The Effect of Hormone Replacement Therapy on Body Composition, Body Fat Distribution, and Insulin Sensitivity in Menopausal Women: A Randomized, Double-Blind, Placebo-Controlled Trial

Sites, Cynthia K.; L'Hommedieu, Georgia D.; Toth, Michael J.; Brochu, Martin; Cooper, Brian C.; Fairhurst, Penny A.

doi:10.1210/jc.2004-1479

Cited by 108 publications

(22 citation statements)

References 42 publications

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“…There is emerging evidence to suggest that hormone replacement therapy (HRT) may protect against NAFLD (51), but improvements in cardiovascular risk in postmenopausal patients may be secondary to changes in lipid profile (52). Contrasting with these data, in a double-blind randomised control trial using insulin-euglycaemic clamps, HRT reduced insulin sensitivity in postmenopausal non-diabetic women, with no benefit in body composition (53).…”

Section: Oestrogensmentioning

confidence: 99%

Mechanisms in endocrinology: Non-alcoholic fatty liver disease in common endocrine disorders

Hazlehurst

Tomlinson

2013

European Journal of Endocrinology

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Non-alcoholic fatty liver disease (NAFLD) is a spectrum of disease spanning from simple benign steatosis to steatohepatitis with fibrosis and scarring that can eventually lead to cirrhosis. Its prevalence is rising rapidly and is developing into the leading indication for liver transplantation worldwide. Abnormalities in endocrine axes have been associated with NALFD, including hypogonadism, hypothyroidism, GH deficiency and hypercortisolaemia. In some instances, correction of the endocrine defects has been shown to have a beneficial impact. While in patients with type 2 diabetes the association with NAFLD is well established and recognised, there is a more limited appreciation of the condition among common endocrine diseases presenting with hormonal excess or deficiency. In this review, we examine the published data that have suggested a mechanistic link between endocrine abnormalities and NAFLD and summarise the clinical data endorsing these observations.

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Section: Oestrogensmentioning

confidence: 99%

Mechanisms in endocrinology: Non-alcoholic fatty liver disease in common endocrine disorders

Hazlehurst

Tomlinson

2013

European Journal of Endocrinology

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“…Furthermore, the decreases in FPG persisted after adjustment for adiposity [21, 22]. Subsequently, it had been hypothesized that estrogen therapy could increase postprandial glucose through reductions in whole-body insulin sensitivity via serum E2 levels [23], even though at least one other study showed no association between exogenous estrogen and insulin sensitivity [24]. …”

Section: Introductionmentioning

confidence: 99%

Endogenous Sex Hormones, Metabolic Syndrome, and Diabetes in Men and Women

Kim

Halter

2014

Curr Cardiol Rep

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Endogenous sex hormones predict impairments of glucose regulation. Cross-sectional studies suggest that lower levels of testosterone in men and higher levels in women increase risk of metabolic syndrome and diabetes, while lower levels of sex hormone binding globulin in both men and women increase risk of metabolic syndrome and diabetes. In a systematic review, we summarize existing longitudinal studies, which suggest similar patterns. However, these studies are often limited to a single sex steroid measure. Whether these associations are primarily a marker of adiposity, and whether these associations differ between younger eugonadal vs. older hypogonadal adults is also uncertain. The impact of exogenous sex steroid therapy may not reflect relationships between sex hormones and impaired glucose regulation that occur without supplementation. Therefore, examination of endogenous sex steroid trajectories and obesity trajectories within individuals might aid our understanding of how sex steroids contribute to glucose regulation.

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“…This change in body composition has been attributed to the loss of estrogen and hypothesized to account for the increase in the risk of cardiovascular events in postmenopausal women [4;23]. Because AI use in postmenopausal women with breast cancer would lead to profound estrogen loss, theoretically one would expect a greater degree of fat redistribution and perhaps loss of lean mass in these women compared to normal postmenopausal women.…”

Section: Discussionmentioning

confidence: 99%

“…This has been attributed to the loss of estrogen as estrogen replacement prevents or attenuates the increase in total body and truncal fat and improves the associated metabolic abnormalities [4;23]. We previously reported that estrogen metabolism into the hydroxylated metabolites is associated with differences in body composition in postmenopausal women [17].…”

Section: Introductionmentioning

confidence: 99%

Genetic polymorphism at Val80 (rs700518) of the CYP19A1 gene is associated with body composition changes in women on aromatase inhibitors for ER (+) breast cancer

Napoli

Rastelli

et al. 2015

Pharmacogenetics and Genomics

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Purpose Polymorphisms in the CYP19A1 (aromatase) gene influence disease-free survival and bone loss in patients taking aromatase inhibitors (AIs) for estrogen receptor positive (ER+) breast cancers. Because AI use results in profound estrogen deficiency which may lead to changes in body composition, the objective of this study was to determine the effect of the rs700518 polymorphism in the CYP19A1 gene, on the changes in body composition among postmenopausal women who were treated with AIs for ER+ breast cancer. Methods This is a 1-year prospective study of changes in body composition in postmenopausal women who were initiated on third-generation AIs for ER+ breast cancer. Body composition was measured by dual energy absorptiometry at 6 and 12 months, serum estradiol by radioimmunoassay and genotyping by Taqman SNP allelic discrimination assay. Results Eighty-two women were able to provide at least one follow-up body composition measurement. Women with the GG genotype for the rs700518 (G/A at Val80) developed a significant increase in Truncal fat mass index (p=0.03) and a significant decrease in fat-free mass index (p=0.01) at 12 months relative to patients carrying the A allele (GA/AA). There was no significant difference in the changes in estradiol levels among the genotypes. Conclusion Patients with the GG genotype for the rs700518 polymorphism in the CYP19A1 gene are at risk for significant loss of fat-free mass and increase in truncal fat with AI therapy. Whether there are associated metabolic abnormalities and whether changes would persist with long-term AI therapy, need to be confirmed in a larger study with a longer duration of follow-up.

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The Effect of Hormone Replacement Therapy on Body Composition, Body Fat Distribution, and Insulin Sensitivity in Menopausal Women: A Randomized, Double-Blind, Placebo-Controlled Trial

Abstract: Conjugated estrogens plus medroxyprogesterone acetate reduce insulin sensitivity in menopausal women without affecting body composition or body fat distribution. The reduction in insulin sensitivity is reversible after discontinuing HRT.

Cited by 108 publications

References 42 publications

Mechanisms in endocrinology: Non-alcoholic fatty liver disease in common endocrine disorders

Mechanisms in endocrinology: Non-alcoholic fatty liver disease in common endocrine disorders

Endogenous Sex Hormones, Metabolic Syndrome, and Diabetes in Men and Women

Genetic polymorphism at Val80 (rs700518) of the CYP19A1 gene is associated with body composition changes in women on aromatase inhibitors for ER (+) breast cancer

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