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Prevalence, Symptomatic Burden, and Diagnosis of Endometriosis in Canada: Cross-Sectional Survey of 30 000 Women
GYNAECOLOGY
Prevalence, Symptomatic Burden, and Diagnosis of Endometriosis in Canada: Cross-Sectional Survey of 30 000 Women Sukhbir Singh, MD;1,2 Ahmed M. Soliman, MS, PhD;3 Yasmine Rahal, MSc;4 Catherine Robert, MBA;4 Isabelle Defoy, PhD;4 Paul Nisbet, PhD;5 Nicholas Leyland, MHCM, MD6 1
Clinical Epidemiology Program, Ottawa Hospital Research Institute, Ottawa, ON
2
Department of Obstetrics and Gynecology, University of Ottawa, Ottawa, ON
3
AbbVie, Inc., North Chicago, IL
4
AbbVie Corporation, Saint-Laurent, QC
5
S. Singh
One Research LLC, Mt. Pleasant, SC
6
McMaster University, Hamilton, ON
Abstract Objective: This study sought to estimate the prevalence of diagnosis of endometriosis (DxE) in Canada and to assess the symptomatic and diagnostic experience of Canadian women with DxE. Method: A cross-sectional, online survey of women in Canada aged 18 to 49 was conducted from December 7, 2018 through January 24, 2019. Survey data were weighted by Canadian population statistics to estimate the prevalence, symptomatic burden, and diagnostic experience of DxE. Logistic regressions were used to assess differences in symptom burden between women with and without DxE. Result: The estimated prevalence of DxE was 7.0% (2004 women of 28 532 women surveyed). Almost half (47.5%) of women with DxE were aged 18 to 29 when they received an endometriosis diagnosis, and 84.1% experienced symptoms before diagnosis. More women with versus without DxE experienced menstrual pelvic pain or cramping (70.3% vs. 50.7%), non-menstrual pelvic pain or cramping (49.5% vs. 18.7%), dyspareunia (52.5% vs. 28.0%), and Key Words: Endometriosis, prevalence, symptoms, diagnosis, clinical practice Corresponding author. Dr. Sukhbir Singh, Clinical Epidemiology Program, Ottawa Hospital Research Institute; Department of Obstetrics and Gynecology, University of Ottawa, Ottawa, ON. [email protected] Competing interests: See Acknowledgements. Each author has indicated that they meet the journal’s requirements for authorship. Data, in part, were presented at the Fourth Annual Conference of the Canadian Society for the Advancement of Gynecologic Excellence (CanSAGE4), September 26−28, 2019, Ottawa, ON [ePoster 119]. Received on August 9, 2019 Accepted on October 29, 2019
infertility (22.3% vs. 6.3%). Women with DxE were more likely to report severe menstrual pelvic pain or cramping (odds ratio [OR] 2.9; 95% confidence interval [CI] 2.5−3.3), non-menstrual pelvic pain or cramping (OR 3.4; 95% CI 2.8−4.2), general abdominal pain (OR 3.0; 95% CI 2.5−3.6), and pelvic pressure (OR 3.0; 95% CI 2.3−3.8). Women with DxE reported an average 5.4-year diagnostic delay, with a 3.1-year delay from onset of symptoms to physician consultation and a 2.3-year delay between physician consultation and diagnosis. Conclusion: Self-reported DxE is prevalent among Canadian women and is associated with a substantial symptomatic burden. The 5.4-year diagnostic delay reported here indicates an important unmet need for more timely diagnosis of endometriosis in Canada.
