Polymorphisms in Estrogen Synthesis Genes and Symptom Clusters During the Menopausal Transition and Early Postmenopause: Observations From the Seattle Midlife Women’s Health Study

Abstract

During the menopausal transition and early postmenopause, participants in the Seattle Midlife Women's Health Study (SMWHS) experienced one of the three symptom severity clusters identified through latent class analysis: severe hot flashes with moderate sleep, mood, cognitive, and pain symptoms (high-severity hot flash); low-severity hot flashes with moderate levels of all other symptom groups (moderate severity); and low levels of all symptom groups (low severity). In an effort to determine whether gene polymorphisms were associated with these symptom severity classes, we tested associations between gene polymorphisms in the estrogen synthesis pathways (cytochrome P450 19 [CYP 19] and 17 beta hydroxysteroid dehydrogenase [ 17HSDB1]) and the three symptom severity clusters. SMWHS participants ( N = 137) recorded symptoms monthly in diaries and provided buccal smears for genotyping. Multilevel latent class analysis with multinomial regression was used to determine associations between gene polymorphisms and symptom severity clusters. Only the 17HSDB1 polymorphisms ( rs615942 and rs592389) were associated significantly with the high-severity hot flash cluster versus the low-severity symptom cluster. None of the polymorphisms was associated with the moderate-severity cluster versus the low-severity symptom cluster. Findings of associations of the 17HSDB1 polymorphisms with the high-severity hot flash symptom cluster are consistent with those of an association between 17HSDB1 polymorphisms and hot flashes in the Study of Women and Health Across the Nation population and our previous findings of associations between these polymorphisms with greater estrone levels.

Identifying the different subtypes in menopausal symptoms among middle-aged women in China: a latent class analysis

“…Different subtypes of menopausal symptoms might share common biological mechanisms or aetiologies, which could better explain their existence. Findings from the current study suggest that there is a need to explore the interrelationship among symptoms by measuring hormones and gene and/or gene polymorphism 36,37 . We also found distinct clinical and psychosocial profiles for the different menopausal symptom subtypes with robust associations observed for chronic diseases, gynecological diseases, neuroticism, mindfulness, and social support.…”

“…Findings from the current study suggest that there is a need to explore the interrelationship among symptoms by measuring hormones and gene and/or gene polymorphism. 36,37 We also found distinct clinical and psychosocial profiles for the different menopausal symptom subtypes with robust associations observed for chronic diseases, gynecological diseases, neuroticism, mindfulness, and social support. These factors could help us differentiate membership in these distinct subgroups of women with similar symptoms.…”

Depression During and After the Perimenopause

“…Finally, genetic analyses from the Seattle Midlife Women’s Health Study focused on the estrogen synthesis pathway, specifically CYYP19 and 17-HSD, but this time in relationship to severity of symptom clusters identified through a latent class analysis of typical perimenopausal symptoms. 85 Though hot flash severity served as the basis for these clusters, depressed mood was included. Investigators found that a 17-beta hydroxysteroid dehydrogenase gene polymorphism was associated with the high-severity group, which included women with high-severity hot flashes and moderate sleep, mood, cognitive and pain symptoms.…”

Taking Another Look: Thoughts on Behavioral Symptoms in Dementia and Their Measurement

“…Other distinguished nurse scientists have come to this conclusion in other clinical populations. For example, Woods and colleagues [85] utilized more innovative analytic techniques, such as Group Based Trajectory Modelling and Latent Class Analysis, to elucidate how menopausal symptoms cluster and are associated with specific single nucleotide polymorphisms (SNPs) [86].…”