{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,8,29]],"date-time":"2026-08-29T06:49:45Z","timestamp":1787986185428,"version":"build-2784847793"},"reference-count":41,"publisher":"Springer Science and Business Media LLC","issue":"6","license":[{"start":{"date-parts":[[2022,1,24]],"date-time":"2022-01-24T00:00:00Z","timestamp":1642982400000},"content-version":"tdm","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0"},{"start":{"date-parts":[[2022,1,24]],"date-time":"2022-01-24T00:00:00Z","timestamp":1642982400000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0"}],"funder":[{"DOI":"10.13039\/501100003407","name":"ministero dell\u2019istruzione, dell\u2019universit\u00e0 e della ricerca","doi-asserted-by":"publisher","award":["PRIN: 2017S9KTNE"],"award-info":[{"award-number":["PRIN: 2017S9KTNE"]}],"id":[{"id":"10.13039\/501100003407","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":["link.springer.com"],"crossmark-restriction":false},"short-container-title":["J Endocrinol Invest"],"published-print":{"date-parts":[[2022,6]]},"abstract":"<jats:title>Abstract<\/jats:title><jats:sec>\n                <jats:title>Purpose<\/jats:title>\n                <jats:p>Female sexual response involves a complex interplay between neurophysiological mechanisms and the nitric oxide (NO)-mediated relaxation of clitoris and vagina. The aim of this study was to evaluate sex steroids regulation of the relaxant pathway in vagina, using a validated animal model.<\/jats:p>\n              <\/jats:sec><jats:sec>\n                <jats:title>Methods<\/jats:title>\n                <jats:p>Subgroups of OVX Sprague\u2013Dawley rats were treated with 17\u03b2-estradiol, testosterone, or testosterone and letrozole, and compared with a group of intact animals. Masson\u2019s trichrome staining was performed for morphological evaluation of the distal vaginal wall, in vitro contractility studies investigated the effect of OVX and in vivo treatments on vaginal smooth muscle activity. RNA from vaginal tissue was analyzed by semi-quantitative RT-PCR.<\/jats:p>\n              <\/jats:sec><jats:sec>\n                <jats:title>Results<\/jats:title>\n                <jats:p>Immunohistochemical analysis showed that OVX induced epithelial and smooth muscle structural atrophy, testosterone and testo\u2009+\u2009letrozole increased the muscle bundles content and organization without affecting the epithelium while 17\u03b2-estradiol mediated the opposite effects. In vitro contractility studies were performed on noradrenaline pre-contracted vaginal strips from each experimental group. Acetylcholine (0.001\u201310\u00a0\u00b5M) stimulation induced a concentration-dependent relaxation, significantly reduced by NO-synthase inhibitor L-NAME and by guanylate cyclase inhibitor ODQ. OVX resulted in a decreased responsiveness to acetylcholine, restored by testosterone, with or without letrozole, but not by 17\u03b2-estradiol. OVX sensitivity to the NO-donor SNP was higher than in the control. Vardenafil, a PDE5 inhibitor, enhanced SNP effect in OVX\u2009+\u2009testosterone as well as in control, as supported by RNA expression analysis.<\/jats:p>\n              <\/jats:sec><jats:sec>\n                <jats:title>Conclusions<\/jats:title>\n                <jats:p>Our study demonstrates that testosterone improves the NO-mediated smooth muscle vaginal cells relaxation confirming its role in maintaining the integrity of muscular relaxant machinery.