Background
Premenstrual disorders (PMDs), encompassing premenstrual syndrome (PMS) and premenstrual dysphoric disorder (PMDD), refer to a wide range of psychological and physical symptoms which cyclically occur 7–10 days before the onset of menstruation [
1]. PMDs are associated with psychiatric comorbidities such as depression and anxiety [
1], substantially impaired quality of life [
2], and negative health outcomes, such as suicidal behavior [
3] and hypertention [
4]. The prevalence is estimated to be 20–40% for PMS and 5–8% for PMDD among women of reproductive age worldwide [
5]. Similar prevalence rates of PMDs have been documented in teenage girls [
6,
7]. Our recent study found that about 70% of women with PMDs reported symptom onset in adolescence [
8], lending support to an early-life origin of PMDs. However, the vast majority of previous studies have focused on risk factors in adulthood, such as dietary factors (e.g., lack of calcium/vitamin D) [
9], obesity [
10], and smoking [
11]. It is therefore of paramount importance to identify other risk factors, which are commonly experienced in childhood and adolescence, for PMDs.
About 56% of American women are exposed to at least one adverse childhood experience (ACE), and 14% report experiencing 4 or more ACEs [
12]. A growing body of evidence suggests that ACEs are associated with numerous negative health outcomes and social behaviors, such as PTSD, depression, and anxiety [
13‐
15]. However, evidence on the association of ACEs and PMDs remains scarce. One case-control study assessed the history of 5 types of ACEs and found a higher prevalence of PMS among those endorsing 2 or more ACEs [
16]. Retrospective data suggest a positive association between childhood abuse, particularly physical and emotional abuse, and PMDs [
17] as well as childhood neglect and premenstrual symptoms [
18]. To our knowledge, no study has addressed the relationship between other types of ACEs or the cumulative number of ACEs and PMDs.
Evidence suggests that neuroendocrine activation in early life may play a role in the development of PMDs after ACEs. For instance, individuals who are exposed to ACEs show dysregulation in the hypothalamic-pituitary-adrenal (HPA) axis in early life, which may lead to higher susceptibility to developing premenstrual symptoms via traumagenic dynamics and emotional dysregulation [
17,
19,
20]. Moreover, posttraumatic stress disorder (PTSD) is a key psychopathology after trauma [
21], which has also been associated with PMDD independently of the number or type of previous traumatic events among trauma survivors [
22]. Additionally, it is well-documented that ACEs are associated with increased risks of depression and anxiety in adulthood [
23] and PMDs are often comorbid with depression and anxiety [
24]. Therefore, an observed association between ACEs and PMDs may be moderated by psychiatric comorbid conditions, although few studies have to date addressed this issue [
17,
18]. Finally, good social support may help mitigate the negative influence of ACEs [
25] and may modify the risk of developing PMDs in adulthood. However, few studies have explored the potential moderation on the association between ACEs and PMDs [
17].
Results
Among 11,973 women (mean age of 35.6 and standard deviation of 9.4 years), 3235 (27%) were classified as probable PMDs, including 2501 PMS (21%) and 734 PMDD (6%). Compared to women without PMDs, women with PMDs were more likely to have suffered childhood deprivation, had lower educational levels or income, and be unemployed and single/widowed at the time of responding. Women with PMDs were younger at menarche, obese, had fewer children, more excessive drinking and smoking, and had probable depression, anxiety, and PTSD (Table
1).
A total of 9211 (77%) women reported at least one ACE. The accumulative number of ACEs was positively associated with PMDs in a graded fashion (fully-adjusted PR 1.12, 95% CI 1.11–1.13; Table
2 and Additional file
1: Fig. S2). The proportion of PMDs increased from 20% among women with no ACEs to 70% among those with ≥4 ACEs (Additional file
1: Fig. S2). Specifically, compared to women with no ACE, women who reported one ACE were about 43% more likely to have PMDs (PR 1.43, 95% CI, 1.27–1.61), while the prevalence was more than two times higher among women with ≥4 ACEs (PR 2.46, 95% CI, 2.21–2.74) (Table
2). A complete-case analysis yielded highly similar results (Additional file
1: Table S2).
