Abstract
Objective To investigate factors associated with anxiety and depression in perimenopausal women experiencing
abnormal uterine bleeding (AUB), with a focus on endocrine markers and lifestyle factors.
Methods
This retrospective cohort study analyzed 1,234 perimenopausal women with AUB treated at a tertiary
hospital from January 2023 to January 2024. Participants were classified based on DSM-5 diagnoses of anxiety and
depression. Data collected included demographics, lifestyle habits, comorbidities, psychiatric history, and endocrine
levels (estradiol, follicle-stimulating hormone [FSH], luteinizing hormone [LH], cortisol, prolactin, testosterone, and
thyroid-stimulating hormone [TSH]). Logistic regression models identified independent predictors, with interaction
and stratified analyses conducted by age group (< 50 and ≥ 50 years).
Results
Factors associated with anxiety and depression included higher BMI (OR 1.08, P = 0.008), longer AUB duration
(OR 1.12, P = 0.001), single/divorced/widowed marital status (OR 1.54, P = 0.015), and lower education levels (OR
1.62, P < 0.001). Smoking history (OR 2.84, P < 0.001) and psychiatric history (OR 3.11, P < 0.001) emerged as strong
predictors, while regular exercise was protective (OR 0.64, P = 0.001). Hormonal factors, including lower estradiol and
elevated levels of FSH, LH, and cortisol, were significantly linked to increased odds of psychological distress (P < 0.01).
Interaction analyses revealed that smoking and elevated cortisol exacerbated risks, whereas regular exercise mitigated
the adverse effects of elevated FSH and LH. These associations were consistent across age groups.
Conclusions
Anxiety and depression in perimenopausal women with AUB are influenced by a combination of
demographic, lifestyle, clinical, and endocrine factors. Addressing modifiable risk factors, such as smoking cessation
and increased physical activity, may alleviate psychological distress. Further research is needed to elucidate the
hormonal pathways connecting endocrine changes to mental health.
Keywords
Anxiety, Depression, Abnormal uterine bleeding, Perimenopause, Endocrine markers
Factors associated with anxiety
and depression in perimenopausal
women with abnormal uterine bleeding: A
retrospective cohort study
Jun Hu1 and Lijuan He2*
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Introduction
Anxiety and depression are common psychological
conditions that significantly affect women during the
perimenopausal period, a transitional phase marked by
hormonal fluctuations and changes in menstrual pat -
terns. The perimenopausal period has been associated
with a higher prevalence of mental health issues, with
studies suggesting that fluctuations in gonadal hormones,
particularly estradiol and follicle-stimulating hormone
(FSH), may contribute to mood disturbances [ 1– 2]. In
addition, alterations in stress-related hormones such as
cortisol—though not necessarily fluctuating in a cyclical
manner—have also been linked to anxiety and depres -
sion during midlife, potentially due to dysregulation
of the hypothalamic-pituitary-adrenal (HPA) axis [ 3].
Abnormal uterine bleeding (AUB), which is also com -
mon during this period, can exacerbate emotional stress,
particularly in women experiencing prolonged or heavy
bleeding [ 4]. However, the interplay between AUB, hor -
monal changes, and psychological distress remains
underexplored.
Hormonal changes in perimenopausal women, includ -
ing declining levels of estradiol and increased FSH and
luteinizing hormone (LH), have been implicated in both
the onset and severity of anxiety and depression [ 5– 6].
Estradiol, in particular, has been shown to have neuro -
protective effects, influencing mood regulation through
its actions on neurotransmitters such as serotonin and
dopamine [ 7]. Cortisol, the body’s primary stress hor -
mone, has also been linked to psychological disorders,
with elevated cortisol levels being associated with an
increased risk of anxiety and depression [ 8– 9]. These
hormonal imbalances may be further compounded
by lifestyle factors, such as smoking, physical inactiv -
ity, and poor sleep quality, all of which are prevalent in
perimenopausal women and have been associated with
adverse mental health outcomes [10– 12].
Previous research has highlighted the role of demo -
graphic and lifestyle factors in influencing the psycholog -
ical well-being of perimenopausal women. For instance,
women with lower education levels, those who are single,
divorced, or widowed, and those with a history of psy -
chiatric illness are more likely to experience anxiety and
depression during the perimenopausal period [ 13– 14].
Additionally, smoking has been identified as a significant
risk factor for depression, while regular physical activ -
ity has been shown to have a protective effect on mental
health [ 15– 16]. Despite these findings, there is a pau -
city of data on how these factors interact with hormonal
changes to influence the risk of anxiety and depression
specifically in women with abnormal uterine bleeding
during the perimenopausal period.
The present study aims to explore the associations
between demographic, lifestyle, and endocrine factors
with anxiety and depression in perimenopausal women
with AUB. We hypothesize that lifestyle factors (such as
smoking and physical inactivity), medical and psychiatric
comorbidities, as well as hormonal imbalances, contrib -
ute to the increased risk of anxiety and depression in this
population. By identifying these associations, this study
seeks to provide a better understanding of the psycho -
logical challenges faced by perimenopausal women with
AUB and to inform targeted interventions for improving
mental health outcomes.