<\/jats:p>\n              <\/jats:sec>","DOI":"10.1007\/s40618-022-01743-4","type":"journal-article","created":{"date-parts":[[2022,1,24]],"date-time":"2022-01-24T08:02:56Z","timestamp":1643011376000},"page":"1161-1172","update-policy":"https:\/\/doi.org\/10.1007\/springer_crossmark_policy","source":"Crossref","is-referenced-by-count":18,"title":["Testosterone positively regulates vagina NO-induced relaxation: an experimental study in rats"],"prefix":"10.1007","volume":"45","author":[{"given":"I.","family":"Cellai","sequence":"first","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"S.","family":"Filippi","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"P.","family":"Comeglio","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"S.","family":"Cipriani","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"E.","family":"Maseroli","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"V.","family":"Di Stasi","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"T.","family":"Todisco","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"S.","family":"Marchiani","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"L.","family":"Tamburrino","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"F.","family":"Villanelli","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"S.","family":"Vezzani","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"C.","family":"Corno","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"M.","family":"Fambrini","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"G.","family":"Guarnieri","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"E.","family":"Sarchielli","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"A.","family":"Morelli","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"G.","family":"Rastrelli","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"M.","family":"Maggi","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-0907-0630","authenticated-orcid":false,"given":"L.","family":"Vignozzi","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"297","published-online":{"date-parts":[[2022,1,24]]},"reference":[{"key":"1743_CR1","doi-asserted-by":"publisher","first-page":"980","DOI":"10.1016\/S2213-8587(15)00284","volume":"3","author":"SR Davis","year":"2015","unstructured":"Davis SR, Wahlin-Jacobsen S (2015) Testosterone in women\u2014the clinical significance. Lancet Diabetes Endocrinol 3:980\u2013992. https:\/\/doi.org\/10.1016\/S2213-8587(15)00284","journal-title":"Lancet Diabetes Endocrinol"},{"key":"1743_CR2","doi-asserted-by":"publisher","first-page":"837","DOI":"10.1097\/GME.0000000000001138","volume":"25","author":"JA Simon","year":"2018","unstructured":"Simon JA, Goldstein I, Kim NN, Davis SR, Kellogg-Spadt S, Lowenstein L, Pinkerton JV, Stuenkel CA, Traish AM, Archer DF, Bachmann G, Goldstein AT, Nappi RE, Vignozzi L (2018) The role of androgens in the treatment of genitourinary syndrome of menopause (GSM): International Society for the Study of Women\u2019s Sexual Health (ISSWSH) expert consensus panel review. Menopause 25:837\u2013847. https:\/\/doi.org\/10.1097\/GME.0000000000001138","journal-title":"Menopause"},{"key":"1743_CR3","doi-asserted-by":"publisher","first-page":"5226","DOI":"10.1210\/jc.2004-1747","volume":"90","author":"J Simon","year":"2005","unstructured":"Simon J, Braunstein