Abstract
Objective
To examine the association of adverse childhood experiences (ACEs) with overall menopausal symptom burden in midlife women.
Study design
This was a cross-sectional study of women between the ages of 40 and 65 years who were seen for specialty consultation in the Menopause and Women’s Sexual Health Clinic, Mayo Clinic, Rochester, MN between May 1, 2015 and December 31, 2016.
Main outcome measures
Participants completed the ACE questionnaire to assess for childhood abuse and neglect, the Menopause Rating Scale (MRS) to assess menopausal symptom burden, the Patient Health Questionnaire (PHQ-9) to assess depression, the Generalized Anxiety Disorder questionnaire (GAD-7) to assess anxiety, and provided information on current abuse (physical, sexual and verbal/emotional).
Results
Women meeting inclusion criteria (N=1670) had a median age of 53.7 years (interquartile range: 49.1, 58.0). Of these women, 977 (58.5%) reported any ACE and 288 (17.2%) reported ≥4 ACEs. As menopausal symptoms increased from the first to fourth quartile, the odds of ACE 1-3 (vs. 0) increased from 1 to 2.50 (trend p<0.01), and the odds of ACE ≥4 (vs. 0) increased from 1 to 9.61 (trend p<0.01), a pattern that was consistent across all menopausal symptom domains. The association between severe menopausal symptoms and higher childhood adversity (ACE score 1-3 or ≥4 vs. ACE = 0) remained significant after adjusting for age, partner status, education, employment, depression, anxiety, and hormone therapy use (OR 1.84 and 4.51, p<0.01).
Conclusion
In this large cross-sectional study, there was a significant association between childhood adversity and self-reported menopausal symptoms that persisted even after adjustment for multiple confounders. These associations highlight the importance of screening women with bothersome menopausal symptoms for childhood adversity, and of offering appropriate management and counseling for the adverse experiences, when indicated.
Keywords: hot flashes, vasomotor symptoms, menopausal symptoms, child abuse, adverse childhood experiences
1. INTRODUCTION
Adverse childhood experiences (ACEs) are highly prevalent in the United States, with nearly 70,000 victims of child abuse annually. In 2015, the most recent year with national data, there were 683,000 reported cases of child abuse and neglect, with a rate of 9.2 per 1,000 children. The rate was slightly higher for girls at 9.6 victims per 1,000 [1, 2]. These statistics are very concerning, not only because of the short-term effect on the health of the children, but also because of the association between child abuse or neglect and numerous adverse long-term health outcomes, such as psychiatric disorders, substance abuse, eating disorders, autoimmune conditions, asthma, obesity, diabetes, and cardiovascular disease [3–11]. In addition, the risk of long-term morbidity increases with an increasing number of ACEs (dose-effect trend) [12].
Although the associations between ACEs and long-term psychiatric and medical morbidities are generally well reported, the association between ACEs and menopausal symptoms has not been equally well studied. Menopause is an inevitable occurrence in midlife women, and it often results in a variety of bothersome symptoms, including hot flashes and night sweats (vasomotor symptoms-VMS), psychiatric symptoms including mood changes and anxiety, cognitive difficulties, sleep disturbance, and genitourinary symptoms (vaginal dryness, dyspareunia, urinary frequency and urgency, among others) [13]. VMS are the most common symptom, occurring in approximately 75% of women at some point during the menopause transition [14]. VMS typically last longer than originally thought, for an average of 7-10 years for frequent or moderate to severe VMS, and even longer for less frequent or less severe VMS [14]. Women with bothersome VMS and other menopausal symptoms report a significant impairment in quality of life [13]. The study of the factors impacting menopausal symptoms is therefore critical for planning appropriate and effective management strategies.
Previous research has shown that childhood abuse or neglect is associated with an increased risk of undergoing bilateral oophorectomy as well as increased VMS in midlife women [15–17]. However, there are no reports on the association between ACEs and the full range of menopausal symptoms, which include somatic symptoms (hot flashes, heart discomfort, sleep problems, physical and mental exhaustion), psychological symptoms (depressive mood, irritability, and anxiety), and urogenital symptoms (sexual problems, bladder problems, and dryness of the vagina). The current study was conducted to examine the association of the overall menopausal symptom burden, including the somatic, psychological, and urogenital domains, with adverse childhood experiences.
