1.
A comparison of oral and transdermal short-term estrogen therapy in postmenopausal women with metabolic syndrome.
Chu, MC, Cosper, P, Nakhuda, GS, Lobo, RA
Fertility and sterility. 2006;(6):1669-75
Abstract
OBJECTIVE To determine whether it would be preferable to prescribe oral or transdermal estrogen to symptomatic postmenopausal women with metabolic syndrome (MBS). DESIGN Prospective, randomized study. SETTING Academic medical center. PATIENT(S): Fifty obese postmenopausal women with MBS. INTERVENTION(S): Women were randomized to receive either oral E(2) (oE(2), 1 mg/d) or transdermal E(2) (tE(2), 0.05 mg/d) for 3 months. Fasting blood was obtained before and after treatment for glucose, insulin, lipid profiles, the adipocytokines (adiponectin, leptin, and resistin), and a gastric peptide (ghrelin). In addition, a 75-g 2-hour oral glucose-tolerance and intravenous insulin-tolerance tests were performed before and after E(2). MAIN OUTCOME MEASURE(S): Changes in parameters of insulin resistance (IR), lipid profiles, and adipocytokine levels. RESULT(S): Mean serum concentrations of E(2) in women using oE(2) and tE(2) were 39.1 +/- 5.6 and 49.2 +/- 28.6 pg/mL, respectively. After oE(2), there was a statistically significant worsening of IR markers, including an increase in baseline insulin (15.28 +/- 1.27 to 22.02 +/- 2.40 microU/mL), a reduction in quantitative insulin-sensitivity check index (0.3177 +/- 0.0043 to 0.2977 +/- 0.0057), and an increase in homeostasis model assessment (3.96 +/- 0.38 to 8.59 +/- 2.08). The only significant change in the lipid profile was an increase in high-density-lipoprotein cholesterol (50.46 +/- 2.34 vs. 55.08 +/- 2.51 mg/dL). Leptin levels increased (81.43 +/- 7.87 ng/mL to 94.10 +/- 6.56 ng/mL), and adiponectin decreased nonsignificantly, resulting in an increased leptin-adiponectin ratio (12.56 +/- 1.70 to 15.86 +/- 2.24); resistin levels increased (9.37 +/- 1.09 ng/mL to 11.72 +/- 1.10 ng/mL); and baseline ghrelin levels decreased (701.64 +/- 59.79 pg/mL to 581.72 +/- 36.07 pg/mL). After tE(2), no significant changes in IR parameters occurred, except for a decrease in glucose-insulin ratio. There were no changes in lipid parameters. Leptin did not change (72.7 +/- 9.3 ng/mL to 78.8 +/- 7.9 ng/mL), whereas adiponectin levels showed statistically significant increase (7.97 +/- 0.7 microg/mL vs. 9.96 +/- 1.1 microg/mL), with no change in the leptin-adiponectin ratio. Resistin levels did not change significantly, and ghrelin levels decreased (888.52 +/- 109.98 pg/mL vs. 579.04 +/- 39.30 pg/mL). CONCLUSION(S): This short-term study suggests that oral E(2) may worsen IR and adipocytokine parameters, worsening cardiovascular risk. Transdermal E(2) had minimal effects on IR and resulted in higher adiponectin. Although these data may not reflect alterations that occur with estrogen therapy in more metabolically normal postmenopausal women or with longer term therapy, the findings suggest that tE(2) may be a preferable treatment for obese women with MBS. Long-term studies are needed to make any recommendations.
2.
Metabolic and endocrine effects of treatment with peroral or transdermal oestrogens in conjunction with peroral cyproterone acetate in women with polycystic ovary syndrome.
Vrbíková, J, Stanická, S, Dvoráková, K, Hill, M, Vondra, K, Bendlová, B, Stárka, L
European journal of endocrinology. 2004;(2):215-23
Abstract
OBJECTIVE To compare the influence of transdermal and peroral oestrogen treatments in conjunction with cyproterone acetate (CPA) on metabolic and hormonal parameters in women with polycystic ovary syndrome (PCOS). PATIENTS AND METHODS Twenty-four women with PCOS, aged 25.4+/-4.3 (mean+/-s.d.) years, body mass index 24.5+/-3.9 kg/m2 were randomly assigned to receive either transdermal oestradiol plus CPA (n=12) or a peroral oestradiol-CPA combination (n=12). Before and after 3 months of treatment, basal blood samples, euglycaemic hyperinsulinaemic clamp combined with indirect calorimetry and arginine tests were performed. ANOVA and Student's t-test or Wilcoxon's test were used for statistical analyses. RESULTS After peroral oestradiol-CPA, insulin sensitivity (P<0.004) and the disposition index as the function of insulin sensitivity and secretion (P<0.0001) decreased significantly. Fasting insulin (P<0.05), cholesterol (P<0.05), high-density lipoprotein cholesterol (P<0.05) and sex-hormone binding globulin (P<0.0001) increased significantly. Dehydroepiandrosterone (P<0.05) and 17-OH progesterone (P<0.01) decreased significantly. After transdermal oestradiol+CPA, no significant changes were observed in sex-hormone binding globulin and androgen concentrations, insulin sensitivity or disposition index. CONCLUSIONS In women with PCOS, peroral oestrogens (at doses common in combined oral contraceptives) led to a significant impairment in insulin secretion and action. In contrast, the transdermal application of oestrogens did not significantly influence insulin sensitivity.