Résumé tude visait a estimer la pre valence des diagnostics Objectif : Cette e triose au Canada et a e valuer l’expe rience des d’endome triose relativement Canadiennes ayant re¸c u un diagnostic d’endome leurs sympto ^mes et au processus diagnostique. a ^te transversale en ligne a e te mene e du Méthodologie : Une enque cembre 2018 au 24 janvier 2019 aupre s de Canadiennes 7 de es de 18 a 49 ans. Les donne es de l’enque ^ te ont e te ponde re es âge mographiques canadiennes pour au moyen des statistiques de valence, le fardeau des sympto ^mes et l’expe rience du estimer la pre triose. Des re gressions processus diagnostique de l’endome te utilise es pour e valuer les diffe rences par rapport logistiques ont e ^mes entre les femmes qui ont ou non re¸c u au fardeau des sympto triose. un diagnostic d’endome valence estime e du diagnostic d’endome triose e tait Résultats : La pre a l’enque ^te). de 7,0% (2004 des 28 532 femmes ayant participe s de la moitie (47,5%) des femmes ayant re¸c u un diagnostic Pre triose avaient entre 18 et 29 ans au moment du diagnostic d’endome prouve des sympto ^mes avant le diagnostic. Par et 84,1% ont e rapport aux autres femmes, celles ayant re¸c u un diagnostic triose ont e te plus nombreuses a e prouver des crampes d’endome
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ou des douleurs pelviennes menstruelles (70,3% par rapport a e prouver des crampes ou des douleurs pelviennes non 50,7%), a 18,7%), a souffrir de dyspareunie menstruelles (49,5% par rapport a 28,0%) et a e ^tre infertiles (22,3% par rapport a (52,5% par rapport a 6,3%). Toujours par rapport aux autres femmes, celles ayant re¸c u triose e taient plus susceptibles; d’affirmer un diagnostic d’endome prouver des crampes ou douleurs pelviennes menstruelles e importantes (rapport de cotes [RC] 2,9; intervalle de confiance [IC] 95% 2,5–3,3), des crampes ou douleurs pelviennes non a menstruelles (RC 3,4; IC de 95% 2,8–4,2), des douleurs ne rales (RC 3,0; IC de 95% 2,5–3,6) et de la abdominales ge e sur le pelvis (RC 3,0; IC de 95% 2,3–3,8). En pression exerce triose ont moyenne, les femmes ayant re¸c u un diagnostic d’endome un temps moyen de 5,4 ans avant d’obtenir un diagnostic rapporte lai de 3,1 ans de l’apparition des sympto ^mes a la avec un de decin et un de lai de 2,3 ans entre la consultation avec un me consultation et le diagnostic. triose autode clare est pre valent Conclusion : Le diagnostic d’endome a un important fardeau des chez les Canadiennes et est associe ^ mes. Le temps de 5,4 ans avant l’obtention d’un diagnostic sympto ci-dessus indique d’importantes lacunes quant a la rapporte cessite d’ame liorer le de lai d’obtention du diagnostic de ne triose au Canada. l’endome © 2019 The Society of Obstetricians and Gynaecologists of Canada/La Société des obstétriciens et gynécologues du Canada. Published by Elsevier Inc. This is an open access article under the CC BY-NC-ND license. (http://creativecommons.org/licenses/by-nc-nd/4.0/)
J Obstet Gynaecol Can 2019;000(000):1−10 https://doi.org/10.1016/j.jogc.2019.10.038
INTRODUCTION
ndometriosis is a chronic inflammatory disease that predominantly affects women of reproductive age and is characterized by the growth of endometrial-like tissue outside of the uterus.1,2 Women with endometriosis experience a range of symptoms, including pelvic pain and cramping during menstruation, non-menstrual pelvic pain, painful intercourse (dyspareunia), heavy menstrual bleeding, and chronic fatigue.2 Subfertility or infertility is also commonly associated with endometriosis.3 The chronicity and severity of endometriosis-related symptoms considerably affect all aspects of women’s quality of life.4,5
E
Although the prevalence of endometriosis in women of reproductive age is commonly cited as 10%,6 global estimates vary widely, ranging from 2% to 45%7−12 and anywhere from 2% to 77% in women with infertility.7 Historically, prevalence estimates have been based on studies of women who were hospitalized or undergoing surgery and were not necessarily representative of the general female population.7,9 Differences in the populations of women included in studies (e.g., surgical cases), the definition of disease, and the diagnostic method used contribute to the substantial variability among prevalence estimates.7,13
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The overlap between endometriosis-related pelvic-abdominal pain symptoms and other chronic pain conditions contributes to difficulty in diagnosing endometriosis.2,14 Furthermore, clinical examination findings in women with endometriosis may often be normal.2 The traditional gold standard for definitively diagnosing endometriosis is laparoscopic visualization of lesions and histologic confirmation, and only recently has there been a push towards nonsurgical methods of diagnosis in Canada.15 For these and other reasons, many women experience a significant delay from the time of symptom onset to diagnosis. Worldwide, estimates of diagnostic delay range from 4 to 11 years.16−19 This lengthy delay in diagnosis may result in prolonged suffering, reduced productivity, and worse health-related quality of life for women with endometriosis.20 Importantly, there have been no studies on the prevalence of endometriosis in Canada. In fact, Levy et al. sought to evaluate the economic burden of endometriosis in Canada but relied on prevalence estimates from a study of women in the United States.21 Moreover, information about the symptom burden and diagnostic experience of Canadian women with endometriosis is lacking. Therefore, in this study, data were collected from a nationally representative, large-scale, cross-sectional survey of women in Canada with the goals of (1) estimating the prevalence of selfreported diagnosis of endometriosis (DxE) in Canada, (2) comparing the symptom experience with that of women without endometriosis, and (3) evaluating the diagnostic experience (e.g., diagnostic methods, diagnosing physician’s specialty, and time to diagnosis) of women with DxE in Canada. METHODS Study Design and Participants
