Burak Zeybek1, Maged Costantine1, Gokhan S Kilic1, Mostafa A Borahay2. 1. 1 Department of Obstetrics & Gynecology, The University of Texas Medical Branch, Galveston, TX, USA. 2. 2 Department of Gynecology and Obstetrics, Johns Hopkins University School of Medicine, Baltimore, MD, USA.
Abstract
INTRODUCTION: Statins are a class of drugs, which act by inhibiting the rate-limiting enzyme of cholesterol biosynthesis (3-hydroxy-3-methyl-glutaryl-CoA reductase). The inhibition of mevalonate synthesis leads to subsequent inhibition of downstream products of this pathway, which explains the pleiotropic effects of these agents in addition to their well-known lipid-lowering effects. Accumulating evidence suggests that statins might be beneficial in various obstetric and gynecologic conditions. METHODS: Literature searches were performed in PubMed and EMBASE for articles with content related to statins in obstetrics and gynecology. The findings are hereby reviewed and discussed. RESULTS: Inhibition of mevalonate pathway leads to subsequent inhibition of downstream products such as geranyl pyrophosphate, farnesyl pyrophosphate, and geranylgeranyl pyrophosphate. These products are required for proper intracellular localization of several proteins, which play important roles in signaling pathways by regulating membrane trafficking, motility, proliferation, differentiation, and cytoskeletal organization. The pleiotropic effects of statins can be summarized in 4 categories: antiproliferative, anti-invasive, anti-inflammatory, and antiangiogenic. The growing body of evidence is promising for these agents to be beneficial in endometriosis, polycystic ovary syndrome, adhesion prevention, ovarian cancer, preeclampsia, and antiphospholipid syndrome. Although in vivo studies showed varying degrees of benefit on fibroids and preterm birth, appropriately designed clinical trials are needed to make definitive conclusions. CONCLUSION: Statins might play a role in the treatment of endometriosis, polycystic ovary syndrome, adhesion prevention, ovarian cancer, preeclampsia, and antiphospholipid syndrome.
INTRODUCTION: Statins are a class of drugs, which act by inhibiting the rate-limiting enzyme of cholesterol biosynthesis (3-hydroxy-3-methyl-glutaryl-CoA reductase). The inhibition of mevalonate synthesis leads to subsequent inhibition of downstream products of this pathway, which explains the pleiotropic effects of these agents in addition to their well-known lipid-lowering effects. Accumulating evidence suggests that statins might be beneficial in various obstetric and gynecologic conditions. METHODS: Literature searches were performed in PubMed and EMBASE for articles with content related to statins in obstetrics and gynecology. The findings are hereby reviewed and discussed. RESULTS: Inhibition of mevalonate pathway leads to subsequent inhibition of downstream products such as geranyl pyrophosphate, farnesyl pyrophosphate, and geranylgeranyl pyrophosphate. These products are required for proper intracellular localization of several proteins, which play important roles in signaling pathways by regulating membrane trafficking, motility, proliferation, differentiation, and cytoskeletal organization. The pleiotropic effects of statins can be summarized in 4 categories: antiproliferative, anti-invasive, anti-inflammatory, and antiangiogenic. The growing body of evidence is promising for these agents to be beneficial in endometriosis, polycystic ovary syndrome, adhesion prevention, ovarian cancer, preeclampsia, and antiphospholipid syndrome. Although in vivo studies showed varying degrees of benefit on fibroids and preterm birth, appropriately designed clinical trials are needed to make definitive conclusions. CONCLUSION: Statins might play a role in the treatment of endometriosis, polycystic ovary syndrome, adhesion prevention, ovarian cancer, preeclampsia, and antiphospholipid syndrome.
Authors: Ryan C Bensen; Gokhan Gunay; Matthew C Finneran; Isha Jhingan; Handan Acar; Anthony W G Burgett Journal: ACS Pharmacol Transl Sci Date: 2021-02-04