Methods
Study design and population
This cross-sectional study, based on a retrospective
review of medical records, was conducted to investigate
the factors associated with anxiety and depression in
perimenopausal women with abnormal uterine bleeding
(AUB). Data were collected from perimenopausal women
diagnosed with AUB who visited the gynecology out -
patient department at a tertiary hospital between Janu -
ary 2023 and January 2024. Perimenopause was defined
based on the STRAW + 10 criteria, as the transitional
period characterized by changes in menstrual cycle regu -
larity—such as a cycle length variation of ≥ 7 days or ≥ 60
days of amenorrhea—accompanied by typical meno -
pausal symptoms. These symptoms included hot flashes,
night sweats, mood disturbances, or sleep disorders.
Women with lifelong menstrual irregularities (e.g., due
to polycystic ovary syndrome) were excluded. The study
included women aged 40 to 55 years. For women within
12 months after their final menstrual period, abnormal
uterine bleeding (AUB) was included if the episode was
consistent with perimenopausal hormonal patterns and
not attributable to postmenopausal pathology. AUB was
diagnosed based on clinical evaluation and transvaginal
ultrasound.
Patients with missing data for any key variables, includ-
ing hormone measurements or psychiatric evaluation
results, were excluded from the analysis. As such, the
final sample only included individuals with complete
clinical and laboratory data. No imputation was applied
for missing values.
Data collection
Data were extracted from the patients’ medical records,
including demographic and lifestyle characteristics (age,
BMI, marital status, education level, smoking history,
alcohol use, and exercise frequency), clinical factors
(duration of abnormal uterine bleeding, comorbidities
such as hypertension and diabetes, psychiatric history),
and laboratory results of endocrine markers (estradiol,
follicle-stimulating hormone [FSH], luteinizing hormone
[LH], cortisol, prolactin, testosterone, and thyroid-stimu-
lating hormone [TSH]).
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Hu and He BMC Psychology (2025) 13:514
Anxiety and depression status was assessed through
clinical psychiatric evaluations conducted during outpa -
tient visits, based on the Diagnostic and Statistical Man -
ual of Mental Disorders, Fifth Edition (DSM-5) criteria.
These evaluations were performed by qualified mental
health professionals and documented in the electronic
medical records. Psychiatric history, including any prior
diagnoses of anxiety, depression, or other mental disor -
ders, was also extracted. Patients with major psychiatric
disorders other than anxiety or depression (e.g., schizo -
phrenia or bipolar disorder) were excluded from the
analysis.
Statistical analysis
Continuous variables were expressed as mean ± stan-
dard deviation for normally distributed variables or
median (interquartile range) for skewed variables. Cat -
egorical variables were presented as frequencies and
percentages. Comparisons between the anxiety and non-
anxiety groups, as well as between the depression and
non-depression groups, were made using independent
t-tests for normally distributed variables, Mann-Whitney
U tests for skewed variables, and Chi-square tests for cat-
egorical variables. A two-sided P-value < 0.05 was consid-
ered statistically significant.
Univariate and multivariate logistic regression analy -
ses were performed to identify factors associated with
anxiety and depression in perimenopausal women with
AUB. The odds ratios (OR) and corresponding 95% con -
fidence intervals (CI) were calculated. All variables with
P-values < 0.05 in univariate analysis were included in the
multivariate logistic regression models. The multivariate
models were adjusted for age, BMI, duration of abnormal
uterine bleeding, marital status, education level, smoking
history, exercise frequency, psychiatric history, endocrine
markers, and sleep quality.
For further analysis, interaction effects between
endocrine markers and lifestyle factors (e.g., smoking
and exercise) were examined using multivariate logis -
tic regression models, with interaction terms included.
Stratified analyses by age group (< 50 vs. ≥50 years) were
conducted to explore whether age modified the associa -
tions between risk factors and psychological outcomes.
However, interaction terms with age were not statistically
significant, and the effect estimates remained consistent
across both groups. Therefore, detailed stratified results
are not shown but are available upon request. Endocrine
markers such as estradiol, FSH, LH, cortisol, prolactin,
testosterone, and TSH were initially screened for inclu -
sion in the regression models. TSH was excluded from
the final models due to lack of independent significance
in multivariate analysis and to avoid redundancy among
correlated hormonal variables. All statistical analyses
were performed using IBM SPSS Statistics version 28.0
(IBM Corp., Armonk, NY, USA). P-values were calcu -
lated using two-tailed tests, and a significance level of
P < 0.05 was considered statistically significant for all
analyses.
Results
Baseline characteristics of perimenopausal women with
abnormal uterine bleeding (n = 1234)
Tables 1 and 2 present the baseline characteristics of the
study population according to anxiety and depression
status, respectively. Age was similar across groups. How -
ever, women with either anxiety or depression were more
likely to have higher BMI, longer duration of abnormal
uterine bleeding, lower education levels, and be unmar -
ried (all P < 0.05). Smoking history and physical inactivity
were significantly more common in both the anxiety and
depression groups ( P < 0.001). Additionally, participants
in both groups exhibited lower estradiol levels and higher
levels of FSH, LH, and cortisol compared to those with -
out anxiety or depression (all P < 0.01). Poor sleep qual -
ity, as indicated by significantly elevated PSQI scores, was
also strongly associated with both psychological condi -
tions (P < 0.001). These findings highlight consistent pat -
terns of demographic, lifestyle, and endocrine differences
in women experiencing anxiety or depression.
