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Submitted on July 16, 2004
Accepted on October 4, 2004
Endocrinology Unit, Hospital Sant Joan de Déu, University of Barcelona, Spain, Department of Pediatrics, University of Leuven, Belgium
* To whom correspondence should be addressed.
Lourdes Ibáñez, E-mail: libanez{at}hsjdbcn.org
Flutamide-metformin with ethinylestradiol-drospirenone is a combination therapy that reduces the total and abdominal fat excess, diminishes the lean mass deficit, and attenuates the dysadipocytokinemia of young and non-obese women with ovarian hyperandrogenism, a variant of Polycystic Ovary Syndrome (PCOS). We have now questioned the need (A) to add metformin at start of flutamide plus ethinylestradiol-drospirenone, and (B) to maintain metformin after >1 yr on full combination therapy.
The additive effects of metformin (850 mg/d) were in studies (A) and (B) assessed over 3 mo in young patients with hyperinsulinemic hyperandrogenism. In study (A), all participants (n = 31; age 
16 yr; body mass index [BMI] 22 Kg/m2) started on flutamide (62.5 mg/d) and an oral contraceptive (ethinyl-estradiol + drospirenone), and they were randomized to receive metformin in addition or not. In study (B), all participants (n = 42; 19 yr; BMI 22 Kg/m2) had been treated with flutamide-metformin plus the same contraceptive for a mean duration of 17 mo, and they were randomized for discontinuation of metformin or not. Fasting blood glucose, serum insulin, testosterone, lipid profile, adiponectin and IL-6 were determined at start and after 3 mo, together with body composition by dual x-ray absorptiometry.
The results of studies (A) and (B) complemented each other; the addition of metformin was found to have consistently (more) normalizing effects on IL-6 and adiponectin, on lean mass [mean metformin benefit of +1.2 Kg in study (A) and +0.6 Kg in study (B)] and in particular on abdominal fat excess [metformin benefit of -0.7 Kg (A) and -0.3 Kg (B)].
In conclusion, metformin proved to be a pivotal component of a prime combination therapy that attenuates the dysadipocytokinemia, the lean mass deficit, and the central adiposity of young patients with PCOS.
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