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Association between BMI, vitamin D, and estrogen levels in postmenopausal women using adjuvant letrozole: a prospective study.

ABSTRACT: Studies have suggested that women with elevated BMI or 25-OH vitamin D levels may derive less benefit from AIs versus tamoxifen. We prospectively investigated whether high BMI or 25-OH vitamin D levels were associated with higher estrogen levels in post-menopausal women receiving standard adjuvant letrozole (2.5?mg/day). Furthermore, we evaluated whether an increased dose of letrozole resulted in lower serum estrogens in women with BMI?>?25?kg/m2. Correlation between entry BMI and day 29 serum biomarkers (estrogens, 25-OH vitamin D, insulin, CRP, leptin) was assessed in all patients. On day 29, participants with BMI?>?25?kg/m2 switched to letrozole 5?mg/day for 4-weeks and blood was drawn upon completion of the study. The change in serum estrogen levels was assessed in these patients (BMI?>?25?kg/m2). 112 patients completed days 1-28. The Pearson correlations of estradiol and estrone with BMI or serum 25-OH vitamin D levels were near zero (-0.04 to 0.07, p?=?0.48-0.69). Similar results were obtained for correlation with markers of obesity (insulin, CRP, and leptin) with estradiol and estrone (-0.15 to 0.12; p?=?0.11-0.82). Thirty-one patients (BMI?>?25?kg/m2) completed the interventional component; Increasing the dose of letrozole did not further reduce estradiol or estrone levels (change 0.1 and 0.4?pmol/L respectively; p?=?0.74 and 0.36). There was no observed association between markers of obesity (BMI, insulin, leptin, and CRP), serum 25-OH vitamin D levels and estradiol or estrone levels. Additionally, an increased dose of letrozole did not further reduce estradiol or estrone levels compared to the standard dose.

SUBMITTER: Elliott MJ

PROVIDER: S-EPMC7293309 | biostudies-literature | 2020

REPOSITORIES: biostudies-literature

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Association between BMI, vitamin D, and estrogen levels in postmenopausal women using adjuvant letrozole: a prospective study.

Elliott Mitchell J MJ Ennis Marguerite M Pritchard Kathleen I KI Townsley Carol C Warr Dave D Elser Christine C Amir Eitan E Bedard Philippe L PL Rao Lakshmi L Stambolic Vuk V Sridhar Srikala S Goodwin Pamela J PJ Cescon David W DW

NPJ breast cancer 20200612

Studies have suggested that women with elevated BMI or 25-OH vitamin D levels may derive less benefit from AIs versus tamoxifen. We prospectively investigated whether high BMI or 25-OH vitamin D levels were associated with higher estrogen levels in post-menopausal women receiving standard adjuvant letrozole (2.5 mg/day). Furthermore, we evaluated whether an increased dose of letrozole resulted in lower serum estrogens in women with BMI > 25 kg/m<sup>2</sup>. Correlation between entry BMI and day ...[more]