Table 2
Associations of accumulative adverse childhood experiences (ACEs) with premenstrual disorders (PMDs)
Total number of ACEs (per ACE) | 11,967 | 3235 (27) | 1.14 (1.13–1.15) | 1.13 (1.11–1.14) | 1.12 (1.11–1.13) |
By number of ACEs |
0 | 2756 | 389 (14) | Ref. | Ref. | Ref. |
1 | 2628 | 551 (21) | 1.49 (1.32–1.67) | 1.45 (1.29–1.64) | 1.43 (1.27–1.61) |
2 | 2003 | 526 (26) | 1.86 (1.65–2.09) | 1.79 (1.60–2.02) | 1.76 (1.56–1.97) |
3 | 1468 | 465 (32) | 2.21 (1.96–2.49) | 2.12 (1.88–2.38) | 2.05 (1.82–2.30) |
≥4 | 3112 | 1304 (42) | 2.73 (2.46–3.04) | 2.56 (2.30–2.85) | 2.46 (2.21–2.74) |
We observed a stronger association for PMDD compared to PMS (PR 1.19 for PMDD vs. 1.10 for PMS;
p for difference <0.001; Table
3). The difference was particularly evident for women who reported ≥4 ACEs (PR 3.44 for PMDD vs. 2.23 for PMS;
p for difference <0.001). In addition, positive associations were consistently found for the total premenstrual symptom
z-score (Additional file
1: Table S3).
Table 3
Associations of adverse childhood experiences (ACEs) with premenstrual syndrome (PMS) and premenstrual dysphoric disorder (PMDD)
Total number of ACEs (per ACE) | 11,967 | 2501 (21) | 1.10 (1.08–1.12) | 734 (6) | 1.19 (1.15–1.22) | <0.001 |
By number of ACEs |
0 | 2756 | 319 (12) | Ref. | 70 (3) | Ref. | – |
1 | 2628 | 453 (17) | 1.45 (1.27–1.66) | 98 (4) | 1.37 (1.01–1.85) | 0.516 |
2 | 2003 | 429 (21) | 1.77 (1.55–2.03) | 97 (5) | 1.71 (1.26–2.32) | 0.706 |
3 | 1468 | 370 (25) | 2.03 (1.77–2.33) | 95 (6) | 2.15 (1.59–2.92) | 0.570 |
≥4 | 3112 | 930 (30) | 2.23 (1.97-2.53) | 374 (12) | 3.44 (2.63–4.50) | <0.001 |
All individual types of ACEs were positively associated with PMDs after adjustment for all covariates (PRs ranged from 1.11 to 1.51; Table
4); the strongest association was observed for emotional neglect. After mutually adjusting for other types of ACEs, the associations attenuated substantially, yet remained significant for sexual abuse, emotional neglect, family violence, mental illness of a household member, and peer and collective violence (PRs ranged from 0.91 to 1.32).
Table 4
Association of an individual type of adverse childhood experiences (ACEs) with premenstrual disorders (PMDs)
Abuse |
Physical |
No | 11,427 | 2992 (26) | Ref. | Ref. |
Yes | 540 | 243 (45) | 1.28 (1.16–1.42) | 0.95 (0.85–1.06) |
Emotional |
No | 10,095 | 2440 (24) | Ref. | Ref. |
Yes | 1872 | 795 (42) | 1.44 (1.34–1.54) | 1.07 (0.99–1.17) |
Sexual |
No | 8725 | 2056 (24) | Ref. | Ref. |
Yes | 3242 | 1179 (36) | 1.37 (1.29–1.46) | 1.23 (1.16–1.31) |
Neglect |
Physical |
No | 11,051 | 2849 (26) | Ref. | Ref. |
Yes | 916 | 386 (42) | 1.22 (1.12–1.34) | 0.96 (0.88–1.06) |
Emotional |
No | 8609 | 1936 (22) | Ref. | Ref. |
Yes | 3358 | 1299 (39) | 1.51 (1.42–1.61) | 1.29 (1.21–1.39) |
Household dysfunction |
Family violence |
No | 9150 | 2154 (24) | Ref. | Ref. |
Yes | 2817 | 1081 (38) | 1.38 (1.29–1.48) | 1.10 (1.02–1.19) |
Parental separation or divorce |
No | 7530 | 1795 (24) | Ref. | Ref. |
Yes | 4437 | 1440 (32) | 1.16 (1.09–1.23) | 1.05 (0.99–1.12) |
Substance abuse |
No | 8172 | 1965 (24) | Ref. | Ref. |
Yes | 3795 | 1270 (33) | 1.20 (1.13–1.28) | 1.01 (0.95–1.08) |
Incarcerated household member |
No | 11,292 | 2971 (26) | Ref. | Ref. |
Yes | 675 | 264 (39) | 1.11 (1.00–1.22) | 0.91 (0.82–1.01) |
Mental illness |
No | 7822 | 1658 (21) | Ref. | Ref. |
Yes | 4145 | 1577 (38) | 1.50 (1.41–1.60) | 1.32 (1.23–1.41) |
Violence |
Community violence |
No | 11,502 | 3027 (26) | Ref. | Ref. |
