{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,3,25]],"date-time":"2026-03-25T18:32:52Z","timestamp":1774463572937,"version":"3.50.1"},"reference-count":27,"publisher":"Springer Science and Business Media LLC","issue":"4","license":[{"start":{"date-parts":[[2024,7,4]],"date-time":"2024-07-04T00:00:00Z","timestamp":1720051200000},"content-version":"tdm","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0"},{"start":{"date-parts":[[2024,7,4]],"date-time":"2024-07-04T00:00:00Z","timestamp":1720051200000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0"}],"funder":[{"DOI":"10.13039\/501100005743","name":"Universit\u00e0 Cattolica del Sacro Cuore","doi-asserted-by":"crossref","id":[{"id":"10.13039\/501100005743","id-type":"DOI","asserted-by":"crossref"}]}],"content-domain":{"domain":["link.springer.com"],"crossmark-restriction":false},"short-container-title":["Arch Gynecol Obstet"],"abstract":"<jats:title>Abstract<\/jats:title><jats:sec>\n                <jats:title>Purpose<\/jats:title>\n                <jats:p>Functional hypothalamic amenorrhea (FHA) is characterized by an estrogen deficiency which in turn can cause vascular dysfunction. The aim of this study is to evaluate any changes in the chorio-retinal circulation in patients affected by FHA. 24 patients with FHA and 24 age-matched controls underwent a gynecological evaluation and an OCT angiography (OCTA) to study chorio-retinal vascularization.<\/jats:p>\n              <\/jats:sec><jats:sec>\n                <jats:title>Results<\/jats:title>\n                <jats:p>OCTA in FHA patients showed an increase in vessel density in the choriocapillaris (CC) layer (both in the fovea area, at 5% <jats:italic>p<\/jats:italic> value\u2009=\u20090.037 and in the whole area, at 5% <jats:italic>p<\/jats:italic> value\u2009=\u20090.028) and an increase in vascular density in the deep fovea (DVP) (at 10% <jats:italic>p<\/jats:italic> value\u2009=\u20090.096) in the whole district compared to controls. Simple linear regressions show a significant negative association between CC vessel density and insulin (<jats:italic>p<\/jats:italic>\u2009=\u20090.0002) and glucose values (<jats:italic>p<\/jats:italic>\u2009=\u20090.0335) for the fovea district and a negative association between DVP vessel density and endometrial thickness (at 10%, <jats:italic>p<\/jats:italic> value: 0.095) in the whole district.<\/jats:p>\n              <\/jats:sec><jats:sec>\n                <jats:title>Conclusion<\/jats:title>\n                <jats:p>Our study shows that CC vessel density is increased in women affected by FHA. This could represent a compensation effort to supply the vascular dysfunction caused by estrogen deficiency. We also found an increasing trend in vascular density in DVP associated with the decrease of endometrial thickness, an indirect sign of estrogenization. Considering that these changes occur in absence of visual defects, they could be used as a biomarker to estimate hypoestrogenism-induced microcirculation changes before clinical appearance.<\/jats:p>\n              <\/jats:sec>","DOI":"10.1007\/s00404-024-07603-1","type":"journal-article","created":{"date-parts":[[2024,7,4]],"date-time":"2024-07-04T07:01:54Z","timestamp":1720076514000},"page":"2247-2252","update-policy":"https:\/\/doi.org\/10.1007\/springer_crossmark_policy","source":"Crossref","is-referenced-by-count":1,"title":["Chorio-retinal vessel density in women affected by functional hypothalamic amenorrhea: a monocentric observational cross-sectional study to evaluate the impact of hypoestrogenism on chorio-retinal