Abstract
Objective
To examine the associations between adverse childhood experiences (ACE) and the risk of hysterectomy and bilateral oophorectomy in a national sample of women in England.
Design
Retrospective cohort study.
Setting
A stratified random sample of households across England.
Population
2648 women aged ≥55 years in 2007 from the English Longitudinal Study of Ageing (ELSA) were included in the bilateral oophorectomy analyses and 2622 in the hysterectomy analyses.
Methods
Logistic and multinomial logistic regression analyses of the associations between categories of the ACE summary score (0, 1, 2, ≥3 ACE), eight individual ACE, and hysterectomy and bilateral oophorectomy.
Results
615 women had undergone hysterectomy and 259 women bilateral oophorectomy. We found graded associations between the summary ACE score and risk of hysterectomy and bilateral oophorectomy. In the fully adjusted model, compared with women with no ACE, those with ≥3 ACE had double the odds of hysterectomy (odds ratio [OR] 2.01, 95% confidence interval [CI] 1.30–3.11) and more than double the odds of bilateral oophorectomy (OR 2.61, 95% CI 1.54–4.42). The exclusion of women with cancer history made the associations stronger, especially in women who underwent hysterectomy at age <40 years or bilateral oophorectomy at age ≤44 years. Several individual ACE were positively associated with both outcomes.
Conclusions
ACE are associated with increased risk of hysterectomy and bilateral oophorectomy. Individual‐level covariates did not explain these associations. Our findings highlight the importance of a life course approach to understanding surgical menopause and add to our knowledge of the societal and public health impact of ACE.
Tweetable abstract
Adverse childhood experiences are associated with increased risk of hysterectomy and bilateral oophorectomy in a national sample of women in England.
Keywords: adverse childhood experiences, adversity, ageing, bilateral oophorectomy, cohort, epidemiology, hysterectomy, life course, observational study, retrospective study, socio‐economic position, surgical menopause
Tweetable abstract
Adverse childhood experiences are associated with increased risk of hysterectomy and bilateral oophorectomy in a national sample of women in England.
Linked article: This article is commented on by Walter A. Rocca, pp. 1491–1492 in this issue. To view this minicommentary visit https://doi.org/10.1111/1471-0528.17105.
1. INTRODUCTION
Hysterectomy (the surgical removal of the uterus) is a common procedure in women of reproductive age with around 600 000 hysterectomies performed yearly in the USA. 1 Around 90% of hysterectomies are performed to treat symptoms such as abnormal uterine bleeding and pelvic pain and benign gynaecological problems causing them, such as leiomyomas (hereafter uterine fibroids) and endometriosis. 1 , 2 , 3 It has been estimated that there is an alternative treatment for >60% of these procedures and 30% of them could have been avoided. 1 , 2 Bilateral oophorectomy (the surgical removal of both ovaries) is often performed along with hysterectomy in the absence of ovarian indication. 4 , 5 , 6 , 7 Compared with natural menopause, surgical menopause that is caused by bilateral oophorectomy happens at younger ages and results in an abrupt termination of the ovarian production of sex steroid hormones, with major health implications. 8 , 9 Bilateral oophorectomy at age <45 years is associated with increased risk of cardiovascular disease, 10 , 11 non‐gynaecological cancers such as colorectal 12 , 13 and kidney cancer, 14 osteoporosis, 8 , 15 and multimorbidity, accelerated ageing and worse cognitive outcomes. 16 , 17 Despite evidence suggesting no association, 6 , 18 bilateral oophorectomy at age <45 years has also been found to be associated with increased risk of mortality. 6 , 19 , 20 , 21 Hysterectomy is associated with multiple adverse health outcomes including cardiovascular disease, 22 , 23 , 24 colorectal and thyroid cancer, 13 , 14 mental health problems 25 and frailty. 26
Adverse childhood experiences (ACE), a term that typically describes experiences of abuse, neglect and family disorganisation in childhood, are systematically associated with poorer physical and mental health. 27 , 28 , 29 , 30 ACE and childhood experiences of poor‐quality parenting are associated with early and late onset of menarche, 31 , 32 , 33 adolescent pregnancy, 34 menopause at younger ages, 32 preterm delivery 35 and miscarriage. 36 , 37 Importantly, ACE are associated with uterine fibroids 38 , 39 and endometriosis, 40 which are common causes of hysterectomy. Within a life course perspective, ACE qualify as a causal factor associated with hysterectomy and bilateral oophorectomy, but evidence for these associations is scarce. 5
Based on evidence suggesting an inverse association between ACE and women's health and the health‐jeopardising potential of ACE and subsequent chronic stress, 41 , 42 , 43 , 44 , 45 we studied whether a summary ACE score was associated with increased risk of bilateral oophorectomy and hysterectomy in a national sample of women. The high prevalence of ACE, hysterectomy and surgical menopause in the population, their societal and public health impacts, and the scarcity of evidence on their association warrant our study and add value to it. To better understand the role of age and cancer in the examined associations, we conducted additional age‐stratified analyses after excluding women with cancer history. Finally, to account for ACE heterogeneity, we also examined the associations between individual ACE items and the two outcome measures.
2. METHODS
2.1. Study population
We used data from the English Longitudinal Study of Ageing (ELSA) (www.elsa‐project.ac.uk), a population‐based longitudinal study of older people. The ELSA baseline survey was carried out in 2002–2003 and involved a nationally representative sample of 11 391 individuals (6205 women) aged ≥50 years living in private addresses in England. Follow‐up surveys took place regularly every 2 years. In 2007, after the 2nd follow‐up survey (ELSA wave 3), a one‐off ELSA Life History survey took place. The aim of this survey was to collect retrospective information about the experiences and life circumstances of the participants before joining ELSA, with an emphasis on childhood and young adulthood. ACE, hysterectomy and bilateral oophorectomy were measured during the 2007 ELSA Life History survey.