Yes | 465 | 208 (45) | 1.31 (1.17–1.45) | 1.10 (0.99–1.23) |
Bullying |
No | 9876 | 2370 (24) | Ref. | Ref. |
Yes | 2091 | 865 (41) | 1.39 (1.30–1.49) | 1.26 (1.18–1.35) |
Collective violence |
No | 11,475 | 3017 (26) | Ref. | Ref. |
Yes | 492 | 218 (44) | 1.42 (1.29–1.58) | 1.25 (1.13–1.38) |
To test whether the association between ACEs and PMDs was modified by psychiatric comorbidities, we performed stratification analyses and found greater PRs among individuals without probable PTSD, anxiety, or depression (
p for interaction <0.001; Table
5). Similarly, we performed stratification analysis by social support levels and found greater associations among those with lower social support (
p for interaction <0.001; Table
5). To alleviate the concern of potential recall bias and to explore the potential modifying role of age on the association between ACEs and PMDs, we conducted stratification analysis and found comparable associations across all groups (Additional file
1: Table S4).
Table 5
Associations between accumulative number of adverse childhood experiences (ACEs) and premenstrual disorders (PMDs), stratified by childhood deprivation, psychiatric comorbidities and social support
By PTSD |
No | 8640 | 1558 (18) | 1.12 (1.10–1.14) |
Yes | 3034 | 1647 (54) | 1.03 (1.02–1.05) |
P for interaction | | | <0.001 |
By anxiety |
No | 8951 | 1580 (18) | 1.14 (1.12–1.16) |
Yes | 3018 | 1654 (55) | 1.03 (1.02–1.05) |
P for interaction | | | <0.001 |
By depression |
No | 8130 | 1156 (14) | 1.12 (1.10–1.14) |
Yes | 3837 | 2077 (54) | 1.04 (1.03–1.06) |
P for interaction | | | <0.001 |
By childhood deprivation |
Never or rarely | 10,585 | 2613 (25) | 1.14 (1.13–1.16) |
Sometimes or often | 1373 | 616 (45) | 1.05 (1.03–1.07) |
P for interaction | | | <0.001 |
By social support |
Low | 3351 | 582 (17) | 1.15 (1.12–1.18) |
Medium | 6104 | 1678 (27) | 1.11 (1.09–1.12) |
High | 2441 | 950 (39) | 1.07 (1.06–1.09) |
P for interaction | | | <0.001 |
Discussion
To the best of our knowledge, this is the first study to comprehensively examine the associations between a cumulative range of ACEs and PMDs in a population-based study. We illustrated a positive, linear relationship between the cumulative number of ACEs and probable PMDs. The association was stronger for the more severe subtype, PMDD, than for PMS. Moreover, the associations were also evident in the absence of common psychiatric comorbidities. All types of ACEs were, albeit to a varying extent, positively associated with PMDs.
Since previous studies on the association between ACEs and PMDs have primarily focused on childhood abuse or neglect [
16‐
18], a comprehensive assessment of the role of different types and numbers of ACEs is needed for an improved understanding of the role of early-life trauma in the development of PMDs. A positive association between exposure to two or more ACEs and PMS was reported recently in a Japanese study [
16]. However, the study was based on a clinical sample and the assessment ACEs only included five types. To date, our study is the first to document the associations between 13 common types of ACEs and PMDs in a population-based sample. Although the data on ACEs were collected retrospectively, the consistent findings on the linear and graded relationship between the accumulative number of ACEs and PMDs, as well as the stronger association observed for more severe PMDs (i.e., PMDD vs. PMS) lend support to the role of ACEs in PMDs development later in life.
