Premature ovarian insufficiency (POI) affects about 1 to 3% of women of reproductive age and is a significant cause of infertility. The condition is characterized by the absence of menstrual periods, low estrogen levels, and high follicle-stimulating hormone (FSH) levels. Although some primordial follicles remain in the ovaries, they rarely develop on their own and typically do not respond to additional hormonal stimulation.
A team led by Professor Kazuhiro Kawamura from Juntendo University previously developed an invasive technique that activates small follicles in ovarian tissue outside the body before reimplanting it into patients. This method resulted in documented pregnancies and live births. "Based on this knowledge, the in-vitro activation technique was developed to activate small follicles in cultured ovarian cortical tissues from patients with POI and then autotransplanted back into the patients under a laparoscopic surgery, resulting in documented pregnancies and live births," said Prof. Kawamura.
Building on these insights, researchers explored whether an oral medication could stimulate follicle development without surgery. Drugs targeting pathways involved in follicle formation are already used for kidney disorders. Professors Kawamura and Kui Liu from the University of Hong Kong (HKU), along with their teams, investigated if such drugs could be repurposed for POI treatment. Their findings were published on February 5, 2026, in Science.
The study identified finerenone—a mineralocorticoid receptor antagonist approved for chronic kidney disease—as a promising candidate due to its antifibrotic properties and established safety profile. When immature mouse ovaries were treated with finerenone in vitro, follicles developed and matured into oocytes.
Further tests showed that adult mice given oral finerenone over 18 weeks had more offspring than those given a placebo. Finerenone also induced follicle formation in older mice with ovarian insufficiency.
Gene analysis revealed that finerenone reduced collagen production in the ovarian cortex. Excess collagen can lead to fibrosis, which may physically limit follicle growth. "Finerenone's antifibrotic effect alleviates ECM-mediated constraints on small follicle growth, thereby allowing follicles to develop. Furthermore, we identified the stromal collagen–granulosa signaling as an important negative regulator of follicular development," said Prof. Kawamura, adding, "Therefore, finerenone stimulates follicular development through its antifibrotic action on the ovarian stroma." Other antifibrotic drugs tested—nintedanib and ruxolitinib—also promoted follicle formation via different mechanisms.
To test whether these results would translate to humans, researchers enrolled 14 women with POI at HKU Shenzhen Hospital for an experimental study using oral finerenone over three to seven months. All participants showed evidence of new follicle development; seven produced mature oocytes suitable for IVF procedures. The quality of these oocytes matched those from women without POI undergoing IVF.
"Further clinical characterization of FDA-approved oral antifibrotic drugs for their abilities in activating small ovarian follicles in patients offers a promising path to repurposing therapies for POI-related infertility," said Prof. Kawamura.
If confirmed by larger trials, antifibrotic therapy like finerenone could offer a less invasive alternative to current treatments for women with POI globally.
