Timing of Estradiol Treatment After Menopause May Determine Benefit or Harm to Insulin Action

Pereira, Rocio I.; Casey, Beret A.; Swibas, Tracy; Erickson, Christopher B.; Wolfe, Pamela; Pelt, Rachael E. Van

doi:10.1210/jc.2015-3084

Cited by 50 publications

(66 citation statements)

References 39 publications

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“…Moreover, estrogen replacement therapy (HRT) restores normal insulin sensitivity (Margolis et al 2004) even if a post-menopausal woman still has a large amount of visceral WAT. Recent evidence suggests that HRT administered earlier in menopause improves insulin sensitivity but delivered 10 or more years after menopause decreases insulin sensitivity (Pereira et al 2015). This shift in the metabolic benefits of HRT could be due to the downregulation of ER in an estrogendeficient environment over time.…”

Section: Insulin Sensitivitymentioning

confidence: 99%

The role of sex steroids in white adipose tissue adipocyte function

Newell-Fugate

2017

Reproduction

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Abstractwith the increasing knowledge that gender influences normal physiology, much biomedical research has begun to focus on the differential effects of sex on tissue function. Sexual dimorphism in mammals is due to the combined effects of both genetic and hormonal factors. Hormonal factors are mutable particularly in females in whom the estrous cycle dominates the hormonal milieu. Given the severity of the obesity epidemic and the fact that there are differences in the obesity rates in men and women, the role of sex in white adipose tissue function is being recognized as increasingly important. Although sex differences in white adipose tissue distribution are well established, the mechanisms affecting differential function of adipocytes within white adipose tissue in males and females remain largely understudied and poorly understood. One of the largest differences in the endocrine environment in males and females is the concentration of circulating androgens and estrogens. This review examines the effects of androgens and estrogens on lipolysis/lipogenesis, adipocyte differentiation, insulin sensitivity and adipokine production in adipocytes from white adipose tissue with a specific emphasis on the sexual dimorphism of adipocyte function in white adipose tissue during both health and disease.Reproduction (2017) 153 R133-R149

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Section: Insulin Sensitivitymentioning

confidence: 99%

The role of sex steroids in white adipose tissue adipocyte function

Newell-Fugate

2017

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“…In that study, the actions of transdermal estradiol on glucose disposal was dependent on the time from menopause with apparent benefits early (≤6 years) and harm later (≥10 years) from menopause. [22] In our study, age and years since menopause were confounders but not effect modifiers of the association between MHT use and incident diabetes.…”

Section: Discussionmentioning

confidence: 58%

“…[21] This concept of age effects and timing from menopause could also apply to diabetes risk. This was illustrated by Pereira et al[22] in a randomized, crossover, placebo-controlled study. In that study, the actions of transdermal estradiol on glucose disposal was dependent on the time from menopause with apparent benefits early (≤6 years) and harm later (≥10 years) from menopause.…”

Section: Discussionmentioning

confidence: 92%

Body fat distribution, menopausal hormone therapy and incident type 2 diabetes in postmenopausal women of the MESA study

et al. 2016

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Objectives We investigated the association between menopausal hormone therapy (MHT) and incident type 2 diabetes in postmenopausal women, and explored the potential modifying role of body fat distribution on this association. Methods We included 2210 postmenopausal women without prevalent diabetes at recruitment (2000-2002) from the Multiethnic Study of Atherosclerosis. Cox proportional hazards models were used to examine associations of MHT and MHT types with incident diabetes, testing for variation according to body fat distribution. Results Over a median follow-up of 11.1 years, there were 226 incident cases of diabetes. There were no significant interactions with central or generalized body fatness. In fully adjusted models, current and past MHT use was associated with a greater risk of incident diabetes [HR: 1.66 (1.18-2.35) and 1.60 (1.11-2.30) respectively]. Estrogen only (ET) and combined progestin and estrogen (PET) formulations were similarly associated with a greater risk of incident diabetes [HR: 1.52 (1.03-2.24) and 1.77 (1.15-2.72) respectively]. Conclusions In our observational study of middle-aged and older, non-diabetic postmenopausal women, a current or past use of MHT was independently associated with a greater risk of incident diabetes. ET and PET are associated with similar risks of incident diabetes in postmenopausal women. The association of MHT use with incident diabetes is the same irrespective of body mass index (BMI) or waist circumference.

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“…Detailed inclusion and exclusion criteria were previously described [5]. Briefly, participants were healthy, non-obese (BMI<30kg/m 2 ), sedentary to moderately active, postmenopausal women (age 45–70 yr) who had not used any estrogen-based hormone therapy.…”

Section: Methodsmentioning

confidence: 99%

“…A 2hr 75g oral glucose tolerance test (OGTT) was employed in the morning following an overnight fast as previously described [5]. Circulating glucose and insulin responses over the 2hr period were measured; area under the curve (AUC) calculated using the trapezoidal method.…”

Section: Methodsmentioning

confidence: 99%

Estradiol-mediated improvements in adipose tissue insulin sensitivity are related to the balance of adipose tissue estrogen receptor α and β in postmenopausal women

et al. 2017

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We recently demonstrated that short-term estradiol (E2) treatment improved insulin-mediated suppression of lipolysis in postmenopausal women, but to a greater extent in those who were late compared to early postmenopausal. In this follow-up study we tested whether subcutaneous adipose tissue (SAT) expression of estrogen receptors (ER) α and β differs between early and late postmenopausal women. We further tested whether the balance of ERα to ERβ in SAT determined the effect of E2 on SAT insulin sensitivity. The present study included 35 women who were ≤6 years past menopause (EPM; n = 16) or ≥10 years past menopause (LPM; n = 19). Fasted SAT samples were taken following 1-week transdermal E2 treatment or placebo (PL) in a random cross-over design. Samples were analyzed for nuclear/cytosolic protein content and mRNA expression using Western blot and qPCR, respectively. While ESR1 increased slightly (~1.4-fold) following E2 treatment in both groups, ERα and ERβ protein expression did not differ between groups at baseline or in response to E2. However, the balance of ERα/ERβ protein in the SAT nuclear fraction increased 10% in EPM compared to a 25% decrease in LPM women (group x treatment interaction, p<0.05). A greater proportion of ERα/ERβ protein in the nuclear fraction of SAT at baseline (placebo day) was associated with greater reduction in SAT insulin resistance (i.e., better suppression of lipolysis, EC50) in response to E2 (r = -0.431, p<0.05). In conclusion, there do not appear to be differences in the proportion of adipose tissue ERα/ERβ protein in late, compared to early, postmenopausal women. However, the balance of ERα/ERβ may be important for E2-mediated improvement in adipose tissue insulin sensitivity.Trial Registration: Clinical Trials#: NCT01605071

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Timing of Estradiol Treatment After Menopause May Determine Benefit or Harm to Insulin Action

Cited by 50 publications

References 39 publications

The role of sex steroids in white adipose tissue adipocyte function

The role of sex steroids in white adipose tissue adipocyte function

Body fat distribution, menopausal hormone therapy and incident type 2 diabetes in postmenopausal women of the MESA study

Estradiol-mediated improvements in adipose tissue insulin sensitivity are related to the balance of adipose tissue estrogen receptor α and β in postmenopausal women

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