Flutamide-metformin plus ethinylestradiol-drospirenone for lipolysis and antiatherogenesis in young women with ovarian hyperandrogenism: the key role of metformin at the start and after more than one year of therapy.
Flutamide (Flu)-metformin (Met) 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 nonobese women with ovarian hyperandrogenism, a variant of polycystic ovary syndrome. We have now questioned the need: 1) to add Met at the start of Flu plus ethinylestradiol-drospirenone; and 2) to maintain Met after more than 1 yr on full combination therapy. The additive effects of Met (850 mg/d) were assessed in studies A and B, over 3 months, in young patients with hyperinsulinemic hyperandrogenism. In study A, all participants [n = 31; age approximately 16 yr; body mass index approximately 22 kg/m(2)] started on Flu (62.5 mg/d) and an oral contraceptive (ethinyl-estradiol + drospirenone), and they were randomized to receive Met in addition or not. In study B, all participants (n = 42; age approximately 19 yr; body mass index approximately 22 kg/m(2)) had been treated with Flu-Met plus the same contraceptive for a mean duration of 17 months, and they were randomized for discontinuation of Met or not. Fasting blood glucose, serum insulin, testosterone, lipid profile, adiponectin, and IL-6 were determined at the start and after 3 months, together with body composition, by dual energy x-ray absorptiometry. The results of studies A and B complemented each other; the addition of Met was found to have consistently (more) normalizing effects on IL-6 and adiponectin, on lean mass (mean Met benefit of +1.2 kg in study A and +0.6 kg in study B), and in particular on abdominal fat excess [Met benefit of -0.7 kg (A) and -0.3 kg (B)]. In conclusion, Met 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 polycystic ovary syndrome.
Endocrinology Unit, Hospital Sant Joan de Déu, University of Barcelona, Passeig de Sant Joan de Déu, 2, 08950 Esplugues, Barcelona, Spain. libanez@hsjdbcn.org
Lourdes
L
Ibáñez
Francis
F
de Zegher
D000293:Adolescent; D000328:Adult; D000736:Androstenes / Q000008:administration & dosage*; D001161:Arteriosclerosis / Q000517:prevention & control*; D004359:Drug Therapy, Combination; D004997:Ethinyl Estradiol / Q000008:administration & dosage*; D005260:Female; D005485:Flutamide / Q000008:administration & dosage*; D006801:Humans; D017588:Hyperandrogenism / Q000188:drug therapy*; D008066:Lipolysis / Q000187:drug effects*; D008687:Metformin / Q000008:administration & dosage*; D011085:Polycystic Ovary Syndrome / Q000188:drug therapy*; D013997:Time Factors
D000736:Androstenes; D004997:Ethinyl Estradiol; D005485:Flutamide; D008687:Metformin; C035144:drospirenone