Effects of interleukin-1 receptor antagonism in women with polycystic ovary syndrome-the FertIL trial.

Chronic low-grade inflammation might contribute to hyperandrogenemia and metabolic complications in polycystic ovary syndrome (PCOS). The proinflammatory cytokine interleukin (IL)-1 stimulates androgen production from ovarian cells, whereas blockade of the IL-1 pathway improves cardiometabolic health. We aimed to investigate whether blocking the IL-1 pathway ameliorates hyperandrogenemia in patients with PCOS. This is a prospective, interventional, single-arm, proof-of-concept trial performed at a tertiary hospital in Switzerland (August 2018 to July 2020) in 18 premenopausal women with a diagnosis of PCOS according to the Rotterdam criteria, total testosterone levels ≥ 1.7 nmol/L, and C-reactive protein (CRP) ≥ 1.0 mg/L. Patients received 100 mg/day of the IL-1-receptor antagonist anakinra for 28 days and underwent weekly blood sampling until 1 week after the end of treatment. The primary endpoint was the change in serum androstenedione levels on day 7 of treatment, assessed with liquid chromatography-tandem mass spectrometry. Seven of these women participated in a subsequent observational sub-study (May 2021 to December 2021). Median [interquartile range (IQR)] androstenedione increased by 0.5 [-0.1, 1.6] nmol/L ( Our findings suggest that anakinra suppresses IL-1-mediated chronic low-grade inflammation in PCOS and might attenuate biochemical hyperandrogenemia.

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Copyright © 2024 Wälchli-Popovic, Monnerat, Taylor, Gilligan, Schiffer, Arlt, Vogt, De Geyter, Hutter, Donath, Sartorius and Christ-Crain.

Déclaration de conflit d'intérêts

Author GS was employed by company Fertisuisse. MD is listed as one of the inventors on a patent filed in 2003 for the use of IL-1 inhibiting drugs against type 2 diabetes. The remaining authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest.