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The Impact of Endometriosis on Quality of Life in Adolescents
Journal of Adolescent Health 63 (2018) 766 772
www.jahonline.org Original article
The Impact of Endometriosis on Quality of Life in Adolescents D1X XJenny Sadler Gallagher, D2X XM.P.H.a,b,*, D3X XAmy D. DiVasta, D4X XM.D., M.M.Sc.a,b,c, D5X XAllison F. Vitonis, D6X XSc.M.a,d, D7X XVishnudas Sarda, D8X XM.B.B.S., M.P.H.a,b, D9X XMarc R. Laufer, D10X XM.D.a,c,d, and D1X XStacey A. Missmer, D12X XSc.D.a,b,e,f a
Boston Center for Endometriosis, Boston Children’s Hospital and Brigham and Women's Hospital, Boston, Massachusetts Division of Adolescent and Young Adult Medicine, Department of Medicine, Boston Children’s Hospital, Boston, Massachusetts c Division of Gynecology, Department of Surgery, Boston Children’s Hospital, Boston, Massachusetts d Department of Obstetrics, Gynecology, and Reproductive Biology, Brigham and Women's Hospital, Boston, Massachusetts e Department of Epidemiology, Harvard T.H. Chan School of Public Health, Boston, Massachusetts f Department of Obstetrics, Gynecology, and Reproductive Biology, College of Human Medicine, Michigan State University, Grand Rapids, Michigan b
Article History: Received February 7, 2018; Accepted June 26, 2018 Keywords: Endometriosis; Adolescent; Young adult; Health-related quality of life; Pelvic pain; WERF EPHect
A B S T R A C T
Purpose: While endometriosis is recognized to have a high patient burden for adults, the level of morbidity it causes for adolescents has been understudied, and may be minimized by clinicians. The purpose of this study was to determine whether endometriosis has a significant impact on quality of life (QOL) for adolescents and young adults. Methods: Five hundred and sixty-seven participants (360 cases and 207 controls) aged <25 years old who are enrolled in the Women’s Health Study: From Adolescence to Adulthood longitudinal study were included in this analysis. Participants were enrolled from medical clinics and the communities surrounding Boston, MA. Participants completed an expanded World Endometriosis Research Foundation Endometriosis Phenome and Biobanking Harmonization Project standard clinical questionnaire that included the Short Form-36 (SF-36), a widely used measure of health-related QOL. We calculated SF-36 physical component summary and mental component summary scores, as well as eight subscale scores. On the SF-36, lower scores reflect greater impairment. Results: Adolescents with endometriosis had significantly lower physical component summary (mean [standard deviation]: 43.4 [11.1] vs. 53.8 [7.6], p < .0001) and mental component summary (43.3 [12.3] vs. 46.3 [10.8], p = .008) scores compared to controls, as well as lower scores on all eight subscales. More cases than controls reported mental health diagnoses, pain medication use, and avoidance of exercise during menstruation. Among cases, earlier age at menarche, more severe pelvic pain, and longer duration of diagnostic delay were associated with poorer QOL. Conclusions: Endometriosis is associated with significantly worse reports of QOL for adolescents and young women with endometriosis compared to unaffected peers. Earlier menarche was associated with poorer physical health-related QOL among cases, whereas severe pelvic pain was associated with both poorer physical and mental health-related QOL among cases. Impairment in QOL is not limited to adults with endometriosis, but affects younger patients as well. © 2018 Society for Adolescent Health and Medicine. All rights reserved.
IMPLICATIONS AND CONTRIBUTION
The effect of endometriosis on quality of life in adolescence has not been well studied. In this populationbased study, young women with endometriosis reported significantly worse healthrelated quality of life than unaffected peers, plus more pain medication usage, mental health disorders, and exercise avoidance.
Conflicts of interest: The authors have no conflicts of interest to disclose. Clinical Trial Registration: NCT00474851, clinicaltrials.gov. * Address correspondence to: Jenny Sadler Gallagher, M.P.H., Division of Adolescent Medicine, Boston Children’s Hospital, 300 Longwood Avenue Mailstop BCH3116, Boston, MA 02115. E-mail address: [email protected] (J.S. Gallagher). 1054-139X/© 2018 Society for Adolescent Health and Medicine. All rights reserved. https://doi.org/10.1016/j.jadohealth.2018.06.027
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Endometriosis is a gynecologic disease that occurs when endometrium-like tissue normally located in the uterus is identified in other areas of the body including the abdominal and pelvic cavities [1]. These ectopic endometrium-like lesions implant on existing tissue where they remain responsive to estrogen. Menstrual cycling causes internal bleeding and the buildup of scar tissue, often accompanied by pelvic pain. An estimated 10% of women of reproductive age have endometriosis [2]. Some are asymptomatic and are diagnosed during the course of an infertility workup or unrelated abdominal surgery. Other women face chronic pain that can be so severe they cannot complete activities of daily living [3]. Endometriosis has various medical and surgical treatments, but no cure [4]. Due to the chronic and often painful nature of the disease, endometriosis is considered to have a high patient burden [5 7]. Cost estimates suggest patients with endometriosis spent about $2,000 per year on treatment and medical visits [6]. Patients are faced with additional costs as a result of work absenteeism and losses in work productivity [5 8]. Endometriosis impacts sexual and intimate relationships, and is also associated with anxiety and depression [7,9,10]. In quality-of-life (QOL) studies, adult women with endometriosis report significant impairment in physical and mental health-related QOL when compared to healthy peers [5,7,9,11]. Among adults with endometriosis, those with severe pelvic pain, more advanced disease stage, and who experienced longer diagnostic delays report greater impairments in QOL [5]. Women who are employed [5] do not have pelvic pain [5], and who have no children [9] report better QOL than other women with endometriosis, but their QOL is still impaired compared to women without endometriosis [5]. Despite increasing awareness that endometriosis may begin during adolescence [5,12], most endometriosis research fails to include this age group [13]. Studies of the effects of endometriosis on QOL in adolescents and young adults (AYA) are limited €vkvist et al. [11] found age-related QOL differences, [7,13,14]. Lo with younger patients faring worse, but this study was limited to patients aged 20 years and older. We previously reported the results of a study of 50 AYA aged 15 22 years old with endometriosis who reported impaired physical health-related, but not mental health-related, QOL [14]. This study offered important insights into the experience of AYA with endometriosis, but was limited to patients whose symptoms were refractive to first-line therapies (generally oral contraceptive pills) and did not include patients whose endometriosis was being successfully managed. The purpose of the current study was to characterize the QOL of AYA with endometriosis as compared to their unaffected peers in a population-based cohort. In addition, we wanted to explore whether presence and degree of pelvic pain, delay from onset of symptoms to diagnosis, and revised American Society for Reproductive Medicine (rASRM) disease stage were associated with QOL in AYA with endometriosis as they are in adults.
