Effects of flutamide on pituitary and adrenal responsiveness to corticotrophin releasing factor (CRF)

OBJECTIVE: Flutamide is a non-steroid antiandrogen that specifically blocks the androgen receptor. We have investigated the effect of flutamide treatment on the adrenal androgen response to corticotrophin releasing factor (CRF) in eight patients with polycystic ovary syndrome (PCOS). PATIENTS: Eight women with moderate to severe hirsutism, ranging in age from 19 to 23 years were enrolled in the study. Basal hormonal pattern showed anovulatory cycles, increased concentrations of LH, androstenedione and testosterone and increased LH/FSH ratio. A baseline ultrasound scan revealed polycystic ovaries in all patients. Each received 250 mg of Flutamide twice a day for 6 months. MEASUREMENTS: Before treatment and at the end of the sixth month, women were evaluated for hirsutism score and a CRF test was performed to evaluate ACTH, cortisol and adrenal androgen responses. RESULTS: Androstenedione (Δ4), DHEA-S, 17-hydroxyprogesterone, testosterone and free- testosterone showed significantly reduced responses after six months of flutamide therapy whereas ACTH and cortisol response were similar to those before treatment. Clinical improvement in the degree of hirsutism was observed in all patients. The Ferriman-Gallwey scores decreased from a mean of 22 ± 2 to 8 ± 1.5. CONCLUSION: Flutamide induces a significant reduction in adrenal androgen response to the CRF test but not in the response of ACTH and cortisol. The finding that flutamide does not alter the pituitary- adrenal axis shows that flutamide acts by reducing adrenal androgens. These results demonstrate that flutamide is not only effective in the treatment of hirsutism but also reduces adrenal androgen secretion.