Troglitazone therapy improves endothelial function to near normal levels in women with polycystic ovary syndrome

Giancarlo Paradisi, Helmut O. Steinberg, Marguerite Shepard, Ginger Hook, Alain D. Baron

Research output: Contribution to journalArticle

97 Citations (Scopus)

Abstract

Obese women with polycystic ovary syndrome (PCOS) exhibit impaired endothelial function, which is strongly and directly correlated with both testosterone levels and insulin resistance. Endothelial dysfunction is considered a potent risk factor for macrovascular disease. Because troglitazone (Tgz) improves both hormonal profiles and insulin sensitivity, we tested whether Tgz treatment ameliorates endothelial function in these patients. We studied leg blood flow (LBF) responses to graded intrafemoral artery infusion of the endothelium-dependent vasodilator methacholine chloride (MCh) and to a 4-h hyperinsulinemic euglycemic clamp (120 mU/m2·min) in 10 PCOS, before and after 3 months treatment with Tgz (600 mg/d). A group of 13 obese women (OBW) matched for age, weight, body fat (>40% in both groups), blood pressure, and total cholesterol served as controls. PCOS patients exhibited elevated free testosterone (fT) and triglycerides (TG) and lower high density lipoprotein cholesterol levels compared with OBW [14.0 ± 1.0 vs. 3.7 ± 0.6 pmol/liter (P < 0.0001), 1.60 ± 0.28 vs. 0.94 ± 0.09 mmol/liter (P < 0.02), and 0.91 ± 0.04 vs. 1.1 ± 0.04 mmol/liter (P < 0.005), respectively]. Tgz treatment reduced fT levels, but did not improve the TG and high density lipoprotein profile [to 9.7 ± 2.8 pmol/liter (P < 0.007), 1.49 ± 0.34 mmol/liter (P = NS), and 0.93 ± 0.07 mmol/liter (P = NS), respectively]. Basal LBF was unchanged after Tgz. In PCOS compared with OBW, insulin stimulated glucose disposal (52.7 ± 6.6 vs. 85.5 ± 4.4 μmol/kg fat-free mass·min; P < 0.0005) and vasodilation (increase in LBF, 22 ± 14% vs. 59 ± 15%; P < 0.05) were significantly improved after Tgz treatment to 68.8 ± 7.2 μmol/kg fat-free mass·min (P < 0.0001) and 101 ± 48% (P < 0.03), respectively. The increase in LBF in response to MCh in PCOS was markedly more pronounced after treatment (P < 0.01, by ANOVA) and was similar to that observed in OBW. Before Tgz treatment, maximal LBF increments in response to MCh were 130 ± 25% and 233 ± 29% in PCOS and OBW, respectively (P < 0.01). After Tgz treatment, PCOS values improved, achieving increments similar to those in OBW (245 ± 45%; P < 0.04). Tgz treatment in PCOS improves both hormonal and metabolic features. These modifications are associated with improvement of endothelial function, suggesting that Tgz could be a useful tool to reduce the risk of macrovascular disease in women with PCOS and perhaps in other insulin-resistant syndromes.

Original languageEnglish
Pages (from-to)576-580
Number of pages5
JournalJournal of Clinical Endocrinology and Metabolism
Volume88
Issue number2
DOIs
StatePublished - Feb 1 2003

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troglitazone
Polycystic Ovary Syndrome
Leg
Blood
Methacholine Chloride
Insulin
Therapeutics
Testosterone
Fats
Insulin Resistance
Triglycerides
Endothelium-Dependent Relaxing Factors
Glucose Clamp Technique
Blood pressure
Clamping devices

ASJC Scopus subject areas

  • Biochemistry
  • Endocrinology, Diabetes and Metabolism

Cite this

Troglitazone therapy improves endothelial function to near normal levels in women with polycystic ovary syndrome. / Paradisi, Giancarlo; Steinberg, Helmut O.; Shepard, Marguerite; Hook, Ginger; Baron, Alain D.

In: Journal of Clinical Endocrinology and Metabolism, Vol. 88, No. 2, 01.02.2003, p. 576-580.

