{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2025,10,22]],"date-time":"2025-10-22T18:10:34Z","timestamp":1761156634813},"reference-count":35,"publisher":"Oxford University Press (OUP)","issue":"3","license":[{"start":{"date-parts":[[2019,2,14]],"date-time":"2019-02-14T00:00:00Z","timestamp":1550102400000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/academic.oup.com\/journals\/pages\/open_access\/funder_policies\/chorus\/standard_publication_model"},{"start":{"date-parts":[[2019,2,14]],"date-time":"2019-02-14T00:00:00Z","timestamp":1550102400000},"content-version":"tdm","delay-in-days":0,"URL":"https:\/\/www.elsevier.com\/tdm\/userlicense\/1.0\/"}],"content-domain":{"domain":["jsm.jsexmed.org","elsevier.com","sciencedirect.com"],"crossmark-restriction":true},"short-container-title":[],"published-print":{"date-parts":[[2019,3,1]]},"abstract":"<jats:title>Abstract<\/jats:title>\n               <jats:sec>\n                  <jats:title>Background<\/jats:title>\n                  <jats:p>The effects of phosphodiesterase-type 5 (PDE5) inhibitors on the in vivo clitoral structure of women with diabetes have never been investigated.<\/jats:p>\n               <\/jats:sec>\n               <jats:sec>\n                  <jats:title>Aim<\/jats:title>\n                  <jats:p>To study the in vivo structural and hemodynamic changes of the clitoris in premenopausal women with type 1 diabetes on PDE5 inhibitors.<\/jats:p>\n               <\/jats:sec>\n               <jats:sec>\n                  <jats:title>Methods<\/jats:title>\n                  <jats:p>38 premenopausal women with type 1 diabetes aged 36 -46 years. A randomized 1:1 study design was used: Study Group (group A) on Tadalafil 5 mg daily, and control group (group B). Blood samples were taken from each woman to measure HbA1c, testosterone, and Free Androgen Index. The women underwent microbiopsy of the clitoral body by means of semiautomatic gun during total anesthesia for surgery therapy of a benign gynecological pathology. The tissue removed was processed for electron microscopy. Translabial color Doppler ultrasound was used to measure the peak systolic velocity (PSV), the end diastolic velocity (EDV), and the pulsatility index (PI) of clitoral arteries.<\/jats:p>\n               <\/jats:sec>\n               <jats:sec>\n                  <jats:title>Main Outcome Measures<\/jats:title>\n                  <jats:p>Micro-ultrastructure observation of clitoral tissue and color Doppler sonography of clitoral blood flow.<\/jats:p>\n               <\/jats:sec>\n               <jats:sec>\n                  <jats:title>Results<\/jats:title>\n                  <jats:p>Of the 38 women, 13 (68.4%) of group A and 15 (78.9%) of group B completed the study. Group A showed a mean PSV and EDV increase, and a mean PI decrease with respect to baseline (P &amp;lt; .001). Group B did not show any change in both the parameters (P = NS). By a quantitative study in both groups a variable degree of ultrastructural abnormalities of smooth muscle cells (SMCs) was observed, consisting in increased glycogen and lipoic deposits, cytoplasmic vacuoles, and focal increase of electron density of SMCs. Moreover, the mean SMC thickness of group A (1.83 \u00b1 0.68 \u00b5m) was larger than that of group B (1.3 \u00b1 0.41 \u00b5m) (P\u00a0=\u00a0.02).<\/jats:p>\n               <\/jats:sec>\n               <jats:sec>\n                  <jats:title>Clinical Implications<\/jats:title>\n                  <jats:p>PDE5 inhibitors could be used to treat diabetic women with genital arousal disorder.<\/jats:p>\n               <\/jats:sec>\n               <jats:sec>\n                  <jats:title>Strengths &amp; Limitations<\/jats:title>\n                  <jats:p>The study shows a clear effect of PDE5 inhibitors on clitoral SMCs. However, a limit was to not have investigated the sexual function\/behavior of women of both groups, this was because of the short time of the study.