Antifibrotic drug finerenone restores fertility in premature ovarian insufficiency

  • Science. 2026 Feb 5;391(6785):eadz4075. doi: 10.1126/science.adz4075.
Zexiong Lin  #  1  2 ,  Yuan Li  #  2 ,  Yu Zhao  #  2 ,  Dongteng Liu  #  1 ,  Shuzi Deng  #  1  2 ,  Jingkai Gu  #  2 ,  Yanyan Li  #  2 ,  Xudong Zhao  #  1 ,  Peishan Wu  #  2 ,  Yuan Xiao  #  1 ,  Jiaping Su  2 ,  Yiting Sun  1  2 ,  Yihui Zhang  1 ,  Yin Lau Lee  1 ,  Yorino Sato  3 ,  Haitao Zeng  4 ,  Haonan Lu  1 ,  Juanhui Zhang  2 ,  Jennifer K Y Ko  1 ,  Jing Zhao  2 ,  Kazuhiro Kawamura  3 ,  Ernest H Y Ng  1 ,  Shanfang Jiang  5 ,  Yu Li  2 ,  Xi Xia  6 ,  Karen K L Chan  1 ,  William S B Yeung  1  2 ,  Tianren R Wang  1  2 ,  Kui Liu  1  2
Affiliations
  • 1. Department of Obstetrics and Gynecology, School of Clinical Medicine, Li Ka Shing Faculty of Medicine, The University of Hong Kong, Pokfulam, Hong Kong, China.
  • 2. Shenzhen Key Laboratory of Fertility Regulation, Center of Assisted Reproduction and Embryology, The University of Hong Kong-Shenzhen Hospital, Shenzhen, Guangdong, China.
  • 3. Department of Obstetrics and Gynecology, Juntendo University Faculty of Medicine, Tokyo, Japan.
  • 4. Center of Reproductive Medicine, The Sixth Affiliated Hospital, Sun Yat-sen University, Guangzhou, Guangdong, China.
  • 5. Shenzhen Guangming District People's Hospital, Shenzhen, China.
  • 6. Department of Reproductive Center, Peking University-Shenzhen Hospital, Shenzhen, Guangdong, China.
  • # Contributed equally.
PMID: 41643022 DOI: 10.1126/science.adz4075
Abstract

Currently, no effective treatment exists for infertility associated with premature ovarian insufficiency (POI) because affected patients lack hormone-responsive antral follicles. By screening a Food and Drug Administration (FDA)-approved drug library, we identified finerenone, a kidney disease medication, as a promising drug for restoring fertility in POI. Finerenone stimulated follicle development in aged mice and restored antral follicle development in patients with POI following oral administration, resulting in mature oocytes and embryos. Mechanistically, finerenone reduced fibrotic deposition in the ovarian stroma, alleviating collagen-mediated suppression of follicular development. Building on this insight, we identified additional FDA-approved oral antifibrotic drugs as potential treatments for POI-related infertility. Our findings highlight the ovarian stroma-rather than the follicles themselves-as the key therapeutic target and offer potential therapeutic leads for POI-related infertility.

Products
Inhibitors & Agonists
Other Products