Association of Endogenous Sex Hormones and Insulin Resistance among Postmenopausal Women: Results from the Postmenopausal Estrogen/Progestin Intervention Trial

Yale University, New Haven, Connecticut, United States
Journal of Clinical Endocrinology & Metabolism (Impact Factor: 6.21). 04/2003; 88(4):1646-52. DOI: 10.1210/jc.2002-021375
Source: PubMed


Most studies of sex hormones and insulin resistance (IR) have focused on androgens; few have examined the association of endogenous estrogens and IR. We determined the cross-sectional association of endogenous levels of total and bioavailable testosterone and estradiol and SHBG with IR among 845 healthy, postmenopausal women aged 45-65 yr. Women were within 10 yr of menopause and not using hormone replacement therapy. Total adiposity was estimated by body mass index, visceral adiposity by waist to hip ratio (WHR), and IR by the homeostasis model assessment. We defined homeostasis model assessment-IR as the highest quartile (cutpoint, 2.1) of the distribution in this cohort. In logistic regression analyses, the odds for IR were significant and increased in a dose-response fashion across each quartile of total estradiol, bioavailable estradiol, and bioavailable testosterone (all P < 0.001 for linear trend). These associations remained significant after adjusting for WHR; adjusted odds ratios were 4.0, 6.1, and 2.7 for total estradiol, bioavailable estradiol, and bioavailable testosterone, respectively, comparing the highest to the lowest quartile (all P < 0.001). Adjusting for body mass index and WHR together eliminated the linear association of IR with total estradiol and bioavailable testosterone, but the association with bioavailable estradiol remained (adjusted odds ratio, 2.7; P < 0.001, comparing the highest to the lowest quartile). IR was not associated with total testosterone before or after adjusting for adiposity. Lower SHBG levels were associated with higher odds of IR, independent of adiposity. These results suggest that estrogen may be equally or more important than testosterone in the pathway to IR in healthy, young postmenopausal women, with differences not entirely explained by body size.