<\/jats:p>\n               <\/jats:sec>\n               <jats:sec>\n                  <jats:title>Conclusion<\/jats:title>\n                  <jats:p>This study could help to understand in what way PDE5 inhibitors act on the ultrastructural pathophysiological clitoral cavernous tissue of women with diabetes. It could support PDE5 inhibitor usage in women with genital sexual arousal disorder due to metabolic diseases.<\/jats:p>\n               <\/jats:sec>","DOI":"10.1016\/j.jsxm.2019.01.003","type":"journal-article","created":{"date-parts":[[2019,2,15]],"date-time":"2019-02-15T00:14:11Z","timestamp":1550189651000},"page":"375-382","update-policy":"http:\/\/dx.doi.org\/10.1016\/elsevier_cm_policy","source":"Crossref","is-referenced-by-count":8,"title":["Ultrastructural Study of Clitoral Cavernous Tissue and Clitoral Blood Flow From Type 1 Diabetic Premenopausal Women on Phosphodiesterase-5 Inhibitor"],"prefix":"10.1093","volume":"16","author":[{"given":"Salvatore","family":"Caruso","sequence":"first","affiliation":[{"name":"Department of General Surgery and Medical Surgical Specialties, Gynecological Clinic \u00a0 \u00a0 , Catania , Italy"},{"name":"Research Group for Sexology \u00a0 \u00a0 , Catania , Italy"},{"name":"University of Catania \u00a0 \u00a0 , Catania , Italy"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Antonio","family":"Cianci","sequence":"additional","affiliation":[{"name":"Department of General Surgery and Medical Surgical Specialties, Gynecological Clinic \u00a0 \u00a0 , Catania , Italy"},{"name":"Research Group for Sexology \u00a0 \u00a0 , Catania , Italy"},{"name":"University of Catania \u00a0 \u00a0 , Catania , Italy"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Stefano","family":"Cianci","sequence":"additional","affiliation":[{"name":"Department of General Surgery and Medical Surgical Specialties, Gynecological Clinic \u00a0 \u00a0 , Catania , Italy"},{"name":"Research Group for Sexology \u00a0 \u00a0 , Catania , Italy"},{"name":"University of Catania \u00a0 \u00a0 , Catania , Italy"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Caterina","family":"Monaco","sequence":"additional","affiliation":[{"name":"Department of General Surgery and Medical Surgical Specialties, Gynecological Clinic \u00a0 \u00a0 , Catania , Italy"},{"name":"Research Group for Sexology \u00a0 \u00a0 , Catania , Italy"},{"name":"University of Catania \u00a0 \u00a0 , Catania , Italy"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Valentina","family":"Fava","sequence":"additional","affiliation":[{"name":"Department of General Surgery and Medical Surgical Specialties, Gynecological Clinic \u00a0 \u00a0 , Catania , Italy"},{"name":"Research Group for Sexology \u00a0 \u00a0 , Catania , Italy"},{"name":"University of Catania \u00a0 \u00a0 , Catania , Italy"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Vittorio","family":"Cavallari","sequence":"additional","affiliation":[{"name":"Unit of Ultrastructural Pathology \u00a0 \u00a0 , Messina , Italy"},{"name":"Department of Human Pathology \u00a0 \u00a0 , Messina , Italy"},{"name":"University of Messina \u00a0 \u00a0 , Messina , Italy"}],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"286","published-online":{"date-parts":[[2019,2,14]]},"reference":[{"key":"2023012309515104100_bib1","doi-asserted-by":"crossref","first-page":"169","DOI":"10.1007\/s40618-016-0542-5","article-title":"Sexual function in young women with type 1 diabetes: The METRO study","volume":"40","author":"Maiorino","year":"2017","journal-title":"J\u00a0Endocrinol Invest"},{"key":"2023012309515104100_bib2","doi-asserted-by":"crossref","first-page":"911","DOI":"10.1007\/s00592-013-0482-x","article-title":"Sexual dysfunction in pre-menopausal diabetic women: Clinical, metabolic, psychological, cardiovascular, and neurophysiologic