Univariate and multivariate logistic regression analysis for
factors associated with anxiety in perimenopausal women
with abnormal uterine bleeding (n = 1234)
In multivariate analysis (Table 3), anxiety in perimeno -
pausal women with AUB was significantly associated
with higher BMI, longer duration of abnormal uterine
bleeding, being single/divorced/widowed, and lower
education levels. Lifestyle factors such as smoking and
physical inactivity were strong predictors, while regu -
lar exercise appeared protective. Notably, elevated PSQI
scores and endocrine markers including lower estradiol
and higher FSH, LH, and cortisol levels were also linked
to increased anxiety risk. These findings suggest that anx-
iety is influenced by an interplay of demographic, behav -
ioral, and hormonal factors.
Univariate and multivariate logistic regression analysis
for factors associated with depression in perimenopausal
women with abnormal uterine bleeding (n = 1234)
As shown in Table 4, depression was significantly asso -
ciated with higher BMI, longer duration of abnormal
uterine bleeding, unmarried status, and lower educa -
tion. A history of smoking and prior psychiatric disorders
emerged as particularly strong predictors. Lower estra -
diol and elevated FSH, LH, and cortisol levels were also
significantly associated with increased depression risk.
As with anxiety, poor sleep quality and lack of regular
physical activity were linked to higher odds of depression.
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Hu and He BMC Psychology (2025) 13:514
These results support a multifactorial model, in which
demographic, behavioral, clinical, and hormonal factors
collectively contribute to depression in this population.
Comparison of clinical and hormonal characteristics
among women with anxiety only, depression only,
comorbid anxiety and depression, and neither condition
Of the 1,234 participants, 298 (24.1%) had anxiety only,
250 (20.3%) had depression only, 418 (33.9%) had both
anxiety and depression, and 268 (21.7%) had neither con-
dition. As shown in Tables 5 and 6, women with comor -
bid anxiety and depression exhibited more pronounced
clinical and hormonal dysregulation compared to those
without psychological symptoms. This group had the
highest BMI and longest duration of AUB, as well as the
highest rates of smoking, psychiatric history, and poor
sleep quality. Endocrine disturbances were also most
evident in the comorbid group, with significantly lower
estradiol and elevated FSH, LH, and cortisol levels (all
P < 0.001), suggesting activation of both gonadotropic and
stress axes. Prolactin, testosterone, and TSH levels were
also elevated. Although TSH was significantly higher in
the comorbid group, it was not retained in multivari -
ate models, indicating a lack of independent predictive
value after adjustment for other clinical and hormonal
variables. These findings support the hypothesis that
comorbid anxiety and depression in perimenopausal
women with AUB are associated with a distinct pattern
of physiological dysregulation.
Multivariate logistic regression analysis for factors
associated with both anxiety and depression in
perimenopausal women with abnormal uterine bleeding
(n = 1234)
As shown in Table 7, the presence of both anxiety and
depression was independently associated with higher
BMI, longer duration of abnormal uterine bleeding,
unmarried status, lower education level, smoking history,
and poor sleep quality. A psychiatric history emerged as
the strongest predictor. Regular physical activity was pro-
tective. Hormonal factors including lower estradiol and
elevated FSH, LH, and cortisol levels were also signifi -
cantly associated with comorbidity. These findings rein -
force the multifactorial nature of psychological distress
in perimenopausal women with AUB, involving demo -
graphic, behavioral, clinical, and endocrine dimensions.
Table 1 Baseline characteristics of perimenopausal women with abnormal uterine bleeding (n = 1234)
Characteristic Total (n = 1234) Anxiety Group
(n = 652)
Non-Anxiety Group
(n = 582)
P-value
Age (years), Mean ± SD 48.7 ± 3.5 48.9 ± 3.4 48.5 ± 3.6 0.182
BMI (kg/m²), Mean ± SD 25.8 ± 4.1 26.1 ± 4.2 25.5 ± 3.9 0.045*
