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

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.

Symptom clusters during the late reproductive stage through the early postmenopause: observations from the Seattle Midlife Women's Health Study.

OBJECTIVE: The aim of this study was to identify symptom clusters that characterize women's experiences through the late reproductive stage, the menopausal transition, and early postmenopause and to explore the influence of the menopausal transition stages and early postmenopause, compared with that of the late reproductive stage, on the clusters of symptoms women experience. METHODS: Participants from the Seattle Midlife Women's Health Study whose symptom calendars were staged for the menopausal transition provided data for a total of 6,857 occasions. Multilevel latent class analysis was used to identify classes using scores for hot flashes and symptom factors (sleep, cognitive, mood, pain, tension). RESULTS: Class 1 included observations of low severity levels for all symptoms, whereas class 2 included low-severity hot flashes and moderate-severity levels for all other symptom factors. Class 3 included high severity hot flashes with lower severity levels of all other symptom factors. During the early and late menopausal transition stages and early postmenopause, the likelihood of being in class 3 was significantly greater than being in class 1 relative to the late reproductive stage. There were no significant effects of the menopausal transition stages on the likelihood of being in class 2. CONCLUSIONS: This effort is the first to examine the latent classes or clusters of symptoms during the prolonged period from late reproductive stage to early postmenopause. As such, the data contribute to the understanding of symptom experiences beyond our early efforts to characterize the late menopausal transition stage.