Of the 4180 women who participated in the ELSA wave 3, 3441 participated in the ELSA Life History survey. The sample of the bilateral oophorectomy analysis included 2648 women aged ≥55 years in 2007 after the exclusion 518 women who did not complete the childhood experiences questionnaire, 28 who were aged ≥90 years, 120 who had their menopause at age <30 or >60 years or had missing/nonvalid menopause information, 44 who underwent bilateral oophorectomy at age <30 or >60 years or had missing/nonvalid oophorectomy information, and 83 with missing values in education and adult total net household wealth. The sample of the hysterectomy analysis included 2622 women, derived using the same exclusion criteria; however, instead of excluding women with missing/nonvalid oophorectomy information, we excluded 70 women with missing/nonvalid hysterectomy information.
ELSA has been approved by the London Multi‐Centre Research Ethics Committee (MREC/01/2/91) and informed consent has been obtained by the participants. Our study was based on secondary analysis of the ELSA data and there was no participant and public involvement.
2.2. Measurement of adverse childhood experiences
We defined ACE as experiences of abuse, household dysfunction and residential social care in childhood. We retrospectively measured the following eight binary ACE variables: (1) lived most of childhood in a single biological mother family, (2) lived most of childhood in social care settings (e.g. in children's home or with foster parents), (3) separation from mother for ≥6 months, (4) victim of serious physical attack/assault at age ≤16 years, (5) victim of sexual assault at age ≤16 years, (6) physically abusive parents, (7) parents with substance abuse or mental health problems and (8) parents argued or fought very often. All ACE measures refer to adversities experienced at age <16 years (unless otherwise stated).
Our study covers most of the childhood adversity domains that the original ACE study examined: abuse (physical and sexual abuse) and household dysfunction (substance abuse and mental health problems in the household, witnessing violence in the household and parental separation/divorce). 46 , 47 We also included a question on having spent most of the childhood in a single mother household, which is a commonly encountered childhood adversity that is related to family life and household function. In addition, we measured experience of residential social care in childhood. This is an important childhood adversity that is included in later versions of ACE measures. 48
To make best use of all available ACE information and avoid the unnecessary exclusion of women with few missing values (the number of missing values in the eight ACE variables ranged from 61 to 3), we treated participants with missing values in the ACE variables as non‐cases, that is, we assumed that they had not experienced the missing ACE. This conservative approach resulted in analyses that were inclusive of more participants and used all ACE information available to us. Additional analyses which excluded the imputed values produced very similar results (data not shown) to those of the main analyses and thus indicated that the imputation of missing values did not bias our findings. The distribution of the eight ACE variables is presented in Tables S2 and S3. We generated a summary ACE score the way the original ACE study did. 46 , 47 We assigned equal weight to all eight ACE items and generated the summary ACE score by adding up all eight items. For the purposes of our analyses, we transformed this score into a categorical variable with the following categories: 0, 1, 2, ≥3 ACE. We also used the eight ACE variables as individual predictors.
2.3. Measurement of hysterectomy and bilateral oophorectomy
Participants were asked whether they ever had an operation to remove their uterus. Women who replied positively, were asked to report the year they had this operation. Based on this information, we generated a binary hysterectomy variable (yes/no). Because premature (at age <40 years) and early (at age 40–44 years) menopause are risk factors for multiple health problems later in life, we also generated a hysterectomy measure that combined information on both hysterectomy status and age with the following categories: no hysterectomy (reference category) and hysterectomy at age: 30–39, 40–44, 45–52 and 53–60 years.
We used the same approach to generate a binary bilateral oophorectomy variable (yes/no) and a status and age at bilateral oophorectomy variable with the following categories: no bilateral oophorectomy (reference category) and bilateral oophorectomy at age: 30–44, 45–52 and 53–60 years.
2.4. Covariates
To account for potential generational differences, we generated a birth cohort variable that divided participants into four birth cohorts (born between 1917 and 1926, 1927 and 1936, 1937 and 1946, and 1947 and 1952). We used this variable instead of continuous age. For a fuller exploration of the role of childhood socio‐economic position (SEP), we measured two markers: number of books in the household at age 10 years and paternal or main carer's occupational class at age 14 years. We also measured age at menarche as a marker of development and exposure to oestrogens. Regarding adult covariates, we measured several that can be on the pathway: adult SEP (education and tertiles of total net household wealth), marital status, smoking history and parity.
2.5. Statistical analyses
We examined the bivariate associations between the summary ACE score and covariates (Table S1). We estimated logistic regression models of the associations between the summary ACE score and the risk of hysterectomy and bilateral oophorectomy in the pooled sample (Tables 1 and 2, respectively). For each association, we computed an odds ratio (OR) and 95% confidence intervals (95% CI). In the absence of data on the indication for undergoing hysterectomy and bilateral oophorectomy and to clarify the role of gynaecological cancer in the examined associations, we performed multinomial logistic regression analyses that excluded women with history of cancer. Because we aimed to examine whether ACE were associated with hysterectomy at younger ages and premature and early surgical menopause, we performed the analyses that excluded women with cancer history were age‐stratified (Tables 3 and 4). In terms of modelling, we first estimated the unadjusted associations, which we adjusted for potential confounders: birth cohort, age at menarche and childhood SEP, and then for adult covariates: adult SEP, parity, marital status and smoking.
TABLE 1.
