Low-dose combination of flutamide, metformin and an oral contraceptive for non-obese, young women with polycystic ovary syndrome.

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Abstract
BACKGROUND: The endocrine‐metabolic status of non‐obese, young women with polycystic ovary syndrome (PCOS) is normalized more effectively by combined treatment with flutamide and metformin than by either of these drugs in monotherapy. In this follow‐up study, we assess whether the endocrine‐metabolic benefits of combined flutamide‐metformin treatment are maintained in the presence of a low‐dose oral contraceptive (OC). METHODS: To a population of non‐obese, young PCOS women already receiving flutamide‐metformin (125 mg/day and 1275 mg/day), a low‐dose OC (ethinyl estradiol 20 µg + gestodene 75 µg) was administered to reduce the risk of pregnancy. A total of 12 women elected to receive the OC and this subgroup (OC+) was matched to a subgroup continuing on flutamide‐metformin alone (OC–), for a total study population of 24 women (mean age ± SEM 18.7 ± 0.3 years; body mass index, 21.8 ± 0.5 kg/m2). Endocrine‐metabolic indices were assessed before any treatment (0 months), on flutamide‐metformin (12 months), and again after a further 6 months with or without additional OC (18 months). RESULTS: In OC– and OC+ women, the beneficial effects of flutamide‐metformin on hyperandrogenaemia, hyperinsulinaemia and dyslipidaemia were maintained. In OC+ women, there was an additional increase in sex hormone‐binding globulin (SHBG), and thus a further drop in the free androgen index. CONCLUSION: When a low‐dose OC is administered with a low‐dose flutamide‐metformin combination in women with PCOS, the beneficial effects are maintained on hyperinsulinaemia‐dyslipidaemia, which are key determinants of long‐term complications. Hence, in daily practice, such a low‐dose quatuor may become a therapeutic option of first choice for young women with PCOS.

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