Low-dose combination of flutamide, metformin and an oral contraceptive for non-obese, young women with polycystic ovary syndrome.
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 microg + gestodene 75 microg) 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/m(2)). 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.


CONCLUSIONS
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.
Ibáñez
Lourdes
L
Hospital Sant Joan de Déu, University of Barcelona, 08950 Esplugues, Barcelona, Spain. libanez@hsjdbcn.org
de Zegher
Francis
F
D000328:Adult; D000726:Androgen Antagonists / Q000008:administration & dosage*; D015331:Cohort Studies; D003276:Contraceptives, Oral / Q000008:administration & dosage*; D004305:Dose-Response Relationship, Drug; D004359:Drug Therapy, Combination; D005260:Female; D005485:Flutamide / Q000008:administration & dosage*; D006801:Humans; D017588:Hyperandrogenism / Q000188:drug therapy / Q000209:etiology; D006946:Hyperinsulinism / Q000188:drug therapy / Q000209:etiology; D006949:Hyperlipidemias / Q000188:drug therapy / Q000209:etiology; D008687:Metformin / Q000008:administration & dosage*; D011085:Polycystic Ovary Syndrome / Q000097:blood / Q000188:drug therapy*; D012738:Sex Hormone-Binding Globulin / Q000032:analysis
D000726:Androgen Antagonists; D003276:Contraceptives, Oral; D012738:Sex Hormone-Binding Globulin; D005485:Flutamide; D008687:Metformin