G, Nachtigall L, Utian W, Katz M, Miller S, Waldbaum A, Bouchard C, Derzko C, Buch A, Rodenberg C, Lucas J, Davis S (2005) Testosterone patch increases sexual activity and desire in surgically menopausal women with hypoactive sexual desire disorder. J Clin Endocrinol Metab 90:5226\u20135233. https:\/\/doi.org\/10.1210\/jc.2004-1747","journal-title":"J Clin Endocrinol Metab"},{"key":"1743_CR4","doi-asserted-by":"publisher","first-page":"37","DOI":"10.1097\/01.gme.0000168061.32917.83","volume":"13","author":"SR Davis","year":"2006","unstructured":"Davis SR, Goldstat R, Papalia MA, Shah S, Kulkarni J, Donath S, Bell RJ (2006) Effects of aromatase inhibition on sexual function and well-being in postmenopausal women treated with testosterone: a randomized, placebo-controlled trial. Menopause 13:37\u201345. https:\/\/doi.org\/10.1097\/01.gme.0000168061.32917.83","journal-title":"Menopause"},{"key":"1743_CR5","doi-asserted-by":"publisher","first-page":"121","DOI":"10.3109\/13697131003675922","volume":"13","author":"N Panay","year":"2010","unstructured":"Panay N, Al-Azzawi F, Bouchard C, Davis SR, Eden J, Lodhi I, Rees M, Rodenberg CA, Rymer J, Schwenkhagen A, Sturdee DW (2010) Testosterone treatment of HSDD in naturally menopausal women: the ADORE study. Climacteric 13:121\u2013131. https:\/\/doi.org\/10.3109\/13697131003675922","journal-title":"Climacteric"},{"key":"1743_CR6","doi-asserted-by":"publisher","first-page":"22","DOI":"10.1016\/j.maturitas.2011.06.005","volume":"70","author":"M Panjari","year":"2011","unstructured":"Panjari M, Davis SR (2011) Vaginal DHEA to treat menopause related atrophy: a review of the evidence. Maturitas 70:22\u201325. https:\/\/doi.org\/10.1016\/j.maturitas.2011.06.005","journal-title":"Maturitas"},{"key":"1743_CR7","doi-asserted-by":"publisher","first-page":"139","DOI":"10.1016\/j.jsbmb.2014.09.003","volume":"145","author":"DF Archer","year":"2015","unstructured":"Archer DF (2015) Dehydroepiandrosterone intra vaginal administration for the management of postmenopausal vulvovaginal atrophy. J Steroid Biochem Mol Biol 145:139\u2013143. https:\/\/doi.org\/10.1016\/j.jsbmb.2014.09.003","journal-title":"J Steroid Biochem Mol Biol"},{"issue":"2","key":"1743_CR8","doi-asserted-by":"publisher","first-page":"bqaa219","DOI":"10.1210\/endocr\/bqaa219","volume":"162","author":"I Cellai","year":"2021","unstructured":"Cellai I, Di Stasi V, Comeglio P, Maseroli E, Todisco T, Corno C, Filippi S, Cipriani S, Sorbi F, Fambrini M, Petraglia F, Scavello I, Rastrelli G, Acciai G, Villanelli F, Danza G, Sarchielli E, Guarnieri G, Morelli A, Maggi M, Vignozzi L (2021) Insight on the intracrinology of menopause: androgen production within the human vagina. Endocrinology 162(2):bqaa219. https:\/\/doi.org\/10.1210\/endocr\/bqaa219","journal-title":"Endocrinology"},{"key":"1743_CR9","doi-asserted-by":"publisher","first-page":"109","DOI":"10.1530\/JME-20-0147","volume":"65","author":"E Maseroli","year":"2020","unstructured":"Maseroli E, Cellai I, Filippi S, Comeglio P, Cipriani S, Rastrelli G, Rosi M, Sorbi F, Fambrini M, Petraglia F, Amoriello R, Ballerini C, Lombardelli L, Piccinni MP, Sarchielli E, Guarnieri G, Morelli A, Maggi M, Vignozzi L (2020) Anti-inflammatory effects of androgens in the human vagina. J Mol Endocrinol 65:109\u2013124. https:\/\/doi.org\/10.1530\/JME-20-0147","journal-title":"J Mol