We found that of all ACEs, emotional neglect was most strongly associated with PMDs, which is in line with previous findings indicating that emotional neglect predicts symptom severity of PMDs [
18]. Depression, irritability, and anxiety symptoms are common complaints among individuals exposed to childhood emotional maltreatment [
18] and are core symptoms of PMDs [
31]. Emotional dysregulation has been reported as an important pathway towards adverse outcomes after childhood adversities [
20]. Girls experiencing emotional neglect during childhood/adolescence may develop emotional dysregulation and impaired interpersonal relationships [
44], which may exacerbate the impact of PMDs. More importantly, our findings add to the knowledge base that household dysfunction and violence experiences during childhood were also positively associated with PMDs. The associations were particularly strong for mental illness of household members, which might, at least partially, be explained by the genetic liability to psychiatric disorders and PMDs [
45,
46]. Our findings on the association between peer-related and collective violence and PMDs highlight the importance of preventing bullying and affirm the devastating effect of collective violence, despite the low prevalence in this specific study population of women.
ACEs are associated with childhood deprivation [
47] and childhood deprivation has repeatedly been associated with adverse physical and mental health outcomes in adult life [
48,
49]. However, previous studies on early life risk factors for PMDs lack information on childhood deprivation [
16‐
18,
50‐
52]. Our findings indicated that the association between ACEs and PMDs was independent of (by adjustment) and particularly evident among those without childhood deprivation. These findings not only confirm the previously reported association between ACEs and PMDs, but also reinforce the role of ACEs as important risk factors for PMDs. Social support may help cultivate resilience among individuals exposed to ACEs and thereby mitigate adverse effects on mental health [
26]. Indeed, our findings indicated a stronger association between the number of ACEs and PMDs among individuals with a lower level of social support. Future studies are needed to explore the impact of varying sources of social support on this association, such as from family, friends, or community.
ACEs are strongly associated with PTSD [
53] and PTSD is associated with subsequent risk of PMDs [
54]. Thus, it is possible that PTSD and other symptoms of psychopathology might account for the observed association through a disrupted biological response to stress or emotional dysregulation [
22,
55]. Our stratification analysis shows that the observed association between ACEs and PMDs is also present among individuals without psychiatric comorbidities, suggesting that the association cannot be entirely explained by psychiatric comorbidities. The dysregulation of HPA axis after ACEs could lead to higher susceptibility to developing premenstrual syndromes [
17,
44]. Larger amygdala volumes after childhood adversities, which is associated with abnormal cortisol response to psychosocial stress, are also noted among women with PMDs [
19]. Nevertheless, future research is needed to understand potential biologic underpinnings.
Our study is nested within a large, nationwide-representative cohort of women with detailed, validated measures of ACEs and PMDs. Yet, there are several limitations to be noted. First, recall bias may be introduced when assessing ACEs. However, we observed similar associations across different age bands, presumably, the bias is smaller in younger participants, relieving some concerns that a particular response style or (systematically) biased recall accounts for our findings [
56]. Moreover, outcome-dependent misclassification might also be introduced in cross-sectional data, assuming there is a general tendency for women with PMDs to report ACEs. Yet, the observed association in the absence of other psychiatric comorbidities argues against the general tendency assumption. Nevertheless, prospective longitudinal studies are needed to confirm the association between ACEs and PMDs. Third, the probable PMDs were not clinically confirmed. However, given the high sensitivity and relatively low specificity of PSST [
29,
30], the misclassification of PMDs would have led to attenuated estimates. The prevalence of PMS and PMDD in our cohort is also comparable to reports from other population-based studies [
57,
58]. Last, we cannot exclude the possibility of unmeasured confounding. Risk factors of ACEs, such as low birth weight and birth defects [
59], could be another class of covariates. However, it is unknown whether these factors impact on PMD risk, to be able to influence the observed associations.
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