correlates","volume":"50","author":"Cortelazzi","year":"2013","journal-title":"Acta Diabetol"},{"key":"2023012309515104100_bib3","first-page":"199","article-title":"Sexual dysfunction in women with diabetes mellitus","volume":"47","author":"Giraldi","year":"2010","journal-title":"J\u00a0Sex Res"},{"key":"2023012309515104100_bib4","doi-asserted-by":"crossref","first-page":"45","DOI":"10.1016\/j.sxmr.2016.07.002","article-title":"Diabetes and sexuality","volume":"5","author":"Kizilay","year":"2017","journal-title":"Sex Med Rev"},{"key":"2023012309515104100_bib5","doi-asserted-by":"crossref","first-page":"230","DOI":"10.1007\/s11892-005-0014-3","article-title":"Diabetes and female sexual dysfunction: Moving beyond \"benign neglect\"","volume":"5","author":"Muniyappa","year":"2005","journal-title":"Curr Diab Rep"},{"key":"2023012309515104100_bib6","doi-asserted-by":"crossref","first-page":"27","DOI":"10.1038\/sj.ijir.3900258","article-title":"Vasculogenic female sexual dysfunction: The hemodynamic basis for vaginal engorgement insufficiency and clitoral erectile insufficiency","volume":"9","author":"Park","year":"1997","journal-title":"Int J Impot Res"},{"key":"2023012309515104100_bib7","first-page":"1011","article-title":"Relationship between cavernosal ischemia and corporal veno-occlusive dysfunction in an animal model","volume":"167","author":"Azadzoi","year":"1997","journal-title":"J\u00a0Urol"},{"key":"2023012309515104100_bib8","doi-asserted-by":"crossref","first-page":"11","DOI":"10.1038\/sj.ijir.3900514","article-title":"Atherosclerosis-induced chronic arterial insufficiency causes clitoral cavernosal fibrosis in the rabbit","volume":"12","author":"Park","year":"2000","journal-title":"Int J Impot Res"},{"key":"2023012309515104100_bib9","first-page":"1675","article-title":"Ultrastructural and quantitative study of clitoral cavernous tissue from living subjects","volume":"8","author":"Caruso","year":"2011","journal-title":"J\u00a0Sex Med"},{"key":"2023012309515104100_bib10","doi-asserted-by":"crossref","first-page":"201","DOI":"10.1016\/S0301-2115(03)00118-0","article-title":"The function of sildenafil on female sexual pathways: A double-blind, cross-over, placebo-controlled study","volume":"110","author":"Caruso","year":"2003","journal-title":"Eur J Obstet Gynecol Reprod Biol"},{"key":"2023012309515104100_bib11","first-page":"623","article-title":"Premenopausal women affected by sexual arousal disorder treated with sildenafil: A double-blind, cross-over, placebo-controlled study","volume":"108","author":"Caruso","year":"2001","journal-title":"Br J Obstet Gynaecol"},{"key":"2023012309515104100_bib12","doi-asserted-by":"crossref","first-page":"161","DOI":"10.1016\/j.urology.2006.01.059","article-title":"Changes in clitoral blood flow in premenopausal women affected by type 1 diabetes after single 100-mg administration of sildenafil","volume":"68","author":"Caruso","year":"2006","journal-title":"Urology"},{"key":"2023012309515104100_bib13","doi-asserted-by":"crossref","first-page":"1496","DOI":"10.1016\/j.fertnstert.2005.10.043","article-title":"Sildenafil improves sexual functioning in premenopausal women with type 1 diabetes who are affected by sexual arousal disorder: A double-blind, crossover, placebo-controlled pilot study","volume":"85","author":"Caruso","year":"2006","journal-title":"Fertil Steril"},{"key":"2023012309515104100_bib14","first-page":"2057","article-title":"Tadalafil 5 mg daily treatment for type 1 diabetic premenopausal women affected by sexual genital arousal disorder","volume":"9","author":"Caruso","year":"2012","journal-title":"J\u00a0Sex Med"},{"key":"2023012309515104100_bib15","doi-asserted-by":"crossref","first-page":"351","DOI":"10.1016\/j.eururo.2006.02.052","article-title":"Evaluation of the efficacy and safety of once-a-day dosing of tadalafil 5 mg and 10 mg in the treatment of erectile dysfunction: Results of a multicenter, randomized, double-blind, placebo-controlled