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Methods The adolescents and young women in our study are participants in the Women’s Health Study: From Adolescence to Adulthood, a longitudinal cohort that enrolls females aged 7 years from two tertiary care medical centers and from the surrounding community. Participants complete an expanded version of the World Endometriosis Research Foundation Endometriosis Phenome and Biobanking Harmonization Project (WERF EPHect) standard clinical questionnaire [15]. Cases were diagnosed with endometriosis on the basis of visual confirmation during a surgical procedure as is the current gold standard; controls had no history of endometriosis. For these analyses, eligible cases and controls were restricted to AYA aged 10 24 years. The study was approved by the Boston Children’s Hospital Institutional Review Board with ceded approval from the IRB of Brigham and Women’s Hospital. Adult participants provided written consent, whereas assent and parental permission were obtained for those <18 years of age. QOL was measured using the Medical Outcomes Study Short Form-36 (SF-36) [16], a widely used measure of health-related QOL that has been validated among many general and disease-specific populations, including for patients with endometriosis [17]. The SF-36 measures eight health concepts: physical functioning, role limitation—physical, bodily pain, general health, vitality, social functioning, role limitation—emotional, and mental health (Table 1). Scores also contribute to two composite scores: the physical component summary (PCS) and the mental component summary (MCS). For all scales, scores range from 0 to 100, with higher scores representing better QOL. Scores were converted to normative-based scores according to SF-36 recommendations to give all subscales a mean of 50 and a standard deviation of 10 [18]. We looked at pelvic pain severity, disease stage, and length of time between symptom onset and diagnosis to mirror studies in the adult population, as well as age at menarche, age at first symptoms, and current body mass index (BMI). Participants reported their usual severity of menstrual pelvic pain using a four-point scale: (1) no pain, (2) mild cramps (medication seldom needed), (3) moderate cramps (medication usually needed), and (4) severe cramps (medication and bed rest needed). Disease stage was quantified using the WERF EPHect standard surgical form [19] and also abstracted from the operative notes within the medical record. Disease staging was based on the rASRM four-stage system [20] as it is the current accepted standard, although rASRM stage has been shown to correlate poorly to patients’ symptoms and treatment response [21]. Current BMI (kg/m2) category for women aged 20 years was categorized as underweight (BMI < 18.5 kg/m2), normal weight (BMI 18.5 24.9 kg/m2), overweight (BMI 25 29.9 kg/m2), or obese (BMI 30 kg/m2) according to World Health Organization criteria [22]. For those <20 years, the age- and gender-specific BMI Z-score was calculated, and participants were categorized as underweight (Z-score ¡2), normal weight (Z-score >¡2 to <1),
Table 1 Subscales of the Short Form-36 measure of quality of life Physical health component General health Bodily pain Role limitation—physical Physical functioning
Evaluation of personal health Limitations due to pain Problems with work or other daily activities due to physical health Ability to perform physical activities
Mental health Role limitation—emotional Social functioning Vitality
Feelings of anxiety and depression Problems with work or other daily activities due to emotional health Interference with social activities due to physical and emotional problems Level of energy/fatigue
Mental health component
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overweight (Z-score 1 2), or obese (Z-score > 2) [23]. Selfreported height, weight, and age at menarche have all been demonstrated repeatedly to be highly valid [24 26]. Length of diagnostic delay was calculated as the difference in months between self-reported age at first symptoms and age at surgically confirmed diagnosis of endometriosis. Participants were asked to report demographic information, health history including current and historical medication use, and other medical and psychological diagnoses, and lifestyle factors. Data were collected and managed in a web-based REDCap database [27]. All analyses were conducted using SAS (R) software (version 9.3, SAS Institute, Cary, NC). We calculated and compared mean SF-36 scores using multivariable linear regression. Means were adjusted for age (continuous), current BMI (underweight, normal weight, overweight, obese), and cigarette smoking (ever, never). To evaluate the trend in associations for categorized continuous variables such as age at menarche and BMI, each category was assigned a value equal to the median for that category, the variable was modeled continuously, and a two-sided Wald test was calculated to test the linearity of the association. Results Between November 2012 and November 2016, 567 participants (360 cases, 207 controls) aged 10 24 years were enrolled and completed the baseline study questionnaire. Cohort members were predominantly white, non-Hispanic, normal-weight, and never cigarette smokers. Controls were on average older and with
a larger proportion of racial minority participants (Table 2). Most endometriosis cases had ASRM stage I or II endometriosis at the time of their surgical diagnosis (stage I: 81%, stage II: 16%, stage III: <1%, stage IV: 3%). Mean age at first symptoms was 13.4 years (standard deviation [SD] = 2.2). Mean age at surgical diagnosis was 16.3 years (SD = 2.5), representing an average diagnostic delay of 2.8 years from onset of first symptoms. QOL of cases compared to controls Current use of over the counter medications for pain was reported by a greater percentage of AYA with endometriosis than by unaffected AYA (currently taking acetaminophen: 16.4% cases vs. 2.9% controls; currently taking ibuprofen: 27.2% cases vs. 7.7% controls; Table 2). Anxiety disorders requiring medication or therapy were more common in cases than controls (25.6% cases vs. 9.7% controls), as were depression/mood disorders requiring medication or therapy (16.4% cases vs. 9.7% controls). Additionally, more AYA with endometriosis reported avoiding exercise during menstruation due to pain or heavy flow (47.5% cases vs. 20.4% controls). After adjusting for age, current BMI, and cigarette smoking, AYA with endometriosis had lower (i.e., poorer) scores than controls on both the PCS (mean [SD]: cases: 43.7 [11.2] vs. controls: 53.9 [7.8], p < .001; Figure 1) and the MCS (cases: 43.5 [12.2] vs. controls: 46.4 [11.1], p = .01; Figure 2) summary scores. Participants with endometriosis also had lower scores on all eight SF-36 health concept subscales (general health, bodily pain, role limitation—
Table 2 Demographic characteristics among the Women’s Health Study: From Adolescence to Adulthood participants aged <25 years at enrollment
Age, years 10 14 15 19 20 24 Race White Black Asian Other More than one race Hispanic No Yes Current BMI category Underweight Normal weight Overweight Obese Ever smoked cigarettes No Yes Age at menarche, years <11 11 12 13 14 Currently taking acetaminophen Currently taking ibuprofen Anxiety disorder requiring medication or therapy Depression/mood disorder requiring medication or therapy Avoid exercise during menstruation BMI = body mass index (kg/m2).
Surgically confirmed cases, N = 360 n (%)
Controls, N = 207 n (%)
37 (10.3%) 210 (58.3%) 113 (31.4%)
7 (3.4%) 57 (27.5%) 143 (69.1%)
317 (90.3%) 7 (2.0%) 1 (0.3%) 13 (3.7%) 13 (3.7%)
127 (63.2%) 17 (8.5%) 35 (17.4%) 6 (3.0%) 16 (8.0%)
327 (93.4%) 23 (6.6%)
185 (90.2%) 20 (9.8%)
5 (1.4%) 235 (66.4%) 87 (24.6%) 27 (7.6%)
7 (3.4%) 142 (68.6%) 39 (18.8%) 19 (9.2%)
351 (98.0%) 7 (2.0%)
199 (96.1%) 8 (3.9%)
70 (19.4%) 89 (24.7%) 99 (27.5%) 72 (20.0%) 30 (8.3%) 59 (16.4%) 98 (27.2%) 92 (25.6%) 59 (16.4%) 170 (47.5%)
23 (11.3%) 36 (17.7%) 57 (28.1%) 46 (22.7%) 41 (20.2%) 6 (2.9%) 16 (7.7%) 20 (9.7%) 20 (9.7%) 42 (20.4%)
J.S. Gallagher et al. / Journal of Adolescent Health 63 (2018) 766 772
769
Controls (207)
Cases (360)
Physical Component Summary
p<0.001
General Health (GH)
p<0.001
Bodily Pain (BP)
p<0.001
Role Limitaon, Physical (RP)
p<0.001
Physical Funconing (PF)
p<0.001
Figure 1. Short Form-36 physical health subscales and PCS summary scores of females aged 10 24 years old with and without endometriosis.