Duration of Abnormal Uterine Bleeding (months),
Median (IQR)
8 (3–12) 10 (5–13) 7 (3–11) 0.003**
Marital Status, n (%)
- Married 954 (77.3) 482 (73.9) 472 (81.1) 0.008**
- Single/Divorced/Widowed 280 (22.7) 170 (26.1) 110 (18.9)
Education Level, n (%)
- Primary/Secondary 645 (52.3) 380 (58.3) 265 (45.5) < 0.001***
- College/University 589 (47.7) 272 (41.7) 317 (54.5)
Smoking History, n (%) 98 (7.9) 74 (11.4) 24 (4.1) < 0.001***
Alcohol Use, n (%) 147 (11.9) 89 (13.7) 58 (10.0) 0.052
Exercise Regularly (≥ 3 times/week), n (%) 546 (44.3) 232 (35.6) 314 (53.9) < 0.001***
Comorbidities, n (%)
- Hypertension 398 (32.2) 220 (33.7) 178 (30.6) 0.253
- Diabetes 148 (12.0) 89 (13.6) 59 (10.1) 0.052
Psychiatric History, n (%) 256 (20.7) 183 (28.1) 73 (12.5) < 0.001***
Endocrine Levels, Mean ± SD
- Estradiol (pg/mL) 62.5 ± 22.4 60.2 ± 21.8 64.9 ± 23.0 0.012*
- FSH (mIU/mL) 25.6 ± 8.9 27.4 ± 8.6 23.7 ± 8.8 < 0.001***
- LH (mIU/mL) 21.8 ± 6.7 22.9 ± 6.5 20.7 ± 6.8 < 0.001***
- Cortisol (µg/dL) 14.2 ± 5.3 15.6 ± 5.1 12.7 ± 5.5 < 0.001***
- Prolactin (ng/mL) 18.9 ± 6.3 19.5 ± 6.5 18.2 ± 6.0 0.002**
Sleep Quality (PSQI Score), Median (IQR) 7 (5–10) 9 (6–12) 6 (4–8) < 0.001***
Note: Data are presented as mean ± standard deviation for normally distributed variables, median (interquartile range) for skewed variables, and frequency
(percentage) for categorical variables. P-values were calculated using t-tests, Mann-Whitney U tests, or Chi-square tests as appropriate.*Significance levels: * P < 0.05,
**P < 0.01, ***P < 0.001
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Interaction effects between endocrine markers and
lifestyle and clinical factors on anxiety and depression in
perimenopausal women with abnormal uterine bleeding
(n = 1234)
Interaction terms between endocrine markers (estra -
diol, FSH, LH, cortisol, prolactin, testosterone, and TSH)
and lifestyle or clinical factors (smoking, regular physi -
cal activity, and psychiatric history) were tested using
multivariate logistic regression. As shown in Table 8,
only statistically significant interactions ( P < 0.05) are
reported; non-significant results are omitted for clarity
but are available upon request. Notably, smoking ampli -
fied the adverse effects of lower estradiol and higher cor -
tisol on anxiety and depression, while regular exercise
mitigated the psychological risk associated with elevated
FSH and LH levels. Additionally, higher TSH levels were
Table 2 Baseline characteristics of perimenopausal women with abnormal uterine bleeding by depression status (n = 1234)
Characteristic Total (n = 1234) Depression Group (n = 604) Non-Depression Group (n = 630) P-value
Age (years), Mean ± SD 48.7 ± 3.5 48.9 ± 3.4 48.6 ± 3.6 0.109
BMI (kg/m²), Mean ± SD 25.8 ± 4.1 26.0 ± 4.2 25.4 ± 3.9 0.033*
Duration of AUB (months), Median (IQR) 8 (3–12) 10 (5–13) 7 (3–11) 0.005**
Marital Status, n (%) 0.019*
– Married 954 (77.3) 455 (75.3) 499 (79.2)
– Single/Divorced/Widowed 280 (22.7) 149 (24.7) 131 (20.8)
Education Level, n (%) < 0.001***
– Primary/Secondary 645 (52.3) 360 (59.6) 285 (45.2)
– College/University 589 (47.7) 244 (40.4) 345 (54.8)
Smoking History, n (%) 98 (7.9) 69 (11.4) 29 (4.6) < 0.001***
Alcohol Use, n (%) 147 (11.9) 83 (13.7) 64 (10.2) 0.058
Exercise Regularly (≥ 3 times/week), n (%) 546 (44.3) 218 (36.1) 328 (52.1) < 0.001***
Comorbidities, n (%)
– Hypertension 398 (32.2) 207 (34.3) 191 (30.3) 0.174
– Diabetes 148 (12.0) 82 (13.6) 66 (10.5) 0.072
Psychiatric History, n (%) 256 (20.7) 170 (28.1) 86 (13.7) < 0.001***
Endocrine Levels, Mean ± SD
– Estradiol (pg/mL) 62.5 ± 22.4 59.3 ± 22.1 65.7 ± 22.6 0.003**
– FSH (mIU/mL) 25.6 ± 8.9 27.1 ± 8.5 24.2 ± 8.9 < 0.001***
– LH (mIU/mL) 21.8 ± 6.7 22.7 ± 6.6 20.9 ± 6.7 < 0.001***
– Cortisol (µg/dL) 14.2 ± 5.3 15.3 ± 5.1 13.2 ± 5.4 < 0.001***
– Prolactin (ng/mL) 18.9 ± 6.3 19.4 ± 6.5 18.3 ± 6.0 0.004**
Sleep Quality (PSQI Score), Median (IQR) 7 (5–10) 9 (6–12) 6 (4–8) < 0.001***
Note: Data are presented as mean ± standard deviation for normally distributed variables, median (interquartile range) for skewed variables, and frequency