The association between the summary ACE score and the risk of hysterectomy (n = 2622)
| Risk of hysterectomy: OR (95% CI) | |
|---|---|
| Model A | |
| No ACE (reference category) | 1.00 |
| 1 ACE | 1.59 (1.19–1.95)** |
| 2 ACEs | 1.53 (1.12–2.10)* |
| ≥3 ACEs | 2.15 (1.42–3.27)** |
| p‐value for linear trend | <0.001 |
| Model B | |
| No ACE (reference category) | 1.00 |
| 1 ACE | 1.60 (1.30–1.97)** |
| 2 ACEs | 1.46 (1.06–2.01)* |
| ≥3 ACEs | 2.06 (1.34–3.16)* |
| p‐value for linear trend | <0.001 |
| Model C | |
| No ACE (reference category) | 1.00 |
| 1 ACE | 1.59 (1.29–1.96)** |
| 2 ACEs | 1.47 (1.07–2.03)* |
| ≥3 ACEs | 2.01 (1.30–3.11)* |
| p‐value for linear trend | <0.001 |
Note: Model A is the unadjusted association. Model B is adjusted for generation/age cohort (10‐year age cohort groups), age at menarche (≤10, 11, 12, 13, 14, 15, ≥16 years) and childhood socio‐economic position (paternal or main carer's occupational class at age 14 years and number of books in the household at age 10 years). Model C is in addition adjusted for parity (0, 1, 2, ≥3 biological children), adult socio‐economic position (education and total net household wealth), smoking history (never a smoker, ex‐smoker, current smoker) and marital status (married vs. not married).
*p ≤ 0.05, **p ≤ 0.001.
TABLE 2.
The association between the summary ACE score and the risk of bilateral oophorectomy (n = 2648)
| Risk of bilateral oophorectomy: OR (95% CI) | |
|---|---|
| Model A | |
| No ACE (reference category) | 1.00 |
| 1 ACE | 1.23 (0.91–1.67) |
| 2 ACEs | 1.85 (1.23–2.79)* |
| ≥3 ACEs | 2.90 (1.75–4.79)** |
| p‐value for linear trend | <0.001 |
| Model B | |
| No ACE (reference category) | 1.00 |
| 1 ACE | 1.24 (0.91–1.68) |
| 2 ACEs | 1.75 (1.15–2.65)* |
| ≥3 ACEs | 2.82 (1.68–4.74)** |
| p‐value for linear trend | <0.001 |
| Model C | |
| No ACE (reference category) | 1.00 |
| 1 ACE | 1.21 (0.89–1.65) |
| 2 ACEs | 1.67 (1.10–2.55)* |
| ≥3 ACEs | 2.61 (1.54–4.42)** |
| p‐value for linear trend | <0.001 |
Note: Model A is the unadjusted association. Model B is adjusted for generation/cohort category (10‐year age cohort groups), age at menarche (≤10, 11, 12, 13, 14, 15, ≥16 years) and childhood socio‐economic position (paternal or main carer's occupational class at age 14 years and number of books in the household at age 10 years). Model C is in addition adjusted for parity (0, 1, 2, ≥3 biological children), adult socio‐economic position (education and total net household wealth), smoking history (never a smoker, ex‐smoker, current smoker) and marital status (married vs. not married).
*p ≤ 0.05, **p ≤ 0.001.
TABLE 3.
The association between the summary ACE score and the risk of hysterectomy a by age at hysterectomy in women with no cancer history (n = 2376)
| Risk of hysterectomy at age 30–39 years: OR (95% CI) | Risk of hysterectomy at age 40–44 years: OR (95% CI) | Risk of hysterectomy at age 45–52 years: OR (95% CI) | |
|---|---|---|---|
| Model A | |||
| No ACE (reference category) | 1.00 | 1.00 | 1.00 |
| 1 ACE | 1.64 (1.08–2.50)* | 1.55 (1.08–2.24)* | 1.96 (1.42–2.72)** |
| 2 ACEs | 2.02 (1.13–3.59)* | 1.34 (0.75–2.37) | 1.43 (0.84–2.44) |
| ≥3 ACEs | 3.58 (1.79–7.17)** | 1.84 (0.85–3.97) | 2.68 (1.42–5.05)* |
| p‐value for linear trend | <0.001 | ||
| Model B | |||
| No ACE (reference category) | 1.00 | 1.00 | 1.00 |
| 1 ACE | 1.65 (1.08–2.53)* | 1.55 (1.07–2.24)* | 1.99 (1.43–2.78)** |
| 2 ACEs | 1.87 (1.05–3.37)* | 1.29 (0.72–2.30) | 1.38 (0.81–2.37) |
| ≥3 ACEs | 3.25 (1.53–6.65)** | 1.74 (0.79–3.83) | 2.72 (1.41–5.25)* |
| p‐value for linear trend | <0.001 | ||
| Model C | |||
| No ACE (reference category) | 1.00 | 1.00 | 1.00 |
| 1 ACE | 1.56 (1.02–2.40)* | 1.58 (1.09–2.29)* | 2.00 (1.43–2.78)** |
| 2 ACEs | 1.84 (1.02–3.33)* | 1.35 (0.75–2.43) | 1.41 (0.82–2.43) |
| ≥3 ACEs | 2.97 (1.43–6.15)* | 1.63 (0.73–3.61) | 2.77 (1.43–5.39)* |
| p value for linear trend | <0.001 | ||
Note: Model A is the unadjusted association. Model B is adjusted for generation/age cohort (10‐year age cohort groups), age at menarche (≤10, 11, 12, 13, 14, 15, ≥16 years) and childhood socio‐economic position (paternal or main carer's occupational class at age 14 years and number of books in the household at age 10 years). Model C is in addition adjusted for parity (0, 1, 2, ≥3 biological children), adult socio‐economic position (education and total net household wealth), smoking history (never a smoker, ex‐smoker, current smoker) and marital status (married vs. not married).
For the purposes of clarity, data for women who had hysterectomy at age 53–60 years are not shown.
*p ≤ 0.05, **p ≤ 0.001.
TABLE 4.