Research output: Contribution to journalArticle

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title = "Troglitazone therapy improves endothelial function to near normal levels in women with polycystic ovary syndrome",
abstract = "Obese women with polycystic ovary syndrome (PCOS) exhibit impaired endothelial function, which is strongly and directly correlated with both testosterone levels and insulin resistance. Endothelial dysfunction is considered a potent risk factor for macrovascular disease. Because troglitazone (Tgz) improves both hormonal profiles and insulin sensitivity, we tested whether Tgz treatment ameliorates endothelial function in these patients. We studied leg blood flow (LBF) responses to graded intrafemoral artery infusion of the endothelium-dependent vasodilator methacholine chloride (MCh) and to a 4-h hyperinsulinemic euglycemic clamp (120 mU/m2·min) in 10 PCOS, before and after 3 months treatment with Tgz (600 mg/d). A group of 13 obese women (OBW) matched for age, weight, body fat (>40{\%} in both groups), blood pressure, and total cholesterol served as controls. PCOS patients exhibited elevated free testosterone (fT) and triglycerides (TG) and lower high density lipoprotein cholesterol levels compared with OBW [14.0 ± 1.0 vs. 3.7 ± 0.6 pmol/liter (P < 0.0001), 1.60 ± 0.28 vs. 0.94 ± 0.09 mmol/liter (P < 0.02), and 0.91 ± 0.04 vs. 1.1 ± 0.04 mmol/liter (P < 0.005), respectively]. Tgz treatment reduced fT levels, but did not improve the TG and high density lipoprotein profile [to 9.7 ± 2.8 pmol/liter (P < 0.007), 1.49 ± 0.34 mmol/liter (P = NS), and 0.93 ± 0.07 mmol/liter (P = NS), respectively]. Basal LBF was unchanged after Tgz. In PCOS compared with OBW, insulin stimulated glucose disposal (52.7 ± 6.6 vs. 85.5 ± 4.4 μmol/kg fat-free mass·min; P < 0.0005) and vasodilation (increase in LBF, 22 ± 14{\%} vs. 59 ± 15{\%}; P < 0.05) were significantly improved after Tgz treatment to 68.8 ± 7.2 μmol/kg fat-free mass·min (P < 0.0001) and 101 ± 48{\%} (P < 0.03), respectively. The increase in LBF in response to MCh in PCOS was markedly more pronounced after treatment (P < 0.01, by ANOVA) and was similar to that observed in OBW. Before Tgz treatment, maximal LBF increments in response to MCh were 130 ± 25{\%} and 233 ± 29{\%} in PCOS and OBW, respectively (P < 0.01). After Tgz treatment, PCOS values improved, achieving increments similar to those in OBW (245 ± 45{\%}; P < 0.04). Tgz treatment in PCOS improves both hormonal and metabolic features. These modifications are associated with improvement of endothelial function, suggesting that Tgz could be a useful tool to reduce the risk of macrovascular disease in women with PCOS and perhaps in other insulin-resistant syndromes.",
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AU - Paradisi, Giancarlo

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AU - Baron, Alain D.

