EFFECTS OF FLUTAMIDE ON PITUITARY AND ADRENAL RESPONSIVENESS TO CORTICOTROPIN-RELEASING FACTOR (CRF)

OBJECTIVE Flutamide is a non-steroid antiandrogen that specifically bl ocks the androgen receptor. We have investigated the effect of flutami de treatment on the adrenal androgen response to corticotrophin releas ing factor (CRF) in eight patients with polycystic ovary syndrome (PCO S), PATIENTS Eight women with moderate to severe hirsutism, ranging in age from 19 to 23 years were enrolled in the study. Basal hormonal pa ttern showed anovulatory cycles, increased concentrations of LH, andro stenedione and testosterone and increased LH/ FSH ratio. A baseline ul trasound scan revealed polycystic ovaries in all patients. Each receiv ed 250 mg of Flutamide twice a day for 6 months. MEASUREMENTS Before t reatment and at the end of the sixth month, women were evaluated for h irsutism score and a CRF test was performed to evaluate ACTH, cortisol and adrenal androgen responses. RESULTS Androstenedione (Delta 4), DH EA-S, 17-hydroxyprogesterone, testosterone and free-testosterone showe d significantly reduced responses after six months of flutamide therap y whereas ACTH and cortisol response were similar to those before trea tment. 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 reduct ion in adrenal androgen response to the CRF test but not in the respon se 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 effect ive in the treatment of hirsutism but also reduces adrenal androgen se cretion.