vascularization"],"prefix":"10.1007","volume":"310","author":[{"ORCID":"https:\/\/orcid.org\/0000-0002-7681-1200","authenticated-orcid":false,"given":"Alice","family":"Diterlizzi","sequence":"first","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Anna","family":"Tropea","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Emanuela","family":"Angelini","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Valentina","family":"Cestrone","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Romina","family":"Fasciani","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Annamaria","family":"Merola","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Giovanna","family":"Notaristefano","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Martina Asia","family":"Policriti","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Teresa","family":"Polimeno","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Monia","family":"Ranalli","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Maria Cristina","family":"Savastano","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Ghazal","family":"Tannous","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Valeria","family":"Versace","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Stanislao","family":"Rizzo","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Giovanni","family":"Scambia","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Antonio","family":"Lanzone","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Rosanna","family":"Apa","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"297","published-online":{"date-parts":[[2024,7,4]]},"reference":[{"issue":"3","key":"7603_CR1","doi-asserted-by":"publisher","first-page":"256","DOI":"10.1055\/s-0037-1603581","volume":"35","author":"CL Shufelt","year":"2017","unstructured":"Shufelt CL, Torbati T, Dutra E (2017) Hypothalamic amenorrhea and the long-term health consequences. Semin Reprod Med 35(3):256\u2013262","journal-title":"Semin Reprod Med"},{"issue":"12A","key":"7603_CR2","doi-asserted-by":"publisher","first-page":"12E","DOI":"10.1016\/S0002-9149(02)02405-0","volume":"89","author":"ME Mendelsohn","year":"2002","unstructured":"Mendelsohn ME (2002) Protective effects of estrogen on the cardiovascular system. Am J Cardiol 89(12A):12E-17E","journal-title":"Am J Cardiol"},{"issue":"12","key":"7603_CR3","doi-asserted-by":"publisher","first-page":"3638","DOI":"10.1210\/jc.2011-1223","volume":"96","author":"E O\u2019Donnell","year":"2011","unstructured":"O\u2019Donnell E, Goodman JM, Harvey PJ (2011) Clinical review: Cardiovascular consequences of ovarian disruption: a focus on functional hypothalamic amenorrhea in physically active women. J Clin Endocrinol Metab 96(12):3638\u20133648","journal-title":"J Clin Endocrinol Metab"},{"key":"7603_CR4","doi-asserted-by":"publisher","first-page":"1741","DOI":"10.1016\/j.jacc.2005.10.076","volume":"47","author":"P Ouyang","year":"2006","unstructured":"Ouyang P, Michos ED, Karas RH (2006) Hormone replacement theray and the cardiovascular system lessons learned and unanswered questions. J Am Coll Cardiol 47:1741\u20131753","journal-title":"J Am Coll Cardiol"},{"issue":"11","key":"7603_CR5","doi-asserted-by":"publisher","first-page":"1049","DOI":"10.1007\/s40618-014-0169-3","volume":"37","author":"B Meczekalski","year":"2014","unstructured":"Meczekalski B, Katulski K, Czyzyk A, Podfigurna-Stopa A, Maciejewska-Jeske M (2014) Functional hypothalamic amenorrhea and its influence on women\u2019s health. J Endocrinol Invest 37(11):1049\u20131056","journal-title":"J Endocrinol