A kidney drug may help restore fertility in premature ovarian insufficiency

A common kidney medication could be the key to treating a type of infertility that affects up to 3% of women under 40, according to a study published in Science.

Premature ovarian insufficiency (POI) is a condition where the ovaries stop functioning properly, leading to low estrogen levels and follicles that often fail to develop or respond to fertility treatments. This leaves the eggs in a dormant state. Current treatments are limited to managing symptoms such as hot flashes and night sweats.

For years, scientists focused on the eggs themselves, but researchers led by Tianren Wang and Kui Liu from the University of Hong Kong suspected the problem could be the environment the eggs live in (the ovarian stroma).

For an egg to wake up, it requires a specific protein called Kit ligand. The researchers realized that if the environment was the problem, they needed a drug that could force the surrounding cells to produce more of this protein.

Drug screening

So they screened nearly 1,300 FDA-approved medications. They applied the drugs to mouse ovarian cells that were designed to glow whenever the Kit ligand protein was produced. For the follicles to wake up, they needed to see an increase in this protein.

Most of the medicines did nothing, and some even made the environment worse. However, a few successfully boosted protein levels, but finerenone (used to treat chronic kidney disease associated with type 2 diabetes) emerged as one of the most promising candidates.

So, how was it working? The researchers found that in POI, the ovary contains excessive collagen (the main component of scar tissue), making it stiff and thick. When they gave the mice finerenone, it blocked a receptor that causes this scarring. As a result, the collagen was removed, and the ovarian tissue softened and changed chemically.

To prove that the environment was key, the researchers placed dormant follicles into a stiff, scarred ovary. Nothing happened. However, when they placed the same type of follicles into an ovary treated with finerenone, the follicles began to grow.

Pilot study

The research team then conducted a pilot clinical trial involving 14 women who had been diagnosed with POI. Each woman took 20 mg of the medication twice a week. In several volunteers, the dormant follicles began to develop into mature eggs. Doctors retrieved these from the ovaries and successfully fertilized them in the lab.

“Targeting the ovarian stroma—rather than the follicles themselves—represents an effective therapeutic strategy for POI-related infertility,” write the researchers in their paper.

“Our findings provide a starting point showing that alleviating ovarian stromal fibrosis through repurposed antifibrotic drugs offers a promising intervention for restoring fertility in patients with POI.”

Following this successful proof-of-concept pilot, the next step for the study authors is larger clinical trials.

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