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N2 - Obese women with polycystic ovary syndrome (PCOS) exhibit impaired endothelial function, which is strongly and directly correlated with both testosterone levels and insulin resistance. Endothelial dysfunction is considered a potent risk factor for macrovascular disease. Because troglitazone (Tgz) improves both hormonal profiles and insulin sensitivity, we tested whether Tgz treatment ameliorates endothelial function in these patients. We studied leg blood flow (LBF) responses to graded intrafemoral artery infusion of the endothelium-dependent vasodilator methacholine chloride (MCh) and to a 4-h hyperinsulinemic euglycemic clamp (120 mU/m2·min) in 10 PCOS, before and after 3 months treatment with Tgz (600 mg/d). A group of 13 obese women (OBW) matched for age, weight, body fat (>40% in both groups), blood pressure, and total cholesterol served as controls. PCOS patients exhibited elevated free testosterone (fT) and triglycerides (TG) and lower high density lipoprotein cholesterol levels compared with OBW [14.0 ± 1.0 vs. 3.7 ± 0.6 pmol/liter (P < 0.0001), 1.60 ± 0.28 vs. 0.94 ± 0.09 mmol/liter (P < 0.02), and 0.91 ± 0.04 vs. 1.1 ± 0.04 mmol/liter (P < 0.005), respectively]. Tgz treatment reduced fT levels, but did not improve the TG and high density lipoprotein profile [to 9.7 ± 2.8 pmol/liter (P < 0.007), 1.49 ± 0.34 mmol/liter (P = NS), and 0.93 ± 0.07 mmol/liter (P = NS), respectively]. Basal LBF was unchanged after Tgz. In PCOS compared with OBW, insulin stimulated glucose disposal (52.7 ± 6.6 vs. 85.5 ± 4.4 μmol/kg fat-free mass·min; P < 0.0005) and vasodilation (increase in LBF, 22 ± 14% vs. 59 ± 15%; P < 0.05) were significantly improved after Tgz treatment to 68.8 ± 7.2 μmol/kg fat-free mass·min (P < 0.0001) and 101 ± 48% (P < 0.03), respectively. The increase in LBF in response to MCh in PCOS was markedly more pronounced after treatment (P < 0.01, by ANOVA) and was similar to that observed in OBW. Before Tgz treatment, maximal LBF increments in response to MCh were 130 ± 25% and 233 ± 29% in PCOS and OBW, respectively (P < 0.01). After Tgz treatment, PCOS values improved, achieving increments similar to those in OBW (245 ± 45%; P < 0.04). Tgz treatment in PCOS improves both hormonal and metabolic features. These modifications are associated with improvement of endothelial function, suggesting that Tgz could be a useful tool to reduce the risk of macrovascular disease in women with PCOS and perhaps in other insulin-resistant syndromes.

AB - Obese women with polycystic ovary syndrome (PCOS) exhibit impaired endothelial function, which is strongly and directly correlated with both testosterone levels and insulin resistance. Endothelial dysfunction is considered a potent risk factor for macrovascular disease. Because troglitazone (Tgz) improves both hormonal profiles and insulin sensitivity, we tested whether Tgz treatment ameliorates endothelial function in these patients. We studied leg blood flow (LBF) responses to graded intrafemoral artery infusion of the endothelium-dependent vasodilator methacholine chloride (MCh) and to a 4-h hyperinsulinemic euglycemic clamp (120 mU/m2·min) in 10 PCOS, before and after 3 months treatment with Tgz (600 mg/d). A group of 13 obese women (OBW) matched for age, weight, body fat (>40% in both groups), blood pressure, and total cholesterol served as controls. PCOS patients exhibited elevated free testosterone (fT) and triglycerides (TG) and lower high density lipoprotein cholesterol levels compared with OBW [14.0 ± 1.0 vs. 3.7 ± 0.6 pmol/liter (P < 0.0001), 1.60 ± 0.28 vs. 0.94 ± 0.09 mmol/liter (P < 0.02), and 0.91 ± 0.04 vs. 1.1 ± 0.04 mmol/liter (P < 0.005), respectively]. Tgz treatment reduced fT levels, but did not improve the TG and high density lipoprotein profile [to 9.7 ± 2.8 pmol/liter (P < 0.007), 1.49 ± 0.34 mmol/liter (P = NS), and 0.93 ± 0.07 mmol/liter (P = NS), respectively]. Basal LBF was unchanged after Tgz. In PCOS compared with OBW, insulin stimulated glucose disposal (52.7 ± 6.6 vs. 85.5 ± 4.4 μmol/kg fat-free mass·min; P < 0.0005) and vasodilation (increase in LBF, 22 ± 14% vs. 59 ± 15%; P < 0.05) were significantly improved after Tgz treatment to 68.8 ± 7.2 μmol/kg fat-free mass·min (P < 0.0001) and 101 ± 48% (P < 0.03), respectively. The increase in LBF in response to MCh in PCOS was markedly more pronounced after treatment (P < 0.01, by ANOVA) and was similar to that observed in OBW. Before Tgz treatment, maximal LBF increments in response to MCh were 130 ± 25% and 233 ± 29% in PCOS and OBW, respectively (P < 0.01). After Tgz treatment, PCOS values improved, achieving increments similar to those in OBW (245 ± 45%; P < 0.04). Tgz treatment in PCOS improves both hormonal and metabolic features. These modifications are associated with improvement of endothelial function, suggesting that Tgz could be a useful tool to reduce the risk of macrovascular disease in women with PCOS and perhaps in other insulin-resistant syndromes.

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