2. METHODS
2.1. Participants
This was a cross-sectional study conducted at the Menopause and Women’s Sexual Health Clinic (MWSHC) at the Mayo Clinic, Rochester, Minnesota. All women seen for consultation in the MWSHC complete several health questionnaires, and the information gathered is recorded in the Data Registry on Experiences of Aging, Menopause and Sexuality (DREAMS) [18]. The current study included women between the ages of 40 and 65 years who consented to the use of their records for research, and were seen in the MWSHC between May 1, 2015 and December 31, 2016. The study was approved by the Mayo Clinic Institutional Review Board.
The participants completed validated questionnaires prior to their clinic visit that assessed ACEs, recent abuse, menopausal symptoms, mood, and anxiety.
2.2. Measures
2.2.1. Adverse Childhood Experiences (ACEs)-
The self-reported ACE questionnaire identifies childhood abuse and neglect. It is comprised of 10 questions about abuse (physical, emotional and sexual), household challenges, and neglect (emotional and physical). The affirmative answers are assigned one point each, and the sum of all the points is the total score [19].
2.2.2. Recent abuse-
A single question (yes or no response) asked the women whether they were exposed to physical, sexual, or emotional/verbal abuse in the year preceding their visit in the MWSHC.
2.2.3. Menopausal Symptoms-
The Menopause Rating Scale (MRS) is a self-reported questionnaire consisting of 11 items covering somatic, psychological, and urogenital subscales. Somatic symptoms include hot flashes, heart discomfort, sleep problems, physical and mental exhaustion, and joint/muscular discomfort. The psychological domain includes depressive mood, irritability, and anxiety, and urogenital symptoms include sexual problems, bladder problems, and dryness of the vagina. Each item is scored on a scale from 0 to 4 for severity (0 = none; 1 = mild; 2 = moderate; 3 = severe; 4 = very severe). The higher the composite score, the higher is the menopausal symptoms burden [20].
2.2.4. Mood-
The Patient Health Questionnaire-9 (PHQ-9) is a 9-question screen to assess the presence and severity of depression. The results of the PHQ-9 may be used to make a depression diagnosis according to DSM-IV criteria [21]. A score ≥ 5 was considered indicative of depression.
2.2.5. Anxiety-
The Generalized Anxiety Disorder 7 (GAD-7) is a self-reported questionnaire to assess the presence and severity of anxiety. It has 7 items and the final assessment regarding the presence and severity of anxiety is based on the sum of the score on all 7 items [22]. A score ≥ 5 was considered indicative of anxiety.
2.3. Covariates
Additional information relating to age, body mass index (BMI), race, ethnicity, educational status (high school graduate or lower, some college education, 4-year college graduate, or postgraduate), employment status (employed, full time homemaker, retired, or other), current menopausal hormone therapy (HT) use, and partner status were gathered from the intake form and the vital signs recorded at the time of the consultation in the MWSHC.
2.4. Data analyses
Descriptive statistics are reported as median and interquartile range for continuous data, and frequencies and percentages for categorical data. Univariate and multivariable nominal logistic regression was used to assess the association between MRS scores (in quartiles) and having an ACE (ACE ≥ 4 and ACE 1-3 versus ACE=0). Multivariable models were adjusted for age, depression, anxiety, partner status, employment, and HT use. We computed an odds ratio (OR) and a 95% confidence interval for MRS score quartiles 2, 3, and 4 compared to quartile 1 for both ACE ≥ 4 versus ACE=0 and ACE 1-3 versus ACE=0. All tests were two-sided, and p-values ≤ 0.05 were considered statistically significant. All analyses were performed using SAS version 9.4 software (SAS Institute, Inc.; Cary, NC).
3. RESULTS
A total of 1,670 women were included in the study. The demographic characteristics of the cohort are summarized in Table 1. More than half the women (977/1670; 58.5%) reported at least one ACE, and 17.2% reported 4 or more ACEs. In addition, 3.1% of the participants (52/1670) reported experiencing abuse in the preceding year. Women with 4 or more ACEs were more likely to report abuse in the preceding year (7.3%) compared to the women with 1-3 ACEs (3.3%) or no ACE at all (1.2%; p <0.01; Table 1). More than three-fourths (84.6%) of the participants reporting recent abuse also reported an ACE.