trial","volume":"50","author":"Porst","year":"2006","journal-title":"Eur Urol"},{"key":"2023012309515104100_bib16","doi-asserted-by":"crossref","first-page":"2238","DOI":"10.1093\/rheumatology\/ket305","article-title":"Clitoral blood flow in systemic sclerosis women: correlation with disease clinical variables and female sexual dysfunction","volume":"52","author":"Rosato","year":"2013","journal-title":"Rheumatology (Oxford)"},{"key":"2023012309515104100_bib17","first-page":"1651","article-title":"Cardiometabolic risk and female sexuality: Focus on clitoral vascular resistance","volume":"13","author":"Maseroli","year":"2016","journal-title":"J\u00a0Sex Med"},{"key":"2023012309515104100_bib18","first-page":"199","article-title":"Nuclear areas in breast cancer: Relationship with estrogen and progesterone receptor expression","volume":"11","author":"Maiorana","year":"1996","journal-title":"Anal Cell Pathol"},{"key":"2023012309515104100_bib19","first-page":"513","article-title":"Immunohistochemical study of the corpora cavernosa of the human clitoris","volume":"188","author":"Toesca","year":"1996","journal-title":"J\u00a0Anat"},{"key":"2023012309515104100_bib20","first-page":"975","article-title":"Long-term safety and effectiveness of sildenafil citrate in men with erectile dysfunction","volume":"3","author":"McMurray","year":"2007","journal-title":"Clin Risk Manag"},{"key":"2023012309515104100_bib21","doi-asserted-by":"crossref","first-page":"901","DOI":"10.1016\/j.eururo.2006.07.041","article-title":"Vardenafil duration of action","volume":"50","author":"S\u00e1enz de Tejada","year":"2006","journal-title":"Eur Urol"},{"key":"2023012309515104100_bib22","first-page":"75","article-title":"Immunohistochemical description of nitric oxide syntheses isoforms in human clitoris","volume":"158","author":"Burnett","year":"1997","journal-title":"J\u00a0Urol"},{"key":"2023012309515104100_bib23","doi-asserted-by":"crossref","first-page":"191","DOI":"10.1016\/S0090-4295(02)01663-1","article-title":"Type 5 phosphodiesterase expression in the human vagina","volume":"60","author":"D\u2019Amati","year":"2000","journal-title":"Urology"},{"key":"2023012309515104100_bib24","doi-asserted-by":"crossref","first-page":"1111","DOI":"10.1016\/j.urology.2005.11.055","article-title":"Expression of cAMP and cGMP-phosphodiesterase isoenzymes 3, 4, and 5 in the human clitoris: Immunohistochemical and molecular biology study","volume":"67","author":"Oelke","year":"2006","journal-title":"Urology"},{"key":"2023012309515104100_bib25","doi-asserted-by":"crossref","first-page":"393","DOI":"10.1007\/s00345-005-0015-5","article-title":"Phosphodiesterase inhibitors in female sexual dysfunction","volume":"23","author":"Mayer","year":"2005","journal-title":"World J Urol"},{"key":"2023012309515104100_bib26","doi-asserted-by":"crossref","first-page":"139","DOI":"10.1016\/j.ijgo.2015.08.015","article-title":"Systematic review and meta-analysis of phosphodiesterase type 5 inhibitors for the treatment of female sexual dysfunction","volume":"133","author":"Gao","year":"2016","journal-title":"Int J Gynaecol Obstet"},{"key":"2023012309515104100_bib27","first-page":"2925","article-title":"Biochemical factors modulating female genital sexual arousal physiology","volume":"7","author":"Traish","year":"2010","journal-title":"J\u00a0Sex Med"},{"key":"2023012309515104100_bib28","doi-asserted-by":"crossref","first-page":"39","DOI":"10.1016\/j.maturitas.2010.04.019","article-title":"Androgen deficiency in women: Role of accurate testosterone measurements","volume":"67","author":"Demers","year":"2010","journal-title":"Maturitas"},{"key":"2023012309515104100_bib29","doi-asserted-by":"crossref","first-page":"27","DOI":"10.1038\/sj.ijir.3900258","article-title":"Vasculogenic female sexual dysfunction: The hemodynamic basis for vaginal engorgement insufficiency and clitoral erectile