The association between the summary ACE score and the risk of bilateral oophorectomy a by age at bilateral oophorectomy in women with no cancer history (n = 2398)
| Risk of bilateral oophorectomy at age 30–44 years: OR (95% CI) | Risk of bilateral oophorectomy at age 45–52 years: OR (95% CI) | |
|---|---|---|
| Model A | ||
| No ACE (reference category) | 1.00 | 1.00 |
| 1 ACE | 1.41 (0.83–2.38) | 1.16 (0.73–1.85) |
| 2 ACEs | 1.92 (0.94–3.91) | 1.56 (0.82–2.97) |
| ≥3 ACEs | 3.89 (1.75–8.63)** | 3.30 (1.62–6.72)** |
| p‐value for linear trend | 0.001 | 0.003 |
| Model B | ||
| No ACE (reference category) | 1.00 | 1.00 |
| 1 ACE | 1.36 (0.80–2.32) | 1.20 (0.75–1.92) |
| 2 ACEs | 1.73 (0.90–3.58) | 1.51 (0.79–2.91) |
| ≥3 ACEs | 3.87 (1.70–8.87)** | 3.31 (1.57–6.95)* |
| p‐value for linear trend | 0.002 | 0.004 |
| Model C | ||
| No ACE (reference category) | 1.00 | 1.00 |
| 1 ACE | 1.32 (0.77–2.27) | 1.17 (0.73–1.88) |
| 2 ACEs | 1.61 (0.77–3.37) | 1.46 (0.76–2.82) |
| ≥3 ACEs | 3.48 (1.49–8.10)* | 3.21 (1.51–6.82)* |
| p‐value for linear trend | 0.006 | 0.007 |
Note: Model A is the unadjusted association. Model B is adjusted for generation/cohort category (10‐year age cohort groups), age at menarche (≤10, 11, 12, 13, 14, 15, ≥16 years) and childhood socio‐economic position (experience of severe financial crisis at age ≤16 years, paternal or main carer's occupational class at age 14 years, number of books in the household at age 10 years). Model C is in addition adjusted for parity (0, 1, 2, ≥3 biological children), adult socio‐economic position (education and total net household wealth), smoking history (never a smoker, ex‐smoker, current smoker) and marital status (married vs. not married).
For the purposes of clarity, data for women who underwent bilateral oophorectomy at age 53–60 years are not shown.
*p ≤ 0.05, **p ≤ 0.001.
To get a fuller picture of the examined associations, we also estimated models of the associations between the eight individual ACE and risk of hysterectomy and bilateral oophorectomy in the pooled sample (Tables S2 and S3). These were adjusted for childhood confounders.
3. RESULTS
Women with multiple ACE were more likely to be younger, of lower childhood SEP and adult wealth, current smokers, either childless or with ≥3 biological children, and reported early (≤10 years) or late menarche (≥16 years) compared with women with no ACE (Table S1).
In the pooled sample analyses, the summary ACE score was associated with increased risk of hysterectomy (Table 1) and bilateral oophorectomy (Table 2) in a graded fashion, with the latter association being stronger. In the fully adjusted model, women with ≥3 ACE had double the risk of hysterectomy (OR 2.01, 95% CI 1.30–3.11) and more than double the risk of bilateral oophorectomy (OR 2.61, 95% CI 1.54–4.42) compared with women with no ACE. The exclusion of women with cancer history made the associations stronger. The association between the summary ACE score and bilateral oophorectomy in women aged 30–44 years who had no cancer history was the strongest observed in our data (OR 3.48, 95% CI 1.49–8.10 for women with ≥3 ACE compared with those with none) (Table 4). The association between the ACE summary score and hysterectomy at age 30–39 in women with no cancer history was also strong (OR 2.97, 95% CI 1.43–6.15 for women with ≥3 ACE compared with those with none) (Table 3).
Regarding specific ACE, separation from mother for ≥6 months, parental mental health and/or substance abuse problems and very frequent parental arguments/fights (all three at age <16 years) were associated with increased risk of hysterectomy and bilateral oophorectomy in the pooled sample after adjustment for childhood confounders (Tables S2 and S3). Having lived most of childhood in a single biological mother household was associated with increased risk of hysterectomy. Physical and sexual abuse were also associated with both outcomes, but these associations did not reach statistical significance (Tables S2 and S3).
4. DISCUSSION
4.1. Main findings
In a national sample of women in England, we found that ACE were associated with increased risk of hysterectomy and bilateral oophorectomy; the greater the number of ACE, the greater the risk of both outcomes. In a similar way, the summary ACE score was associated with the risk of hysterectomy at age 30–39 years and bilateral oophorectomy at age 30–44 years in women with no cancer indication. Finally, we found that some ACE were individually associated with both outcomes.
4.2. Strengths and limitations
Our study is one of the first population‐based longitudinal studies on the associations between ACE and the risk of hysterectomy and bilateral oophorectomy. Unlike previous studies that used smaller regional samples, 5 , 49 we used data from a nationally representative sample, and this makes our findings more generalisable to community‐dwelling women. The use of data from a well‐characterised high‐quality study such as ELSA adds to the validity of our work and, along with the use of a standard set of ACE items, makes our findings more easily replicable and comparable with those of other studies. The adequate measurement of socio‐economic position over the life course allows a better understanding of the role of material deprivation and social disadvantage in the examined associations and is a strength of our study. Finally, the examination of individual ACE items next to the summary ACE score makes our work a fuller account of the association between childhood psychosocial adversity, hysterectomy and bilateral oophorectomy.
The use of retrospective data is a concern, as such data are more susceptible to measurement bias. In addition, to reduce item non‐response bias, we have recoded a few missing ACE values into negative ones. A consequence of both the retrospective measurement and recoding of missing values might be a misclassification of ACE and the inclusion of several false‐negative ACE cases in the analyses. Based on this, we assume that our findings likely underestimate the magnitude of the true associations between ACE and the two outcome measures, and are a conservative account of them. In relation to the retrospective measurement of hysterectomy, our data appear to be valid. We found that 23.5% of our participants had experienced hysterectomy, which is an estimate similar to previous estimates from both the UK and other countries. 50 , 51 Our retrospective childhood SEP measures have been used before and have good predictive validity. The retrospective paternal/main carer's occupation data have been found to be valid and directly comparable to prospective birth cohort data. 52
As with most observational studies, it was impossible to eliminate confounding. Nevertheless, we were able to confirm that potentially confounding factors such as childhood SEP and age at menarche did not explain our findings. Survey non‐response is another potential source of bias. We believe that this bias has not disproportionately affected our findings, as after excluding people who died, became institutionalized or migrated, the overall individual response rate in ELSA wave 3 was 73%, 84.4% of whom participated in the ELSA Life History in 2007. 53 Finally, we need to acknowledge the lack of statistical power in some parts of our analyses, which increased the probability of type II error and non‐significant associations. This is relevant to some of the age‐stratified analyses and analyses involving some of the individual ACE.
