Premium
Low‐dose pioglitazone and low‐dose flutamide added to metformin and oestro‐progestagens for hyperinsulinaemic women with androgen excess: add‐on benefits disclosed by a randomized double‐placebo study over 24 months
Author(s) -
Ibáñez Lourdes,
LópezBermejo Abel,
Díaz Marta,
Enríquez Goya,
Del Río Luis,
De Zegher Francis
Publication year - 2009
Publication title -
clinical endocrinology
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.055
H-Index - 147
eISSN - 1365-2265
pISSN - 0300-0664
DOI - 10.1111/j.1365-2265.2008.03472.x
Subject(s) - flutamide , endocrinology , medicine , metformin , pioglitazone , placebo , androgen , androgen excess , antiandrogen , androgen receptor , prostate cancer , type 2 diabetes , insulin resistance , insulin , hormone , diabetes mellitus , cancer , polycystic ovary , alternative medicine , pathology
Summary Context and aim Metformin plus oestro‐progestagen is a combination treatment for non‐obese women with hyperinsulinaemic androgen excess. We explored whether low‐dose pioglitazone (Pio) and flutamide (Flu) has readily detectable add‐on effects. Design patients, intervention Randomized, double‐placebo pilot study over 24 months; 38 women with hyperinsulinaemic androgen excess (mean age 20 years; BMI 23·7 kg/m 2 ); all women received metformin and an oestro‐progestagen for 24 months, and add‐on Flu (62·5 mg/day; 21/28 days) for 18 months. A first randomization was performed at start of the study, for Pio (7·5 mg/day; 21/28 days) vs. Pio‐placebo, with a cross‐over of Pio subgroups at 18 month. A second randomization was performed at 18 months, for Flu vs. Flu‐placebo until 24 months. Main outcomes Intima media thickness (IMT); body composition by absorptiometry; abdominal fat partitioning by magnetic resonance; circulating glucose, insulin, IGF‐I, androgens, LDL : HDL ratio, RBP4, vaspin. Results Add‐on effects of Pio included a gain of lean mass (mirrored by a loss of fat) and an accelerated lowering of IMT ( P ≤ 0·001). Add‐on effects of flutamide included a further reduction of androgen excess. Between 0 and 18 months, women lost a quarter of their visceral fat ( P < 0·001; independently of Pio); beyond 18 months, a rebound of visceral fat occurred in women who had stopped Pio and Flu. Between 0 and 24 months, insulin sensitivity increased, as did circulating RBP‐4 and vaspin (all P = 0·001). Conclusion Low‐dose Pio and Flu further improve long‐term markers – such as IMT, lean mass and visceral fat – when jointly added to a treatment of metformin plus an oestro‐progestagen in non‐obese women with hyperinsulinaemic androgen excess.