Dataset Information

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

ABSTRACT:

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.

SUBMITTER: Ebong IA

PROVIDER: S-EPMC4968885 | biostudies-literature | 2016 Sep

REPOSITORIES: biostudies-literature

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Publications

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

Ebong Imo A IA Watson Karol E KE Hairston Kristen G KG Carnethon Mercedes R MR Ouyang Pamela P Szklo Moyses M Bertoni Alain G AG

Maturitas 20160628

<h4>Objectives</h4>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.<h4>Methods</h4>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, t ...[more]

PMID: 27451334

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Project description:ImportanceMenopausal hormone therapy (MHT) is the treatment of choice for symptoms of menopause. However, its adoption is hindered by the risk-benefit trade-off in relation to acute and chronic diseases.ObjectiveTo evaluate trends in and correlates of MHT use among postmenopausal women in the US from 1999 to March 2020.Design, setting, and participantsThis serial cross-sectional analysis of MHT use used data from the nationally representative National Health and Nutrition Examination Survey (NHANES). Participants included noninstitutionalized US postmenopausal women from 10 NHANES study cycles (1999-2000 to 2017-March 2020 [pre-COVID-19 pandemic]). Data were analyzed from December 2023 to April 2024.ExposuresNHANES study cycle.Main outcomes and measuresPrevalence of MHT use was extracted from the prescription medication data collected during NHANES household interviews. MHT formulations were determined by hormone type.ResultsData on 13 048 US postmenopausal women (47.1% ≥65 years old) were analyzed. From 1999 to 2020, the prevalence of MHT use decreased among women of all age groups, from 26.9% (95% CI, 22.6%-31.7%) in 1999 to 4.7% (95% CI, 3.4%-6.5%) in 2020. Until 2002, MHT use was highest among women aged 52 to 65 years, but since 2005, MHT use has been highest among women younger than 52 years. MHT use decreased by 23.5% (95% CI, 11.4%-35.6%), 31.4% (95% CI, 23.4%-39.5%), and 10.6% (95% CI, 6.3%-14.8%) for women younger than 52 years, 52 years to younger than 65 years, and 65 years and older, respectively. Prevalence of MHT use decreased from 13.8% (95% CI, 8.5%-21.7%) to 2.6% (95% CI, 1.5%-4.6%) for Hispanic women, 11.9% (95% CI, 8.5%-16.3%) to 0.5% (95% CI, 0.2%-1.1%) for non-Hispanic Black women, and 31.4% (95% CI, 27.1%-36.1%) to 5.8% (95% CI, 4.1%-8.2%) for non-Hispanic White women. Non-Hispanic White women consistently had the highest prevalence of MHT use. Estrogen-only formulation accounted for more than 50% of the MHT for most study periods. The prevalence of MHT use varied by family income-to-poverty ratio, health insurance coverage in all racial and ethnic groups, weight, and smoking status among non-Hispanic White women, as well as by education attainment among non-Hispanic Black and Hispanic women.Conclusions and relevanceResults of this cross-sectional study show that over the past 2 decades, MHT use declined among US postmenopausal women of all age and racial and ethnic groups. Women of racial and ethnic minority groups had lower prevalence of MHT use compared to non-Hispanic White women.

Project description:Title: Transcriptome analysis of human endometrial tissues from healthy post-menoupausal women reflecting the endometrial response to 3-weeks treatment with tibolone, E2 and E2+MPA. In an observational, open, non-randomized, controlled study uterine tissues were collected in order to generate endometrial gene expression profiles. healthy postmenopausal women were enrolled into the following treatment groups: Control-group; Tibolone-group, 2,5 mg of tibolone (administered orally) every day, starting 21 days prior to surgery; Estradiol-group, 2 mg of estradiol (administered orally) every day, starting 21 days prior to surgery; Estradiol+progestagen-group, 2 mg of estradiol (administered orally) and 5 mg of MPA (Medroxy Progesteroneacetate, administered orally) every day, starting 21 days prior to surgery. Pure (100%) endometrium was isolated from the snap-frozen uterine tissues and used for RNA isolation. RNA was labeled and hybridized to whole genome Affymetrix U133plus2 GeneChips containing 54,614 probe sets, representing approximately 47,000 transcripts. Relative to the control group, 940 genes are regulated in the endometrium of E2 treated patients, whereas only 198 genes are significantly regulated in endometria from tibolone or E2+MPA treated patients. Furthermore, only 9% of E2 regulated genes are also regulated by tibolone (85 out of 940), only 5% are also regulated by E2+MPA treatment and the overlap between tibolone and E2+MPA treatment is about 10%. This indicated that tibolone-treatment results in a weak endometrial profile similarity to E2 treatment and no profile similarity to E2+MPA treatment. A more detailed analysis showed that down stream processes, such as regulation of the cell cycle, angiogenesis and cell proliferation are almost not affected by tibolone treatment but, in contrast, are significantly affected by E2. For example, upon staining with Ki67, a marker for mitotic activity, significantly increased stromal as well as glandular cell proliferation was observed in the endometria from the E2-only treated group, while tibolone treatment resulted only in a slight increase in stromal cell proliferation (and no increase in glandular cell proliferation). These results indicate that in contrast to long-term tibolone use, short-term (21-days) use results in some estrogenic stimulation of the endometrium, which is clearly far less and rather different from what is observed during E2 treatment. References: Klaassens et al., 2006 Hanifi-Moghaddam et al., 2007 Verheul et al., 2007

Project description:BackgroundCardiovascular disease (CVD) remains the leading cause of death among postmenopausal women but standard primary prevention strategies in women are not as effective as in men. By comparison, the Early versus Late Intervention Trial with Estradiol (ELITE) study demonstrated that hormone therapy (HT) was associated with significant reduction in atherosclerosis progression in women who were within six years of menopause compared to those who were 10 or more years from menopause. These findings are consistent with other studies showing significant reductions in all-cause mortality and CVD with HT, particularly when initiated in women younger than 60 years of age or within 10 years since menopause. To explore the biological mechanisms underlying the age-related atheroprotective effects of HT, we investigated changes in methylation of blood cells of postmenopausal women who participated in ELITE.ResultsWe first validated the epigenetic data generated from blood leukocytes of ELITE participants by replicating previously known associations between smoking and methylation levels at previously identified CpG sites, such as cg05575921 at the AHRR locus. An epigenome-wide association study (EWAS) evaluating changes in methylation through interactions with time-since-menopause and HT revealed two significantly associated CpG sites on chromosomes 12 (cg19552895; p = 1.1 × 10-9) and 19 (cg18515510; p = 2.4 × 10-8). Specifically, HT resulted in modest, but significant, increases in methylation levels at both CpGs but only in women who were 10 or more years since menopause and randomized to HT. Changes in carotid artery intima-media thickness (CIMT) from baseline to 36 months after HT were not significantly correlated with changes in methylation levels at either cg19552895 or cg18515510. Evaluation of other previously identified CpG sites at which methylation levels in either blood or vascular tissue were associated with atherosclerosis also did not reveal any differences in methylation as a function of HT and time-since-menopause or with changes in CIMT.ConclusionsWe identified specific methylation differences in blood in response to HT among women who were 10 or more years since menopause. The functional consequence of these change with respect to atherosclerosis progression and protective effects of HT remains to be determined and will require additional studies.

Dataset Information

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

Objectives

Methods

Results

Conclusions

Publications

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

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