PMID: 32566743

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Project description:Abstract Vitamin D binding protein (DBP) is one of regulators of vitamin D serum levels. rs4588 and rs7041 polymorphisms of the DBP gene constitute the genetic basis of the three major isoforms of circulating DBP, called GC1s, GC1f and GC2. We evaluated the association between the rs4588, rs7041, rs2282679 SNPs and of DBP isoforms with DBP and 25(OH)D serum levels and investigated whether these gene variants influence on the presence of vitamin D deficiency in a non-selected women sample. In this cross-sectional study, bio-repository samples of 443 apparently healthy women aged 20 to 72 years were analyzed. Most of the participants were ppostmenopausal (n=359). Sufficient circulating levels of 25(OH)D was considered as ≥20ng/mL and deficiency as <20ng/mL. Clinical and biochemical profile were collected. Participants were genotyped for rs4588, rs7041, and rs2282679 polymorphisms by RT-PCR. BDP isoforms were constructed from the combination of the rs4588 and rs7041 polymorphisms, where GC1s= rs4588CC and rs7041GG; GC1f= rs4588CC and rs7041TT and Gc2= rs4588AA and rs7041TT. Mean age and BMI were 53.4±9.4 years and 27.8±5.8, respectively. 25(OH)D levels in total sample was 22.8±8.3ng/mL and 60% had adequate circulating 25(OH)D levels. rs4588, rs2282679 SNPs and the GC2 isoforms were associated with lower DBP levels (rs4588: CC=203.0±28.3; CA=196.5±29.9; AA=184.0±36.9; linear p trend<0.001, B=-8.4; rs2282679: AA=203.1±27.9; AC=196.4±30.0; CC=180.9±38.2; linear p trend<0.001, B=-9.3; and DBP isoforms: GC1s=199.4±29.9; GC1f=204.8±31.6; GC2=180.8±37.6; linear p trend=0.012, B=-7.7) and rs2282689 as well as GC2 isoform were associated with lower 25(OH)D levels (rs2282679: AA=23.4±8.8; AC=22.8±7.8; CC=19.7±7.2; linear p trend=0.034, B=-1.3; and DBP isoforms: GC1s=23.8±9.2; GC1f=20.6±8.3; GC2=20.3±7.4; linear p trend=0.015, B=-1.9). CC genotype of rs2282679 (PR 1.74; 95%CI 1.30;2.24; p<0.001), GC2 isoform (PR 1.66; 95%CI 1.17; 2.38; p=0.005), time since menopause (PR 1.02; 95%CI 1.003;1.03, p= 0.016) and HOMA-IR (PR 1.02; 95%CI 1.01;1.03, p= 0.004) were associated with higher prevalence ratios for 25(OH)D deficiency. DBP levels (per 30 ug/mL of DBP increase, PR 0.89; 95%CI 0.80;0.99; p=0.027) were related to lower prevalence ratios for 25(OH)D deficiency. Except for HOMA-IR, these PR remained significant after adjustment for age and BMI. In conclusion, the present results suggest that rs2282679 and the GC2 isoform of DBP are related to lower DBP serum levels and with the susceptibility to 25(OH)D deficiency in adult and postmenopausal women. Support: CNPq, FAPERGS and FIPE/HCPA

Project description:ImportanceHalf of women who are postmenopausal have genitourinary discomfort after menopause. Recommended therapies include low-dose vaginal estrogen. Individuals with a history of breast cancer or venous thromboembolism may have concerns about the safety of this intervention.ObjectiveTo compare serum estrogen concentrations with the use of vaginal estrogen, 10 μg, tablet vs placebo in women who are postmenopausal.Design, setting, and participantsThis is a secondary, post hoc analysis of data from a randomized clinical trial of treatment for moderate to severe genitourinary syndrome in women who are postmenopausal. The study was conducted at Kaiser Permanente Washington Health Research Institute and the University of Minnesota from April 11, 2016, to April 23, 2017. Measurements and data analysis were performed from November 3, 2020, to September 23, 2022.InterventionsParticipants were randomly assigned to vaginal estradiol tablet (10 μg/d for 2 weeks and then twice weekly) plus placebo gel (3 times weekly) or dual placebo for 12 weeks.Main outcomes and measuresIn this post hoc analysis, baseline and week 12 serum estradiol, estrone, and sex hormone-binding globulin (SHBG) concentrations were measured by a chemiluminescent assay. Week 12 values of the 3 analytes were compared by baseline participant characteristics. Linear models compared week 12 estradiol concentrations between treatment groups, adjusted for baseline characteristics.ResultsA total of 174 women, mean (SD) age 61 (4) years, were included. Those in the estrogen group (n = 88) were more likely to have higher geometric mean (SD) week 12 serum estradiol concentrations (4.3 [2.2 pg/mL]) than those in the placebo group (n = 86) (3.5 [2.1] pg/mL) (P = .01). Adjusted for pretreatment hormone concentrations, age, clinical site, and body mass index, assignment to the estrogen vs placebo treatment group was significantly associated with higher week 12 estradiol concentrations (23.8% difference; 95% CI, 6.9%-43.3%). Most (121 of 174 [69.5%]) participants had enrollment serum estradiol concentrations higher than 2.7 pg/mL. Of women starting treatment at estradiol levels lower than or equal to 2.7 pg/mL, 38.1% (8 of 21) in the estrogen group and 34.4% (11 of 32) in the placebo group had estradiol concentrations higher than 2.7 pg/mL after 12 weeks of study participation (P = .78). Treatment assignment was not associated with week 12 estrone or SHBG concentrations.Conclusions and relevanceIn this secondary analysis of a randomized clinical trial, a significant, although small, increase in serum estradiol levels was noted after 12 weeks of vaginal estrogen administration. The clinical relevance of this small increase is uncertain.Trial registrationClinicalTrials.gov Identifier: NCT02516202.

Dataset Information

Association between BMI, vitamin D, and estrogen levels in postmenopausal women using adjuvant letrozole: a prospective study.

Publications

Association between BMI, vitamin D, and estrogen levels in postmenopausal women using adjuvant letrozole: a prospective study.

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