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Breast Cancer Risk in Postmenopausal Women with Medical History of Thyroid Disorder in the Women's Health Initiative.

ABSTRACT: Background: The association between thyroid disorders and breast cancer remains controversial, in part, due to small cohort sizes and inconsistent findings. We investigated this association in postmenopausal women to determine whether hyper- or hypothyroidism is associated with the risk of developing breast cancer and to determine whether menopausal hormone therapy (MHT) further modifies the risk. Methods: We conducted a prospective cohort study of multiethnic U.S. postmenopausal women aged 50 to 79 years enrolled in both clinical trial and observational study arms between 1993 and 1998 and followed up through February 28, 2017. Development of invasive breast cancer after enrollment was recorded and a history of hyper- or hypothyroidism before the diagnosis of breast cancer was identified. The effect modification by MHT in both study arms was analyzed. All statistical tests were two sided. Results: Among a total of 134,122 women who were included in our study, 8137 participants developed invasive breast cancer during the follow-up period. There was a significant inverse association of invasive breast cancer among women with a history of hypothyroidism (hazard ratio [HR] 0.91, confidence interval [95% CI] 0.86-0.97) and among women who had taken levothyroxine [HR 0.89, 95% CI 0.82-0.96]. Evaluating effect modification by MHT use, the inverse association between hypothyroidism treated with thyroid replacement medications and breast cancer risk was strongest in non-MHT users [HR 0.80, 95% CI 0.69-0.93]. The results did not significantly differ by race/ethnicity. Although a history of hyperthyroidism was associated with an increased risk of invasive breast cancer [HR 1.11, 95% CI 0.91-1.35], this finding did not reach statistical significance. We did not see significant differences in the breast cancer Surveillance, Epidemiology, and End Results stages, histologic types, morphologic grades, or receptor status (estrogen receptor, progesterone receptor, human epidermal growth factor receptor 2) according to thyroid disorder status. Conclusions: Compared with women with no history of thyroid disorder, hypothyroidism was associated with a lower risk of breast cancer. This was mainly seen among those who received thyroid replacement therapy and had never used MHT. Among the treatment options for hypothyroidism, levothyroxine had the strongest inverse association with breast cancer risk.

SUBMITTER: Weng CH

PROVIDER: S-EPMC7187984 | biostudies-literature |

REPOSITORIES: biostudies-literature

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Project description:Study questionWhat is the association between reproductive health history (e.g. age at menarche, menopause, reproductive lifespan) with abdominal adiposity in postmenopausal women?Summary answerHigher visceral adipose tissue (VAT) and subcutaneous adipose tissue (SAT) tissue levels were observed among women with earlier menarche, earlier menopause, and greater parity.What is known alreadyPostmenopausal women are predisposed to accumulation of VAT and SAT. Reproductive health variables are known predictors of overall obesity status in women, defined by BMI.Study design, size, durationThis study is a secondary analysis of data collected from the baseline visit of the Women's Health Initiative (WHI). The WHI is a large prospective study of postmenopausal women, including both a randomized trial and observational study. There were 10 184 women included in this analysis.Participants/materials, setting, methodsData were collected from a reproductive health history questionnaire, dual-energy x-ray absorptiometry scans, and anthropometric measures at WHI baseline. Reproductive history was measured via self-report, and included age at menarche, variables related to pregnancy, and age at menopause. Reproductive lifespan was calculated as age at menopause minus age at menarche. Statistical analyses included descriptive analyses and multivariable linear regression models to examine the association between reproductive history with VAT, SAT, total body fat, and BMI.Main results and the role of chanceWomen who reported early menarche (<10 years) or early menopause (<40 years) had the highest levels of VAT. Adjusted multivariable linear regression results demonstrate women who experienced menarche >15 years had 23 cm2 less VAT (95% CI: -31.4, -14.4) and 47 cm2 less SAT (95% CI: -61.8, -33.4) than women who experienced menarche at age 10 years or earlier. A similar pattern was observed for age at menopause: compared to women who experienced menopause <40 years, menopause at 50-55 years was associated with 19.3 cm2 (95% CI: -25.4, -13.3) less VAT and 27.4 cm2 (-29.6, 10.3) less SAT. High parity (>3 pregnancies) was also associated with VAT and SAT. For example, adjusted beta coefficients for VAT were 8.36 (4.33, 12.4) and 17.9 (12.6, 23.2) comparing three to four pregnancies with the referent, one to two pregnancies.Limitations, reasons for cautionThe WHI reproductive health history questionnaire may be subject to poor recall owing to a long look-back window. Residual confounding may be present given lack of data on early life characteristics, such as maternal and pre-menarche characteristics.Wider implications of the findingsThis study contributes to our understanding of reproductive lifespan, including menarche and menopause, as an important predictor of late-life adiposity in women. Reproductive health has also been recognized as a sentinel marker for chronic disease in late life. Given established links between adiposity and cardiometabolic outcomes, this research has implications for future research, clinical practice, and public health policy that makes use of reproductive health history as an opportunity for chronic disease prevention.Study funding/competing interest(s)HRB and AOO are supported by the National Institute of Health National Institute of Aging (R01AG055018-04). JWB reports royalties from 'ACSM'S Body Composition Assessment Book' and consulting fees from the WHI. The remaining authors have no competing interests to declare.Trial registration numberN/A.

