The Progesterone Challenge Test as a Functional Biomarker of Endometrial Cancer Risk: Results from a Prospective...

Area of Science:

• Gynecology
• Oncology
• Preventive Medicine

Background:

• Global endometrial cancer (EC) incidence is rising, primarily due to obesity.
• Current EC diagnosis relies on symptoms, lacking methods for asymptomatic risk stratification.
• The Progesterone Challenge Test (PCT) assesses endometrial hormonal responsiveness for potential EC prevention.

Purpose of the Study:

• To evaluate the feasibility, tolerability, and acceptability of the PCT as a community-based risk-stratification tool for EC prevention.
• To assess the PCT's utility in identifying asymptomatic postmenopausal individuals at higher risk for EC.
• To provide evidence for a scalable, low-cost strategy for targeted EC prevention.

Main Methods:

• The RESToRE study (NCT05651282) prospectively enrolled asymptomatic postmenopausal individuals (BMI ≥34.9 kg/m²) in British Columbia.
• Participants completed a 10-day course of oral medroxyprogesterone acetate (MPA) 10 mg daily.
• Feasibility, tolerability, acceptability, and withdrawal bleeding (+PCT) were evaluated.

Main Results:

• Of 96 eligible individuals, 51 completed the PCT, with 30.2% experiencing withdrawal bleeding (+PCT).
• Participants and providers found the PCT acceptable due to its simplicity and low burden.
• Side effects were mild, with only 3.8% discontinuing MPA; 3 individuals showed proliferative endometrium or simple hyperplasia upon biopsy.

Conclusions:

• The Progesterone Challenge Test (PCT) is a feasible, well-tolerated, and acceptable tool for higher-risk postmenopausal individuals.
• The PCT serves as a physiologic biomarker for endometrial responsiveness, aiding EC risk stratification.
• Findings support the PCT's potential for scalable, low-cost targeted endometrial cancer prevention.