Endocrinol"},{"key":"1743_CR10","doi-asserted-by":"publisher","first-page":"75","DOI":"10.1097\/00005392-199707000-00020","volume":"158","author":"AL Burnett","year":"1997","unstructured":"Burnett AL, Calvin DC, Silver RI, Peppas DS, Docimo SG (1997) Immunohistochemical description of nitric oxide synthase isoforms in human clitoris. J Urol 158:75\u201378. https:\/\/doi.org\/10.1097\/00005392-199707000-00020","journal-title":"J Urol"},{"key":"1743_CR11","doi-asserted-by":"publisher","first-page":"1627","DOI":"10.1038\/sj.bjp.0702278","volume":"125","author":"S Cellek","year":"1998","unstructured":"Cellek S, Moncada S (1998) Nitrergic neurotransmission mediates the non-adrenergic non-cholinergic responses in the clitoral corpus cavernosum of the rabbit. Br J Pharmacol 125:1627\u20131629. https:\/\/doi.org\/10.1038\/sj.bjp.0702278","journal-title":"Br J Pharmacol"},{"key":"1743_CR12","doi-asserted-by":"publisher","first-page":"23","DOI":"10.1016\/s0024-3205(00)00596-8","volume":"67","author":"S Vemulapalli","year":"2000","unstructured":"Vemulapalli S, Kurowski S (2000) Sildenafil relaxes rabbit clitoral corpus cavernosum. Life Sci 67:23\u201329. https:\/\/doi.org\/10.1016\/s0024-3205(00)00596-8","journal-title":"Life Sci"},{"key":"1743_CR13","doi-asserted-by":"publisher","first-page":"1022","DOI":"10.1177\/153537020222701111","volume":"227","author":"JK Park","year":"2002","unstructured":"Park JK, Kim JU, Lee SO, Hwang PH, Yi HK, Kim YG, Cho KW (2002) Nitric oxide cyclic GMP signaling pathway in the regulation of rabbit clitoral cavernosum tone. Exp Biol Med (Maywood) 227:1022\u20131030. https:\/\/doi.org\/10.1177\/153537020222701111","journal-title":"Exp Biol Med (Maywood)"},{"key":"1743_CR14","doi-asserted-by":"publisher","first-page":"612","DOI":"10.1006\/bbrc.1998.9206","volume":"249","author":"K Park","year":"1998","unstructured":"Park K, Moreland RB, Goldstein I, Atala A, Traish A (1998) Sildenafil inhibits phosphodiesterase type 5 in human clitoral corpus cavernosum smooth muscle. Biochem Biophys Res Commun 249:612\u2013617. https:\/\/doi.org\/10.1006\/bbrc.1998.9206","journal-title":"Biochem Biophys Res Commun"},{"key":"1743_CR15","doi-asserted-by":"publisher","first-page":"191","DOI":"10.1016\/s0090-4295(02)01663-1","volume":"60","author":"G D'Amati","year":"2002","unstructured":"D\u2019Amati G, di Gioia CR, Bologna M, Giordano D, Giorgi M, Dolci S, Jannini EA (2002) Type 5 phosphodiesterase expression in the human vagina. Urology 60:191\u2013195. https:\/\/doi.org\/10.1016\/s0090-4295(02)01663-1","journal-title":"Urology"},{"key":"1743_CR16","doi-asserted-by":"publisher","first-page":"1604","DOI":"10.1111\/j.1743-6109.2007.00595.x","volume":"4","author":"S \u00dcckert","year":"2007","unstructured":"\u00dcckert S, Ellinghaus P, Albrecht K, Jonas U, Oelke M (2007) Expression of messenger ribonucleic acid encoding for phosphodiesterase isoenzymes in human female genital tissues. J Sex Med 4:1604\u20131609. https:\/\/doi.org\/10.1111\/j.1743-6109.2007.00595.x","journal-title":"J Sex Med"},{"key":"1743_CR17","doi-asserted-by":"publisher","first-page":"206","DOI":"10.1038\/ijir.2011.29","volume":"23","author":"S \u00dcckert","year":"2011","unstructured":"\u00dcckert S, Oelke M, Albrecht K, Breitmeier D, Kuczyk MA, Hedlund P (2011) Expression and distribution of key enzymes of the cyclic GMP signaling in the human clitoris: relation to phosphodiesterase type 5 (PDE5). Int J Impot Res 23:206\u2013212. https:\/\/doi.org\/10.1038\/ijir.2011.29","journal-title":"Int J Impot Res"},{"key":"1743_CR18","doi-asserted-by":"publisher","first-page":"1858","DOI":"10.1016\/j.jsxm.2016.10.007","volume":"13","author":"P Comeglio","year":"2016","unstructured":"Comeglio P, Cellai I, Filippi S, Corno C, Corcetto F, Morelli A, Maneschi E, Maseroli E, Mannucci E, Fambrini M, Maggi M, Vignozzi L (2016) Differential effects of testosterone and estradiol on clitoral function: an experimental study in rats. J Sex Med 13:1858\u20131871. https:\/\/doi.org\/10.1016\/j.jsxm.2016.10.007","journal-title":"J Sex Med"},{"key":"1743_CR19","doi-asserted-by":"publisher","first-page":"397","DOI":"10.1038\/sj.ijir.3901097","volume":"15","author":"AM Traish","year":"2003","unstructured":"Traish AM, Kim NN, Huang YH, Min K, Munarriz R, Goldstein I (2003) Sex steroid hormones differentially regulate nitric oxide synthase and arginase activities in the proximal and distal rabbit vagina. Int J Impot Res 15:397\u2013404. https:\/\/doi.org\/10.1038\/sj.ijir.3901097","journal-title":"Int J Impot Res"},{"key":"1743_CR20","doi-asserted-by":"publisher","first-page":"43","DOI":"10.1038\/sj.ijir.3901138","volume":"16","author":"NN Kim","year":"2004","unstructured":"Kim NN, Min K, Pessina MA, Munarriz R, Goldstein I, Traish AM (2004) Effects of ovariectomy and steroid hormones on vaginal smooth muscle contractility. Int J Impot Res 16:43\u201350. https:\/\/doi.org\/10.1038\/sj.ijir.3901138","journal-title":"Int J Impot Res"},{"key":"1743_CR21","doi-asserted-by":"publisher","first-page":"545","DOI":"10.1007\/978-1-61779-415-5_34","volume":"816","author":"AI Idris","year":"2012","unstructured":"Idris AI (2012) Ovariectomy\/orchidectomy in rodents. Methods Mol Biol 816:545\u2013551. https:\/\/doi.org\/10.1007\/978-1-61779-415-5_34","journal-title":"Methods Mol Biol"},{"key":"1743_CR22","doi-asserted-by":"publisher","first-page":"335","DOI":"10.1016\/j.tjog.2012.11.003","volume":"52","author":"CC Liang","year":"2013","unstructured":"Liang CC, Lee TH, Chang SD (2013) Effects of sex hormones on cell proliferation and apoptosis in the urinary bladder muscle of ovariectomized rat. Taiwan J Obstet Gynecol 52:335\u2013340. https:\/\/doi.org\/10.1016\/j.tjog.2012.11.003","journal-title":"Taiwan J Obstet Gynecol"},{"key":"1743_CR23","doi-asserted-by":"publisher","first-page":"180","DOI":"10.7150\/ijms.6283","volume":"11","author":"F Dehghan","year":"2014","unstructured":"Dehghan F, Muniandy S, Yusof A, Salleh N (2014) Sex-steroid regulation of relaxin receptor isoforms (RXFP1 & RXFP2) expression in the patellar tendon and lateral collateral ligament of female WKY rats. Int J Med Sci 11:180\u2013191. https:\/\/doi.org\/10.7150\/ijms.6283","journal-title":"Int J Med Sci"},{"key":"1743_CR24","doi-asserted-by":"publisher","first-page":"745","DOI":"10.1167\/iovs.12-10457","volume":"55","author":"X Song","year":"2014","unstructured":"Song X, Zhao P, Wang G, Zhao X (2014) The effects of estrogen and androgen on tear secretion and matrix metalloproteinase-2 expression in lacrimal glands of ovariectomized rats. Invest Ophthalmol Vis Sci 55:745\u2013751. https:\/\/doi.org\/10.1167\/iovs.12-10457","journal-title":"Invest Ophthalmol Vis Sci"},{"issue":"7","key":"1743_CR25","doi-asserted-by":"publisher","DOI":"10.1371\/journal.pbio.3000410","volume":"18","author":"N Percie du Sert","year":"2020","unstructured":"Percie