Genetic polymorphisms, hormone levels, and hot flashes in midlife women

Abstract

Objective-Hot flashes disrupt the lives of millions of women each year. Although hot flashes are a public health concern, little is known about risk factors that predispose women to hot flashes. Thus, the objective of this study was to examine whether sex steroid hormone levels and genetic polymorphisms in hormone biosynthesis and degradation enzymes are associated with the risk of hot flashes.Methods-In a cross-sectional study design, midlife women aged 45 to 54 years (n=639) were recruited from Baltimore and its surrounding counties. Participants completed a questionnaire and donated a blood sample for steroid hormone analysis and genotyping. The associations between genetic polymorphisms and hormone levels, as well as the associations between genetic polymorphisms, hormone levels, and hot flashes were examined using statistical models.Results-A polymorphism in CYP1B1 was associated with lower dehydroepiandrosterone-sulfate (DHEA-S) and progesterone levels, while a polymorphism in CYP19 (aromatase) was associated with higher testosterone and DHEA-S levels. Lower progesterone and sex hormone binding globulin levels, lower free estradiol index, and a higher ratio of total androgens to total estrogens were associated with the experiencing of hot flashes. A polymorphism in CYP1B1 and a polymorphism in 3βHSD were both associated with hot flashes.Conclusion-Some genetic polymorphisms may be associated with altered levels of hormones in midlife women. Further, selected genetic polymorphisms and altered hormone levels may be associated with the risk of hot flashes in midlife women.

Factors That May Influence the Experience of Hot Flushes by Healthy Middle-Aged Women

“…Similarly, Woods et al 51 reported that women with two CYP19 11r alleles had significantly more days of HFs during the middle and late menopausal transition and postmenopause than those with one or no allele. In contrast, Schilling et al 26 did not find any association between selected polymorphisms in the CYP19 or COMT genes and HFs. These differences in results might stem from differences in study design (e.g., the tested populations and analysis assumptions, such as including menopausal stage in the analysis).…”

“…25 The association between HFs and lower levels of estradiol is fairly consistent. 3,13,[26][27][28] For example, Fentiman et al 28 showed, in a cross-sectional study, that a decrease in symptom severity was correlated with high estradiol levels. This finding was also observed in other cross-sectional, 26,27 1906 ZIV-GAL AND FLAWS review, 3 and longitudinal prospective 13 studies.…”

“…Schilling et al, 26 in a cross-sectional study, investigated the associations among other sex steroid hormones, sex hormonebinding proteins, and HFs. The authors found that lower sex hormone-binding globulin (SHBG), estrone, and free estradiol index (FEI) levels and a higher ratio of total androgens=total estrogens levels were significantly associated with HFs.…”

“…11,26,28,38 Thus, researchers hypothesized that genetic variation in hormone biosynthesis and metabolizing enzymes might play a role in the variability of HFs. To date, the literature describing associations between genetic polymorphisms and HFs is limited.…”

“…This hypothesis, however, has not been verified. In a more recent cross-sectional study, Schilling et al 26 focused on genetic polymorphisms in the CYP1B1 (rs1056836), 3bHSD, CYP19, and COMT genes. The authors concluded that women who carried the examined polymorphisms in CYP1B1 and 3bHSD had a significantly greater risk of experiencing HFs (any=moderate or severe, respectively) compared with women who did not carry the selected polymorphisms.…”