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. 2025 Dec;45(1):2502083.
doi: 10.1080/01443615.2025.2502083. Epub 2025 May 9.

Simvastatin-loaded liposomal nanoparticles as treatment for adenomyosis in a patient-derived xenograft mouse model: a pilot study

Rachel Michel  1 , Kathleen L Vincent  2 , Gregory W Kirschen  3 , Massoud Motamedi  4 , Jamal Saada  5 , Jinping Yang  4 , Bulent Ozpolat  6   7 , Gokhan S Kilic  2 , Mostafa A Borahay  1
Affiliations

Simvastatin-loaded liposomal nanoparticles as treatment for adenomyosis in a patient-derived xenograft mouse model: a pilot study

Rachel Michel et al. J Obstet Gynaecol. 2025 Dec.

Abstract

Background: Adenomyosis is a common gynaecological condition where ectopic endometrial glands and stroma grow within the myometrium. This condition has a high clinical burden impacting those afflicted with debilitating symptoms including heavy painful periods. Simvastatin is an oral hydroxymethylglutaryl-coenzyme A (HMG-CoA) reductase inhibitor, typically used to treat hyperlipidaemia. Simvastatin has recently shown promise for treating gynaecological conditions such as endometriosis and uterine fibroids with nanoliposomal formulations demonstrating improved efficacy. In this pilot study, we tested simvastatin-loaded liposomal nanoparticles on xenografted adenomyosis tissues in a patient-derived mouse model.

Methods: We surgically inserted oestrogen/progesterone pellets into mice, followed by adenomyosis tissue xenografts 15 days later. Mice were then randomised into three groups: control, simvastatin, and simvastatin-loaded liposomal nanoparticles (simvastatin-NP). We quantified the changes in adenomyosis xenograft size weekly using a calliper as well as ultrasound imaging 28 days after treatment, prior to sacrifice. We also measured the proliferation of biomarker Ki67 in the xenografted tissues using immunohistochemistry after animal sacrifice.

Results: Treatment with simvastatin-NP significantly reduced volume and weight of adenomyosis xenografts while attenuating Ki67 expression when compared to the control and simvastatin groups. Conclusions: This pilot study demonstrates promising improved efficacy of simvastatin delivered via liposomal nanoparticles. However, larger studies are needed to fully explore the potential of simvastatin-NP in adenomyosis.

Keywords: Adenomyosis; nanoparticles, animal; simvastatin.

Plain language summary

Adenomyosis is a condition where the inner lining of the uterus exists within the muscle wall of the uterus, resulting in painful periods, heavy bleeding, and bloating. Despite adenomyosis’ debilitating symptoms, treatment options remain limited. Previous research suggests simvastatin – a medication used to treat patients with high cholesterol – is a promising treatment for gynaecological conditions. Therefore, in this study, we implanted adenomyosis tissue from humans into mice to test the efficacy of two different forms of simvastatin – regular simvastatin and simvastatin in nanoparticle form – in reducing adenomyosis lesion size. We found that simvastatin in nanoparticle form significantly reduced the adenomyosis lesion volume and weight in mice. We then examined the tissue for a marker of cellular proliferation and found that it was significantly reduced in adenomyosis tissue treated with simvastatin in nanoparticle form. Therefore, our results suggest that simvastatin in its nanoparticle form should be further investigated as a potential treatment option for adenomyosis.

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Conflict of interest statement

Disclosure statement

No potential conflict of interest was reported by the authors.

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