ArticleAnnals of translational medicine2023
Diane-35 and metformin therapy in rats with endometrial lesions induced by dihydrotestosterone exposure.
Article in Annals of translational medicine, 2023. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 3 papers.
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The abstract states no effect estimate the extractor could read, or names no intervention and outcome on the map, so this paper lights no cell and moves no belief. It is still indexed, cited and linked below.
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Who cites it
3 citing papers in PubMed, 4 citations in OpenAlex.
- 3D visualization of uterus and ovary: tissue clearing techniques and biomedical applications.Frontiers in bioengineering and biotechnology · 2025Review
- Impact of Diane-35 on Hormone Levels and Pregnancy Outcomes in Patients with Polycystic Ovary Syndrome: A Retrospective Analysis.International journal of women's health · 2025Article
- Evaluating the therapeutic potential of moxibustion on polycystic ovary syndrome: a rat model study on gut microbiota and metabolite interaction.Frontiers in cellular and infection microbiology · 2024Article
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Authors and funding
11 authors at 4 institutions in 1 country.
Funding
No grant is acknowledged in the PubMed record.
Abstract
Background: Cotreatment with metformin and Diane-35 is conventionally used in the clinic to ameliorate ovulatory dysfunction and insulin resistance in women with polycystic ovary syndrome (PCOS). We previously showed that this combination treatment could reverse endometrial hyperplasia and endometrial cancer (EC) in patients with PCOS. Here, we aimed to investigate the influence of dihydrotestosterone (DHT) and this cotreatment on the endometrium, along with the related mechanisms. Methods: We treated a DHT-exposed rat model with Diane-35 or metformin alone or their combination and investigated the 3-dimensional (3D) endometrial structure to determine the role of these treatments in reversing endometrial lesions and to clarify the underlying mechanisms. Uterine segments were made transparent with clear, unobstructed brain/body imaging cocktails and a computational analysis protocol and then labeled with 4',6-diamidino-2-phenylindole (DAPI), antiandrogen receptor (AR) antibody, and antiglucose transportation protein 4 (GLUT4) antibody. We visualized and analyzed the endometrial structure, AR expression, and GLUT4 expression under 3D conditions using light sheet microscopy and Imaris software (Bitplane, Zurich, Switzerland). Results: Long-term DHT treatment contributed to hyperandrogenism and insulin resistance in female Wistar rats. After DHT treatment, rats exhibited other PCOS-like characteristics, such as polycystic ovary morphology, hypothalamic-pituitary-ovarian axis disorder, and relative endometrial hyperplasia. After metformin and Diane-35 treatment, the PCOS-like characteristics and endometrial hyperplasia were alleviated. Conclusions: Hyperandrogenism and insulin resistance likely play important roles in the pathophysiological changes of PCOS and lead to PCOS-like characteristics as well as endometrial lesions. Hypoandrogenic and insulin sensitization therapy can alleviate DHT-induced endometrial hyperplasia by regulating AR and GLUT4 expression.
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