(percentage) for categorical variables. P-values were calculated using t-tests, Mann-Whitney U tests, or Chi-square tests as appropriate. *Significance levels: * P < 0.05,
**P < 0.01, ***P < 0.001
Table 3 Univariate and multivariate logistic regression analysis for factors associated with anxiety in perimenopausal women with
abnormal uterine bleeding (n = 1234)
Variable Univariate OR (95% CI) P-value Multivariate OR (95% CI) P-value
Age (years) 1.03 (0.98–1.07) 0.182 1.02 (0.97–1.06) 0.215
BMI (kg/m²) 1.07 (1.02–1.12) 0.041* 1.06 (1.01–1.11) 0.049*
Duration of Abnormal Uterine Bleeding (months) 1.09 (1.03–1.15) 0.003** 1.08 (1.02–1.14) 0.006**
Marital Status (Single/Divorced/Widowed vs. Married) 1.56 (1.11–2.18) 0.010* 1.42 (1.01-2.00) 0.042*
Education Level (Primary/Secondary vs. College/University) 1.71 (1.34–2.19) < 0.001*** 1.58 (1.22–2.05) < 0.001***
Smoking History (Yes vs. No) 3.07 (1.89–4.98) < 0.001*** 2.91 (1.78–4.76) < 0.001***
Exercise Regularly (≥ 3 times/week) (Yes vs. No) 0.53 (0.42–0.68) < 0.001*** 0.61 (0.47–0.79) < 0.001***
Psychiatric History (Yes vs. No) 2.71 (1.94–3.79) < 0.001*** 2.44 (1.72–3.47) < 0.001***
Estradiol (pg/mL) 0.98 (0.96–0.99) 0.014* 0.98 (0.96–0.99) 0.018*
FSH (mIU/mL) 1.06 (1.04–1.09) < 0.001*** 1.05 (1.03–1.08) < 0.001***
LH (mIU/mL) 1.04 (1.02–1.07) < 0.001*** 1.03 (1.01–1.06) 0.002**
Cortisol (µg/dL) 1.09 (1.04–1.14) < 0.001*** 1.07 (1.02–1.13) 0.005**
Sleep Quality (PSQI Score) 1.26 (1.19–1.33) < 0.001*** 1.24 (1.17–1.32) < 0.001***
Note: OR = Odds Ratio; CI = Confidence Interval. P-values were calculated using univariate and multivariate logistic regression models. Multivariate models adjusted
for all variables listed in the table.*Significance levels: * P < 0.05, **P < 0.01, ***P < 0.001
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Hu and He BMC Psychology (2025) 13:514
associated with a reduced risk among women who exer -
cised regularly. The interaction between cortisol and
psychiatric history further intensified psychological vul -
nerability. These findings underscore the moderating role
of behavioral and clinical history factors on the mental
health impact of endocrine dysregulation in perimeno -
pausal women.
Discussion
This study sought to explore the factors associated with
anxiety and depression in perimenopausal women with
abnormal uterine bleeding (AUB), focusing on the roles
of demographic, lifestyle, and endocrine factors. Our
findings provide critical insights into the multifacto -
rial nature of psychological distress in this population,
demonstrating the combined effects of hormonal imbal -
ances, social factors, and lifestyle habits on mental health
outcomes.
Table 4 Univariate and multivariate logistic regression analysis for factors associated with depression in perimenopausal women with
abnormal uterine bleeding (n = 1234)
Variable Univariate OR (95% CI) P-value Multivariate OR (95% CI) P-value
Age (years) 1.04 (0.99–1.08) 0.085 1.03 (0.98–1.07) 0.109
BMI (kg/m²) 1.08 (1.03–1.13) 0.027* 1.07 (1.02–1.12) 0.033*
Duration of Abnormal Uterine Bleeding (months) 1.12 (1.05–1.18) 0.002** 1.09 (1.03–1.15) 0.005**
Marital Status (Single/Divorced/Widowed vs. Married) 1.62 (1.18–2.24) 0.007** 1.49 (1.06–2.09) 0.019*
Education Level (Primary/Secondary vs. College/University) 1.84 (1.45–2.33) < 0.001*** 1.66 (1.28–2.17) < 0.001***
Smoking History (Yes vs. No) 2.94 (1.83–4.72) < 0.001*** 2.72 (1.69–4.40) < 0.001***
Exercise Regularly (≥ 3 times/week) (Yes vs. No) 0.59 (0.45–0.78) < 0.001*** 0.68 (0.52–0.89) 0.006**
Psychiatric History (Yes vs. No) 3.02 (2.14–4.26) < 0.001*** 2.67 (1.88–3.78) < 0.001***
Estradiol (pg/mL) 0.96 (0.94–0.98) < 0.001*** 0.97 (0.95–0.99) 0.003**
FSH (mIU/mL) 1.05 (1.03–1.08) < 0.001*** 1.04 (1.02–1.07) < 0.001***
LH (mIU/mL) 1.03 (1.01–1.06) 0.004** 1.02 (1.00-1.05) 0.012*
Cortisol (µg/dL) 1.11 (1.06–1.16) < 0.001*** 1.09 (1.04–1.15) 0.002**
Sleep Quality (PSQI Score) 1.32 (1.25–1.39) < 0.001*** 1.29 (1.22–1.36) < 0.001***
Note: OR = Odds Ratio; CI = Confidence Interval. P-values were calculated using univariate and multivariate logistic regression models. Multivariate models adjusted
for all variables listed in the table. *Significance levels: * P < 0.05, **P < 0.01, ***P < 0.001