4.3. Interpretation of findings
To our knowledge, two studies have previously examined the associations between ACE and bilateral oophorectomy and hysterectomy. 5 , 49 Notwithstanding methodological differences, those studies reported findings similar to ours. A case–control study of 128 women who underwent bilateral oophorectomy with non‐cancer indication at age <46 years and 128 controls found individual ACE as well as a 10‐item summary ACE score to be associated with increased risk of bilateral oophorectomy. 5 This study also found that these associations were stronger in women who had bilateral oophorectomy at age <40 years or without ovarian indication and were not explained after adjustment for education, unhealthy behaviours, obesity, reproductive history markers or marital status. Another US study of 1004 premenopausal military veterans aged ≤52 years focused exclusively on sexual abuse and found it to be associated with an increased risk of hysterectomy. 49 In addition, two other studies reported a positive association between ACE and the risk of uterine fibroids, 38 , 39 a condition that is a common indication for hysterectomy and thus directly relevant to our findings. Similar associations have been reported between ACE and the risk of endometriosis, 40 a condition that is also a common indication for hysterectomy.
There are several reasons for undergoing hysterectomy or oophorectomy. Cancer could be one such reason. Our findings, though, indicate that cancer indication did not explain the associations. The exclusion of women with cancer history from our analyses made the associations stronger, especially in younger ages.
Many women undergo hysterectomy and bilateral oophorectomy because they experience symptoms such as abnormal uterine bleeding and pain that are caused by conditions such as uterine fibroids and endometriosis. These conditions likely are on the causal pathway. We lacked data to test this hypothesis directly, but on the understanding that oestrogens are important to the development of uterine fibroids and endometriosis, 54 , 55 we examined age at menarche as a marker of exposure to oestrogens. We found that age at menarche explained a small part of the associations. The same applies to parity, which only explained a small part of the associations.
In the absence of data to use to examine their role, we can only speculate that ACE‐induced epigenetic alterations and chronic low‐grade inflammation, obesity and unhealthy behaviours likely are on the causal pathway. We were, however, able to examine lifetime history of smoking and found that it only explained a very small part of the associations. Another pathway that we did not examine but is relevant, is that of mental health problems. 56
The decision to undergo hysterectomy with or without bilateral oophorectomy also involves various non‐medical factors, including patient‐, physician‐ and context‐related factors. 9 It is reasonable to assume that patient preferences and ability to understand and play an active role in treatment decisions are possibly on the pathway. Nevertheless, our findings indicate that childhood and adult SEP including education explained a small part of the associations. These findings concur with previous findings. 5 Childhood SEP, despite its association with ACE, appears not to be the key to explain the observed associations. This likely indicates that the effect of ACE on the risk of hysterectomy/bilateral oophorectomy has a strong psychosocial dimension. In a country with universal healthcare access such as the UK, the inability to explain the associations using individual‐level SEP markers does not preclude other contextual and systematic factors including societal, cultural and social organisation factors from partially explaining the associations. For example, previous findings suggest a positive association between perceived racism and the risk of uterine fibroids. 57
5. CONCLUSION
Adverse childhood experiences are strongly associated with increased risk of hysterectomy and bilateral oophorectomy. Future research should try to determine the role of gynaecological conditions such as uterine fibroids and endometriosis in these associations and explore implicated biological pathways. Our working hypothesis is that ACE‐induced chronic stress and resultant hormonal and immune imbalances are related to the observed associations. Evidence on a positive association between stress and uterine fibroids supports this hypothesis. 58 Mental health problems may also be relevant. 56 On the understanding that there is a biological core in the examined associations, it is likely that our findings are relevant to and replicable in younger cohorts irrespective of the projected decline in the rate of hysterectomy. 1 Low SEP did not explain the examined associations in our study. However, given the importance of social disadvantage for health, there is scope for more research on the direct and indirect effects of childhood social disadvantage on the examined associations.
We believe that our findings can inform clinical practice and highlight the need for a trauma‐informed approach. They can also inform and support prevention strategies.
CONFLICT OF INTERESTS
PD reports no conflict of interest. AS holds grants from the National Institute on Aging (NIA/NIH), the National Institute for Health Research (NIHR) and the UK Research and Innovation (UKRI). GDM is the director of the Australian National Health and Medical Research Council (NHMRC) Centre for Research Excellence in women and NCD. She holds grants from the Australian Government Department of Health to conduct the Australian Longitudinal Study on Women's Health and is a senior advisor to the European Society of Menopause and Andropause. Completed disclosure of interest forms are available to view online as supporting information.
AUTHOR CONTRIBUTIONS
PD conceived and designed the study, analysed the data, drafted the manuscript, and approved the final version to be published. AS and GDM made substantial contributions to the analysis and interpretation of the data, revised the article critically for important intellectual content article, and approved the final version to be published.
ETHICS APPROVAL
ELSA has been approved by the London Multi‐Centre Research Ethics Committee (MREC/01/2/91) and informed consent has been obtained by the participants.
Supporting information
Table S1–S3
ACKNOWLEDGEMENTS
The English Longitudinal Study of Ageing (ELSA) has been developed by a team of researchers based at University College London, NatCen Social Research, the Institute for Fiscal Studies, the University of Manchester and the University of East Anglia. The data were collected by NatCen Social Research. The funding is currently provided by the National Institute on Aging in the US, and a consortium of UK government departments coordinated by the National Institute for Health Research. Funding has also been received by the Economic and Social Research Council.