du Sert N, Hurst V, Ahluwalia A, Alam S, Avey MT, Baker M, Browne WJ, Clark A, Cuthill IC, Dirnagl U, Emerson M, Garner P, Holgate ST, Howells DW, Karp NA, Lazic SE, Lidster K, MacCallum CJ, Macleod M, Pearl EJ, Petersen O, Rawle F, Peynolds P, Rooney K, Sena ES, Silberberg SD, Steckler T, Wurbel H (2020) The ARRIVE guidelines 2.0: updated guidelines for reporting animal research. PLoS Biol 18(7):e3000410. https:\/\/doi.org\/10.1371\/journal.pbio.3000410","journal-title":"PLoS Biol"},{"key":"1743_CR26","doi-asserted-by":"publisher","first-page":"271","DOI":"10.1038\/sj.ijir.3900886","volume":"14","author":"A Giraldi","year":"2002","unstructured":"Giraldi A, Alm P, Werkstrom V, Myllymaki L, Wagner G, Andersson KE (2002) Morphological and functional characterization of a rat vaginal smooth muscle sphrincter. Int J Impot Res 14:271\u2013282. https:\/\/doi.org\/10.1038\/sj.ijir.3900886","journal-title":"Int J Impot Res"},{"key":"1743_CR27","doi-asserted-by":"publisher","first-page":"402","DOI":"10.1006\/meth.2001.1262","volume":"25","author":"KJ Livak","year":"2001","unstructured":"Livak KJ, Schmittgen TD (2001) Analysis of relative gene expression data using real-time quantitative PCR and the 2(-Delta C(T)) Method. Methods 25:402\u2013408. https:\/\/doi.org\/10.1006\/meth.2001.1262","journal-title":"Methods"},{"issue":"2","key":"1743_CR28","doi-asserted-by":"publisher","first-page":"E97","DOI":"10.1152\/ajpendo.1978.235.2.E97","volume":"235","author":"A DeLean","year":"1978","unstructured":"DeLean A, Munson PJ, Rodbard D (1978) Simultaneous analysis of families of sigmoidal curves: application to bioassay, radioligand assay, and physiological dose-response curves. Am J Physiol 235(2):E97\u2013E102. https:\/\/doi.org\/10.1152\/ajpendo.1978.235.2.E97","journal-title":"Am J Physiol"},{"issue":"Suppl","key":"1743_CR29","doi-asserted-by":"publisher","first-page":"S7","DOI":"10.1016\/0378-5122(95)00957-4","volume":"22","author":"JG Forsberg","year":"1995","unstructured":"Forsberg JG (1995) A morphologist\u2019s approach to the vagina\u2013age-related changes and estrogen sensitivity. Maturitas 22(Suppl):S7\u2013S15. https:\/\/doi.org\/10.1016\/0378-5122(95)00957-4","journal-title":"Maturitas"},{"key":"1743_CR30","doi-asserted-by":"publisher","first-page":"116","DOI":"10.1038\/sj.ijir.3900655","volume":"13","author":"K Park","year":"2001","unstructured":"Park K, Ahn K, Lee S, Ryu S, Park Y, Azadzoi KM (2001) Decreased circulating levels of estrogen alter vaginal and clitoral blood flow and structure in the rabbit. Int J Impot Res 13:116\u2013124. https:\/\/doi.org\/10.1038\/sj.ijir.3900655","journal-title":"Int J Impot Res"},{"key":"1743_CR31","doi-asserted-by":"publisher","first-page":"233","DOI":"10.1111\/j.1743-6109.2006.00216","volume":"3","author":"FF Onol","year":"2006","unstructured":"Onol FF, Ercan F, Tarcan T (2006) The effect of ovariectomy on rat vaginal tissue contractility and histomorphology. J Sex Med 3:233\u2013241. https:\/\/doi.org\/10.1111\/j.1743-6109.2006.00216","journal-title":"J Sex Med"},{"key":"1743_CR32","doi-asserted-by":"publisher","first-page":"26","DOI":"10.1055\/s-2005-869480","volume":"23","author":"SA Ballagh","year":"2005","unstructured":"Ballagh SA (2005) Vaginal hormone therapy for urogenital and menopausal symptoms. Semin Reprod Med 23:26\u201340. https:\/\/doi.org\/10.1055\/s-2005-869480","journal-title":"Semin