Table 5 Comparison of endocrine levels between women with and without anxiety and depression (n = 1234)
Endocrine Marker Anxiety & Depression Group (n = 418) Non-Anxiety & Non-Depression Group (n = 416) P-value
Estradiol (pg/mL), Mean ± SD 58.7 ± 22.0 67.5 ± 23.5 < 0.001***
FSH (mIU/mL), Mean ± SD 27.9 ± 8.4 22.5 ± 8.6 < 0.001***
LH (mIU/mL), Mean ± SD 23.5 ± 6.9 19.8 ± 6.7 < 0.001***
Cortisol (µg/dL), Mean ± SD 15.8 ± 5.2 13.1 ± 5.4 < 0.001***
Prolactin (ng/mL), Mean ± SD 19.6 ± 6.1 17.8 ± 6.0 0.002**
Testosterone (ng/dL), Mean ± SD 0.52 ± 0.15 0.49 ± 0.13 0.034*
TSH (mIU/L), Mean ± SD 2.71 ± 1.14 2.41 ± 1.10 0.012*
Note: Data are presented as mean ± standard deviation. P-values were calculated using t-tests to compare the mean endocrine levels between the anxiety &
depression group and the non-anxiety & non-depression group. *Significance levels: * P < 0.05, **P < 0.01, ***P < 0.001
Table 6 Comparison of key characteristics among four mental health subgroups
Variable Anxiety Only
(n = 298)
Depression Only
(n = 250)
Comorbid A&D
(n = 418)
Neither (n = 268) P-value
Age (years), Mean ± SD 48.8 ± 3.3 48.9 ± 3.4 49.0 ± 3.5 48.5 ± 3.6 0.217
BMI (kg/m²), Mean ± SD 25.9 ± 4.1 25.8 ± 4.0 26.3 ± 4.2 25.2 ± 3.8 0.019*
Duration of AUB (months), Median (IQR) 9 (5–12) 9 (5–13) 10 (6–14) 6 (3–10) < 0.001***
Smoking History (%) 10.1% 9.6% 11.5% 2.6% < 0.001***
Psychiatric History (%) 22.1% 23.6% 34.5% 9.3% < 0.001***
Estradiol (pg/mL) 61.8 ± 22.3 60.5 ± 22.5 58.7 ± 22.0 67.5 ± 23.5 < 0.001***
FSH (mIU/mL) 26.5 ± 8.7 26.7 ± 8.4 27.9 ± 8.4 22.5 ± 8.6 < 0.001***
Cortisol (µg/dL) 14.8 ± 5.1 14.9 ± 5.2 15.8 ± 5.2 13.1 ± 5.4 < 0.001***
Sleep Quality (PSQI), Median (IQR) 8 (5–10) 8 (5–11) 9 (6–12) 5 (3–7) < 0.001***
Note: Comparison across four mental health subgroups. P-values derived using ANOVA, Kruskal-Wallis, or Chi-square tests as appropriate. A&D = Anxiety and
Depression. *Significance levels: * P < 0.05, **P < 0.01, ***P < 0.001
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Consistent with previous studies, we found that higher
BMI was significantly associated with increased odds
of anxiety and depression in perimenopausal women.
Barghandan et al. (2021) reported that postmenopausal
women with elevated BMI and body fat mass (BFM)
experienced more severe menopausal symptoms and
higher levels of trait anxiety, highlighting a clear link
between excess adiposity and psychological distress
during this transitional period [ 17]. Obesity is widely
recognized as a risk factor for mental health disorders,
primarily due to the metabolic and inflammatory dis -
turbances associated with excess body fat. In particular,
central obesity has been linked to disruptions in neuro -
endocrine signaling, increased systemic inflammation,
and insulin resistance, all of which contribute to mood
dysregulation and heightened vulnerability to anxiety and
depression [18]. Moreover, Barghandan et al. also empha-
sized that negative body image perceptions related to
physiological changes in menopause may further amplify
emotional distress, reinforcing the psychological burden
in women with higher BMI during the perimenopausal
and postmenopausal phases. Research shows that meta -
bolic abnormalities, such as alterations in glucocorti -
coids, insulin resistance, and increased inflammatory
signaling from dysfunctional adipose tissue, may signifi -
cantly impact mood regulation and emotional control,
thereby contributing to the higher incidence of depres -
sion in obese individual [ 19]. Additionally, the pro -
longed duration of abnormal uterine bleeding (AUB) was
another significant predictor, underscoring the emotional
burden imposed by persistent bleeding. Women with
longer durations of AUB frequently experience height -
ened anxiety and depression due to the ongoing uncer -
tainty and physical discomfort associated with irregular
menstrual cycles. As Lebduska et al. (2023) note, AUB
often presents with variations in frequency, duration, and
volume of bleeding, contributing to psychological stress
and discomfort in affected women [ 20]. This prolonged
disruption of daily life can exacerbate feelings of anxiety
and emotional distress, further impacting mental health
outcomes.
