Impact of Estradiol Variability and Progesterone on Mood in Perimenopausal Women With Depressive Symptoms

Abstract

Context Women are at increased risk for depressive symptoms during the menopause transition. Changes in estradiol secretion and presence of vasomotor symptoms (VMS) contribute to perimenopausal depressive symptoms, but links with progesterone have not been investigated. Objective To determine whether estradiol variability, ovulatory levels of progesterone, and VMS burden are independently associated with perimenopausal depressive symptomatology. Design and Intervention Depressive symptoms, serum levels of estradiol and progesterone, and VMS frequency were assessed weekly in an 8-week observational study. Association of mood with estradiol variability, ovulatory levels of progesterone, and VMS frequency were estimated using generalized estimating equation models. Setting Academic medical center. Patients Fifty unmedicated perimenopausal women with mild-to-moderate depressive symptoms (mean Montgomery-Åsberg Depression Rating Scale [MADRS] score 15.5 ± 5.3). Main Outcome Measure Depressive symptoms (MADRS score). Results During the study, 90.0% of participants had varying estradiol levels, 51.1% had ovulatory progesterone levels, and 90% had VMS. Greater estradiol variability and absence of progesterone levels consistent with ovulation, but not VMS frequency, are associated with higher levels of depressive symptoms (β = 0.11 [95% confidence interval (95% CI), 0.04 to 0.18; P = 0.001]; β = −2.62 [95% CI, −4.52 to −0.71; P = 0.007], respectively), after accounting for higher body mass index, lifetime history of depression, and stressful life events. Conclusions Increasing dysregulation of ovarian hormones, but not VMS, associates with more depressive symptom burden during perimenopause. These results suggest that perimenopausal mood instability is driven by the underlying hormonal dysregulation of the menopause transition involving changes in both estradiol and progesterone.

Hormonal Fluctuations Related to Depressive Symptoms in Menopause

“…[ [26]. They exert their influence by a slower genomic mode of action, including binding of estrogen to nuclear estrogen receptors and subsequent transcription control and subsequent calcium, ion and kinase signaling modulation of nongenomic membrane pathways [20].…”

“…In another research, Joffe et al found 50 women between 35-50 years old with perimenopausal symptoms and reported that the absence of progesterone at rates suggesting recent ovulation and estradiol variation is correlated with depression symptomatology throughout the menopause process. They discovered that for an increase of 10% of estradiol variability, there is an increase of 1.1 on the Montgomery-Asberg Depression Rating Scale of depression score and a decrease of 2.7 for those with progesterone level [20].…”

Changes in the regional homogeneity of resting-state magnetic resonance imaging in perimenopausal women

“…It gradually decreased with the prolongation of perimenopause. Emotional instability and cognitive impairment may be associate with such hormonal imbalances [ 4 , 5 ], which can also lead to functional or structural changes in certain brain regions. However,to the best of our knowledge, there is a noticeable lack of systematic researches on evaluating the correlation between serum estrogen levels and changes in brain functional areas of perimenopausal women.…”

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

“…Details of exclusion criteria are described in our previous work reporting the association of estradiol and progesterone variability with depressive symptoms severity. 322 All participants provided written informed consent for study procedures, which were approved by the Partners HealthCare Institutional Review Board and conducted at Massachusetts General Hospital and Brigham and Women's Hospital. The dataset is comprised of 420 visits collected in 50 women in whom information on irritability occurring during the past week was available.…”

“…Patterns of reproductive hormones are of particular interest as the perimenopause is characterized by more marked fluctuations of serum estradiol, alternating with periods of sustained lower and unchanging levels of estradiol, resulting in less predictable ovulation. 20,108 Moreover, previous research has shown that greater variability in estradiol levels, 116,117,322 and absence of ovulation as measured with progesterone, 322 is associated with more depressive symptomatology during the perimenopause.…”