Project description:IMPORTANCE:Considerable efforts have been undertaken to relate single nutrients to bone health. To this point, results are inconsistent. Suboptimal single nutrient intake does not occur in isolation but rather reflects a poor diet quality. OBJECTIVE:To assess the association between adherence to a diet quality index constructed on the basis of dietary recommendations or existing healthy dietary patterns and fractures in postmenopausal women. DESIGN, SETTING, AND PARTICIPANTS:Post hoc analysis was conducted of longitudinal data from 40 clinical centers throughout the United States included in the Women's Health Initiative (WHI) observational study. Participants in the prospective cohort included 93?676 women who were eligible for the WHI if they were aged 50 to 79 years. Recruitment was conducted from October 1, 1993, to December 31, 1998, with the study ending August 29, 2014. The WHI food frequency questionnaire was used to derive nutrient and food intake at baseline. Diet quality and adherence were assessed by scores on the alternate Mediterranean Diet (aMED), a 9-category measure of adherence to a Mediterranean dietary pattern; the Healthy Eating Index 2010 (HEI-2010), a 100-point measure of 12 food components; the 11-item Alternate Healthy Eating Index 2010 (AHEI-2010); or the 8-component Dietary Approaches to Stop Hypertension (DASH) diet score. MAIN OUTCOMES AND MEASURES:Outcome measures included incident total and hip fractures. Hazard ratios (HRs) by quintiles of dietary index scores were estimated using Cox proportional hazards regression analyses. RESULTS:Of the 93?676 participants, 90?014 were included in the analysis (mean [SD] age, 63.6 [7.4]) years. During a median follow-up time of 15.9 years, there were 2121 cases of hip fractures and 28?718 cases of total fractures. Women scoring in the highest quintile (Q5) of the aMED index had a lower risk for hip fractures (HR, 0.80; 95% CI, 0.66-0.97), with an absolute risk reduction of 0.29% and a number needed to treat of 342 (95% CI, 249-502). No association between the aMED score and total fractures was observed (Q5 HR, 1.01; 95% CI, 0.95-1.07). Higher HEI-2010 or DASH scores tended to be inversely related to hip fracture risk, but the results were nonsignificant (Q5 HR, 0.87; 95% CI, 0.75-1.02; and Q5 HR, 0.89; 95% CI, 0.75-1.06, respectively). The AHEI-2010 score was associated with neither hip nor total fractures. CONCLUSIONS AND RELEVANCE:Higher adherence to a Mediterranean diet is associated with a lower risk for hip fractures. These results support that a healthy dietary pattern may play a role in maintaining bone health in postmenopausal women.

Project description:OBJECTIVE:Rheumatoid arthritis (RA) patients have an increased risk of cardiovascular disease (CVD) and mortality. We measured anti-cyclic citrullinated peptide (anti-CCP) antibody levels and determined use of disease-modifying antirheumatic drugs (DMARDs) among women in the Women's Health Initiative (WHI). Using these data, we undertook this study to assess total mortality over 10 years of followup among white, black, or Hispanic women with self-reported RA in the WHI. METHODS:Using stored baseline serum, we measured anti-CCP, rheumatoid factor (RF), and antinuclear antibodies (ANAs) in 9,988 women who reported having RA. Based on a previous chart review study, probable RA was defined as either self-reported RA and anti-CCP positivity, or anti-CCP negativity and DMARD use. Cox proportional hazards regression was used to model the relationship of self-reported RA, DMARD exposure, and anti-CCP positivity to total mortality, using followup data through April 2009. RESULTS:At baseline, the mean age was 62.8 years; 24.5% of subjects were black and 10% were Hispanic. Prevalence of anti-CCP positivity was 8.1% (n = 812), and 217 women were anti-CCP negative but had reported use of DMARDs; therefore, 1,029 women (of 9,988) were classified as having probable RA, and 8,958 were classified as unlikely to have RA (with data on DMARD use missing for 1 subject). Age-adjusted mortality rates were ?2-fold higher for anti-CCP-positive women, with 20.2 deaths per 1,000 person-years, as compared to 11.4 deaths per 1,000 person-years among anti-CCP-negative women with self-reported RA who never used DMARDs. Among women who did not report any arthritis at baseline, we found 8.3 deaths per 1,000 person-years. The increased risk among anti-CCP-positive women with RA was not explained by age, RF positivity, ANA positivity, or DMARD use. CONCLUSION:Anti-CCP-positive RA was associated with substantial excess mortality among postmenopausal women in the WHI. This result was not explained by the risk factors we measured.

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Breast Cancer Risk in Postmenopausal Women with Medical History of Thyroid Disorder in the Women's Health Initiative.

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