physical, physical functioning, mental health, social functioning, vitality, all p < .001; role limitation—emotional, p = .001; Figures 1 and 2) compared to control AYA. The bodily pain subscale was the most substantially impaired, with a mean of 39.4 (SD = 11.1) in AYA with endometriosis as compared to 51.9 (8.7) for controls (p < .001).
pain also had worse MCS scores than those with moderate pain (severe pain: 42.6 [12.1] vs. moderate pain: 45.9 [12.2], p = .03), driven by differences in the vitality, social functioning, and mental health subscales). Early menarche (menarche before age 11) was associated with a poorer PCS summary score when compared to a more average age at menarche (<11 years at menarche: 41.6 [11.2] vs. 12 years at menarche: 45.7 [11.2], p = .02; Table 3). This difference was driven by deficits in the physical functioning and the role-physical subscales (Supplementary Table 1). This relationship between early menarche and physical healthrelated QOL was not present in the control group (data not shown). There was no relationship between age at menarche and mental health-related QOL scores.
Factors associated with QOL among cases Among AYA with endometriosis, those with severe pelvic pain had worse PCS scores than those with moderate pain (severe pain: 42.8 [11.1] vs. moderate pain: 45.9 [11.2], p = .02; Table 3), driven by lower scores in the physical functioning, bodily pain, and general health subscales (Supplementary Table 1). Those with severe
Controls (207)
Cases (360)
Mental Component Summary (MCS)
P=0.01
Mental Health (MH)
p<0.001
Role Limitaon, Emoonal (RE)
P=.001
Social Funconing (SF)
p<0.001
Vitality (VT)
p<0.001
0
10
20
30
40
50
60
Figure 2. Short Form-36 mental health subscales and MCS summary scores of females aged 10 24 years old with and without endometriosis.
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Table 3 Associations between Short Form-36 QOL composite scores and demographic factors of females aged 10 24 years old with endometriosis (cases; N = 360) n
PCS
MCS a
Severity of pelvic pain with periods No pain or mild pain Moderate pain Severe pain p-trend Age at menarche, years <11 11 12 13 14 p-trend Current BMI category Underweight Normal weight Overweight Obese p-trend Length of diagnostic delay, years 1 2 3 >3 p-trend Age at first symptoms, years 12 13 14 >14 p-trend
Adjusted mean (SD)
p
Adjusteda mean (SD)
p
24 96 233
44.2 (11.1) 45.9 (11.2) 42.8 (11.1)
.55 .02 Ref. .08
42.2 (12.1) 45.9 (12.2) 42.6 (12.1)
.89 .03 Ref. .27
70 89 98 71 30
41.6 (11.2) 42.6 (11.4) 45.7 (11.2) 44.6 (11.4) 43.1 (11.3)
.02 .06 Ref. .53 .26 .12
44.0 (12.3) 44.2 (12.5) 44.0 (12.3) 42.3 (12.5) 41.1 (12.4)
.97 .93 Ref. .38 .25 .23
5 235 86 27
34.0 (11.3) 44.2 (11.2) 43.6 (11.2) 41.7 (11.3)
.05 Ref. .69 .28 .49
44.0 (12.3) 43.4 (12.2) 42.6 (12.2) 44.0 (12.4)
.93 Ref. .60 .83 .94
109 98 114
43.0 (11.3) 41.6 (11.4) 45.0 (11.4)
.20 .04 Ref. .09
44.0 (12.3) 43.7 (12.4) 42.5 (12.4)
.39 .51 Ref. .36
106 120 95
43.0 (11.7) 44.6 (11.3) 41.9 (11.9)
Ref. .3 .53 .37
43.6 (12.8) 44.0 (12.3) 42.4 (12.9)
Ref. .79 .52 .45
Length of diagnostic delay calculated as time from reported age at first symptoms to age at surgical diagnosis. BMI = body mass index; MCS = mental component summary score; PCS = physical component summary score; QOL = quality of life; Ref = reference group; SD = standard deviation. a Means and p values from linear regression models adjusted for age (continuous), current BMI (underweight, normal weight, overweight, obese), and smoking (never, ever).
Current BMI was not associated with PCS, but was associated with differences in physical health-related subscales. Underweight adolescents with endometriosis had poorer general health subscale scores than their normal weight peers (underweight: 26.0 [12.0] vs. normal weight: 41.1 [11.9], p = .01; Supplementary Table 1), a relationship that was not present in the control group. There were no associations between current BMI and MCS or its subscales. Those with a diagnostic delay of 2 3 years had worse PCS scores than those with a diagnostic delay of >3 years (2 3 year delay: 41.6 [11.4] vs. >3 year delay: 45.0 [11.4], p = .04, Table 3). There was no relationship between MCS and length of diagnostic delay. We did not see any relationship between age at first symptoms and QOL scores (Table 3). We did not evaluate disease stage due to small numbers of participants (<4%) diagnosed as stage III or IV. Discussion Researchers have previously established the presence of impaired QOL in adults with endometriosis [5 11]. For the first time, we provide evidence from a population-based study that AYA with endometriosis also experience deficits in QOL. In this study of nearly 600 AYA, both physical health-related QOL and mental health-related QOL were impaired in AYA with surgically confirmed endometriosis when compared to peers without diagnosed endometriosis. Affected AYA reported poor physical functioning, bodily pain, general health, vitality, social functioning, and mental health, as well as limitations in functioning due to both
physical and emotional health, despite ongoing treatment for endometriosis-associated symptoms. In this study, pain was one of the major sources of QOL impairment for AYA (bodily pain, Figure 1). This finding is not unexpected, as pelvic and abdominal pain is often the major reason that AYA seek medical care that leads to a diagnosis of endometriosis [28], unlike adult women who may be diagnosed with endometriosis during a fertility investigation. The SF-36 queries both pain severity (“How much physical pain have you had during the past 4 weeks?”) and pain interfering with daily activities (“During the past 4 weeks, how much did pain interfere with your normal work?”), both of which impacted QOL in AYA with endometriosis. A strength of the SF-36 is that it is not limited to only capturing reports of cyclic menstrual pain but also includes the impact of acyclic pain that is common in AYA with endometriosis [29,30]. Greater prevalence of over the counter pain medication usage by affected young women provides evidence of somewhat unsuccessful attempts to mitigate this pain. Further, among cases, those with severe pelvic pain reported worse QOL than those with moderate pelvic pain, corresponding with Nnoaham et al.’s findings in the adult population that those with more severe pain report greater QOL impairments [5]. In addition to pain, participants’ QOL was impacted by difficulties completing daily activities (e.g., “vigorous activities such as running, lifting heavy objects, participating in strenuous sports,” “climbing several flights of stairs,” “bathing or dressing yourself”) due to impairment of both physical and emotional health, as well as trouble engaging in social activities (e.g., “normal social activities with family, friends, neighbors, or groups”) due to health