Invest"},{"issue":"5","key":"7603_CR6","doi-asserted-by":"publisher","first-page":"1798","DOI":"10.1210\/jc.2013-3398","volume":"99","author":"E O\u2019Donnell","year":"2014","unstructured":"O\u2019Donnell E, Goodman JM, Mak S, Harvey PJ (2014) Impaired vascular function in physically active premenopausal women with functional hypothalamic amenorrhea is associated with low shear stress and increased vascular tone. J Clin Endocrinol Metab 99(5):1798\u20131806","journal-title":"J Clin Endocrinol Metab"},{"issue":"2","key":"7603_CR7","doi-asserted-by":"publisher","first-page":"119","DOI":"10.1097\/JSM.0b013e3182042a9a","volume":"21","author":"AZ Hoch","year":"2011","unstructured":"Hoch AZ, Papanek P, Szabo A, Widlansky ME, Schimke JE, Gutterman DD (2011) Association between the female athlete triad and endothelial dysfunction in dancers. Clin J Sport Med 21(2):119\u2013125","journal-title":"Clin J Sport Med"},{"issue":"3","key":"7603_CR8","doi-asserted-by":"publisher","first-page":"413","DOI":"10.1016\/S0735-1097(02)02763-8","volume":"41","author":"CN Bairey Merz","year":"2003","unstructured":"Bairey Merz CN, Johnson BD, Sharaf BL, Bittner V, Berga SL, Braunstein GD, WISE Study Group et al (2003) Hypoestrogenemia of hypothalamic origin and coronary artery disease in premenopausal women: a report from the NHLBI-sponsored WISE study. J Am Coll Cardiol 41(3):413\u2013419","journal-title":"J Am Coll Cardiol"},{"issue":"2","key":"7603_CR9","doi-asserted-by":"publisher","first-page":"201","DOI":"10.3109\/02713683.2014.906625","volume":"40","author":"D Schmidl","year":"2015","unstructured":"Schmidl D, Schmetterer L, Garh\u00f6fer G, Popa-Cherecheanu A (2015) Gender differences in ocular blood flow. Curr Eye Res 40(2):201\u2013212","journal-title":"Curr Eye Res"},{"issue":"5","key":"7603_CR10","doi-asserted-by":"publisher","first-page":"680","DOI":"10.1007\/s10517-013-2224-z","volume":"155","author":"AS Obrubov","year":"2013","unstructured":"Obrubov AS, Obrubov SA, Medvedev IB, Dreval AA, Maximova NV, Falhut OS (2013) Changes in the retina in induced hypoestrogenia (according to optical coherent tomography data). Bull Exp Biol Med 155(5):680\u2013681","journal-title":"Bull Exp Biol Med"},{"issue":"8","key":"7603_CR11","doi-asserted-by":"publisher","first-page":"1128","DOI":"10.1136\/bjo.2009.177899","volume":"95","author":"MM Moschos","year":"2011","unstructured":"Moschos MM, Gonidakis F, Varsou E et al (2011) Anatomical and functional impairment of the retina and optic nerve in patients with anorexia nervosa without vision loss. Br J Ophthalmol 95(8):1128\u20131133","journal-title":"Br J Ophthalmol"},{"issue":"4","key":"7603_CR12","doi-asserted-by":"publisher","first-page":"386","DOI":"10.1002\/eat.22471","volume":"49","author":"MM Moschos","year":"2016","unstructured":"Moschos MM, Moustafa GA, Gonidakis F, Papageorgiou C (2016) Retinal and choroidal alterations in patients with anorexia nervosa without vision loss. Int J Eat Disord 49(4):386\u2013390","journal-title":"Int J Eat Disord"},{"issue":"11","key":"7603_CR13","doi-asserted-by":"publisher","first-page":"2196","DOI":"10.1097\/IAE.0000000000000635","volume":"35","author":"MC Savastano","year":"2015","unstructured":"Savastano MC, Lumbroso B, Rispoli M (2015) In vivo characterization of retinal vascularization morphology using optical coherence tomography angiography. Retina 35(11):2196\u20132203","journal-title":"Retina"},{"issue":"5","key":"7603_CR14","doi-asserted-by":"publisher","first-page":"1413","DOI":"10.1210\/jc.2017-00131","volume":"102","author":"CM Gordon","year":"2017","unstructured":"Gordon