Table 1:
Sociodemographic and clinical characteristics in women with and without adverse childhood experiences
| Characteristic | Total N (%) | ACE = 0 N (%) | ACE 1-3 N (%) | ACE ≥ 4 N (%) |
|---|---|---|---|---|
| Number of women | 1,670 | 693 | 689 | 288 |
| Age (years), median (IQR) | 53.7 (49.1, 58.0) | 53.9 (50.0, 58.2) | 53.6 (49.1, 58.0) | 52.7 (47.3, 57.7) |
| BMI (kg/m2), median (IQR) | 25.4 (22.4, 29.6) | 24.8 (21.9, 28.5) | 25.8 (22.5, 30.0) | 26.9 (23.0, 31.7) |
| Race-White | 1,553 (93.0) | 645 (93.1) | 644 (93.5) | 264 (91.7) |
| Married | 1,384 (82.9) | 587 (84.7) | 571 (82.9) | 226 (78.5) |
| Education | ||||
| High school graduate/GED or lower | 125 (7.6) | 50 (7.2) | 48 (7.1) | 27 (9.6) |
| Some college or 2 year degree | 467 (28.3) | 169 (24.5) | 203 (29.9) | 95 (33.9) |
| 4-year college graduate | 548 (33.2) | 237 (34.3) | 229 (33.7) | 82 (29.3) |
| Post graduate studies | 510 (30.9) | 235 (34.0) | 199 (29.3) | 76 (27.1) |
| Employment | ||||
| Employed | 1,074 | 477 (68.9) | 441 (64.6) | 156 (55.1) |
| Full time homemaker | (64.8) | 95 (13.7) | 106 (15.5) | 36 (12.7) |
| Other | 237 (14.3) | 49 (7.1) | 68 (10.0) | 57 (20.1) |
| Retired | 174 (10.5) | 71 (10.3) | 68 (10.0) | 34 (12.0) |
| 173 (10.4) | ||||
| Hormone therapy use | 431 (29.0) | 173 (27.7) | 188 (31.2) | 70 (27.1) |
| Abuse in the preceding year | 52 (3.1) | 8 (1.2) | 23 (3.3) | 21 (7.3) |
| Anxiety (GAD-7 ≥ 5) | 503 (31.9) | 144 (22.1) | 215 (32.9) | 144 (53.3) |
| Depression (PHQ-9 ≥ 5) | 604 (38.2) | 173 (26.2) | 266 (40.7) | 165 (61.3) |
| MRS score, total, median (IQR) | 13 (9, 18) | 11 (7, 16) | 14 (9, 18) | 17 (13, 23) |
| MRS score, Psychological symptoms, median (IQR) | 4 (2, 7) | 3 (1, 5) | 4 (2, 7) | 6 (3, 9.5) |
| MRS score, Somatic symptoms, median (IQR) | 5 (3, 7) | 5 (3, 6) | 5 (3, 7) | 6 (4, 9) |
| MRS score, Urogenital symptoms, median (IQR) | 4 (2, 6) | 3 (2, 5) | 4 (2, 6) | 5 (3, 7) |
ACE: adverse childhood experiences; IQR: interquartile range; BMI: body mass index; GED: general education development; GAD-7: generalized anxiety disorder questionnaire; PHQ-9: patient health questionnaire; MRS: menopause rating scale
Women with the most severe menopausal symptoms were more likely to report 4 or more adverse childhood experiences, as compared to women with less severe menopausal symptoms, a pattern that was consistent across all menopausal symptom domains (Table 2). As menopausal symptoms increased from the first to fourth quartile, the odds of ACE 1-3 (vs. 0) increased from 1 to 2.50 (p<0.01), and the odds of ACE ≥4 (vs. 0) increased from 1 to 9.61 (trend p<0.01;Table 2 and Figure 1). This pattern was persistent in all the menopausal symptom domains, however it was less pronounced after adjustment for multiple confounders, including age, depression, anxiety, partner status, employment, and HT use (Table 2 and Figure 2). The odds ratio for reporting a childhood adversity (ACE = 1-3 and ACE≥ 4 versus ACE=0) increased monotonically with increasing severity of menopausal symptoms. In addition to the differences in MRS scores by ACE category, there were also differences in abuse in the preceding year and depression and anxiety scores with increased ACE category. Women who reported any abuse in the past year had 2.96 times the odds of reporting ACE 1-3 as compared to ACE=0 (p<0.01); for ACE≥4 as compared to ACE=0 this odds ratio increased to 6.73 (p<0.01). Women who reported greater scores for depression had 1.94 greater odds of reporting ACE 1-3 and 4.48 greater odds of reporting ACE≥4 as compared to ACE=0 (both p<0.01). Similarly, women who reported higher anxiety had 1.73 greater odds of also reporting ACE 1-3 and 4.74 greater odds of reporting ACE≥4 as compared to ACE=0 (both p<0.01). These patterns were attenuated after adjustment for multiple confounders.