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concerns. Almost half of affected AYA reported skipping exercise during menstruation due to pain and/or heavy flow (Table 2). Therefore, menstruation—a sign of good health for the majority of women—could thus mean an inability to participate in physical education classes and extramural sports teams for adolescents with endometriosis. While menstrual complaints are common in adolescents [28,31], less than one fifth of controls in the study reported avoiding exercise during menstruation, suggesting that those with endometriosis are facing a greater burden. Impairment was not contained only to physical health. There was a higher prevalence of mental health disorders requiring medication and/or therapy among cases (Table 2), and poorer scores on all SF-36 mental health-related scales. For adults, disease impact is discussed in terms of work productivity [5 7] and cost [5,6], and anxiety and depression are seen as a result of impacted sexual relationships [8,10,11] and fertility [8,10,32]. Among AYA, anxiety and depression are also present, but are accompanied by impairment in the ability to attend school, participate in social activities, and exercise. More research is needed to understand the temporality and causal pathways among these factors. Given these deficits in QOL, our second goal was to explore what characteristics were associated with QOL in AYA with endometriosis, to compare results from studies of adults with endometriosis, and ultimately to understand who may be at greatest risk for impaired QOL. As previously discussed, the degree of pelvic pain plays a role, with severe pain associated with worse QOL— similar to findings in studies of adults. A delay of 2 3 years from symptom onset to diagnosis was associated with poorer physical health-related QOL than a delay of >3 years, perhaps because of a more recent initiation of treatment for those with shorter delays, or additional time to develop coping mechanisms in those with longer delays. We did not observe a relationship between mental health-related QOL and diagnostic delay. Determining the reason for their physical symptoms, that is, a valid diagnosis of endometriosis, despite the length of time it may have taken, may have alleviated for these patients the anxiety and worry regarding the cause of their pain. We should also point out the relatively shorter delays those successfully diagnosed in adolescence face than those with onset of symptoms in adolescence who are not diagnosed until adulthood, who face delays averaging 7 years [5]. Age at menarche was also associated with QOL, with participants with menarche before age of 11 years reporting worse physical health-related QOL than those who had a more typical age at menarche. Early menarche has been suggested as a potential risk factor for endometriosis due to increased exposure to menstruation [33], and may also have deleterious effects on QOL in those with endometriosis. There may also be a relationship between underweight BMI and physical health-related QOL (Table 3). When compared with normal weight peers, AYA who were classified as underweight reported significantly worse general health, and the difference in PCS scores approached significance. This relationship was not seen in the control group (data not shown), for whom obesity but not underweight was associated with poorer QOL. Among this small group of cases with low BMI, there were no reports of eating disorder or other causes of low weight that could also impact QOL. Given the small sample size, further study is needed. However, this observation is interesting given the robustly observed inverse relationship between BMI and endometriosis risk [34]. While we feel this study is an important addition to the burgeoning field of adolescent endometriosis research, we acknowledge several limitations. Our control group was recruited through
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online advertising and the gynecologic and primary care clinics from which the cases were enrolled. While controls did not report a prior endometriosis diagnosis, they were not screened for chronic pelvic pain and some are likely to have undiagnosed endometriosis, meaning our estimates may be conservative— driven toward the null due to misclassification of endometriosis cases among the controls. Additionally, these data are cross-sectional; longitudinal studies are needed to understand the temporal relationship between endometriosis and QOL. The relationships between QOL and modifiable factors such as physical activity and diet should also be examined as potential targets for improving QOL. In this study of nearly 600 participants, AYA with endometriosis reported impaired physical and mental health-related QOL. They reported significant pain, as well as trouble participating in daily activities, social events, and physical activity. Among AYA with endometriosis, those with more severe pelvic pain and earlier menarche reported greater impairments. The associations with physical and mental health during adolescence that are evident in this study suggest a critical window for attention and intervention among girls and young women with symptoms suggestive of endometriosis. As the diagnosis of endometriosis in AYA becomes more common, and as adolescence is a time of development and change, the potential effects of the disease on QOL should be recognized and addressed. Longitudinal study should be undertaken to determine if early diagnosis and treatment improve current health and wellness, and increase the likelihood of a positive QOL trajectory into adulthood. Acknowledgments Data collection was facilitated by and conducted in compliance with the World Endometriosis Research Foundation Endometriosis Phenome and Biobanking Harmonization Project (WERF EPHect). The authors thank the WHS: A2A participants and their families, and the Boston Center for Endometriosis Research Assistants. Funding Sources This work was supported by the Boston Center for Endometriosis and the J. Willard and Alice S. Marriott Foundation, who had no role in the conduct or reporting of this research. Supplementary data Supplementary data related to this article can be found at doi:10.1016/j.jadohealth.2018.06.027. References [1] Strauss JF, Barbieri R. Yen and Jaffe’s reproductive endocrinology: Physiology, pathophysiology, and clinical management. 7th ed. Philadelphia: Elsevier Saunders. [2] Missmer SA, Hankinson SE, Spiegelman D, et al. Incidence of laparoscopically confirmed endometriosis by demographic, anthropometrics, and lifestyle factors. Am J Epidemiol 2004;160:784–96. [3] U.S. Department of Health and Human Services. The Third National Health and Nutrition Examination Survey (NHANES III, 1998 1994). Hyattsville, MD: National Center for Health Statistics. [4] ACOG Practice Bulletin. Management of endometriosis. Obstet Gynecol 2010;116:223–36. [5] Nnoaham K, Hummershoj L, Webster P, et al. Impact of endometriosis on quality of life and work productivity: a multicenter study across ten countries. Fertil Steril 2011;96:366–73. [6] Simeons S, Hummelshoj L, D’Hooge T. Endometriosis: Cost estimates and methodological perspectives. Hum Reprod Update 2007;13:395–404.