Demakakos P, Steptoe A, Mishra GD. Adverse childhood experiences are associated with increased risk of hysterectomy and bilateral oophorectomy: A national retrospective cohort study of women in England. BJOG: Int J Obstet Gy. 2022;129:1481–1489. 10.1111/1471-0528.17088
Linked article: This article is commented on by Walter A. Rocca, pp. 1491–1492 in this issue. To view this minicommentary visit https://doi.org/10.1111/1471-0528.17105.
DATA AVAILABILITY STATEMENT
The data that support the findings of this study are openly available in the UK Data Service at http://doi.org/10.5255/UKDA‐SN‐5050‐23.
REFERENCES
- 1. Simms KT, Yuill S, Killen J, Smith MA, Kulasingam S, de Kok I, et al. Historical and projected hysterectomy rates in the USA: implications for future observed cervical cancer rates and evaluating prevention interventions. Gynecol Oncol. 2020;158(3):710–8. [DOI] [PMC free article] [PubMed] [Google Scholar]
- 2. Corona LE, Swenson CW, Sheetz KH, Shelby G, Berger MB, Pearlman MD, et al. Use of other treatments before hysterectomy for benign conditions in a statewide hospital collaborative. Am J Obstet Gynecol. 2015;212(3):304.e1–7. [DOI] [PubMed] [Google Scholar]
- 3. Morgan DM, Kamdar NS, Swenson CW, Kobernik EK, Sammarco AG, Nallamothu B. Nationwide trends in the utilization of and payments for hysterectomy in the United States among commercially insured women. Am J Obstet Gynecol. 2018;218(4):425.e1–18. [DOI] [PMC free article] [PubMed] [Google Scholar]
- 4. Evans EC, Matteson KA, Orejuela FJ, Alperin M, Balk EM, El‐Nashar S, et al. Salpingo‐oophorectomy at the time of benign hysterectomy: a systematic review. Obstet Gynecol. 2016;128(3):476–85. [DOI] [PMC free article] [PubMed] [Google Scholar]
- 5. Gazzuola Rocca L, Smith CY, Grossardt BR, Faubion SS, Shuster LT, Stewart EA, et al. Adverse childhood or adult experiences and risk of bilateral oophorectomy: a population‐based case‐control study. BMJ Open. 2017;7(5):e016045. [DOI] [PMC free article] [PubMed] [Google Scholar]
- 6. Adelman MR, Sharp HT. Ovarian conservation vs removal at the time of benign hysterectomy. Am J Obstet Gynecol. 2018;218(3):269–79. [DOI] [PubMed] [Google Scholar]
- 7. Mahal AS, Rhoads KF, Elliott CS, Sokol ER. Inappropriate oophorectomy at time of benign premenopausal hysterectomy. Menopause. 2017;24(8):947–53. [DOI] [PubMed] [Google Scholar]
- 8. Rodriguez M, Shoupe D. Surgical menopause. Endocrinol Metab Clin North Am. 2015;44(3):531–42. [DOI] [PubMed] [Google Scholar]
- 9. Rocca WA, Mielke MM, Gazzuola Rocca L, Stewart EA. Premature or early bilateral oophorectomy: a 2021 update. Climacteric. 2021;24(5):466–73. [DOI] [PMC free article] [PubMed] [Google Scholar]
- 10. Atsma F, Bartelink ML, Grobbee DE, van der Schouw YT. Postmenopausal status and early menopause as independent risk factors for cardiovascular disease: a meta‐analysis. Menopause. 2006;13(2):265–79. [DOI] [PubMed] [Google Scholar]
- 11. Honigberg MC, Zekavat SM, Aragam K, Finneran P, Klarin D, Bhatt DL, et al. Association of premature natural and surgical menopause with incident cardiovascular disease. JAMA. 2019;322(24):2411–21. [DOI] [PMC free article] [PubMed] [Google Scholar]
- 12. Segelman J, Lindstrom L, Frisell J, Lu Y. Population‐based analysis of colorectal cancer risk after oophorectomy. Br J Surg. 2016;103(7):908–15. [DOI] [PubMed] [Google Scholar]
- 13. Luo G, Zhang Y, Wang L, Huang Y, Yu Q, Guo P, et al. Risk of colorectal cancer with hysterectomy and oophorectomy: a systematic review and meta‐analysis. Int J Surg. 2016;34:88–95. [DOI] [PubMed] [Google Scholar]
- 14. Wilson LF, Tuesley KM, Webb PM, Dixon‐Suen SC, Stewart LM, Jordan SJ. Hysterectomy and risk of breast, colorectal, thyroid, and kidney cancer – an Australian Data Linkage Study. Cancer Epidemiol Biomarkers Prev. 2021;30(5):904–11. [DOI] [PubMed] [Google Scholar]
- 15. Choi HG, Jung YJ, Lee SW. Increased risk of osteoporosis with hysterectomy: a longitudinal follow‐up study using a national sample cohort. Am J Obstet Gynecol. 2019;220(6):573.e1–13. [DOI] [PubMed] [Google Scholar]
- 16. Rocca WA, Gazzuola Rocca L, Smith CY, Grossardt BR, Faubion SS, Shuster LT, et al. Bilateral oophorectomy and accelerated aging: cause or effect? J Gerontol A Biol Sci Med Sci. 2017;72(9):1213–7. [DOI] [PMC free article] [PubMed] [Google Scholar]
- 17. Georgakis MK, Beskou‐Kontou T, Theodoridis I, Skalkidou A, Petridou ET. Surgical menopause in association with cognitive function and risk of dementia: a systematic review and meta‐analysis. Psychoneuroendocrinology. 2019;106:9–19. [DOI] [PubMed] [Google Scholar]
- 18. Merritt MA, Riboli E, Murphy N, Kadi M, Tjønneland A, Olsen A, et al. Reproductive factors and risk of mortality in the European Prospective Investigation into Cancer and Nutrition; a cohort study. BMC Med. 2015;13:252. [DOI] [PMC free article] [PubMed] [Google Scholar]