Table 2:
Analyses of cross-sectional association between adverse childhood experiences and menopausal symptoms
| ACE = 1-3 vs ACE = 0 |
ACE ≥ 4 vs ACE = 0 |
|||||||||||
|---|---|---|---|---|---|---|---|---|---|---|---|---|
| Clinical characteristic | ACE = 0 N (%) | ACE 1-3 N (%) | OR (95% CI) | p | aOR (95% CI)a | p | ACE = 0 N (%) | ACE ≥ 4 N (%) | OR (95% CI) | p | aOR (95% CI)a | p |
| MRS Score, Total | ||||||||||||
| Q1 (0-9) | 273 (39.4) | 180 (26.1) | reference | reference | 273 (39.4) | 35 (12.2) | reference | reference | ||||
| Q2 (10-13) | 169 (24.4) | 152 (22.1) | 1.36 (1.02-1.82) | 0.04 | 1.29 (0.95-1.80) | 0.12 | 169 (24.4) | 47 (16.3) | 2.17 (1.35-3.50) | <0.01 | 1.86 (1.06-3.27) | 0.03 |
| Q3 (14-18) | 148 (21.4) | 187 (27.1) | 1.92 (1.44-2.55) | <0.01 | 1.65 (1.17-2.32) | <0.01 | 148 (21.4) | 79 (27.4) | 4.16 (2.67-6.50) | <0.01 | 2.94 (1.70-5.08) | <0.01 |
| Q4 (19-44) | 103 (14.9) | 170 (24.7) | 2.50 (1.84-3.41) | <0.01 | 1.84 (1.20-2.81) | <0.01 | 103 (14.9) | 127 (44.1) | 9.61 (6.21-14.89) | <0.01 | 4.51 (2.46-8.25) | <0.01 |
| MRS Score, Psychological Symptoms | ||||||||||||
| Q1 (0-2) | 329 (47.5) | 220 (31.9) | reference | reference | 329 (47.5) | 48 (16.7) | reference | reference | ||||
| Q2 (3-4) | 153 (22.1) | 167 (24.2) | 1.63 (1.24-2.16) | <0.01 | 1.41 (1.03-1.93) | 0.03 | 153 (22.1) | 61 (21.2) | 2.73 (1.79-4.18) | <0.01 | 2.10 (1.27-3.46) | <0.01 |
| Q3 (5-7) | 122 (17.6) | 159 (23.1) | 1.95 (1.46-2.61) | <0.01 | 1.59 (1.11-2.30) | 0.01 | 122 (17.6) | 70 (24.3) | 3.93 (2.58-6.00) | <0.01 | 2.24 (1.30-3.88) | <0.01 |
| Q4 (8-16) | 89 (12.8) | 143 (20.8) | 2.40 (1.75-3.29) | <0.01 | 1.61 (1.01-2.57) | 0.05 | 89 (12.8) | 109 (37.9) | 8.39 (5.56-12.68) | <0.01 | 3.21 (1.73-5.95) | <0.01 |
| MRS Score, Somatic Symptoms | ||||||||||||
| Q1 (0-3) | 251 (36.2) | 193 (28.0) | reference | reference | 251 (36.2) | 50 (17.4) | reference | reference | ||||
| Q2 (4-5) | 178 (25.7) | 185 (26.9) | 1.35 (1.02-1.79) | 0.03 | 1.15 (0.84-1.58) | 0.39 | 178 (25.7) | 62 (21.5) | 1.75 (1.15-2.66) | <0.01 | 1.72 (1.03-2.88) | 0.04 |
| Q3 (6-7) | 148 (21.4) | 150 (21.8) | 1.32 (0.98-1.77) | 0.07 | 1.17 (0.83-1.64) | 0.37 | 148 (21.4) | 79 (27.4) | 2.68 (1.78-4.03) | <0.01 | 2.25 (1.34-3.78) | <0.01 |
| Q4 (8-16) | 116 (16.7) | 161 (23.4) | 1.81 (1.33-2.45) | <0.01 | 1.22 (0.83-1.81) | 0.31 | 116 (16.7) | 97 (33.7) | 4.20 (2.80-6.30) | <0.01 | 2.16 (1.23-3.78) | <0.01 |