This comprehensive cross-sectional survey was undertaken to determine the prevalence and symptomatic burden of DxE among the general population of women in Canada and to characterize the diagnostic experience of Canadian women with DxE. Three independent response panels were used as sampling frames for this research to maximize the response rate and ensure adequate representation of the Canadian female population: the Survey Sampling International (SSI) panel (now Dynata, Shelton, CT; http://www.dynata.com), the Leger panel (Toronto, ON; https://leger360.com), and the Lightspeed panel (now Kantar, Vancouver, BC; http://www.lightspeedresearch. com/). Panel members were invited to participate in the survey via an email stating that the latest SSI survey was open and directing those interested to the survey website. Female Canadian residents aged 18 to 49 who completed
Prevalence, Symptomatic Burden, and Diagnosis of Endometriosis in Canada
the study consent form were eligible to participate. Survey responses from 30 000 Canadian women were collected from December 7, 2018 through January 24, 2019. To ensure the survey sample was representative of the national Canadian population of women, survey data were weighted on the basis of the 2016 Canada Census data22 on distributions of age, education, geographic region, and household income by using a random iterative method. The survey contained two sections. The first section, a prevalence screener, included questions on demographics, whether respondents had received a DxE and, if so, the diagnostic method or methods used, and questions regarding symptom experience. DxE was self-reported, and no cross-referencing or verification was possible. For diagnostic methods, respondents were asked to select all methods that applied, and methods were grouped into four broader categories during analysis. Surgical methods included laparoscopy, laparotomy, and other surgical procedures. Empirical methods included patient description of pain, confirmed diagnosis that was based on response to medication, and physician suspects endometriosis but has not confirmed with surgery. Diagnostic methods leading physician to suspect endometriosis (physician-suspected methods) included ultrasound or sonogram, other imaging testing (e.g., magnetic resonance imaging), physical or pelvic examination, patient description of heavy or irregular bleeding, family history, blood test for anemia, hysterectomy, and infertility. The other or unsure category included the responses “other” or “unsure” and patients who declined to answer. Respondents were asked to select symptoms they had ever experienced from an extensive list of endometriosis-related symptoms, to select symptoms currently being experienced (within 4 weeks before the survey), to indicate symptom severity (mild, moderate, or severe), and to describe how bothersome symptoms were (not at all, somewhat, or extremely bothersome). The second part of the survey asked participants about endometriosis-specific information such as diagnostic experience, treatment patterns, health-related quality of life, health-related productivity losses, and health care resource use. This report focuses on prevalence, symptom burden, and diagnostic experience. Data Analyses
Data for each survey question were reported only for respondents who answered the question; participants with missing responses about a symptom were assigned to the “no symptom” category for that specific question or symptom. Continuous variables were summarized by means, and categorical variables were reported as percentages.
Trends in the prevalence of DxE across age groups and geographic regions were assessed. Comparisons were made between the percentages of women with DxE and women without DxE who ever experienced symptoms, those currently experiencing symptoms, those currently experiencing severe symptoms, and the degree to which symptoms bothered women. Logistic regression models controlling for age were used to assess differences in the frequencies of symptoms experienced by women with DxE versus women without DxE. The likelihood (odds ratio [OR]) of experiencing symptoms, along with the corresponding 95% confidence interval (CI), were determined. Logistic models that controlled for age were used to determine the odds of a respondent reporting a severe symptom or an extremely bothersome symptom as a function of whether the respondent had DxE. All data analyses were performed using IBM SPSS Statistics software version 25 (IBM Corp., Armonk, NY). This study was reviewed and approved by the Copernicus Group Institutional Review Board. RESULTS Prevalence
A total of 30 000 women in Canada met the inclusion criteria and completed the survey prevalence screener. Sampling weights were applied to survey data according to Canada population statistics.22 After weighting, a total of 2004 women (7.0%) reported receiving a DxE (Figure A). Demographics of the study population are shown in Table 1. All Canadian provinces and territories were represented by respondents of the survey. Extrapolating these results to the overall population projects that an estimated 516 327 women in Canada aged 18 to 49 have a selfreported DxE. The average age at the time of DxE was 27.9 years, and approximately half (47.5%) of women with DxE were in the 18 to 29 age group when they received a DxE. The majority (84.1%) of women with DxE experienced symptoms before diagnosis. The prevalence of selfreported DxE was highest among women in the 35 to 39 age group (9.6%), followed by the 30 to 34 age group (8.4%) (Figure A). Similar prevalence rates were reported for women in Ontario, the Prairies, the Atlantic, and Quebec, with the highest prevalence in western Canada (Figure B). Symptom Burden
Canadian women with self-reported DxE were more likely to have ever experienced endometriosis-related symptoms than women without DxE, according to ageadjusted ORs (Table 2). Women with DxE had the
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Figure. Total population prevalence of endometriosis by age group and geographic region. (A) Total population prevalence of endometriosis: overall and by age group. (B) Total population prevalence of endometriosis by Canada geographic region.
