozu, M. Fukami, T. Ogata, Understanding the pathological manifestations of aromatase excess syndrome: lessons for clinical diagnosis. Expert Rev. Endocrinol. Metab. 9(4), 397\u2013409 (2014). https:\/\/doi.org\/10.1586\/17446651.2014.926810","journal-title":"Expert Rev. Endocrinol. Metab."}],"container-title":["Endocrine"],"original-title":[],"language":"en","link":[{"URL":"http:\/\/link.springer.com\/article\/10.1007\/s12020-019-01850-y\/fulltext.html","content-type":"text\/html","content-version":"vor","intended-application":"text-mining"},{"URL":"http:\/\/link.springer.com\/content\/pdf\/10.1007\/s12020-019-01850-y.pdf","content-type":"application\/pdf","content-version":"vor","intended-application":"text-mining"},{"URL":"http:\/\/link.springer.com\/content\/pdf\/10.1007\/s12020-019-01850-y.pdf","content-type":"application\/pdf","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2024,7,14]],"date-time":"2024-07-14T08:20:39Z","timestamp":1720945239000},"score":1,"resource":{"primary":{"URL":"http:\/\/link.springer.com\/10.1007\/s12020-019-01850-y"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2019,1,30]]},"references-count":80,"journal-issue":{"issue":"2","published-print":{"date-parts":[[2019,5]]}},"alternative-id":["1850"],"URL":"https:\/\/doi.org\/10.1007\/s12020-019-01850-y","relation":{},"ISSN":["1355-008X","1559-0100"],"issn-type":[{"value":"1355-008X","type":"print"},{"value":"1559-0100","type":"electronic"}],"subject":[],"published":{"date-parts":[[2019,1,30]]},"assertion":[{"value":"2 November 2018","order":1,"name":"received","label":"Received","group":{"name":"ArticleHistory","label":"Article History"}},{"value":"18 January 2019","order":2,"name":"accepted","label":"Accepted","group":{"name":"ArticleHistory","label":"Article History"}},{"value":"30 January 2019","order":3,"name":"first_online","label":"First Online","group":{"name":"ArticleHistory","label":"Article History"}},{"order":1,"name":"Ethics","group":{"name":"EthicsHeading","label":"Compliance with ethical standards"}},{"value":"The authors declare that they have no conflict of interest.","order":2,"name":"Ethics","group":{"name":"EthicsHeading","label":"Conflict of interest"}},{"value":"This article does not contain any studies with human participants performed by any of the authors.","order":3,"name":"Ethics","group":{"name":"EthicsHeading","label":"Ethical approval"}}]}}