| MRS Score, Urogenital Symptoms | ||||||||||||
| Q1 (0-2) | 267 (38.5) | 218 (31.6) | reference | reference | 267 (38.5) | 61 (21.2) | reference | reference | ||||
| Q2 (3-4) | 192 (27.7) | 171 (24.8) | 1.09 (0.83-1.43) | 0.53 | 1.01 (0.74-1.38) | 0.95 | 192 (27.7) | 71 (24.7) | 1.62 (1.10-2.39) | 0.02 | 1.66 (1.03-2.69) | 0.04 |
| Q3 (5-6) | 128 (18.5) | 159 (23.1) | 1.52 (1.13-2.04) | <0.01 | 1.41 (1.01-1.98) | 0.05 | 128 (18.5) | 64 (22.2) | 2.19 (1.45-3.30) | <0.01 | 1.79 (1.06-3.01) | 0.03 |
| Q4 (7-12) | 106 (15.3) | 141 (20.5) | 1.63 (1.20-2.22) | <0.01 | 1.49 (1.03-2.15) | 0.03 | 106 (15.3) | 92 (31.9) | 3.80 (2.56-5.63) | <0.01 | 3.01 (1.81-5.00) | <0.01 |
| Abuse in the preceding year | 8 (1.2) | 23 (3.3) | 2.96 (1.31-6.66) | <0.01 | 2.35 (1.02-5.43) | 0.05 | 8 (1.2) | 21 (7.3) | 6.73 (2.95-15.39) | <0.01 | 2.47 (0.99-6.13) | 0.06 |
| Depression (PHQ-9 ≥ 5) | 173 (26.2) | 266 (40.7) | 1.94 (1.54-2.45) | <0.01 | 1.64 (1.22-2.19) | <0.01 | 173 (26.2) | 165 (61.3) | 4.48 (3.31-6.04) | <0.01 | 2.60 (1.74-3.90) | <0.01 |
| Anxiety (GAD-7 ≥ 5) | 144 (22.1) | 215 (32.9) | 1.73 (1.35-2.22) | <0.01 | 1.32 (0.97-1.80) | 0.08 | 144 (22.1) | 144 (53.3) | 4.04 (2.99-5.47) | <0.01 | 2.32 (1.54-3.51) | <0.01 |
Adjusted for age, partner status, education, employment status, hormone therapy, anxiety, depression, and abuse in the preceding year (when applicable)
ACE: adverse childhood experience; PHQ-9: patient health questionnaire; GAD-7: generalized anxiety disorder questionnaire; MRS: menopause rating scale; OR: odds ratio; aOR: adjusted odds ratio; CI: confidence interval
Figure1.
Associations between ACE (ACE ≥ 4 versus ACE=0 and ACE 1-3 versus ACE=0) and A) Menopause rating scale (MRS) total score quartiles, B) MRS psychological symptoms score quartiles, C) MRS somatic symptoms score quartiles, and D) MRS urogenital symptoms score quartiles.
Figure2.
Associations between ACE (ACE ≥ 4 versus ACE=0 and ACE 1-3 versus ACE=0) and A) Menopause rating scale (MRS) total score quartiles, B) MRS psychological symptoms score quartiles, C) MRS somatic symptoms score quartiles, and D) MRS urogenital symptoms score quartiles, adjusted for age, partner status, education, employment status, hormone therapy, anxiety, depression, and abuse in the preceding year.