Reprod Med"},{"key":"1743_CR33","doi-asserted-by":"publisher","first-page":"138","DOI":"10.1016\/j.maturitas.2009.03.021","volume":"63","author":"RE Nappi","year":"2009","unstructured":"Nappi RE, Lachowsky M (2009) Menopause and sexuality: prevalence of symptoms and impact on quality of life. Maturitas 63(2):138\u2013141. https:\/\/doi.org\/10.1016\/j.maturitas.2009.03.021","journal-title":"Maturitas"},{"key":"1743_CR34","doi-asserted-by":"publisher","first-page":"609","DOI":"10.1111\/j.1743-6109.2007.00491.x","volume":"4","author":"AM Traish","year":"2007","unstructured":"Traish AM, Kim SW, Stankovic M, Goldstein I, Kim NN (2007) Testosterone increases blood flow and expression of androgen and estrogen receptors in the rat vagina. J Sex Med 4:609\u2013619. https:\/\/doi.org\/10.1111\/j.1743-6109.2007.00491.x","journal-title":"J Sex Med"},{"key":"1743_CR35","doi-asserted-by":"publisher","first-page":"243","DOI":"10.1007\/s00345-010-0517-7","volume":"29","author":"G Pace","year":"2011","unstructured":"Pace G, Palumbo P, Miconi G, Silvestri V, Cifone MG, Vicentini C (2011) PDE-5 and NOS II mRNA expression in menopausal women: a molecular biology study. World J Urol 29:243\u2013248. https:\/\/doi.org\/10.1007\/s00345-010-0517-7","journal-title":"World J Urol"},{"key":"1743_CR36","doi-asserted-by":"publisher","first-page":"431","DOI":"10.1007\/s00192-016-3159-5","volume":"28","author":"KJ Cho","year":"2017","unstructured":"Cho KJ, Lee KS, Choo MS, Seo JT, Kim JH, Choi JB, Oh SJ, Kim JC (2017) Expressions of vaginal endothelial nitric oxide synthase and phosphodiesterase 5 in female sexual dysfunction: a pilot study. Int Urogynecol J 28:431\u2013436. https:\/\/doi.org\/10.1007\/s00192-016-3159-5","journal-title":"Int Urogynecol J"},{"issue":"2 Pt 2","key":"1743_CR37","doi-asserted-by":"publisher","first-page":"858","DOI":"10.1111\/j.1743-6109.2009.01599.x","volume":"7","author":"ML Chivers","year":"2010","unstructured":"Chivers ML, Rosen RC (2010) Phosphodiesterase type 5 inhibitors and female sexual response: faulty protocols or paradigms? J Sex Med 7(2 Pt 2):858\u2013872. https:\/\/doi.org\/10.1111\/j.1743-6109.2009.01599.x","journal-title":"J Sex Med"},{"key":"1743_CR38","doi-asserted-by":"publisher","first-page":"810","DOI":"10.1111\/j.1743-6109.2012.02983.x","volume":"10","author":"S Poels","year":"2013","unstructured":"Poels S, Bloemers J, van Rooij K, Goldstein I, Gerritsen J, van Ham D, van Mameren F, Chivers M, Everaerd W, Koppeschaar H, Olivier B, Tuiten A (2013) Toward personalized sexual medicine (part 2): testosterone combined with a PDE5 inhibitor increases sexual satisfaction in women with HSDD and FSAD, and a low sensitive system for sexual cues. J Sex Med 10:810\u2013823. https:\/\/doi.org\/10.1111\/j.1743-6109.2012.02983.x","journal-title":"J Sex Med"},{"key":"1743_CR39","doi-asserted-by":"publisher","first-page":"1433","DOI":"10.1016\/j.jsxm.2019.06.015","volume":"16","author":"J Bloemers","year":"2019","unstructured":"Bloemers J, Gerritsen J, van Rooij K, de Leede L, van der Geest R, Frijlink HW, Koppeschaar HPF, Olivier B, Tuiten A (2019) The effect of food on the pharmacokinetics of sildenafil after single administration of a sublingual testosterone and oral sildenafil combination tablet in healthy female subjects. J Sex Med 16:1433\u20131443. https:\/\/doi.org\/10.1016\/j.jsxm.2019.06.015","journal-title":"J Sex