BC: British Columbia; NB: New Brunswick; NL: Newfoundland and Labrador; NS: Nova Scotia; PEI: Prince Edward Island.
highest odds of experiencing non-menstrual pelvic pain or cramping (OR 4.4; 95% CI 4.0−4.9), infertility (OR 4.1; 95% CI 3.6−4.6), pelvic pressure (OR 3.9; 95% CI 3.5−4.3), and dyspareunia (OR 3.0; 95% CI 2.7−3.3) compared with women without DxE. A greater percentage of women with DxE were experiencing “typical” endometriosis symptoms in the 4 weeks before the survey than women without DxE: menstrual pelvic pain or cramping (54.0% vs. 39.3%), non-menstrual pelvic pain or cramping (39.4% vs. 14.2%), and dyspareunia (38.3% vs. 17.7%) (Table 3). Although all endometriosis-related symptoms were reported with greater prevalence by women with DxE than by those without DxE, the age-adjusted OR was highest for infertility
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(OR 4.4; 95% CI 3.8−5.1), non-menstrual pelvic pain or cramping (OR 4.2; 95% CI 3.8−4.6), and pelvic pressure (OR 4.1; 95% CI 3.7−4.6). In addition to a higher prevalence of endometriosis symptoms, women with DxE were also more likely to experience severe symptoms than women without DxE. For example, 37.3% of women with DxE versus 17.6% of women without DxE were experiencing severe menstrual pelvic pain or cramping (OR 2.9; 95% CI 2.5−3.3) in the 4 weeks before the survey. Other severe symptoms with high age-adjusted ORs included non-menstrual pelvic pain or cramping (OR 3.4; 95% CI 2.8−4.2), general abdominal pain (OR 3.0; 95% CI 2.5−3.6), and pelvic pressure (OR
Prevalence, Symptomatic Burden, and Diagnosis of Endometriosis in Canada
Table 1. Demographics of study population Women with DxE (n = 2004)
Women without DxE (n = 26 528)
35.5 § 8.1
33.6 § 9.2
18−29
25.6
37.2
30−34
19.5
16.0
35−39
21.4
15.3
40−44
16.0
15.5
45−49
17.6
16.1
27.9 § 8.1
—
<18
8.4
—
18−29
47.5
—
30−34
25.9
—
35−39
11.8
—
40−44
5.3
—
45−49
1.0
—
White
88.8
78.0
Black
1.0
3.1
Hispanic
1.0
1.1
Other
8.4
16.3
Before diagnosis
84.1
—
At time of diagnosis
3.7
—
After diagnosis
6.0
—
Unsure
6.2
—
29.4
3.7
Ontario
37.5
39.1
bec Que
18.6
24.0
British Columbia
16.7
12.7
Alberta
15.3
10.4
Parameter Average age, years, mean § SD Age group, years, %
Average age at diagnosis, years, mean § SD Age group at diagnosis, years, %
Ethnicity, %
When patients began experiencing symptoms, %
Had hysterectomy, %
3.0; 95% CI 2.3−3.8). A substantial percentage of women with DxE indicated that endometriosis-related symptoms were extremely bothersome, compared with women without DxE (Table 4). Women with DxE were most likely to report extremely bothersome menstrual pelvic pain or cramping (OR 2.3; 95% CI 2.0−2.6), non-menstrual pelvic pain or cramping (OR 2.6; 95% CI 2.2−3.1), general abdominal pain (OR 2.6; 95% CI 2.2−3.0), and pelvic pressure (OR 2.3; 95% CI 1.8−2.9). Diagnostic Experience
Among 1686 women with DxE who reported experiencing symptoms before DxE, the mean overall delay from symptom onset to diagnosis was 5.4 years. The mean patient-related delay (time from symptom onset to the first consultation with a physician) was 3.1 years, and the mean physician-related delay (time from the first consultation with a physician to receiving a diagnosis) was 2.3 years. More than half (53.0%) of women with DxE were diagnosed by an obstetriciangynaecologist. Approximately 19.0% of women with DxE reported receiving a diagnosis from a primary care physician, 17.0% from a general surgeon, 7.3% from an infertility specialist, 1.1% from a urologist, and 2.5% from an “other” specialist. On average, women with DxE reported consulting three physicians about endometriosis. As part of the survey, women with DxE indicated the method or methods used to confirm the DxE, with the option to select multiple methods. Surgical diagnostic methods were reported by 30.8% of women, whereas empirical and physician-suspected diagnostic methods were reported by 32.7% and 56.4% of women, respectively. Approximately 2% of women with DxE selected response options in the “other or unsure” category.