Marital status also played a significant role in men -
tal health outcomes, with single, divorced, or widowed
women being more likely to experience anxiety and
depression compared to their married counterparts. This
observation is supported by studies highlighting the pro -
tective role of social support against mental health dis -
orders. Li et al. (2023), in their longitudinal study, found
Table 7 Multivariate logistic regression analysis for factors associated with both anxiety and depression in perimenopausal women
with abnormal uterine bleeding (n = 1234)
Variable Multivariate OR (95% CI) P-value
Age (years) 1.01 (0.97–1.05) 0.268
BMI (kg/m²) 1.08 (1.02–1.14) 0.008**
Duration of Abnormal Uterine Bleeding (months) 1.12 (1.05–1.18) 0.001***
Marital Status (Single/Divorced/Widowed vs. Married) 1.54 (1.09–2.18) 0.015*
Education Level (Primary/Secondary vs. College/University) 1.62 (1.24–2.12) < 0.001***
Smoking History (Yes vs. No) 2.84 (1.79–4.51) < 0.001***
Exercise Regularly (≥ 3 times/week) (Yes vs. No) 0.64 (0.49–0.84) 0.001***
Psychiatric History (Yes vs. No) 3.11 (2.16–4.48) < 0.001***
Estradiol (pg/mL) 0.96 (0.94–0.98) < 0.001***
FSH (mIU/mL) 1.05 (1.03–1.08) < 0.001***
LH (mIU/mL) 1.03 (1.01–1.06) 0.006**
Cortisol (µg/dL) 1.10 (1.04–1.16) < 0.001***
Sleep Quality (PSQI Score) 1.30 (1.22–1.38) < 0.001***
Note: OR = Odds Ratio; CI = Confidence Interval. P-values were calculated using multivariate logistic regression analysis. *Significance levels: * P < 0.05, **P < 0.01,
***P < 0.001
Table 8 Interaction effects between endocrine markers and lifestyle and clinical factors on anxiety and depression in perimenopausal
women with abnormal uterine bleeding (n = 1234)
Interaction Term Multivariate OR (95% CI) P-value
Estradiol (pg/mL) × Smoking History 1.08 (1.02–1.14) 0.006**
FSH (mIU/mL) × Exercise Regularly (≥ 3 times/week) 0.92 (0.88–0.97) < 0.001***
Cortisol (µg/dL) × Smoking History 1.12 (1.05–1.18) < 0.001***
LH (mIU/mL) × Exercise Regularly (≥ 3 times/week) 0.95 (0.91–0.99) 0.015*
TSH (mIU/L) × Exercise Regularly (≥ 3 times/week) 0.89 (0.82–0.97) 0.005**
Cortisol (µg/dL) × Psychiatric History 1.14 (1.06–1.23) < 0.001***
Note: OR = Odds Ratio; CI = Confidence Interval. P-values were calculated using multivariate logistic regression models that included interaction terms between
endocrine markers and lifestyle factors (smoking, exercise) and clinical history (psychiatric history). *Significance levels: * P < 0.05, **P < 0.01, ***P < 0.001
Page 8 of 10
Hu and He BMC Psychology (2025) 13:514
that individuals with greater social support, such as
close confidants or access to practical help, had reduced
depressive symptoms [ 21]. Their research indicated that
social support can buffer against the effects of loneli -
ness, thus mitigating depressive symptoms, especially in
men. Similarly, Gariépy et al. (2016) conducted a system -
atic review and meta-analysis and confirmed that social
support, particularly from spouses and family members,
serves as a protective factor against depression across
various life stages [ 22]. They found that support from a
spouse had the strongest protective effect in adulthood
and older age. These findings underline the critical role of
marital status and close social connections in maintain -
ing mental well-being, especially during vulnerable peri -
ods such as perimenopause.
Lower education levels were similarly associated with
higher odds of anxiety and depression, which aligns with
previous research linking lower socioeconomic status
to poorer mental health outcomes. Cohen et al. (2020)
found that individuals with lower educational attain -
ment had a higher likelihood of experiencing depression
in midlife, emphasizing that education shapes access to
health resources and coping mechanisms across the lifes-
pan [ 23]. Similarly, Hoebel et al. (2017) demonstrated
that lower education, as a core dimension of socioeco -
nomic status, was significantly associated with depressive
symptoms, as education is closely related to cognitive
abilities and health-related behaviors [ 24]. Furthermore,
a meta-analysis by Lorant et al. (2003) revealed that indi -
viduals with lower education levels had higher odds of
both new episodes and persistent depression, confirming
the dose-response relationship between education and
mental health outcomes [ 25]. Education not only pro -
vides access to better resources but also improves health
literacy and enhances coping mechanisms, all of which
can mitigate the psychological effects of perimenopausal
symptoms.
Lifestyle factors, including smoking and physical
inactivity, further compounded the risk of anxiety and
depression in this cohort. Smoking has been identified as
a significant modifiable risk factor for depression, likely
due to its impact on neurochemistry and its association
with unhealthy coping mechanisms [26]. Conversely, reg-
ular physical activity was found to have a protective effect
on mental health, supporting the well-established ben -
efits of exercise on mood regulation and stress reduction
[27]. These findings underscore the importance of life -
style interventions in mitigating the psychological burden
of perimenopausal symptoms.
Although our analysis revealed a statistically significant
association between lower estradiol levels and anxiety,
the effect size was relatively small. Therefore, estradiol
may play a contributory rather than a central role in the
development of anxiety in this population. Estradiol,
known for its neuroprotective properties, plays a critical
role in mood regulation by modulating neurotransmit -
ters such as serotonin and dopamine. As estradiol levels
decline during perimenopause, women become more
susceptible to mood disturbances. Raglan et al. (2020)
emphasized that hormonal fluctuations, particularly
declining estradiol, are closely linked to the increased
incidence of depression during perimenopause, a period
of heightened vulnerability for mood disorders [ 5]. Simi-
larly, Freeman (2015) reviewed the accumulating evi -
dence linking the changing hormonal milieu, including
increased FSH and cortisol levels, to depressive symp -
toms in the menopause transition [ 6]. Elevated cortisol
levels, indicative of heightened stress responses, have
been consistently associated with anxiety and depres -
sion during this life stage. Additionally, the interaction
between endocrine markers and lifestyle factors, such as
smoking and physical activity, suggests that these hor -
monal imbalances may be either exacerbated or mitigated
by behavioral factors. Higher cortisol levels in smokers,
for example, have been shown to amplify the risk of anxi -
ety and depression, whereas regular physical activity can
moderate the effects of elevated FSH and LH levels, pro -
viding a protective effect against mood disturbances dur -
ing perimenopause. Although elevated TSH levels were
associated with anxiety and depression, it is important to
note that TSH levels may naturally increase with age, and
age could act as a potential confounder in this relation -
ship. Future studies with age-stratified thyroid function
analysis are warranted to clarify this association.
