Mood sensitivity to estradiol predicts depressive symptoms in the menopause transition

Abstract

Background The risk for depression markedly rises during the 5–6 years leading up to the cessation of menstruation, known as the menopause transition. Exposure to extreme estradiol levels may help explain this increase but few studies have examined individual sensitivity to estradiol in predicting perimenopausal depression. Method The current study recruited 101 perimenopausal women. During Phase 1, we quantified each woman's sensitivity to changes in estradiol using 12 weekly measures of estrone-3-glucuronide (E1G), a urinary metabolite of estradiol, and concurrent depressive symptoms. The weekly cortisol awakening response was measured to examine the hypothalamic-pituitary-adrenal (HPA) axis in mediating mood sensitivity to estradiol. In Phase 2, depressive symptoms and major depression diagnoses were assessed monthly for 9 months. The relationship between Phase 1 E1G sensitivity and Phase 2 depressive symptoms and major depressive episodes was examined. Several baseline characteristics were examined as potential moderators of this relationship. Results The within-person correlation between weekly E1G and mood varied greatly from woman to woman, both in strength and direction. Phase 1 E1G mood sensitivity predicted the occurrence of clinically significant depressive symptoms in Phase 2 among certain subsets of women: those without a prior history of depression, reporting a low number of baseline stressful life events, and reporting fewer months since their last menstrual period. HPA axis sensitivity to estradiol fluctuation did not predict Phase 2 outcomes. Conclusion Mood sensitivity to estradiol predicts risk for perimenopausal depression, particularly among women who are otherwise at low risk and among those who are early in the transition.

Cognitive profiles in perimenopause: hormonal and menopausal symptom correlates

“…Although not measured in the RICAM, factors associated with VMS and depression, such as smoking history, alcohol use, physical activity, social support, current stress and trauma history, may also increase risk or protect against cognitive declines. Recent work has demonstrated significant variability in women's mood sensitivity to E 2 changes [59] and identified dysregulated cellular response to estrogen in women with premenstrual dysphoric disorder [60]. Similarly, women likely differ in their cognitive sensitivity to E 2 changes.…”

Role of Nurses in the Management of Common Gynecological Diseases: Recent Advances

“…Menopause is the condition when a women's menstrual cycle ends due to the natural aging process. At this stage, they will not be considered fertile as of loss of follicular activity and ovulation [77,78] . Women possessed six hundred thousand fertile oocytes at the time of puberty but the number decreased significantly during the natural aging process.…”

Can hormones get you down? studies on sex steroids and depression

“…These findings suggest that weekly changes in estradiol do not explain changes in irritability during that same week. In studies of hormonal links with perimenopausal depressive symptoms, others 329 have highlighted the importance of accounting for the between-women variability in the direction of the association between estradiol levels and mood, indicating that mood in some women may relate to changing levels regardless of the direction of the change while the direction of the change (increase versus decrease) might have a more important effect on mood for others. Hence, analyzing all women together, might "cancel out" a significant finding.…”

“…We As a second post-hoc analysis, we explored whether inter-individual differences in the direction of the associations between the weekly changes in estradiol and irritability might explain why the overall variability variable of estradiol was a predictor of irritability, but the weekly change variable was not. 329 The withinwoman association of both crude and absolute values of weekly changes in estradiol with irritability varied greatly between women in strength and direction (range b for crude values of weekly changes: -26.50 to 5.09; for absolute values of weekly changes: -3.10 to 4.00). Analysis of the largest association in magnitude for each woman showed that some were sensitive to increases of estradiol (8.5%), some to decreases of estradiol (8.5%), and some to either increases or decreases (6.4%).…”

“…In a separate analysis, we explored to what extent the direction of the association between the weekly changes in estradiol and irritability varied between women, consistent with a recent study. 329 We calculated for each woman the association of both crude and absolute values of weekly changes in estradiol with irritability and examined whether the association for each women was best described by absolute changes (increase and decrease in estradiol) or crude changes (increase or decrease, depending on the direction of the β) based on which β was largest in magnitude for a given woman.…”