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[21] Adamson GD. Endometriosis fertility index: Is it better than present staying systems? Curr Opin Obstet Gynecol 2013;25:186–92. [22] World Health Organization. BMI classification. Accessed January 18, 2017. Available at: http://apps.who.int/bmi/index.jsp?introPage=intro_3.html. [23] Barlow SE. Expert committee recommendations regarding the prevention, assessment, and treatment of child and adolescent overweight and obesity: Summary report. Pediatrics 2007;1209(suppl):S164–92. [24] Global BMI Mortality CollaborationDi Angelantonio E, Bhupathiraju SN, et al. Body-mass index and all-cause mortality: Individual-participantdata meta-analysis of 239 prospective studies in four continents. Lancet 2016;388:776–86. [25] Must A, Phillips SM, Naumova EN, et al. Recall of early menstrual history and Menarcheal body size: After 30 years, how well do women remember? Am J Epidemiol 2002;155:672–9. [26] Lundblad MW, Jacobsen BK. The reproducibility of self-reported age at menarche: The Tromsù Study. BMC Womens Health 2017;17:62. [27] Harris PA, Taylor R, Thielke R, et al. Research electronic data capture (REDCap)—a metadata-driven methodology and workflow process for providing translational research informatics support. J Biomed Inform 2009;42:377–81. [28] Youngster M, Laufer MR, DiVasta AD. Endometriosis for the primary care physician. Curr Opin Pediatr 2013;25:454–62. [29] Laufer MR, Sanfilippo J, Rose G. Adolescent endometriosis: diagnosis and treatment approaches. J Pediatr Adolescen Gynecol 2003;16:S3–11. [30] DiVasta AD, Vitonis AF, Laufer MR, Missmer SA. Spectrum of symptoms in women diagnosed with endometriosis during adolescence vs adulthood. Am J Obstet Gynecol 2018;218:324. [31] Suvitie PA, Hallamaa MK, Matomaki JM, et al. Prevalence of pain symptoms suggesting of endometriosis among Finnish Adolescent Girls (TEENMAPS study). J Pediatr Adolesc Gynecol 2016;29:97–103. [32] Jia S, Leng J, Sji J, et al. Health-related quality of life in women with endometriosis: A systematic review. J Ovarian Res 2012;5:29. [33] Nnoaham KE, Webster P, Zondervan KT. Is early age at menarche a risk factor for endometriosis? A systematic review and meta-analysis of case-control studies. Fertil Steril 2012;98:702–12. [34] Shah DK, Correia KF, Vitonis AF, Missmer SA. Body size and endometriosis: Results from 20 years of follow-up within the Nurses’ Health Study II prospective cohort. Hum Reprod 2013;28:1783–92.
www.jahonline.org Original article
The Impact of Endometriosis on Quality of Life in Adolescents D1X XJenny Sadler Gallagher, D2X XM.P.H.a,b,*, D3X XAmy D. DiVasta, D4X XM.D., M.M.Sc.a,b,c, D5X XAllison F. Vitonis, D6X XSc.M.a,d, D7X XVishnudas Sarda, D8X XM.B.B.S., M.P.H.a,b, D9X XMarc R. Laufer, D10X XM.D.a,c,d, and D1X XStacey A. Missmer, D12X XSc.D.a,b,e,f a
Boston Center for Endometriosis, Boston Children’s Hospital and Brigham and Women's Hospital, Boston, Massachusetts Division of Adolescent and Young Adult Medicine, Department of Medicine, Boston Children’s Hospital, Boston, Massachusetts c Division of Gynecology, Department of Surgery, Boston Children’s Hospital, Boston, Massachusetts d Department of Obstetrics, Gynecology, and Reproductive Biology, Brigham and Women's Hospital, Boston, Massachusetts e Department of Epidemiology, Harvard T.H. Chan School of Public Health, Boston, Massachusetts f Department of Obstetrics, Gynecology, and Reproductive Biology, College of Human Medicine, Michigan State University, Grand Rapids, Michigan b
Article History: Received February 7, 2018; Accepted June 26, 2018 Keywords: Endometriosis; Adolescent; Young adult; Health-related quality of life; Pelvic pain; WERF EPHect
A B S T R A C T
Purpose: While endometriosis is recognized to have a high patient burden for adults, the level of morbidity it causes for adolescents has been understudied, and may be minimized by clinicians. The purpose of this study was to determine whether endometriosis has a significant impact on quality of life (QOL) for adolescents and young adults. Methods: Five hundred and sixty-seven participants (360 cases and 207 controls) aged <25 years old who are enrolled in the Women’s Health Study: From Adolescence to Adulthood longitudinal study were included in this analysis. Participants were enrolled from medical clinics and the communities surrounding Boston, MA. Participants completed an expanded World Endometriosis Research Foundation Endometriosis Phenome and Biobanking Harmonization Project standard clinical questionnaire that included the Short Form-36 (SF-36), a widely used measure of health-related QOL. We calculated SF-36 physical component summary and mental component summary scores, as well as eight subscale scores. On the SF-36, lower scores reflect greater impairment. Results: Adolescents with endometriosis had significantly lower physical component summary (mean [standard deviation]: 43.4 [11.1] vs. 53.8 [7.6], p < .0001) and mental component summary (43.3 [12.3] vs. 46.3 [10.8], p = .008) scores compared to controls, as well as lower scores on all eight subscales. More cases than controls reported mental health diagnoses, pain medication use, and avoidance of exercise during menstruation. Among cases, earlier age at menarche, more severe pelvic pain, and longer duration of diagnostic delay were associated with poorer QOL. Conclusions: Endometriosis is associated with significantly worse reports of QOL for adolescents and young women with endometriosis compared to unaffected peers. Earlier menarche was associated with poorer physical health-related QOL among cases, whereas severe pelvic pain was associated with both poorer physical and mental health-related QOL among cases. Impairment in QOL is not limited to adults with endometriosis, but affects younger patients as well. © 2018 Society for Adolescent Health and Medicine. All rights reserved.
IMPLICATIONS AND CONTRIBUTION
The effect of endometriosis on quality of life in adolescence has not been well studied. In this populationbased study, young women with endometriosis reported significantly worse healthrelated quality of life than unaffected peers, plus more pain medication usage, mental health disorders, and exercise avoidance.
Conflicts of interest: The authors have no conflicts of interest to disclose. Clinical Trial Registration: NCT00474851, clinicaltrials.gov. * Address correspondence to: Jenny Sadler Gallagher, M.P.H., Division of Adolescent Medicine, Boston Children’s Hospital, 300 Longwood Avenue Mailstop BCH3116, Boston, MA 02115. E-mail address: [email protected] (J.S. Gallagher). 1054-139X/© 2018 Society for Adolescent Health and Medicine. All rights reserved. https://doi.org/10.1016/j.jadohealth.2018.06.027
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Endometriosis is a gynecologic disease that occurs when endometrium-like tissue normally located in the uterus is identified in other areas of the body including the abdominal and pelvic cavities [1]. These ectopic endometrium-like lesions implant on existing tissue where they remain responsive to estrogen. Menstrual cycling causes internal bleeding and the buildup of scar tissue, often accompanied by pelvic pain. An estimated 10% of women of reproductive age have endometriosis [2]. Some are asymptomatic and are diagnosed during the course of an infertility workup or unrelated abdominal surgery. Other women face chronic pain that can be so severe they cannot complete activities of daily living [3]. Endometriosis has various medical and surgical treatments, but no cure [4]. Due to the chronic and often painful nature of the disease, endometriosis is considered to have a high patient burden [5 7]. Cost estimates suggest patients with endometriosis spent about $2,000 per year on treatment and medical visits [6]. Patients are faced with additional costs as a result of work absenteeism and losses in work productivity [5 8]. Endometriosis impacts sexual and intimate relationships, and is also associated with anxiety and depression [7,9,10]. In quality-of-life (QOL) studies, adult women with endometriosis report significant impairment in physical and mental health-related QOL when compared to healthy peers [5,7,9,11]. Among adults with endometriosis, those with severe pelvic pain, more advanced disease stage, and who experienced longer diagnostic delays report greater impairments in QOL [5]. Women who are employed [5] do not have pelvic pain [5], and who have no children [9] report better QOL than other women with endometriosis, but their QOL is still impaired compared to women without endometriosis [5]. Despite increasing awareness that endometriosis may begin during adolescence [5,12], most endometriosis research fails to include this age group [13]. Studies of the effects of endometriosis on QOL in adolescents and young adults (AYA) are limited €vkvist et al. [11] found age-related QOL differences, [7,13,14]. Lo with younger patients faring worse, but this study was limited to patients aged 20 years and older. We previously reported the results of a study of 50 AYA aged 15 22 years old with endometriosis who reported impaired physical health-related, but not mental health-related, QOL [14]. This study offered important insights into the experience of AYA with endometriosis, but was limited to patients whose symptoms were refractive to first-line therapies (generally oral contraceptive pills) and did not include patients whose endometriosis was being successfully managed. The purpose of the current study was to characterize the QOL of AYA with endometriosis as compared to their unaffected peers in a population-based cohort. In addition, we wanted to explore whether presence and degree of pelvic pain, delay from onset of symptoms to diagnosis, and revised American Society for Reproductive Medicine (rASRM) disease stage were associated with QOL in AYA with endometriosis as they are in adults.
