{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,8,17]],"date-time":"2026-08-17T23:26:16Z","timestamp":1787009176977,"version":"build-2736575974"},"reference-count":70,"publisher":"Oxford University Press (OUP)","issue":"7","license":[{"start":{"date-parts":[[2023,4,21]],"date-time":"2023-04-21T00:00:00Z","timestamp":1682035200000},"content-version":"vor","delay-in-days":1,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"DOI":"10.13039\/501100003946","name":"European Society for Sexual Medicine","doi-asserted-by":"publisher","award":["RG-16-03"],"award-info":[{"award-number":["RG-16-03"]}],"id":[{"id":"10.13039\/501100003946","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":[],"published-print":{"date-parts":[[2023,6,28]]},"abstract":"<jats:title>Abstract<\/jats:title>\n                  <jats:sec>\n                    <jats:title>Background<\/jats:title>\n                    <jats:p>Peyronie\u2019s disease (PD) is a fibrotic disorder characterized by plaque formation in the tunica albuginea (TA) of the penis, and we have previously shown that inhibition of transformation of TA-derived fibroblasts to myofibroblasts using a combination phosphodiesterase type 5 (PDE5) inhibitors and selective estrogen receptor modulators (SERMs) is effective in slowing the progression of early PD.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Aim<\/jats:title>\n                    <jats:p>The study sought to investigate whether combinations of statins with PDE5 inhibitors or SERMs would affect myofibroblast transformation in vitro.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Methods<\/jats:title>\n                    <jats:p>Primary fibroblasts were isolated from TA of patients with PD and stimulated with transforming growth factor \u03b21 in the absence and presence of a range of concentrations of statins, PDE5 inhibitors, SERMs, and their combinations for 72\u00a0hours before quantifying \u03b1-smooth muscle actin using in-cell enzyme-linked immunosorbent assay.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Outcomes<\/jats:title>\n                    <jats:p>The prevention of transforming growth factor \u03b21\u2013induced transformation of TA-derived fibroblasts to myofibroblasts was measured in vitro.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Results<\/jats:title>\n                    <jats:p>Statins (simvastatin, lovastatin) inhibited myofibroblast transformation in a concentration-dependent manner with half maximal inhibitory concentration values of 0.77\u2009\u00b1\u20090.07\u00a0\u03bcM and 0.8\u2009\u00b1\u20090.13\u00a0\u03bcM, respectively. Simvastatin inhibited myofibroblast transformation in a synergistic fashion when combined with vardenafil (a PDE5 inhibitor; log alpha &amp;gt;0). Combination of tamoxifen (a SERM) and simvastatin did not show synergy (log alpha &amp;lt;0). When 3 drugs (simvastatin, vardenafil, and tamoxifen) were combined, the effect was not synergistic, but rather was additive.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Clinical implications<\/jats:title>\n                    <jats:p>A combination of a statin with a PDE5 inhibitor might be useful in the clinic to slow the progression of the disease in patients with early PD; however, caution should be taken with such a combination because of the reported myopathy as a side effect.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Strengths and limitations<\/jats:title>\n                    <jats:p>The use of primary human cells from patients with PD is a strength of this study. The mechanisms by which these drug classes exert synergy when used in combination was not investigated.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Conclusion<\/jats:title>\n                    <jats:p>This is the first demonstration of an antifibrotic synergy between statins and PDE5 inhibitors.<\/jats:p>\n                  <\/jats:sec>","DOI":"10.1093\/jsxmed\/qdad051","type":"journal-article","created":{"date-parts":[[2023,4,21]],"date-time":"2023-04-21T03:21:08Z","timestamp":1682047268000},"page":"925-934","source":"Crossref","is-referenced-by-count":4,"title":["Statins synergize with phosphodiesterase type 5 inhibitors but not with selective estrogen receptor modulators to prevent myofibroblast transformation in an in vitro model of Peyronie\u2019s disease"],"prefix":"10.1093","volume":"20","author":[{"given":"Marcus M","family":"Ilg","sequence":"first","affiliation":[{"name":"Anglia Ruskin University Medical Technology Research Centre, School of Allied Health, Faculty of Health, Education, Medicine and Social Care, , Chelmsford CM1 1SQ , United Kingdom"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"David J","family":"Ralph","sequence":"additional","affiliation":[{"name":"Anglia Ruskin University Medical Technology Research Centre, School of Allied Health, Faculty of Health, Education, Medicine and Social Care, , Chelmsford CM1 1SQ , United Kingdom"},{"name":"University College Hospital Urology Department, , London W1G 8PH , United Kingdom"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Selim","family":"Cellek","sequence":"additional","affiliation":[{"name":"Anglia Ruskin University Medical Technology Research Centre, School of Allied Health, Faculty of Health, Education, Medicine and Social Care, , Chelmsford CM1 1SQ , United Kingdom"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"286","published-online":{"date-parts":[[2023,4,20]]},"reference":[{"key":"2023063007135480300_ref1","doi-asserted-by":"crossref","first-page":"2115","DOI":"10.1016\/S0022-5347(06)00270-9","article-title":"An analysis of the natural history of Peyronie\u2019s disease","volume":"175","author":"Mulhall","year":"2006","journal-title":"J Urol"},{"key":"2023063007135480300_ref2","doi-asserted-by":"crossref","first-page":"70","DOI":"10.1016\/j.ajur.2015.04.019","article-title":"All about Peyronie\u2019s disease","volume":"2","author":"Hussein","year":"2015","journal-title":"Asian J Urol"},{"issue":"3","key":"2023063007135480300_ref3","doi-asserted-by":"crossref","first-page":"172","DOI":"10.1038\/s41585-018-0117-7","article-title":"Nonsurgical management of Peyronie\u2019s disease","volume":"16","author":"Tsambarlis","year":"2018","journal-title":"Nat Rev Urol"},{"issue":"8","key":"2023063007135480300_ref4","doi-asserted-by":"crossref","first-page":"733","DOI":"10.1038\/s41443-021-00469-w","article-title":"Is there a line between ethics and market competition? 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