Canadian province, %
Manitoba
3.3
3.5
Nova Scotia
3.2
2.8
Saskatchewan
2.5
3.0
Newfoundland and Labrador
1.4
1.5
New Brunswick
1.1
2.4
Prince Edward Island
0.3
0.4
Northwest Territories
0
0.1
Nunavut
0
0.1
Yukon
0
0.1
DxE: diagnosis of endometriosis.
DISCUSSION
The current study is the first to estimate the prevalence of self-reported DxE among women in Canada on the basis of a large survey and to characterize the symptomatic burden and diagnostic experience of Canadian women with DxE. The prevalence of DxE among Canadian women was 7.0% in this survey, which is greater than that reported by a small, population-based study of Canadian women aged 15 to 49 (5.2%)12 and similar to prevalence estimates of DxE among women in the United States (6.1%−6.6%).10,12 In this survey, at least 65% of Canadian women with DxE reported ever experiencing menstrual pelvic pain or cramping; fatigue, weariness, or anemia; heavy menstrual
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Table 2. Endometriosis symptoms ever experienced Symptom
Women with DxE (n = 2 004), %
Women without DxE (n = 26 528), %
Odds ratio (95% CI)
Menstrual pelvic pain or cramping
70.3
50.7
2.4 (2.1−2.6)
Non-menstrual pelvic pain or cramping
49.5
18.7
4.4 (4.0−4.9)
Dyspareunia
52.5
28.0
3.0 (2.7−3.3)
Fatigue, weariness, or anemia
67.4
56.3
1.6 (1.5−1.8)
Heavy menstrual bleeding
68.7
47.1
2.5 (2.2−2.7)
Excessive or irregular bleeding (e.g., spotting between periods)
47.6
25.7
2.7 (2.4−2.9)
Passage of clots
43.5
23.5
2.4 (2.2−2.6)
Irregular periods (timing and/or duration)
61.4
47.6
1.8 (1.7−2.0)
Pelvic pressure
32.7
11.3
3.9 (3.5−4.3)
Lower back pain
66.5
63.4
1.1 (1.0−1.3)
General abdominal pain
52.2
33.7
2.2 (2.0−2.5)
Constipation, bloating, or diarrhea
66.5
62.6
1.2 (1.1−1.3)
Difficulty having bowel movement
47.6
36.1
1.6 (1.5−1.8)
Frequent urination or urinary urgency
40.5
27.1
1.8 (1.7−2.0)
Infertility
22.3
6.3
4.1 (3.6−4.6)
Depressed feelings or mood swings
64.2
62.8
1.1 (1.0−1.2)
Dizziness during period
44.6
26.3
2.5 (2.2−2.7)
Anxiety or stress
74.1
73.8
1.1 (1.0−1.2)
Complications during pregnancy and labour
25.3
14.1
1.9 (1.7−2.1)
DxE: diagnosis of endometriosis.
bleeding; lower back pain; constipation, bloating, or diarrhea; and anxiety or stress. In contrast, the only symptom ever experienced by at least 65% of women without DxE was anxiety or stress. These findings are consistent with symptomatology of women with DxE in the United States.4 The high odds of Canadian women with DxE experiencing infertility in the month before the survey is in line with the strong association between infertility and endometriosis.3 For most endometriosis-related symptoms, two to three times as many women with DxE experienced severe symptoms as women without DxE, and the most frequently severe symptoms (non-menstrual pelvic pain, general abdominal pain, pelvic pressure, menstrual pelvic pain or cramping) were also most often reported as extremely bothersome. These results suggest that Canadian women with DxE have a substantial disease burden. Understanding the frequency and severity of endometriosis symptoms lays the foundation for assessing the impact of endometriosis on Canadian women’s health-related quality of life because previous studies have shown a correlation between a greater number and severity of symptoms and worse health-related quality of life.4,23 Canadian women with DxE reported an average diagnostic delay of approximately 5 years from the time of