767
Methods The adolescents and young women in our study are participants in the Women’s Health Study: From Adolescence to Adulthood, a longitudinal cohort that enrolls females aged 7 years from two tertiary care medical centers and from the surrounding community. Participants complete an expanded version of the World Endometriosis Research Foundation Endometriosis Phenome and Biobanking Harmonization Project (WERF EPHect) standard clinical questionnaire [15]. Cases were diagnosed with endometriosis on the basis of visual confirmation during a surgical procedure as is the current gold standard; controls had no history of endometriosis. For these analyses, eligible cases and controls were restricted to AYA aged 10 24 years. The study was approved by the Boston Children’s Hospital Institutional Review Board with ceded approval from the IRB of Brigham and Women’s Hospital. Adult participants provided written consent, whereas assent and parental permission were obtained for those <18 years of age. QOL was measured using the Medical Outcomes Study Short Form-36 (SF-36) [16], a widely used measure of health-related QOL that has been validated among many general and disease-specific populations, including for patients with endometriosis [17]. The SF-36 measures eight health concepts: physical functioning, role limitation—physical, bodily pain, general health, vitality, social functioning, role limitation—emotional, and mental health (Table 1). Scores also contribute to two composite scores: the physical component summary (PCS) and the mental component summary (MCS). For all scales, scores range from 0 to 100, with higher scores representing better QOL. Scores were converted to normative-based scores according to SF-36 recommendations to give all subscales a mean of 50 and a standard deviation of 10 [18]. We looked at pelvic pain severity, disease stage, and length of time between symptom onset and diagnosis to mirror studies in the adult population, as well as age at menarche, age at first symptoms, and current body mass index (BMI). Participants reported their usual severity of menstrual pelvic pain using a four-point scale: (1) no pain, (2) mild cramps (medication seldom needed), (3) moderate cramps (medication usually needed), and (4) severe cramps (medication and bed rest needed). Disease stage was quantified using the WERF EPHect standard surgical form [19] and also abstracted from the operative notes within the medical record. Disease staging was based on the rASRM four-stage system [20] as it is the current accepted standard, although rASRM stage has been shown to correlate poorly to patients’ symptoms and treatment response [21]. Current BMI (kg/m2) category for women aged 20 years was categorized as underweight (BMI < 18.5 kg/m2), normal weight (BMI 18.5 24.9 kg/m2), overweight (BMI 25 29.9 kg/m2), or obese (BMI 30 kg/m2) according to World Health Organization criteria [22]. For those <20 years, the age- and gender-specific BMI Z-score was calculated, and participants were categorized as underweight (Z-score ¡2), normal weight (Z-score >¡2 to <1),
Table 1 Subscales of the Short Form-36 measure of quality of life Physical health component General health Bodily pain Role limitation—physical Physical functioning
Evaluation of personal health Limitations due to pain Problems with work or other daily activities due to physical health Ability to perform physical activities
Mental health Role limitation—emotional Social functioning Vitality
Feelings of anxiety and depression Problems with work or other daily activities due to emotional health Interference with social activities due to physical and emotional problems Level of energy/fatigue
Mental health component
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overweight (Z-score 1 2), or obese (Z-score > 2) [23]. Selfreported height, weight, and age at menarche have all been demonstrated repeatedly to be highly valid [24 26]. Length of diagnostic delay was calculated as the difference in months between self-reported age at first symptoms and age at surgically confirmed diagnosis of endometriosis. Participants were asked to report demographic information, health history including current and historical medication use, and other medical and psychological diagnoses, and lifestyle factors. Data were collected and managed in a web-based REDCap database [27]. All analyses were conducted using SAS (R) software (version 9.3, SAS Institute, Cary, NC). We calculated and compared mean SF-36 scores using multivariable linear regression. Means were adjusted for age (continuous), current BMI (underweight, normal weight, overweight, obese), and cigarette smoking (ever, never). To evaluate the trend in associations for categorized continuous variables such as age at menarche and BMI, each category was assigned a value equal to the median for that category, the variable was modeled continuously, and a two-sided Wald test was calculated to test the linearity of the association. Results Between November 2012 and November 2016, 567 participants (360 cases, 207 controls) aged 10 24 years were enrolled and completed the baseline study questionnaire. Cohort members were predominantly white, non-Hispanic, normal-weight, and never cigarette smokers. Controls were on average older and with
a larger proportion of racial minority participants (Table 2). Most endometriosis cases had ASRM stage I or II endometriosis at the time of their surgical diagnosis (stage I: 81%, stage II: 16%, stage III: <1%, stage IV: 3%). Mean age at first symptoms was 13.4 years (standard deviation [SD] = 2.2). Mean age at surgical diagnosis was 16.3 years (SD = 2.5), representing an average diagnostic delay of 2.8 years from onset of first symptoms. QOL of cases compared to controls Current use of over the counter medications for pain was reported by a greater percentage of AYA with endometriosis than by unaffected AYA (currently taking acetaminophen: 16.4% cases vs. 2.9% controls; currently taking ibuprofen: 27.2% cases vs. 7.7% controls; Table 2). Anxiety disorders requiring medication or therapy were more common in cases than controls (25.6% cases vs. 9.7% controls), as were depression/mood disorders requiring medication or therapy (16.4% cases vs. 9.7% controls). Additionally, more AYA with endometriosis reported avoiding exercise during menstruation due to pain or heavy flow (47.5% cases vs. 20.4% controls). After adjusting for age, current BMI, and cigarette smoking, AYA with endometriosis had lower (i.e., poorer) scores than controls on both the PCS (mean [SD]: cases: 43.7 [11.2] vs. controls: 53.9 [7.8], p < .001; Figure 1) and the MCS (cases: 43.5 [12.2] vs. controls: 46.4 [11.1], p = .01; Figure 2) summary scores. Participants with endometriosis also had lower scores on all eight SF-36 health concept subscales (general health, bodily pain, role limitation—
Table 2 Demographic characteristics among the Women’s Health Study: From Adolescence to Adulthood participants aged <25 years at enrollment
Age, years 10 14 15 19 20 24 Race White Black Asian Other More than one race Hispanic No Yes Current BMI category Underweight Normal weight Overweight Obese Ever smoked cigarettes No Yes Age at menarche, years <11 11 12 13 14 Currently taking acetaminophen Currently taking ibuprofen Anxiety disorder requiring medication or therapy Depression/mood disorder requiring medication or therapy Avoid exercise during menstruation BMI = body mass index (kg/m2).