CM, Ackerman KE, Berga SL et al (2017) Functional hypothalamic amenorrhea: an Endocrine Society Clinical Practice Guideline. J Clin Endocrinol Metab 102(5):1413\u20131439","journal-title":"J Clin Endocrinol Metab"},{"issue":"1","key":"7603_CR15","doi-asserted-by":"publisher","first-page":"48","DOI":"10.1186\/s40662-021-00269-9","volume":"8","author":"X Liu","year":"2021","unstructured":"Liu X, Lin Z, Wang F, Peng X, He W, Chen D et al (2021) Choroidal thickness and choriocapillaris vascular density in myopic anisometropia. Eye Vis (Lond) 8(1):48","journal-title":"Eye Vis (Lond)"},{"key":"7603_CR16","doi-asserted-by":"publisher","DOI":"10.1016\/j.preteyeres.2021.100997","volume":"87","author":"R Lejoyeux","year":"2022","unstructured":"Lejoyeux R, Benillouche J, Ong J, Errera MH, Rossi EA, Singh SR et al (2022) Choriocapillaris: fundamentals and advancements. Prog Retin Eye Res 87:100997","journal-title":"Prog Retin Eye Res"},{"issue":"6","key":"7603_CR17","first-page":"2857","volume":"35","author":"RS Ramrattan","year":"1994","unstructured":"Ramrattan RS, van der Schaft TL, Mooy CM, de Bruijn WC, Mulder PG, de Jong PT (1994) Morphometric analysis of Bruch\u2019s membrane, the choriocapillaris, and the choroid in aging. Invest Ophthalmol Vis Sci 35(6):2857\u20132864","journal-title":"Invest Ophthalmol Vis Sci"},{"issue":"8","key":"7603_CR18","doi-asserted-by":"publisher","first-page":"850","DOI":"10.1111\/j.1755-3768.2009.01607.x","volume":"88","author":"D Kavroulaki","year":"2010","unstructured":"Kavroulaki D, Gugleta K, Kochkorov A, Katamay R, Flammer J, Orgul S (2010) Influence of gender and menopausal status on peripheral and choroidal circulation. Acta Ophthalmol 88(8):850\u2013853","journal-title":"Acta Ophthalmol"},{"issue":"31","key":"7603_CR19","doi-asserted-by":"publisher","first-page":"606","DOI":"10.1053\/ob.1996.v175.a73597","volume":"175","author":"M Penotti","year":"1996","unstructured":"Penotti M, Farina M, Castiglioni E, Gaffuri B, Barletta L, Gabrielli et al (1996) Alteration in the pulsatility index values of the internal carotid and middle cerebral arteries after suspension of postmenopausal hormone replacement therapy: a randomized crossover study. Am J Obstet Gynecol 175(31):606\u2013611","journal-title":"Am J Obstet Gynecol"},{"issue":"8","key":"7603_CR20","doi-asserted-by":"publisher","first-page":"1076","DOI":"10.1001\/archopht.118.8.1076","volume":"118","author":"A Harris","year":"2000","unstructured":"Harris A, Harris M, Biller J et al (2000) Aging affects the retrobulbar circulation differently in women and men. Arch Ophthalmol 118(8):1076\u20131080","journal-title":"Arch Ophthalmol"},{"issue":"10","key":"7603_CR21","first-page":"882","volume":"61","author":"L St\u00e1rka","year":"2015","unstructured":"St\u00e1rka L, Du\u0161kov\u00e1 M (2015) Funk\u010dn\u00ed hypotalamick\u00e1 amenorea [functional hypothalamic amenorrhea]. Vnitr Lek 61(10):882\u2013885","journal-title":"Vnitr Lek"},{"issue":"Suppl 1","key":"7603_CR22","doi-asserted-by":"publisher","first-page":"18","DOI":"10.4274\/jcrpe.galenos.2019.2019.S0178","volume":"12","author":"ME Sophie Gibson","year":"2020","unstructured":"Sophie Gibson ME, Fleming N, Zuijdwijk C, Dumont T (2020) Where have the periods gone? the evaluation and management of functional hypothalamic amenorrhea. J Clin Res Pediatr Endocrinol 12(Suppl 1):18\u201327","journal-title":"J Clin Res Pediatr Endocrinol"},{"issue":"1","key":"7603_CR23","first-page":"25","volume":"83","author":"GA Laughlin","year":"1998","unstructured":"Laughlin GA, Dominguez CE, Yen SS (1998) Nutritional and