Therapeutic Roles of Statins in Gynecology and Obstetrics: The Current Evidence

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Statins, through inhibition of the mevalonate pathway, exhibit antiproliferative, anti-invasive, anti-inflammatory, and antiangiogenic effects with potential benefits for various gynecologic and obstetric conditions.

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This paper reviews evidence on statins in obstetrics and gynecology, focusing on how inhibition of HMG-CoA reductase affects mevalonate pathway products that influence protein localization and signaling linked to antiproliferative, anti-invasive, anti-inflammatory, and antiangiogenic effects. Across the compiled literature, the authors report promising roles for statins in conditions including endometriosis, polycystic ovary syndrome, adhesion prevention, ovarian cancer, preeclampsia, and antiphospholipid syndrome, with in vivo studies showing variable benefit for fibroids and preterm birth. The major limitation is that the review concludes that appropriately designed clinical trials are still needed for definitive conclusions, implying heterogeneity and incomplete clinical evidence. This paper is centrally about endometriosis — it is a broad evidence review arguing statins might benefit endometriosis among several obstetric and gynecologic conditions.

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Abstract

IntroductionStatins 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.MethodsLiterature 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.ResultsInhibition 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.ConclusionStatins might play a role in the treatment of endometriosis, polycystic ovary syndrome, adhesion prevention, ovarian cancer, preeclampsia, and antiphospholipid syndrome.
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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. Similar content being viewed by others

References

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Author information Authors and Affiliations Corresponding author Rights and permissions About this article Cite this article Zeybek, B., Costantine, M., Kilic, G.S. et al. Therapeutic Roles of Statins in Gynecology and Obstetrics: The Current Evidence. Reprod. Sci. 25, 802–817 (2018). https://doi.org/10.1177/1933719117750751 Published: Version of record: Issue date: DOI: https://doi.org/10.1177/1933719117750751

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Female Urogenital Diseases Hydroxymethylglutaryl-CoA Reductase Inhibitors Female Female Urogenital Diseases Female Urogenital Diseases Gynecology Humans Hydroxymethylglutaryl-CoA Reductase Inhibitors Mevalonic Acid Mevalonic Acid Mevalonic Acid Obstetrics Signal Transduction Treatment Outcome

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