Combined low-dose pioglitazone, flutamide, and metformin for women with androgen excess
Por:
Ibañez-Toda L, López-Bermejo A, del Rio L, Enríquez G, Valls C and de Zegher F
Publicada:
1 may 2007
Resumen:
Context and Objective: One of the treatments for hyperinsulinemic hyperandrogenism in nonobese women is combined androgen receptor blockade (with flutamide; Flu), insulin sensitization (with metformin; Met) plus an estroprogestagen contraceptive. We tested whether adding low-dose pioglitazone (Pio; 7.5 mg/d) confers more benefit.
Setting: The study was conducted at a university hospital.
Study Population and Design: This double-blind study enrolled 38 young women with hyperinsulinemic hyperandrogenism [mean body mass index (BMI) 24 kg/m(2)], all of whom started on Flu (62.5 mg/d) and Met (850 mg/d) plus a transdermal estroprogestagen, each for 21 of 28 d over 6 months. Patients were randomly assigned to receive, in addition, placebo (n = 19) or Pio (n = 19; 7.5 mg/ d) for the same 21 of 28 d over 6 months.
Main Outcomes: BMI, waist to hip ratio, hirsutism score, fasting endocrine-metabolic markers, body composition, abdominal fat (visceral vs. sc), and carotid intima-media thickness were measured at study start and after 6 months.
Results: PioFluMet reduced intima-media thickness more than Flu-Met and lowered glucose, IGF-I, and C-reactive protein more as well as the ratio of low-density lipoprotein to high-density lipoprotein cholesterol and the ratio of neutrophils to lymphocytes. PioFluMet treatment was followed by a leaner body composition and a loss of visceral fat (both P < 0.001). In the total group, the changes included not only decreases in waist to hip ratio, hirsutism score, and testosterone (all P < 0.001) but also minor drops in alanine aminotransferase, aspartate aminotransferase, gamma-glutamyl transpeptidase, and lactate dehydrogenase (all P < 0.005), indicating absence of hepatotoxicity; BMI remained unchanged. Clinical side effects were not detected.
Conclusion: In this proof-of-concept study, addition of Pio to FluMet plus an estroprogestagen led to improvements in the endocrine-metabolic condition, in low-grade inflammation, in total and visceral adiposity, and in markers of cardiovascular health.
Filiaciones:
Ibañez-Toda L:
Endocrinology Unit, Hospital Sant Joan de Déu, University of Barcelona, Passeig de Sant Joan de Déu 2, 08950 Esplugues, Barcelona, Spain.
López-Bermejo A:
Endocrinology Unit, Hospital Sant Joan de Déu, University of Barcelona, Passeig de Sant Joan de Déu 2, 08950 Esplugues, Barcelona, Spain.
del Rio L:
Endocrinology Unit, Hospital Sant Joan de Déu, University of Barcelona, Passeig de Sant Joan de Déu 2, 08950 Esplugues, Barcelona, Spain.
Enríquez G:
Endocrinology Unit, Hospital Sant Joan de Déu, University of Barcelona, Passeig de Sant Joan de Déu 2, 08950 Esplugues, Barcelona, Spain.
Valls C:
Endocrinology Unit, Hospital Sant Joan de Déu, University of Barcelona, Passeig de Sant Joan de Déu 2, 08950 Esplugues, Barcelona, Spain.
de Zegher F:
Endocrinology Unit, Hospital Sant Joan de Déu, University of Barcelona, Passeig de Sant Joan de Déu 2, 08950 Esplugues, Barcelona, Spain.
Univ Barcelona, Endocrinol Unit, Hosp Sant Joan de Deu, Esplugues 08950, Barcelona, Spain
Univ Barcelona, Hormonal Lab, Hosp Sant Joan de Deu, Esplugues 08950, Barcelona, Spain
Dr Josep Trueta Hosp, Diabet Endocrinol & Nutr Unit, Girona 17007, Spain
Cetrir Ctr Med, Barcelona 08029, Spain
Univ Autonoma Barcelona, Hosp Materno Infantil Vall Dhebron, Dept Radiol, Barcelona 08035, Spain
Katholieke Univ Leuven, Dept Woman & Child, B-3000 Louvain, Belgium
Univ Barcelona, Endocrinol Unit, Hosp Sant Joan de Deu, Esplugues 08950, Barcelona, Spain
Univ Barcelona, Hormonal Lab, Hosp Sant Joan de Deu, Esplugues 08950, Barcelona, Spain
Dr Josep Trueta Hosp, Diabet Endocrinol & Nutr Unit, Girona 17007, Spain
Cetrir Ctr Med, Barcelona 08029, Spain
Univ Autonoma Barcelona, Hosp Materno Infantil Vall Dhebron, Dept Radiol, Barcelona 08035, Spain
Katholieke Univ Leuven, Dept Woman & Child, B-3000 Louvain, Belgium
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