- 19. Tuesley KM, Protani MM, Webb PM, Dixon‐Suen SC, Wilson LF, Stewart LM, et al. Hysterectomy with and without oophorectomy and all‐cause and cause‐specific mortality. Am J Obstet Gynecol. 2020;223(5):723.e1–16. [DOI] [PubMed] [Google Scholar]
- 20. Parker WH, Feskanich D, Broder MS, Chang E, Shoupe D, Farquhar CM, et al. Long‐term mortality associated with oophorectomy compared with ovarian conservation in the nurses' health study. Obstet Gynecol. 2013;121(4):709–16. [DOI] [PMC free article] [PubMed] [Google Scholar]
- 21. Rocca WA, Grossardt BR, de Andrade M, Malkasian GD, Melton LJ 3rd. Survival patterns after oophorectomy in premenopausal women: a population‐based cohort study. Lancet Oncol. 2006;7(10):821–8. [DOI] [PubMed] [Google Scholar]
- 22. Howard BV, Kuller L, Langer R, Manson JE, Allen C, Assaf A, et al. Risk of cardiovascular disease by hysterectomy status, with and without oophorectomy: the Women's Health Initiative Observational Study. Circulation. 2005;111(12):1462–70. [DOI] [PubMed] [Google Scholar]
- 23. Ingelsson E, Lundholm C, Johansson AL, Altman D. Hysterectomy and risk of cardiovascular disease: a population‐based cohort study. Eur Heart J. 2011;32(6):745–50. [DOI] [PubMed] [Google Scholar]
- 24. Laughlin‐Tommaso SK, Khan Z, Weaver AL, Smith CY, Rocca WA, Stewart EA. Cardiovascular and metabolic morbidity after hysterectomy with ovarian conservation: a cohort study. Menopause. 2018;25(5):483–92. [DOI] [PMC free article] [PubMed] [Google Scholar]
- 25. Laughlin‐Tommaso SK, Satish A, Khan Z, Smith CY, Rocca WA, Stewart EA. Long‐term risk of de novo mental health conditions after hysterectomy with ovarian conservation: a cohort study. Menopause. 2020;27(1):33–42. [DOI] [PMC free article] [PubMed] [Google Scholar]
- 26. Verschoor CP, Tamim H. Frailty is inversely related to age at menopause and elevated in women who have had a hysterectomy: an analysis of the Canadian Longitudinal Study on Aging. J Gerontol A Biol Sci Med Sci. 2019;74(5):675–82. [DOI] [PMC free article] [PubMed] [Google Scholar]
- 27. Hughes K, Bellis MA, Hardcastle KA, Sethi D, Butchart A, Mikton C, et al. The effect of multiple adverse childhood experiences on health: a systematic review and meta‐analysis. Lancet Public Health. 2017;2(8):e356–66. [DOI] [PubMed] [Google Scholar]
- 28. Hughes K, Ford K, Bellis MA, Glendinning F, Harrison E, Passmore J. Health and financial costs of adverse childhood experiences in 28 European countries: a systematic review and meta‐analysis. Lancet Public Health. 2021;6(11):e848–57. [DOI] [PMC free article] [PubMed] [Google Scholar]
- 29. Petruccelli K, Davis J, Berman T. Adverse childhood experiences and associated health outcomes: a systematic review and meta‐analysis. Child Abuse Negl. 2019;97:104127. [DOI] [PubMed] [Google Scholar]
- 30. Godoy LC, Frankfurter C, Cooper M, Lay C, Maunder R, Farkouh ME. Association of adverse childhood experiences with cardiovascular disease later in life: a review. JAMA Cardiol. 2021;6(2):228–35. [DOI] [PubMed] [Google Scholar]
- 31. Yermachenko A, Dvornyk V. Nongenetic determinants of age at menarche: a systematic review. Biomed Res Int. 2014;2014:371583. [DOI] [PMC free article] [PubMed] [Google Scholar]
- 32. Demakakos P, Pashayan N, Chrousos G, Linara‐Demakakou E, Mishra GD. Childhood experiences of parenting and age at menarche, age at menopause and duration of reproductive lifespan: evidence from the English Longitudinal Study of Ageing. Maturitas. 2019;122:66–72. [DOI] [PMC free article] [PubMed] [Google Scholar]
- 33. Li L, Denholm R, Power C. Child maltreatment and household dysfunction: associations with pubertal development in a British birth cohort. Int J Epidemiol. 2014;43(4):1163–73. [DOI] [PMC free article] [PubMed] [Google Scholar]
- 34. Madigan S, Wade M, Tarabulsy G, Jenkins JM, Shouldice M. Association between abuse history and adolescent pregnancy: a meta‐analysis. J Adolesc Health. 2014;55(2):151–9. [DOI] [PubMed] [Google Scholar]
- 35. Selk SC, Rich‐Edwards JW, Koenen K, Kubzansky LD. An observational study of type, timing, and severity of childhood maltreatment and preterm birth. J Epidemiol Community Health. 2016;70(6):589–95. [DOI] [PubMed] [Google Scholar]
- 36. Hillis SD, Anda RF, Dube SR, Felitti VJ, Marchbanks PA, Marks JS. The association between adverse childhood experiences and adolescent pregnancy, long‐term psychosocial consequences, and fetal death. Pediatrics. 2004;113(2):320–7. [DOI] [PubMed] [Google Scholar]
- 37. Demakakos P, Linara‐Demakakou E, Mishra GD. Adverse childhood experiences are associated with increased risk of miscarriage in a national population‐based cohort study in England. Hum Reprod. 2020;35(6):1451–60. [DOI] [PMC free article] [PubMed] [Google Scholar]
- 38. Boynton‐Jarrett R, Rich‐Edwards JW, Jun HJ, Hibert EN, Wright RJ. Abuse in childhood and risk of uterine leiomyoma: the role of emotional support in biologic resilience. Epidemiology. 2011;22(1):6–14. [DOI] [PMC free article] [PubMed] [Google Scholar]