4. DISCUSSION
This large cross-sectional study conducted in a tertiary care center demonstrated a significant association between the severity of menopausal symptoms and the odds of reporting childhood adversity, across the entire spectrum of self-reported menopausal symptoms, including somatic, psychological, and urogenital symptoms. The strength of the association correlated with the number of childhood adversities, such that a greater childhood adversity burden was associated with a higher menopausal symptom score. These associations persisted despite adjustment for multiple confounders, including age, partner status, education, employment status, anxiety, depression, and hormone therapy use, suggesting that these extensive covariates do not fully explain or mediate the observed difference in childhood adversity burden.
It has been well recognized that childhood abuse and neglect have far reaching consequences beyond the early years of an individual’s life, and childhood adversity is associated with chronic medical conditions, psychiatric disorders, cardiovascular disease and premature mortality [3–11]. However, there is limited evidence linking childhood adversity with menopausal symptoms. There are reports of association of childhood adversity with menopausal VMS [15, 16] but to the best of our knowledge, this is the first report of the association between childhood adversity and overall menopausal symptom burden. The strong associations shown by our study highlight the importance of screening women with bothersome menopausal symptoms for ACEs, and offering appropriate management and counseling for the childhood adversity, when indicated.
A study conducted on a large longitudinal cohort, the Study of Women’s Health Across the Nation (SWAN), showed an association between a history of childhood abuse and self-reported VMS in midlife women [15]. In the MsHeart Study, the authors reported an association between childhood abuse and physiologically measured menopausal VMS [16]. Our results relating to the association between ACEs and VMS are concordant with the results from previous studies, and add to the limited existing literature on this topic. Although VMS are a common symptom experienced by a majority of women during the menopause transition, and can result in significant impairment in mood, sleep and quality of life, they are not the only symptoms related to menopause that are bothersome to women [13]. Other menopausal symptoms, including sleep disturbances, as well as psychological and urogenital symptoms also contribute to significant impairment in quality of life [13]. Thus, the current study extended the previous observations by evaluating the total menopausal symptom burden.
Given that menopause is a universal experience for midlife women, the quality of life, health care utilization, and financial burdens associated with menopausal symptoms can be significant [23]. The study of factors that influence the experience of menopause is important to guide individualized and effective treatment strategies. For example, a woman with severe menopausal symptoms and a prior history of childhood adversity may respond more effectively to conventional treatments for menopausal symptoms if the psychological and emotional consequences of childhood adversity are also appropriately addressed. Moreover, women often underreport childhood adversity [17], and the childhood experiences remain unrecognized unless the information is specifically sought from the patient. Therefore, screening women with severe menopausal symptoms for childhood adversity provides an opportunity to uncover this issue in women who may not otherwise report it. Also, given the under-reporting of ACEs, the true rate of ACEs in our study population may have been even higher, and the association with menopausal symptom burden may, in fact, be even greater than what was found in this study.
Although our multivariable models may have over-adjusted for possible confounding and mediating variables, we chose these models to determine the risk attributable to childhood adversity after adjusting for a host of factors: age, partner status, education, employment status, hormone therapy, anxiety, depression, and abuse in the preceding year. Despite this potential over-adjustment, the multivariable models consistently reflected additional childhood adversity burden with increased menopausal symptom score, suggesting that there is a component of childhood adversity associated with menopausal symptom score not explained by the variables that we included in the model. Further research is needed to elucidate specific causes of this additional burden.
The association between childhood abuse and neglect and psychiatric disorders in general, including depression and anxiety, is well recognized [5, 24]. Therefore, the impact of childhood adversity on the psychological symptoms in midlife women is not entirely surprising. In our cohort, the strongest association between childhood adversity and menopausal symptoms was, in fact, seen in the psychological domain. However, significant associations were also noted in the somatic and urogenital domains, albeit less pronounced. The menopausal symptom score is self-reported, so it is possible that a history of childhood adversity impacts the rate of reporting somatic and urogenital symptoms in midlife women. It is also important to note that the total MRS scores retained significant association with the number of ACEs after adjustment for anxiety and depression, highlighting the influence of factors other than mood disturbances in this association.