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    • "This suggests that underlying sex-specific characteristics (e.g. hormone levels, adiposity, lifestyle habits, and quantity of muscle mass) are influencing this relationship [30,31]. In short, our study has identified numerous ethnic-specific associations between FA and markers of IR, and the majority of these associations appeared to be more robust in men. "
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    ABSTRACT: Background Although evidence indicates that fatty acids (FA) can affect insulin resistance (IR), not all FA contribute equally to the process. Indeed, monounsaturated FA (MUFA) and polyunsaturated FA (PUFA) are reported to reduce IR, whereas saturated FA (SFA) and trans FA appear to increase IR. However, it is not yet clear how individual FA are associated with markers of IR, and whether these relationships are influenced by ethnicity and/or sex. Therefore, the goal of this study was to examine the ethnic- and sex-specific relationships between plasma FA and markers of IR in a cohort of healthy young Caucasian, East Asian, and South Asian adults. Methods Gas chromatography was used to quantify fasting plasma FA from young Canadian adults (22.6 ± 0.1 yrs) of Caucasian (n = 461), East Asian (n = 362), or South Asian (n = 104) descent. Linear regression models were used to investigate associations between plasma FA and markers of IR (i.e. fasting insulin, glucose, and HOMA-IR) according to ethnicity and sex. Results Numerous significant associations (P < 0.05, adjusted for multiple testing) were identified between individual FA and markers of IR, with the majority identified in Caucasians. For SFA, positive associations were found between 14:0 and fasting insulin and HOMA-IR in Caucasian and East Asian populations, and 18:0 and fasting glucose in Caucasians only. Several positive associations were also found for specific MUFA (18:1t11 and 18:1t6-8 with HOMA-IR, and 18:1c9 with fasting glucose) and PUFA (18:2n6 with fasting glucose and 18:2c9t11 with HOMA-IR) in Caucasian adults only. Most of the aforementioned associations were stronger in males compared to females. Interestingly, no significant associations were found between FA and markers of IR in South Asian adults. Conclusions We report numerous associations between plasma FA and markers of IR in Caucasian and East Asian populations, but not in South Asian individuals. Furthermore, these associations appeared to be more robust in men. This demonstrates the importance of investigating associations between FA and markers of IR in an ethnic- and sex-specific manner in order to better understand the contribution of plasma FA to the development of IR and type-2 diabetes.
    Full-text · Article · Jun 2013 · Nutrition & Metabolism
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    • "In the present study, women with Mets had higher mean levels of testosterone and lower SHBG levels. In some studies the association between Mets and lower SHBG has been suggested in postmenopausal women (6–12). The increased prevalence of Mets after menopause may be due to a direct result of ovarian failure or an indirect result of the metabolic consequences of central fat distribution due to estrogen deficiency. "
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    ABSTRACT: Objective To compare the hormonal status in postmenopausal women with and without metabolic syndrome. Materials and methods In this cross sectional study 110 postmenopausal women were enrolled. Participants completed a questionnaire and underwent a medical exam and serum evaluation for serum lipids including cholesterol (Chol), high density lipoprotein cholesterol (HDL), low density lipoprotein (LDL), triglyceride (TG), fasting blood sugar (FBS), sex hormone binding globulin (SHBG), estradiol and testosterone. Metabolic syndrome was defined according to the definition of the National Cholesterol Education Program- Adult Treatment Panel III. In this study P value less than 0.05 was accepted as significant. Results There were significant differences between the two groups of participants with and without metabolic syndrome in age, years after menopause, BMI, weight, SHBG and testosterone (p< 0.01). Conclusion SHBG and testosterone are the most significant correlated factors to metabolic syndrome in postmenopausal women.
    Full-text · Article · Jun 2013
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    • "Men with higher serum DHEA-S had a longer life span in a Baltimore longitudinal study of aging male humans [19]. Estradiol (E2) is more important than testosterone in the pathway to insulin resistance in healthy, young postmenopausal women [20]. "
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    ABSTRACT: Background Royal jelly is a widely ingested supplement for health, but its effects on humans are not well known. The objective was to evaluate the effects of long-term royal jelly ingestion on humans. Methods We conducted a randomized placebo-controlled, double-blind trial. A total of 61 healthy volunteers aged 42-83 years were enrolled and were randomly divided into a royal jelly group (n = 31) and a control group (n = 30). Three thousand mg of royal jelly (RJ) or a placebo in 100 ml liquid/day were ingested for 6 months. The primary outcomes were changes in anthropometric measurements and biochemical indexes from baseline to 6 months after intervention. Results Thirty subjects in the RJ group and 26 in the control group were included in the analysis of endpoints. In an adjusted mean change of the variables from the baseline, significant differences between the two groups could be found in red blood cell counts (+0.16x106 /μL for the RJ group vs. -0.01x106 /μL for the control group, P = 0.0134), hematocrit (+0.9% vs. -0.8%, P = 0.0251), log (fasting plasma glucose) (+0.01 ± 0.01 log mg/dL vs. +0.05 ± 0.01 log mg/dL, P = 0.0297), log (insulinogenic index) (+0.25 vs. -0.13, P = 0.0319), log dehydroepiandrosterone sulfate (DHEA-S) (+0.08 log μg/dL vs. +0.20 log μg/dL, P = 0.0483), log testosterone (T) (+0.12 ± 0.04 log ng/mL vs. -0.02 ± 0.05 log ng/mL, P = 0.0416), log T/DHEA-S ratio (+0.05 ± 0.05 vs. -0.23 ± 0.59, P = 0.0015), and in one of the SF-36 subscale scores, mental health (MH) (+4 vs. -7, P = 0.0276). Conclusions Six-month ingestion of RJ in humans improved erythropoiesis, glucose tolerance and mental health. Acceleration of conversion from DHEA-S to T by RJ may have been observed among these favorable effects.
    Full-text · Article · Sep 2012 · Nutrition Journal
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