Our study also highlighted the critical role of sleep
quality, with poor sleep being a significant contributor
to anxiety and depression. This is particularly evident in
perimenopausal women, who are vulnerable due to hor -
monal fluctuations, often leading to night sweats and
insomnia. Zhou et al. (2021) found a strong relationship
between hot flashes, sweating, and poor sleep quality,
with anxiety and depression mediating this relationship
[28]. Their study revealed that anxiety accounted for
17.86% of the mediating effect, while depression contrib -
uted 5.36%, indicating that both symptoms play crucial
roles in worsening sleep quality for women in this transi -
tional period. These findings support the notion that hor-
monal imbalances during perimenopause significantly
impact sleep, which, in turn, exacerbates mental health
issues like anxiety and depression.
One of the strengths of this study is the comprehensive
assessment of both hormonal and lifestyle factors, which
provides a more holistic understanding of the contribu -
tors to anxiety and depression in perimenopausal women
with abnormal uterine bleeding (AUB). However, sev -
eral limitations should be noted. First, the retrospective
design may introduce recall bias, particularly regarding
self-reported lifestyle factors such as smoking, physical
Page 9 of 10
Hu and He BMC Psychology (2025) 13:514
activity, and sleep quality. Second, the study population
was drawn from a single tertiary care gynecology outpa -
tient clinic, which may limit the generalizability of the
findings to the broader population of perimenopausal
women. Third, hormone levels were measured only
once, which does not account for the natural circadian
and menstrual cycle-related fluctuations of key endo -
crine markers such as estradiol, FSH, LH, and cortisol.
Although blood samples were collected under standard -
ized conditions in the early morning (between 7:30 and
9:30 AM) following an overnight fast to minimize diur -
nal variation, the phase of the menstrual cycle at the time
of sampling was not recorded. This may have introduced
variability in hormone measurements and limits the
interpretation of their associations with psychological
symptoms. Future research should incorporate longi -
tudinal and repeated hormone measurements, include
a more diverse and representative sample, and consider
menstrual cycle phase to more accurately assess the tem -
poral and causal relationships between hormonal fluctua-
tions, lifestyle factors, and mental health outcomes in this
population.
The findings of this study have important clinical impli-
cations. Given the identified associations between demo -
graphic, lifestyle, and hormonal factors with anxiety and
depression, clinicians should consider systematically
evaluating these risk factors during the initial assessment
of perimenopausal women with AUB. Early identification
of high-risk individuals—particularly those with elevated
BMI, a history of smoking or psychiatric illness, poor
sleep quality, or abnormal hormone levels—may enable
timely mental health screening and intervention. Inte -
grating psychological evaluation into routine gynecologic
care could significantly improve the holistic management
and quality of life of these patients.
In conclusion, our findings highlight the complex inter-
play between hormonal, demographic, and lifestyle fac -
tors in the development of anxiety and depression in
perimenopausal women with AUB. Targeted interven -
tions addressing modifiable risk factors, such as smok -
ing cessation, physical activity promotion, and sleep
improvement, may offer substantial benefits in alleviat -
ing psychological distress during this vulnerable period.
Further research is needed to explore the mechanisms
underlying these associations and to develop tailored
interventions for women at higher risk of mental health
disorders during perimenopause.
Acknowledgements
The authors wish to thank the staff and clinicians at the Department of
Gynecology, The Affiliated Hospital, Southwest Medical University, for their
support during data collection and analysis. Additionally, we extend our
gratitude to any individuals or institutions who contributed to the study but
do not meet the criteria for authorship.
Author contributions
Jun Hu and Lijuan He contributed equally to the conceptualization and design
of the study. Jun Hu was primarily responsible for data collection, statistical
analysis, and drafting the initial manuscript. Lijuan He supervised the study,
provided critical revisions to the manuscript, and ensured the scientific rigor
of the analysis. Both authors reviewed and approved the final manuscript for
submission.
Funding
This research received no external funding.
Data availability
The datasets analyzed during the current study are available from the
corresponding author on reasonable request.
Declarations
Ethical statement
This study was conducted in accordance with the ethical principles outlined in
the Declaration of Helsinki and was approved by the Ethics Committee of The
Affiliated Hospital, Southwest Medical University (Ethics Approval Number:
KY2024498). Due to the retrospective nature of the study, the requirement for
informed consent to participate was formally waived by the ethics committee.
All patient data were anonymized and handled in strict confidentiality, in
compliance with applicable data protection regulations.
Patient consent for publication
Not applicable.
Competing interests
The authors declare no competing interests.
Received: 19 December 2024 / Accepted: 8 May 2025
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