Surgically confirmed cases, N = 360 n (%)
Controls, N = 207 n (%)
37 (10.3%) 210 (58.3%) 113 (31.4%)
7 (3.4%) 57 (27.5%) 143 (69.1%)
317 (90.3%) 7 (2.0%) 1 (0.3%) 13 (3.7%) 13 (3.7%)
127 (63.2%) 17 (8.5%) 35 (17.4%) 6 (3.0%) 16 (8.0%)
327 (93.4%) 23 (6.6%)
185 (90.2%) 20 (9.8%)
5 (1.4%) 235 (66.4%) 87 (24.6%) 27 (7.6%)
7 (3.4%) 142 (68.6%) 39 (18.8%) 19 (9.2%)
351 (98.0%) 7 (2.0%)
199 (96.1%) 8 (3.9%)
70 (19.4%) 89 (24.7%) 99 (27.5%) 72 (20.0%) 30 (8.3%) 59 (16.4%) 98 (27.2%) 92 (25.6%) 59 (16.4%) 170 (47.5%)
23 (11.3%) 36 (17.7%) 57 (28.1%) 46 (22.7%) 41 (20.2%) 6 (2.9%) 16 (7.7%) 20 (9.7%) 20 (9.7%) 42 (20.4%)
J.S. Gallagher et al. / Journal of Adolescent Health 63 (2018) 766 772
769
Controls (207)
Cases (360)
Physical Component Summary
p<0.001
General Health (GH)
p<0.001
Bodily Pain (BP)
p<0.001
Role Limitaon, Physical (RP)
p<0.001
Physical Funconing (PF)
p<0.001
Figure 1. Short Form-36 physical health subscales and PCS summary scores of females aged 10 24 years old with and without endometriosis.
physical, physical functioning, mental health, social functioning, vitality, all p < .001; role limitation—emotional, p = .001; Figures 1 and 2) compared to control AYA. The bodily pain subscale was the most substantially impaired, with a mean of 39.4 (SD = 11.1) in AYA with endometriosis as compared to 51.9 (8.7) for controls (p < .001).
pain also had worse MCS scores than those with moderate pain (severe pain: 42.6 [12.1] vs. moderate pain: 45.9 [12.2], p = .03), driven by differences in the vitality, social functioning, and mental health subscales). Early menarche (menarche before age 11) was associated with a poorer PCS summary score when compared to a more average age at menarche (<11 years at menarche: 41.6 [11.2] vs. 12 years at menarche: 45.7 [11.2], p = .02; Table 3). This difference was driven by deficits in the physical functioning and the role-physical subscales (Supplementary Table 1). This relationship between early menarche and physical healthrelated QOL was not present in the control group (data not shown). There was no relationship between age at menarche and mental health-related QOL scores.
Factors associated with QOL among cases Among AYA with endometriosis, those with severe pelvic pain had worse PCS scores than those with moderate pain (severe pain: 42.8 [11.1] vs. moderate pain: 45.9 [11.2], p = .02; Table 3), driven by lower scores in the physical functioning, bodily pain, and general health subscales (Supplementary Table 1). Those with severe
Controls (207)
Cases (360)
Mental Component Summary (MCS)
P=0.01
Mental Health (MH)
p<0.001
Role Limitaon, Emoonal (RE)
P=.001
Social Funconing (SF)
p<0.001
Vitality (VT)
p<0.001
0
10
20
30
40
50
60
Figure 2. Short Form-36 mental health subscales and MCS summary scores of females aged 10 24 years old with and without endometriosis.
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Table 3 Associations between Short Form-36 QOL composite scores and demographic factors of females aged 10 24 years old with endometriosis (cases; N = 360) n
PCS
MCS a
Severity of pelvic pain with periods No pain or mild pain Moderate pain Severe pain p-trend Age at menarche, years <11 11 12 13 14 p-trend Current BMI category Underweight Normal weight Overweight Obese p-trend Length of diagnostic delay, years 1 2 3 >3 p-trend Age at first symptoms, years 12 13 14 >14 p-trend
Adjusted mean (SD)
p
Adjusteda mean (SD)
p
24 96 233
44.2 (11.1) 45.9 (11.2) 42.8 (11.1)
.55 .02 Ref. .08
42.2 (12.1) 45.9 (12.2) 42.6 (12.1)
.89 .03 Ref. .27
70 89 98 71 30
41.6 (11.2) 42.6 (11.4) 45.7 (11.2) 44.6 (11.4) 43.1 (11.3)
.02 .06 Ref. .53 .26 .12
44.0 (12.3) 44.2 (12.5) 44.0 (12.3) 42.3 (12.5) 41.1 (12.4)
.97 .93 Ref. .38 .25 .23
5 235 86 27
34.0 (11.3) 44.2 (11.2) 43.6 (11.2) 41.7 (11.3)
.05 Ref. .69 .28 .49
44.0 (12.3) 43.4 (12.2) 42.6 (12.2) 44.0 (12.4)
.93 Ref. .60 .83 .94
109 98 114
43.0 (11.3) 41.6 (11.4) 45.0 (11.4)
.20 .04 Ref. .09
44.0 (12.3) 43.7 (12.4) 42.5 (12.4)
.39 .51 Ref. .36
106 120 95
43.0 (11.7) 44.6 (11.3) 41.9 (11.9)
Ref. .3 .53 .37
43.6 (12.8) 44.0 (12.3) 42.4 (12.9)
Ref. .79 .52 .45
Length of diagnostic delay calculated as time from reported age at first symptoms to age at surgical diagnosis. BMI = body mass index; MCS = mental component summary score; PCS = physical component summary score; QOL = quality of life; Ref = reference group; SD = standard deviation. a Means and p values from linear regression models adjusted for age (continuous), current BMI (underweight, normal weight, overweight, obese), and smoking (never, ever).
