Premature ovarian insufficiency (POI) is a condition in which the ovaries cease to function properly in young women, leading to loss of fertility. A new study points to a possible cause of the early insufficiency—the development of scar tissue that “strangles” the ovarian tissue. Is there a treatment? An existing medication for kidney disease succeeded in restoring fertility in mice and has even shown promising preliminary results in women.
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About 1%–3% of women under the age of forty are diagnosed with POI. This is a condition in which the ovaries stop functioning well before the average age, leading to cessation of menstruation and to the hormonal changes characteristic of menopause [1]. Until now, the prevailing view was that in such cases the “ovarian reserve” is depleted, or that the eggs simply no longer respond to hormones. But could it be that the syndrome does not originate in the eggs themselves?
Previous studies have shown that women with POI, as well as women during natural menopause, still retain a small pool of primordial follicles (the ovarian structures in which eggs mature and become ready for fertilization [2]). Theoretically, under the right conditions, mature, fertilizable eggs can be produced from these follicles.
In the present study, the researchers found that the main obstacle is a fibrotic process in the ovary. Fibrosis occurs when soft connective tissue becomes scarred, stiff, and collagen-rich—much like a large scar on the skin. The researchers hypothesized that in women with POI the supporting connective tissue in the ovary becomes so stiff that it physically and molecularly prevents follicles from being exposed to the hormonal signals needed to “wake them up” and trigger their development [3].
To identify a potential treatment, the team screened a library of 1300 FDA-approved medications for their effects on follicle development in culture (in vitro high-throughput screening). They discovered that finerenone had a significant effect on follicular growth. Finerenone is currently used to treat kidney and heart disease; it blocks a receptor involved in inflammation and tissue scarring [4]. To their surprise, the scientists found that this receptor is expressed at very high levels in the ovary, and that its activation drives fibrosis. Two other anti-fibrotic drugs showed similar results, reinforcing the notion that fibrosis is a key driver of POI-related infertility.
Next, the researchers administered finerenone to aging female mice—a model for ovarian insufficiency. The results were striking: The drug reduced collagen levels in the ovarian tissue, making it less stiff. As a result, the remaining primordial follicles were once again exposed to hormonal signals and began to grow, producing mature, fertilizable eggs. Aging mice treated with finerenone produced more offspring than untreated controls. Safety tests showed no genetic defects in the eggs or developmental problems in the offspring.
Because the drug is already approved for human use, the researchers conducted a small first-in-human pilot trial involving 14 women with POI. The participants took one tablet of finerenone twice a week (a lower dose than in its intended use) and were monitored for three to seven months. Ultrasound examinations revealed the development of mature follicles, which is considered impossible in women with this condition. Thirteen women then underwent ovarian stimulation. Mature oocytes were retrieved from seven of them, and some were successfully fertilized to create viable embryos.
What do these findings mean? This study is a classic example of drug repurposing—using a safe, established medication for an entirely new purpose. Beyond treating POI, the results suggest that anti-fibrotic drugs might slow the natural ovarian aging, improve the success rates of fertility treatments in older women, and perhaps even delay menopause. While larger trials are required before such therapy can be approved, this research represents a genuine breakthrough and offers new hope to women who believed they had lost their chance to conceive.
Hebrew editing: Smadar Raban
English editing: Elee Shimshoni
Sources and further reading
Irit serves as Scientific Director at “Little, Big Science”. She holds a PhD from Tel Aviv University and has conducted her postdoctoral training at the University of California, San Francisco. Her expertise is in fertility endocrinology, developmental biology, stem cells and tissue regeneration.
