Treatment with flutamide, metformin, and their combination added to a hypocaloric diet in overweight-obese women with polycystic ovary syndrome: a randomized, 12-month, placebo-controlled study.Gambineri A,Patton L,Vaccina A, Cacciari M,Morselli-Labate AM, Cavazza C,Pagotto U,Pasquali R.
Division of Endocrinology, Department of Internal Medicine, S. Orsola-Malpighi Hospital, Via Massarenti 9, 40138 Bologna, Italy.
Context:
The few controlled trials performed so far indicate that the addition of metformin and/or flutamide to a hypocaloric diet in obese women with polycystic ovary syndrome (PCOS) effectively influences different phenotypic aspects of the syndrome. All these studies are, however, characterized by a short to medium period of treatment.
Objectives:
Our objective was to investigate the long-term effects of these therapies.
Design and Settings:
We conducted a prospective, randomized, placebo-controlled trial at a medical center.
Patients:
Of 80 overweight-obese women with PCOS, 76 completed the study.
Interventions:
Patients were placed on a hypocaloric diet for the first month and then on a hypocaloric diet plus placebo, metformin (850 mg, orally, twice a day), flutamide (250 mg, orally, twice a day), or metformin plus flutamide for the subsequent 12 months (20 subjects in each group).
Settings, Design and Main Outcome Measures:
We assessed clinical features, computerized tomography measurement of fat distribution, androgens, lipids, and fasting and glucose-stimulated glucose and insulin levels at baseline and after 6 and 12 months of treatment.
Results:
After 6 months, compared with placebo, flutamide further decreased visceral/sc fat mass (P = 0.044), androstenedione (P<0.001), dehydroepiandrosterone sulfate (P<0.001), and hirsutism score (P<0.001), whereas metformin further increased Frequency of menstruation (P = 0.039). After 12 months, flutamide maintained the effects observed after 6 months on visceral/sc fat mass (P = 0.033) and androstenedione (P<0.001), whereas it produced an additional decrease in dehydroepiandrosterone sulfate (P = 0.020) and hirsutism score (P = 0.019); metformin further improved the menstrual pattern (P = 0.013). Moreover, after 12 months, flutamide improved more than placebo the menstrual pattern (P = 0.008), glucose-stimulated glucose levels (P = 0.041), insulin sensitivity (P<0.001), and low-density lipoprotein cholesterol levels (P = 0.003), whereas metformin decreased glucose-stimulated insulin levels (P = 0.014). The combination of the two drugs maintained the specific effect of each of the compounds, without any additive or synergistic effect.
Conclusions:
These findings add relevance to the usefulness of metformin and flutamide in the treatment of dieting overweight-obese PCOS women and provide a rationale for targeting different therapeutic options according to the required outcomes in the long term.
See Also:
PCOS - Polycystic Ovary Syndrome
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