Dataset Information

Effect of hormone therapy and calcitriol on serum lipid profile in postmenopausal older women: association with estrogen receptor-? genotypes.

ABSTRACT: The aim of this study was to examine the effect of conjugated equine estrogens alone (ET), conjugated equine estrogens + medroxyprogesterone (EPT), calcitriol alone, calcitriol + EPT/ET, or placebo on serum lipid profile and analyze the interaction with estrogen receptor-? gene single nucleotide polymorphisms (ESR-? SNPs) on the response to therapy.A total of 489 postmenopausal women older than 65 years were enrolled into a 3-year double-blind, placebo-controlled clinical trial.In both intent-to-treat and complier (>80% adherent) analysis, there was a significant increase in serum high-density lipoproteins and a significant decrease in serum low-density lipoproteins (LDLs) and the LDL/high-density lipoprotein ratio in all hormone treatment groups compared with placebo (P < 0.05). However, serum triglycerides and very low-density lipoproteins increased in the EPT and ET + calcitriol groups versus placebo (P < 0.05). ESR-? SNPs PvuII and XbaI seemed to have a significant effect on the response to treatment. Genotypes containing the p allele showed a significantly greater decrease in serum cholesterol and very low-density lipoprotein than those having the P allele in the ET + calcitriol group (P < 0.05), and those with the x allele had a significantly greater decrease in serum cholesterol in the hormone therapy + calcitriol group at the end of 3 years versus the X allele, and a greater decrease in serum LDL in alleles x versus the X in the ET + calcitriol group (P < 0.05).ET with or without progesterone had a favorable effect on lipid profile in postmenopausal older women, and this was dependent on estrogen receptor SNPs--PvuII and XbaI. However, this interaction with ESR-? SNPs needs to be confirmed in larger studies.

SUBMITTER: Sai AJ

PROVIDER: S-EPMC3183360 | biostudies-literature | 2011 Oct

REPOSITORIES: biostudies-literature

ACCESS DATA

Publications

Effect of hormone therapy and calcitriol on serum lipid profile in postmenopausal older women: association with estrogen receptor-α genotypes.

Sai Adarsh J AJ Gallagher J Christopher JC Fang Xiang X

Menopause (New York, N.Y.) 20111001 10

<h4>Objective</h4>The aim of this study was to examine the effect of conjugated equine estrogens alone (ET), conjugated equine estrogens + medroxyprogesterone (EPT), calcitriol alone, calcitriol + EPT/ET, or placebo on serum lipid profile and analyze the interaction with estrogen receptor-α gene single nucleotide polymorphisms (ESR-α SNPs) on the response to therapy.<h4>Methods</h4>A total of 489 postmenopausal women older than 65 years were enrolled into a 3-year double-blind, placebo-controlle ...[more]

PMID: 21712736

Similar Datasets

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:ObjectiveTo identify factors associated with serum estradiol (E2) levels among healthy postmenopausal women using hormone therapy (HT).MethodsThis is an unplanned post hoc analysis of data from ELITE (Early versus Late Intervention Trial with Estradiol), a randomized controlled trial of 1 mg oral E2 with or without vaginal progesterone in healthy early compared with late (<6 years compared with 10 or more years since menopause) postmenopausal women. We included results from visits when women reported at least 80% compliance with HT. Mixed-effects linear models identified factors associated with serum E2 levels while participants were taking HT, assessed every 6 months over a median follow-up of 4.8 years and adjusted for baseline E2 level, visit, and reduced E2 dose. Possible correlates evaluated included demographics, clinical characteristics, medication use, and biomarkers of liver and kidney metabolic function.ResultsThe analysis included 2,160 E2 measurements in 275 postmenopausal women. Mean±SD age was 55.4±3.9 vs 64.4±5.5 years, and mean±SD time since menopause was 3.6±1.8 vs 16.0±5.6 years for early vs late postmenopausal women. Adjusted for pretreatment E2 level, visit, and reduced dose indicator, higher serum E2 levels were associated with higher body mass index (BMI), higher weight, surgical menopause, alcohol use, and antihypertensive medication use. Current and past smoking and antifungal medication use were associated with lower serum E2 levels. In the multivariable model, higher BMI and alcohol use were associated with higher serum E2 levels, whereas current and past smoking were associated with lower serum E2 levels. These factors were similar between early and late postmenopausal women.ConclusionFactors associated with serum E2 levels among postmenopausal women taking HT include BMI, alcohol use, and smoking. As serum E2 levels relate to HT effect, achievement of desirable E2 levels may be maximized through personalized intervention.Clinical trial registrationClinicalTrials.gov, NCT00114517.

Project description:Early diagnosis of the onset of osteoporosis is key to the delivery of effective therapy. Biochemical markers of bone turnover provide a means of evaluating skeletal dynamics that complements static measurements of BMD by DXA. Conventional clinical measurements of bone turnover, primarily the estimation of collagen and its breakdown products in the blood or urine, lack both sensitivity and specificity as a reliable diagnostic tool. As a result, improved tests are needed to augment the use of BMD measurements as the principle diagnostic modality. In this study, the serum proteome of 58 postmenopausal women with high or low/normal bone turnover (training set) was analyzed by surface enhanced laser-desorption/ionization time-of-flight mass spectrometry, and a diagnostic fingerprint was identified using a variety of statistical and machine learning tools. The diagnostic fingerprint was validated in a separate distinct test set, consisting of serum samples from an additional 59 postmenopausal women obtained from the same Mayo cohort, with a gap of 2 yr. Specific protein peaks that discriminate between postmenopausal patients with high or low/normal bone turnover were identified and validated. Multiple supervised learning approaches were able to classify the level of bone turnover in the training set with 80% sensitivity and 100% specificity. In addition, the individual protein peaks were also significantly correlated with BMD measurements in these patients. Four of the major discriminatory peaks in the diagnostic profile were identified as fragments of interalpha-trypsin-inhibitor heavy chain H4 precursor (ITIH4), a plasma kallikrein-sensitive glycoprotein that is a component of the host response system. These data suggest that these serum protein fragments are the serum-borne reflection of the increased osteoclast activity, leading to the increased bone turnover that is associated with decreasing BMD and presumably an increased risk of fracture. In conjunction with the identification of the individual proteins, this protein fingerprint may provide a novel approach to evaluate high bone turnover states.

Dataset Information

Effect of hormone therapy and calcitriol on serum lipid profile in postmenopausal older women: association with estrogen receptor-? genotypes.

Publications

Effect of hormone therapy and calcitriol on serum lipid profile in postmenopausal older women: association with estrogen receptor-α genotypes.

Similar Datasets

OmicsDI is part of the ELIXIR infrastructure

Tweets