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symptom onset. Delayed diagnosis contributes to the disease burden of endometriosis by prolonging pain symptoms and preventing women from receiving appropriate treatment.20 Previous studies have reported an average endometriosis diagnostic delay of 6.8 years12 and 10 years in Canadian women.21 The latter study surveyed only a small number of women with surgically confirmed endometriosis, a factor that could increase reported time to diagnosis.21 Furthermore, 53% of women in this study were diagnosed by obstetriciangynaecologists, which may account for a shorter time to diagnosis than previously reported for Canadian women.16 Only 31% of women here reported a surgical diagnosis, a finding suggesting that other non-invasive methods were used to evaluate suspected endometriosis. The influence of diagnostic method on time to DxE remains to be determined. Various factors contribute to diagnostic delay of endometriosis on the part of both patients and physicians. Women may be unable to distinguish “normal” from “abnormal” menstrual experiences or may normalize pain symptoms as a result of embarrassment, thereby delaying consultation with a physician after onset of symptoms.20 Physicians may also normalize pain symptoms reported by patients or
Prevalence, Symptomatic Burden, and Diagnosis of Endometriosis in Canada
Table 3. Endometriosis-related symptoms and severity Currently experiencing symptoms
Currently experiencing severe symptoms
Women with DxE (n = 2004), %
Women without DxE (n = 26 528), %
Odds ratio (95% CI)
Women with DxE (n = 2004), %
Women without DxE (n = 26 528), %
Odds ratio (95% CI)
Menstrual pelvic pain or cramping
54.0
39.3
1.9 (1.7−2.1)
37.3
17.6
2.9 (2.5−3.3)
Non-menstrual pelvic pain or cramping
39.4
14.2
4.2 (3.8−4.6)
25.3
9.3
3.4 (2.8−4.2)
Dyspareunia
38.3
17.7
3.1 (2.8−3.4)
17.3
9.2
2.1 (1.7−2.6)
Heavy menstrual bleeding
48.0
33.3
2.0 (1.8−2.2)
38.3
22.8
2.1 (1.8−2.4)
Excessive or irregular bleeding (e.g., spotting between periods)
31.8
15.6
2.6 (2.4−2.9)
24.8
12.3
2.3 (1.9−2.9)
Passage of clots
26.4
14.9
2.0 (1.8−2.2)
22.7
11.3
2.3 (1.8−2.8)
Irregular periods (timing and/or duration)
41.7
31.3
1.7 (1.5−1.8)
30.0
17.6
2.1 (1.8−2.4)
Pelvic pressure
27.6
8.7
4.1 (3.7−4.6)
20.2
7.9
3.0 (2.3−3.8)
Symptom
Lower back pain
61.6
56.2
1.2 (1.1−1.4)
26.9
16.9
1.8 (1.6−2.1)
General abdominal pain
44.9
27.4
2.3 (2.1−2.5)
22.4
9.1
3.0 (2.5−3.6)
Constipation, bloating, or diarrhea
60.1
52.2
1.4 (1.3−1.5)
18.5
10.2
2.0 (1.7−2.4)
Difficulty having bowel movement
41.8
28.8
1.8 (1.6−2.0)
16.8
10.8
1.7 (1.4−2.0)
Fatigue, weariness, or anemia
61.7
51.7
1.5 (1.4−1.7)
31.7
20.0
1.9 (1.7−2.2)
Frequent urination or urinary urgency
34.8
20.7
2.0 (1.8−2.2)
23.5
15.2
1.7 (1.4−2.1)
Infertility
15.0
3.8
4.4 (3.8−5.1)
55.3
54.4
1.0 (0.8−1.3)
Depressed feelings or mood swings
60.4
55.8
1.3 (1.2−1.4)
27.7
22.7
1.5 (1.3−1.7)
Dizziness during period
32.3
19.3
2.2 (2.0−2.4)
19.3
8.8
2.7 (2.1−3.3)
Anxiety or stress
70.9
69.5
1.1 (1.0−1.3)
31.0
26.8
1.4 (1.2−1.5)
Complications during pregnancy and labour
10.0
3.9
2.6 (2.2−3.1)
43.8
34.6
1.5 (1.1−2.0)
DxE: diagnosis of endometriosis.
may misdiagnose conditions.20,24 In this survey, the average time from symptom onset to physician consultation was slightly longer than the delay between consulting a physician and receiving a diagnosis. Additional research is needed to better understand factors contributing to diagnostic delay to reduce the overall time to diagnosis. Further studies are also needed to determine the impact of delayed pain symptom management on the development of chronic pain syndromes that are resistant to endometriosis therapy.25 Initiatives to raise awareness about endometriosis and programs that educate young women about menstrual health may improve symptom recognition and reduce the stigma associated with menstrual irregularities, thus prompting patients to seek care earlier.20,26−28 Similarly, education of health care providers regarding endometriosis symptoms and diagnostic strategies may help reduce the time to diagnosis.26,27 The large sample size and weighting of data to accurately represent the Canadian general population reinforce the generalizability of these findings. The limitations of the current study are common to cross-sectional surveys.