There are some potential explanations for the long-lasting impact of childhood adversity that manifests during the menopause transition. Adversity in childhood has been associated with changes in the sympathetic nervous system [25] and in the hypothalamic-pituitary-adrenal (HPA) axis [26]. While the mechanisms underlying VMS are poorly understood, they have also been linked with alterations in the sympathetic nervous system and the HPA axis [27, 28]. Thus, there may be some shared pathways in the pathophysiology of VMS and a history of childhood adversity. Further, victims of childhood adversity may have persistent alterations in serotonergic pathways that control executive function. These alterations may manifest as cognitive complaints during estrogen deprivation that accompanies the menopause transition, thereby revealing the lasting impact of early life adversity on serotonergic circuits [29]. It is conceivable that there are other unknown influences of childhood adversity on the developing brain that become clinically relevant during the menopause transition. It is also possible that childhood adversity alters behaviors in adult women, predisposing them to conditions and lifestyle factors such as obesity and nicotine use which potentially influence the experience of menopausal symptoms [9, 30, 31]. These hypotheses and other potential mechanisms linking childhood adversity with menopausal symptoms require further study.
The current study also highlights the previously described association between childhood adversity and current or recent abuse [32]. Women with greater childhood adversity were more likely to report recent abuse, compared to the women with fewer childhood adversities or those with no childhood adversity. Previous research has also shown an association between menopausal symptoms and recent abuse [33]. The interactions between childhood adversity, current abuse, and menopausal symptoms require further study.
The strengths of the current study include the large sample size, assessment of childhood adversity and total menopausal symptom burden (versus only VMS) with robust, validated instruments, and adjustment for multiple potential confounders known to influence reporting of menopausal symptoms, including education status, depression, anxiety, and HT use. The limitations include potential recall bias associated with use of self-reported information, particularly regarding the events that occurred in the remote past, and the lack of objective measurement of VMS. Additionally, our cohort included mainly white, educated, and employed women, which may limit the generalizability of these results to women of other ethnicities and lower socio-economic status. These more diverse groups of women should be studied to assess the impact of ACEs on the menopause experience in specific patient populations.
5. CONCLUSION
In this large cross-sectional study, there was a significant association between childhood adversity and total menopausal symptom burden in a cohort of mostly white, educated menopausal women. These associations persisted after adjustment for multiple confounders, including depression and anxiety, and the menopausal symptom burden increased monotonically with the increasing number of ACEs. These associations highlight the importance of screening women with bothersome menopausal symptoms for childhood adversity, and of offering appropriate management for the ACEs, when indicated.
Highlights.
Adverse experiences in childhood are associated with chronic illness in adulthood.
The association of childhood adversity and the menopause experience is not well studied.
The study reports an association between childhood adversity and menopause symptoms.
The association persisted even after adjustment for multiple confounders.
Women with severe menopause symptoms should be screened for childhood adversity.
Funding
This research did not receive any specific grant from funding agencies in the public, commercial, or not-for-profit sectors.
ABBREVIATIONS
- ACE
Adverse childhood experience
- BMI
Body Mass Index
- HT
Hormone Therapy
- VMS
Vasomotor Symptoms
- MRS
The Menopause Rating Scale
- PHQ-9
Patient Health Questionnaire
- GAD-7
Generalized Anxiety Disorder questionnaire
Footnotes
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Abstract presented at International Menopause Society Meeting, June 2018
Conflict of interest
The authors declare that they have no conflict of interest.
Ethical approval
The study was approved by the Mayo Clinic Institutional Review Board.
Provenance and peer review
This article was not commissioned and was externally peer reviewed.
Research data (data sharing and collaboration)
There are no linked research data sets for this paper. Additional details can be sought by contacting the corresponding author, Ekta Kapoor, MBBS (kapoor.ekta@mayo.edu). De-identified participant data that underlie the reported results in this article (i.e., text, tables, and figures) can be made available beginning at 9 months and ending at 36 months after article publication for individual participant data meta-analysis, if the proposed use has been approved by an independent review committee. Proposals should be directed Ekta Kapoor, MBBS (kapoor.ekta@mayo.edu). To gain access, data requestors will need to sign a data access agreement.
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