Med"},{"key":"1743_CR40","doi-asserted-by":"publisher","first-page":"1949","DOI":"10.1111\/jsm.12589","volume":"11","author":"J Bertin","year":"2014","unstructured":"Bertin J, Dury AY, Ouellet J, Pelletier G, Labrie F (2014) Localization of the androgen-synthesizing enzymes, androgen receptor, and sex steroids in the vagina: possible implications for the treatment of postmenopausal sexual dysfunction. J Sex Med 11:1949\u20131961. https:\/\/doi.org\/10.1111\/jsm.12589","journal-title":"J Sex Med"},{"key":"1743_CR41","doi-asserted-by":"publisher","first-page":"379","DOI":"10.1016\/j.sxmr.2020.03.003","volume":"8","author":"E Maseroli","year":"2020","unstructured":"Maseroli E, Vignozzi L (2020) Testosterone and vaginal function. Sex Med Rev 8:379\u2013392. https:\/\/doi.org\/10.1016\/j.sxmr.2020.03.003","journal-title":"Sex Med Rev"}],"container-title":["Journal of Endocrinological Investigation"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/link.springer.com\/content\/pdf\/10.1007\/s40618-022-01743-4.pdf","content-type":"application\/pdf","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/link.springer.com\/article\/10.1007\/s40618-022-01743-4\/fulltext.html","content-type":"text\/html","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/link.springer.com\/content\/pdf\/10.1007\/s40618-022-01743-4.pdf","content-type":"application\/pdf","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2022,5,12]],"date-time":"2022-05-12T10:37:48Z","timestamp":1652351868000},"score":1,"resource":{"primary":{"URL":"https:\/\/link.springer.com\/10.1007\/s40618-022-01743-4"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2022,1,24]]},"references-count":41,"journal-issue":{"issue":"6","published-print":{"date-parts":[[2022,6]]}},"alternative-id":["1743"],"URL":"https:\/\/doi.org\/10.1007\/s40618-022-01743-4","relation":{},"ISSN":["1720-8386"],"issn-type":[{"value":"1720-8386","type":"electronic"}],"subject":[],"published":{"date-parts":[[2022,1,24]]},"assertion":[{"value":"12 July 2021","order":1,"name":"received","label":"Received","group":{"name":"ArticleHistory","label":"Article History"}},{"value":"1 December 2021","order":2,"name":"accepted","label":"Accepted","group":{"name":"ArticleHistory","label":"Article History"}},{"value":"24 January 2022","order":3,"name":"first_online","label":"First Online","group":{"name":"ArticleHistory","label":"Article History"}},{"order":1,"name":"Ethics","group":{"name":"EthicsHeading","label":"Declarations"}},{"value":"IC, SF, PC, SC, EM, VDS, TT, SM, LT, FV, SV, CC, MF, GG, ES, AM, GR, MM and LV declare that they have no relevant financial or non-financial interests to disclose.","order":2,"name":"Ethics","group":{"name":"EthicsHeading","label":"Conflict of interest"}},{"value":"Animal handling and total number of animals employed in the study complied with Animal Welfare Body and Institutional Animal Care and Use Committee of the University of Florence, Florence, Italy, in accordance with the Italian Ministerial Law no. 26\/2014. The study complied with the Ministry of Health authorizations no. 937\/2017 (29 November 2017), and no. 227\/2020 (27 March 2020), endorsing the principles of laboratory animal care.","order":3,"name":"Ethics","group":{"name":"EthicsHeading","label":"Ethical approval"}},{"value":"Informed consent is not applicable.","order":4,"name":"Ethics","group":{"name":"EthicsHeading","label":"Informed consent"}}]}}