Non-response bias may arise from the exclusion of women not registered with the online panels used. Respondents may have received a DxE several years before the survey, and this could introduce recall bias regarding diagnostic experience. The accuracy of DxE and disease severity could not be confirmed because this study relied on patient reports not substantiated by medical records or clinical evaluations. Therefore, a similar patient survey study with use of electronic medical records databases to confirm DxE against patient-reported diagnoses would provide useful information. Given the frequency with which women reported non-surgical diagnostic methods, which can be less precise than surgical diagnosis, the prevalence reported here may be an underestimate or overestimate. It is important to note that women without DxE in this study may have included women with symptomatic but undiagnosed or unsuspected endometriosis; therefore, the prevalence and symptomatic differences between groups may be underestimated. This analysis did not control for potential impacts of prior or current treatments on symptomatic burden. Finally, surveys are needed to determine the perceptions of health care providers regarding DxE and
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Table 4. Degree to which survey respondents were bothered by endometriosis-related symptoms Not at all bothersome
Symptom
Women Women with DxE without DxE (n = 2004), % (n = 26 528), %
Somewhat bothersome Odds ratio (95% CI)
Women Women with DxE without DxE (n = 2004), % (n = 26 528), %
Odds ratio (95% CI)
Extremely bothersome Women Women with DxE without DxE (n = 2004), % (n = 26 528), %
Odds ratio (95% CI)
Menstrual pelvic pain or cramping
11.9
18.1
0.6 (0.5−0.7)
47.1
57.2
0.7 (0.6−0.7)
41.0
24.7
2.3 (2.0−2.6)
Non-menstrual pelvic pain or cramping
12.4
23.4
0.5 (0.4−0.6)
53.6
59.4
0.8 (0.7−0.9)
34.0
17.2
2.6 (2.2−3.1)
Dyspareunia
13.3
20.6
0.6 (0.5−0.7)
50.2
57.0
0.7 (0.6−0.9)
36.5
22.4
2.1 (1.8−2.4)
Heavy menstrual bleeding
8.6
15.7
0.5 (0.4−0.6)
43.9
49.0
0.8 (0.7−0.9)
47.5
35.3
1.7 (1.4−1.9)
Excessive or irregular bleeding (e.g., spotting between periods)
15.7
24.8
0.6 (0.5−0.7)
47.1
50.8
0.9 (0.7−1.0)
37.2
24.5
1.8 (1.5−2.2)
Passage of clots
30.9
44.1
0.6 (0.5−0.7)
44.8
41.3
1.1 (0.9−1.4)
24.3
14.6
1.8 (1.5−2.3)
Irregular periods (timing and/or duration)
18.1
29.4
0.5 (0.4−0.6)
46.5
50.5
0.9 (0.7−1.0)
35.4
20.0
2.2 (1.9−2.6)
Pelvic pressure
10.9
26.2
0.3 (0.3−0.5)
61.1
59.2
1.1 (0.9−1.3)
28.0
14.6
2.3 (1.8−2.9)
Lower back pain
11.2
17.4
0.6 (0.5−0.7)
51.7
57.0
0.8 (0.7−0.9)
37.1
25.7
1.8 (1.6−2.0)
General abdominal pain
10.9
22.3
0.4 (0.3−0.5)
57.8
61.7
0.8 (0.7−1.0)
31.3
16.1
2.6 (2.2−3.0)
Constipation, bloating, or diarrhea
13.1
20.4
0.6 (0.5−0.7)
58.0
59.9
0.9 (0.8−1.0)
28.9
19.7
1.7 (1.5−2.0)
Difficulty having bowel movement
16.0
20.6
0.7 (0.6−0.9)
54.3
58.8
0.8 (0.7−0.9)
29.7
20.6
1.7 (1.4−2.0)
8.3
13.6
0.6 (0.5−0.7)
51.8
56.3
0.8 (0.7−0.9)
39.8
30.2
1.6 (1.4−1.8)
Frequent urination or urinary urgency
11.6
15.7
0.7 (0.6−0.9)
52.5
56.7
0.8 (0.7−1.0)
35.9
27.7
1.5 (1.2−1.7)
Infertility
18.6
21.5
0.8 (0.6−1.2)
31.6
24.8
1.4 (1.1−1.9)
49.8
53.7
0.9 (0.7−1.1)
9.6
10.6
0.8 (0.7−1.0)
44.4
50.8
0.7 (0.6−0.8)
46.0
38.7
1.5 (1.3−1.7)
15.6
20.4
0.7 (0.6−0.9)
55.0
60.9
0.8 (0.7−0.9)
29.4
18.7
1.9 (1.5−2.2)
Fatigue, weariness, or anemia
Depressed feelings or mood swings Dizziness during period Anxiety or stress Complications during pregnancy and labour CI: confidence interval; DxE: diagnosis of endometriosis.