Current BMI was not associated with PCS, but was associated with differences in physical health-related subscales. Underweight adolescents with endometriosis had poorer general health subscale scores than their normal weight peers (underweight: 26.0 [12.0] vs. normal weight: 41.1 [11.9], p = .01; Supplementary Table 1), a relationship that was not present in the control group. There were no associations between current BMI and MCS or its subscales. Those with a diagnostic delay of 2 3 years had worse PCS scores than those with a diagnostic delay of >3 years (2 3 year delay: 41.6 [11.4] vs. >3 year delay: 45.0 [11.4], p = .04, Table 3). There was no relationship between MCS and length of diagnostic delay. We did not see any relationship between age at first symptoms and QOL scores (Table 3). We did not evaluate disease stage due to small numbers of participants (<4%) diagnosed as stage III or IV. Discussion Researchers have previously established the presence of impaired QOL in adults with endometriosis [5 11]. For the first time, we provide evidence from a population-based study that AYA with endometriosis also experience deficits in QOL. In this study of nearly 600 AYA, both physical health-related QOL and mental health-related QOL were impaired in AYA with surgically confirmed endometriosis when compared to peers without diagnosed endometriosis. Affected AYA reported poor physical functioning, bodily pain, general health, vitality, social functioning, and mental health, as well as limitations in functioning due to both
physical and emotional health, despite ongoing treatment for endometriosis-associated symptoms. In this study, pain was one of the major sources of QOL impairment for AYA (bodily pain, Figure 1). This finding is not unexpected, as pelvic and abdominal pain is often the major reason that AYA seek medical care that leads to a diagnosis of endometriosis [28], unlike adult women who may be diagnosed with endometriosis during a fertility investigation. The SF-36 queries both pain severity (“How much physical pain have you had during the past 4 weeks?”) and pain interfering with daily activities (“During the past 4 weeks, how much did pain interfere with your normal work?”), both of which impacted QOL in AYA with endometriosis. A strength of the SF-36 is that it is not limited to only capturing reports of cyclic menstrual pain but also includes the impact of acyclic pain that is common in AYA with endometriosis [29,30]. Greater prevalence of over the counter pain medication usage by affected young women provides evidence of somewhat unsuccessful attempts to mitigate this pain. Further, among cases, those with severe pelvic pain reported worse QOL than those with moderate pelvic pain, corresponding with Nnoaham et al.’s findings in the adult population that those with more severe pain report greater QOL impairments [5]. In addition to pain, participants’ QOL was impacted by difficulties completing daily activities (e.g., “vigorous activities such as running, lifting heavy objects, participating in strenuous sports,” “climbing several flights of stairs,” “bathing or dressing yourself”) due to impairment of both physical and emotional health, as well as trouble engaging in social activities (e.g., “normal social activities with family, friends, neighbors, or groups”) due to health
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concerns. Almost half of affected AYA reported skipping exercise during menstruation due to pain and/or heavy flow (Table 2). Therefore, menstruation—a sign of good health for the majority of women—could thus mean an inability to participate in physical education classes and extramural sports teams for adolescents with endometriosis. While menstrual complaints are common in adolescents [28,31], less than one fifth of controls in the study reported avoiding exercise during menstruation, suggesting that those with endometriosis are facing a greater burden. Impairment was not contained only to physical health. There was a higher prevalence of mental health disorders requiring medication and/or therapy among cases (Table 2), and poorer scores on all SF-36 mental health-related scales. For adults, disease impact is discussed in terms of work productivity [5 7] and cost [5,6], and anxiety and depression are seen as a result of impacted sexual relationships [8,10,11] and fertility [8,10,32]. Among AYA, anxiety and depression are also present, but are accompanied by impairment in the ability to attend school, participate in social activities, and exercise. More research is needed to understand the temporality and causal pathways among these factors. Given these deficits in QOL, our second goal was to explore what characteristics were associated with QOL in AYA with endometriosis, to compare results from studies of adults with endometriosis, and ultimately to understand who may be at greatest risk for impaired QOL. As previously discussed, the degree of pelvic pain plays a role, with severe pain associated with worse QOL— similar to findings in studies of adults. A delay of 2 3 years from symptom onset to diagnosis was associated with poorer physical health-related QOL than a delay of >3 years, perhaps because of a more recent initiation of treatment for those with shorter delays, or additional time to develop coping mechanisms in those with longer delays. We did not observe a relationship between mental health-related QOL and diagnostic delay. Determining the reason for their physical symptoms, that is, a valid diagnosis of endometriosis, despite the length of time it may have taken, may have alleviated for these patients the anxiety and worry regarding the cause of their pain. We should also point out the relatively shorter delays those successfully diagnosed in adolescence face than those with onset of symptoms in adolescence who are not diagnosed until adulthood, who face delays averaging 7 years [5]. Age at menarche was also associated with QOL, with participants with menarche before age of 11 years reporting worse physical health-related QOL than those who had a more typical age at menarche. Early menarche has been suggested as a potential risk factor for endometriosis due to increased exposure to menstruation [33], and may also have deleterious effects on QOL in those with endometriosis. There may also be a relationship between underweight BMI and physical health-related QOL (Table 3). When compared with normal weight peers, AYA who were classified as underweight reported significantly worse general health, and the difference in PCS scores approached significance. This relationship was not seen in the control group (data not shown), for whom obesity but not underweight was associated with poorer QOL. Among this small group of cases with low BMI, there were no reports of eating disorder or other causes of low weight that could also impact QOL. Given the small sample size, further study is needed. However, this observation is interesting given the robustly observed inverse relationship between BMI and endometriosis risk [34]. While we feel this study is an important addition to the burgeoning field of adolescent endometriosis research, we acknowledge several limitations. Our control group was recruited through
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online advertising and the gynecologic and primary care clinics from which the cases were enrolled. While controls did not report a prior endometriosis diagnosis, they were not screened for chronic pelvic pain and some are likely to have undiagnosed endometriosis, meaning our estimates may be conservative— driven toward the null due to misclassification of endometriosis cases among the controls. Additionally, these data are cross-sectional; longitudinal studies are needed to understand the temporal relationship between endometriosis and QOL. The relationships between QOL and modifiable factors such as physical activity and diet should also be examined as potential targets for improving QOL. In this study of nearly 600 participants, AYA with endometriosis reported impaired physical and mental health-related QOL. They reported significant pain, as well as trouble participating in daily activities, social events, and physical activity. Among AYA with endometriosis, those with more severe pelvic pain and earlier menarche reported greater impairments. The associations with physical and mental health during adolescence that are evident in this study suggest a critical window for attention and intervention among girls and young women with symptoms suggestive of endometriosis. As the diagnosis of endometriosis in AYA becomes more common, and as adolescence is a time of development and change, the potential effects of the disease on QOL should be recognized and addressed. Longitudinal study should be undertaken to determine if early diagnosis and treatment improve current health and wellness, and increase the likelihood of a positive QOL trajectory into adulthood. Acknowledgments Data collection was facilitated by and conducted in compliance with the World Endometriosis Research Foundation Endometriosis Phenome and Biobanking Harmonization Project (WERF EPHect). The authors thank the WHS: A2A participants and their families, and the Boston Center for Endometriosis Research Assistants. Funding Sources This work was supported by the Boston Center for Endometriosis and the J. Willard and Alice S. Marriott Foundation, who had no role in the conduct or reporting of this research. Supplementary data Supplementary data related to this article can be found at doi:10.1016/j.jadohealth.2018.06.027. References [1] Strauss JF, Barbieri R. Yen and Jaffe’s reproductive endocrinology: Physiology, pathophysiology, and clinical management. 7th ed. Philadelphia: Elsevier Saunders. [2] Missmer SA, Hankinson SE, Spiegelman D, et al. Incidence of laparoscopically confirmed endometriosis by demographic, anthropometrics, and lifestyle factors. Am J Epidemiol 2004;160:784–96. [3] U.S. Department of Health and Human Services. The Third National Health and Nutrition Examination Survey (NHANES III, 1998 1994). Hyattsville, MD: National Center for Health Statistics. [4] ACOG Practice Bulletin. Management of endometriosis. Obstet Gynecol 2010;116:223–36. [5] Nnoaham K, Hummershoj L, Webster P, et al. Impact of endometriosis on quality of life and work productivity: a multicenter study across ten countries. Fertil Steril 2011;96:366–73. [6] Simeons S, Hummelshoj L, D’Hooge T. Endometriosis: Cost estimates and methodological perspectives. Hum Reprod Update 2007;13:395–404.
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