Estetrol Inhibits the Prostate Cancer Tumor Stimulators FSH and IGF-1

Area of Science:

• Endocrinology
• Oncology
• Pharmacology

Background:

• Advanced prostate cancer (PCa) requires endocrine therapy, often androgen deprivation therapy (ADT).
• Estetrol (E4), a fetal estrogen, is being investigated for co-treatment with ADT to enhance anti-cancer effects.
• Previous studies indicated ADT+E4 suppressed testosterone and PSA; this study details FSH suppression and examines IGF-1 effects.

Purpose of the Study:

• To evaluate the detailed effect of E4 co-treatment with ADT on follicle-stimulating hormone (FSH) suppression.
• To assess the impact of ADT+E4 on insulin-like growth factor-1 (IGF-1) levels in advanced PCa patients.
• To determine if E4 enhances the anti-tumor activity of ADT by modulating these key endocrine factors.

Main Methods:

• A Phase II, double-blind, randomized, placebo-controlled study (PCombi) involving advanced PCa patients on ADT.
• Patients were randomized to receive either 40 mg E4 or placebo for 24 weeks alongside ADT.
• FSH and IGF-1 levels were monitored, with analyses performed on the per-protocol population.

Main Results:

• ADT+E4 achieved near-complete FSH suppression in 98% of patients, compared to 37% with ADT alone (p < 0.0001).
• IGF-1 levels decreased by 41% in the ADT+E4 group, whereas they increased by 10% in the ADT+placebo group (p < 0.0001).
• These effects were observed consistently across individual patients in the ADT+E4 arm.

Conclusions:

• ADT combined with E4 demonstrates potent suppression of the tumor stimulator FSH in all treated patients.
• E4 augments the effects of ADT by significantly reducing IGF-1 levels, contrasting with the increase seen with ADT alone.
• These findings suggest that E4 co-treatment may enhance the anti-cancer efficacy of ADT in advanced prostate cancer.