endocrine-metabolic aberrations in women with functional hypothalamic amenorrhea. J Clin Endocrinol Metab 83(1):25\u201332","journal-title":"J Clin Endocrinol Metab"},{"issue":"5","key":"7603_CR24","doi-asserted-by":"publisher","first-page":"469","DOI":"10.1007\/s00592-018-1115-1","volume":"55","author":"D Cao","year":"2018","unstructured":"Cao D, Yang D, Huang Z, Zeng Y, Wang J, Hu Y et al (2018) Optical coherence tomography angiography discerns preclinical diabetic retinopathy in eyes of patients with type 2 diabetes without clinical diabetic retinopathy. Acta Diabetol 55(5):469\u2013477","journal-title":"Acta Diabetol"},{"key":"7603_CR25","doi-asserted-by":"publisher","first-page":"602","DOI":"10.1038\/eye.2001.193","volume":"15","author":"G Dimitrova","year":"2001","unstructured":"Dimitrova G, Kato S, Tamaki Y et al (2001) Choroidal circulation in diabetic patients. Eye (Lond) 15:602\u2013607","journal-title":"Eye (Lond)"},{"issue":"1","key":"7603_CR26","doi-asserted-by":"publisher","first-page":"190","DOI":"10.1167\/iovs.16-20531","volume":"58","author":"G Dimitrova","year":"2017","unstructured":"Dimitrova G, Chihara E, Takahashi H, Amano H, Okazaki K (2017) Quantitative retinal optical coherence tomography angiography in patients with diabetes without diabetic retinopathy. Invest Ophthalmol Vis Sci 58(1):190\u2013196","journal-title":"Invest Ophthalmol Vis Sci"},{"issue":"1","key":"7603_CR27","doi-asserted-by":"publisher","first-page":"187","DOI":"10.1186\/s12886-022-02397-9","volume":"22","author":"N Yang","year":"2022","unstructured":"Yang N, Li MX, Peng XY (2022) Effects of intensive insulin therapy on the retinal microvasculature in patients with type 2 diabetes mellitus: a prospective observational study. BMC Ophthalmol 22(1):187","journal-title":"BMC Ophthalmol"}],"container-title":["Archives of Gynecology and Obstetrics"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/link.springer.com\/content\/pdf\/10.1007\/s00404-024-07603-1.pdf","content-type":"application\/pdf","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/link.springer.com\/article\/10.1007\/s00404-024-07603-1\/fulltext.html","content-type":"text\/html","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/link.springer.com\/content\/pdf\/10.1007\/s00404-024-07603-1.pdf","content-type":"application\/pdf","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2024,9,12]],"date-time":"2024-09-12T08:24:31Z","timestamp":1726129471000},"score":1,"resource":{"primary":{"URL":"https:\/\/link.springer.com\/10.1007\/s00404-024-07603-1"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2024,7,4]]},"references-count":27,"journal-issue":{"issue":"4","published-online":{"date-parts":[[2024,10]]}},"alternative-id":["7603"],"URL":"https:\/\/doi.org\/10.1007\/s00404-024-07603-1","relation":{},"ISSN":["1432-0711"],"issn-type":[{"value":"1432-0711","type":"electronic"}],"subject":[],"published":{"date-parts":[[2024,7,4]]},"assertion":[{"value":"7 April 2024","order":1,"name":"received","label":"Received","group":{"name":"ArticleHistory","label":"Article History"}},{"value":"12 June 2024","order":2,"name":"accepted","label":"Accepted","group":{"name":"ArticleHistory","label":"Article History"}},{"value":"4 July 2024","order":3,"name":"first_online","label":"First Online","group":{"name":"ArticleHistory","label":"Article History"}},{"order":1,"name":"Ethics","group":{"name":"EthicsHeading","label":"Declarations"}},{"value":"The authors have not disclosed any competing interests.","order":2,"name":"Ethics","group":{"name":"EthicsHeading","label":"Conflict of interest"}}]}}