Flutamide-metformin plus an oral contraceptive (OC) for young women with polycystic ovary syndrome: switch from third- to fourth-generation OC reduces body adiposity

BACKGROUND: Low-dose flutamide-metformin has been developed as a background therapy for non-obese adolescents and young women with hyperinsulinaemic hyperandrogenism, a variant of polycystic ovary syndrome (PCOS). We verified whether the lipolytic efficacy of flutamide-metformin in women with PCOS is enhanced by giving an oral contraceptive (OC) co-therapy that contains drospirenone, instead of gestodene, as progestin. METHODS: An open-labelled study was carried out in which non-obese women with PCOS (n = 29; age approximately 20 years), who had been on a combination of flutamide (62.5 mg/day), metformin (850 mg/day) and ethinylestradiol-gestodene for 8-15 months, were randomized for replacement of the gestodene OC by a drospirenone OC. Assessments of endocrine-metabolic state and body composition (by dual-energy X-ray absorptiometry) were performed at randomization and after 6 months. RESULTS: The switch to drospirenone OC was accompanied by a reduction of total and abdominal fat (mean -0.8 and -0.5 kg) and by an increment of lean body mass (+0.6 kg; all P < 0.01), so that body adiposity was strikingly reduced without changing body weight. CONCLUSION: In non-obese women with PCOS, low-dose flutamide-metformin reduces total and abdominal fat excess more effectively if contraceptive co-therapy contains drospirenone, instead of gestodene, as progestin.