- 39. Wise LA, Palmer JR, Rosenberg L. Lifetime abuse victimization and risk of uterine leiomyomata in black women. Am J Obstet Gynecol. 2013;208(4):272.e1–13. [DOI] [PMC free article] [PubMed] [Google Scholar]
- 40. Harris HR, Wieser F, Vitonis AF, Rich‐Edwards J, Boynton‐Jarrett R, Bertone‐Johnson ER, et al. Early life abuse and risk of endometriosis. Hum Reprod. 2018;33(9):1657–68. [DOI] [PMC free article] [PubMed] [Google Scholar]
- 41. Gunnar M, Quevedo K. The neurobiology of stress and development. Annu Rev Psychol. 2007;58:145–73. [DOI] [PubMed] [Google Scholar]
- 42. Lupien SJ, McEwen BS, Gunnar MR, Heim C. Effects of stress throughout the lifespan on the brain, behaviour and cognition. Nat Rev Neurosci. 2009;10(6):434–45. [DOI] [PubMed] [Google Scholar]
- 43. Hunter AL, Minnis H, Wilson P. Altered stress responses in children exposed to early adversity: a systematic review of salivary cortisol studies. Stress. 2011;14(6):614–26. [DOI] [PubMed] [Google Scholar]
- 44. Slopen N, Koenen KC, Kubzansky LD. Childhood adversity and immune and inflammatory biomarkers associated with cardiovascular risk in youth: a systematic review. Brain Behav Immun. 2012;26(2):239–50. [DOI] [PubMed] [Google Scholar]
- 45. Elwenspoek MMC, Kuehn A, Muller CP, Turner JD. The effects of early life adversity on the immune system. Psychoneuroendocrinology. 2017;82:140–54. [DOI] [PubMed] [Google Scholar]
- 46. Felitti VJ, Anda RF, Nordenberg D, Williamson DF, Spitz AM, Edwards V, et al. Relationship of childhood abuse and household dysfunction to many of the leading causes of death in adults. The Adverse Childhood Experiences (ACE) Study. Am J Prev Med. 1998;14(4):245–58. [DOI] [PubMed] [Google Scholar]
- 47. Anda RF, Croft JB, Felitti VJ, Nordenberg D, Giles WH, Williamson DF, et al. Adverse childhood experiences and smoking during adolescence and adulthood. JAMA. 1999;282(17):1652–8. [DOI] [PubMed] [Google Scholar]
- 48. Cronholm PF, Forke CM, Wade R, Bair‐Merritt MH, Davis M, Harkins‐Schwarz M, et al. Adverse childhood experiences: expanding the concept of adversity. Am J Prev Med. 2015;49(3):354–61. [DOI] [PubMed] [Google Scholar]
- 49. Ryan GL, Mengeling MA, Summers KM, Booth BM, Torner JC, Syrop CH, et al. Hysterectomy risk in premenopausal‐aged military veterans: associations with sexual assault and gynecologic symptoms. Am J Obstet Gynecol. 2016;214(3):352.e1–13. [DOI] [PubMed] [Google Scholar]
- 50. Redburn JC, Murphy MF. Hysterectomy prevalence and adjusted cervical and uterine cancer rates in England and Wales. BJOG. 2001;108(4):388–95. [DOI] [PubMed] [Google Scholar]
- 51. Jordan SJ, Nagle CM, Coory MD, Maresco D, Protani MM, Pandeya NA, et al. Has the association between hysterectomy and ovarian cancer changed over time? A systematic review and meta‐analysis. Eur J Cancer. 2013;49(17):3638–47. [DOI] [PubMed] [Google Scholar]
- 52. Jivraj S, Goodman A, Ploubidis GB, de Oliveira C. Testing comparability between retrospective life history data and prospective birth cohort study data. J Gerontol B Psychol Sci Soc Sci. 2020;75(1):207–17. [DOI] [PMC free article] [PubMed] [Google Scholar]
- 53. Scholes S, Medina J, Cheshire H, Cox K, Hacker E, Lessof C. Living in the 21st century older people in England The 2006 English Longitudinal Study of Ageing – Technical Rep. 2009. [cited 2022 Jan 26]. Available from: http://doc.ukdataservice.ac.uk/doc/5050/mrdoc/pdf/5050_Wave_3_Technical_Report.pdf
- 54. Zondervan KT, Becker CM, Koga K, Missmer SA, Taylor RN, Vigano P. Endometriosis. Nat Rev Dis Primers. 2018;4(1):9. [DOI] [PubMed] [Google Scholar]
- 55. Walker CL, Stewart EA. Uterine fibroids: the elephant in the room. Science. 2005;308(5728):1589–92. [DOI] [PubMed] [Google Scholar]
- 56. Gazzuola Rocca L, Smith CY, Bobo WV, Grossardt BR, Stewart EA, Laughlin‐Tommaso SK, et al. Mental health conditions diagnosed before bilateral oophorectomy: a population‐based case‐control study. Menopause. 2019;26(12):1395–404. [DOI] [PMC free article] [PubMed] [Google Scholar]
- 57. Wise LA, Palmer JR, Cozier YC, Hunt MO, Stewart EA, Rosenberg L. Perceived racial discrimination and risk of uterine leiomyomata. Epidemiology. 2007;18(6):747–57. [DOI] [PMC free article] [PubMed] [Google Scholar]
- 58. Qin H, Lin Z, Vasquez E, Xu L. The association between chronic psychological stress and uterine fibroids risk: a meta‐analysis of observational studies. Stress Health. 2019;35(5):585–94. [DOI] [PubMed] [Google Scholar]
Associated Data
This section collects any data citations, data availability statements, or supplementary materials included in this article.
Supplementary Materials
Table S1–S3
Data Availability Statement
The data that support the findings of this study are openly available in the UK Data Service at http://doi.org/10.5255/UKDA‐SN‐5050‐23.