insufficiency","volume":"9","author":"Park","year":"1997","journal-title":"Int J Impot Res"},{"key":"2023012309515104100_bib30","first-page":"2693","article-title":"Influence of sildenafil on genital engorgement in women with female sexual arousal disorder","volume":"9","author":"Leddy","year":"2012","journal-title":"J\u00a0Sex Med"},{"key":"2023012309515104100_bib31","doi-asserted-by":"crossref","first-page":"1014","DOI":"10.1111\/j.1471-0528.2003.02438.x","article-title":"Sexual psychophysiology and effects of sildenafil citrate in oestrogenised women with acquired genital arousal disorder and impaired orgasm: A randomised controlled trial","volume":"110","author":"Basson","year":"2003","journal-title":"BJOG"},{"key":"2023012309515104100_bib32","first-page":"1604","article-title":"Expression of messenger ribonucleic acid encoding for phosphodiesterase isoenzymes in human female genital tissues","volume":"4","author":"Uckert","year":"2007","journal-title":"J\u00a0Sex Med"},{"issue":"Pt 1","key":"2023012309515104100_bib33","first-page":"2333","article-title":"Safety and efficacy of sildenafil citrate for the treatment of female sexual arousal disorder: A double-blind, placebo controlled study","volume":"170","author":"Berman","year":"2003","journal-title":"J\u00a0Urol"},{"key":"2023012309515104100_bib34","first-page":"2251","article-title":"Women taking the \"blue pill\" (sildenafil citrate): Such a big deal?","volume":"8","author":"Lo Monte","year":"2014","journal-title":"Drug Des Devel Ther"},{"issue":"2 Pt 2","key":"2023012309515104100_bib35","first-page":"858","article-title":"Phosphodiesterase type 5 inhibitors and female sexual response: Faulty protocols or paradigms?","volume":"7","author":"Chivers","year":"2010","journal-title":"J\u00a0Sex Med"}],"container-title":["The Journal of Sexual Medicine"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/api.elsevier.com\/content\/article\/PII:S1743609519300049?httpAccept=text\/xml","content-type":"text\/xml","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/api.elsevier.com\/content\/article\/PII:S1743609519300049?httpAccept=text\/plain","content-type":"text\/plain","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/academic.oup.com\/jsm\/article-pdf\/16\/3\/375\/48589599\/jsm_16_3_375.pdf","content-type":"application\/pdf","content-version":"vor","intended-application":"syndication"},{"URL":"https:\/\/academic.oup.com\/jsm\/article-pdf\/16\/3\/375\/48589599\/jsm_16_3_375.pdf","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2023,1,23]],"date-time":"2023-01-23T10:30:05Z","timestamp":1674469805000},"score":1,"resource":{"primary":{"URL":"https:\/\/academic.oup.com\/jsm\/article\/16\/3\/375\/6980726"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2019,2,14]]},"references-count":35,"journal-issue":{"issue":"3","published-online":{"date-parts":[[2019,2,14]]},"published-print":{"date-parts":[[2019,3,1]]}},"URL":"https:\/\/doi.org\/10.1016\/j.jsxm.2019.01.003","relation":{},"ISSN":["1743-6109","1743-6095"],"issn-type":[{"value":"1743-6109","type":"electronic"},{"value":"1743-6095","type":"print"}],"subject":[],"published-other":{"date-parts":[[2019,3]]},"published":{"date-parts":[[2019,2,14]]},"assertion":[{"value":"Elsevier","name":"publisher","label":"This article is maintained by"},{"value":"Ultrastructural Study of Clitoral Cavernous Tissue and Clitoral Blood Flow From Type 1 Diabetic Premenopausal Women on Phosphodiesterase-5 Inhibitor","name":"articletitle","label":"Article Title"},{"value":"The Journal of Sexual Medicine","name":"journaltitle","label":"Journal Title"},{"value":"https:\/\/doi.org\/10.1016\/j.jsxm.2019.01.003","name":"articlelink","label":"CrossRef DOI link to publisher maintained version"},{"value":"article","name":"content_type","label":"Content Type"},{"value":"\u00a9 2019 International Society for Sexual Medicine. Published by Elsevier Inc.","name":"copyright","label":"Copyright"}]}}