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Association of Hot Flushes With Ghrelin and Adipokines in Early Versus Late Postmenopausal Women

Roksana Karim 1 2, Ha M Dang 2, Howard N Hodis 1 3, Frank Z Stanczyk 4, Roberta D Brinton 5, Wendy J Mack 1 2

DOI: 10.1097/GME.0000000000001508

Abstract
Objective: Vasomotor flushing (hot flushes) is a common menopausal symptom experienced by most women going through the menopausal transition; flushing continues for a variable period in postmenopause. Primarily due to lack of ovarian estrogen, other biomarkers of hot flushes have not been clearly identified. We examined the relationship of hot flushes with ghrelin and adipokines.

Methods: Baseline data from two clinical trials, the Women’s Isoflavone Soy Health (WISH) trial and Early versus Late Intervention Trial of Estrogen (ELITE), were used in this post hoc cross-sectional study. Both WISH and ELITE had similar study designs, inclusion criteria, and data collection processes. Study participants were healthy postmenopausal women not taking estrogen-based hormone therapy, free of cardiovascular disease, or any other chronic diseases. Both trials used the same hot flush diary in which participants recorded the number of daily hot flushes by severity over a month on average. Serum concentrations of ghrelin, leptin, adiponectin, and resistin were assessed in stored fasting blood samples using highly specific radioimmunoassay. In this analysis, self-reported flushing experience was tested for an association with leptin, adiponectin, resistin, and ghrelin concentrations using logistic regression and mean comparisons.

Results: A total of 898 postmenopausal women from the ELITE and WISH trials contributed to this analysis. Mean (SD) age was 60.4 (7.0) years, body mass index (BMI) 27 (5.3) kg/m, 67% were white, and 47% were within 10 years of menopause. Reported flushing was significantly associated with younger age, lower education, lower BMI, being married, and more recent menopause. Adjusted for these factors other than BMI, women in the highest quartile of ghrelin had significantly greater likelihood of experiencing hot flushes (OR [95% CI] = 1.84 [1.21-2.85]) compared to women in the lowest quartile. The association was more pronounced among overweight or obese women (OR [95% CI] = 2.36 [1.28-4.35]) compared to those with normal BMI (1.24 [0.54, 2.86]; interaction P value = 0.46). The association between ghrelin and hot flushes was similar among early (within 10 y) and late (over 10 y) postmenopausal women. Blood levels of adiponectin and resistin were not associated with hot flushes.

Conclusions: Higher concentrations of ghrelin were associated with greater likelihood of hot flushes in both early- and late-postmenopausal women. Leptin, adiponectin, and resistin levels were not associated with hot flushes in postmenopausal women.