8.6
11.6
0.7 (0.5−0.8)
45.5
49.4
0.8 (0.7−0.9)
45.9
38.9
1.5 (1.3−1.7)
14.5
26.7
0.5 (0.3−0.7)
40.5
32.9
1.4 (1.0−1.9)
45.0
40.4
1.2 (0.9−1.6)
Prevalence, Symptomatic Burden, and Diagnosis of Endometriosis in Canada
disease burden and whether these reflect patient-reported experiences.
5. Culley L, Law C, Hudson N, et al. The social and psychological impact of endometriosis on women’s lives: a critical narrative review. Hum Reprod Update 2013;19:625–39.
CONCLUSION
6. Wheeler JM. Epidemiology of endometriosis-associated infertility. J Reprod Med 1989;34:41–6.
In this large, cross-sectional survey, there was a 7.0% prevalence of self-reported DxE in Canada, which equates to over half a million Canadian women affected by endometriosis. Similar prevalence rates were reported across all provinces, except for slightly higher rates in western Canada. Moreover, women with DxE reported a substantial symptomatic burden and an average diagnostic delay of 5 years. These findings indicate that further research is needed to examine the impact of symptomatic burden on women’s health-related quality of life and to establish the direct and indirect costs of endometriosis in Canada. Future studies are required to ascertain factors contributing to diagnostic delay and to identify steps to reduce time to diagnosis. Acknowledgements
This study was funded by AbbVie, Inc. AbbVie sponsored the study; contributed to the design; participated in collection, analysis, and interpretation of data; and participated in writing, reviewing, and approval of the final version. Medical writing assistance was provided by Dr. Emily Mercadante of JK Associates, Inc., a member of the Fishawack Group of Companies, and was funded by AbbVie, Inc. Dr. Singh was a study investigator in therapeutic trials for endometriosis and fibroids sponsored by Allergan, AbbVie, and Bayer; and served as a speaker and advisor for Allergan, AbbVie, Bayer, Hologic, and Cooper Surgical. Dr. Soliman, Ms. Rahal, Ms. Robert, and Dr. Defoy are AbbVie employees and have stock or stock options. Dr. Nisbet is the president of One Research. Dr. Leyland has received grant support and lecture fees from AbbVie, Bayer, and Allergan and lecture fees from Johnson & Johnson. REFERENCES
7. Eskenazi B, Warner ML. Epidemiology of endometriosis. Obstet Gynecol Clin North Am 1997;24:235–58. 8. Guo SW, Wang Y. Sources of heterogeneities in estimating the prevalence of endometriosis in infertile and previously fertile women. Fertil Steril 2006;86:1584–95. 9. Rawson JM. Prevalence of endometriosis in asymptomatic women. J Reprod Med 1991;36:513–5. 10. Fuldeore MJ, Soliman AM. Prevalence and symptomatic burden of diagnosed endometriosis in the United States: national estimates from a cross-sectional survey of 59,411 women. Gynecol Obstet Invest 2017;82:453–61. 11. Ballard KD, Seaman HE, de Vries CS, et al. Can symptomatology help in the diagnosis of endometriosis? Findings from a national case-control study −Part 1. BJOG 2008;115:1382–91. 12. Bernuit D, Ebert AD, Halis G, et al. Female perspectives on endometriosis: findings from the Uterine Bleeding and Pain Women’s Research Study. J Endometr 2011;3:73–85. 13. Zondervan KT, Cardon LR, Kennedy SH. What makes a good case-control study? Design issues for complex traits such as endometriosis. Hum Reprod 2002;17:1415–23. 14. Seaman HE, Ballard KD, Wright JT, et al. Endometriosis and its coexistence with irritable bowel syndrome and pelvic inflammatory disease: findings from a national case-control study−Part 2. BJOG 2008;115: 1392–6. 15. Leyland N, Casper R, Laberge P, et al. Society of Obstetricians and Gynaecologists of Canada. Endometriosis: diagnosis and management. J Obstet Gynaecol Can 2010;32(7 Suppl 2):S1–32. 16. Soliman AM, Fuldeore M, Snabes MC. Factors associated with time to endometriosis diagnosis in the United States. J Womens Health (Larchmt) 2017;26:788–97. 17. Fourquet J, Sinaii N, Stratton P, et al. Characteristics of women with endometriosis from the USA and Puerto Rico. J Endometr Pelvic Pain Disord 2015;7:129–35. 18. Moradi M, Parker M, Sneddon A, et al. Impact of endometriosis on women’s lives: a qualitative study. BMC Womens Health 2014;14: 123. 19. Nnoaham KE, Hummelshoj 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. e8.
1. Reis FM, Petraglia F, Taylor RN. Endometriosis: hormone regulation and clinical consequences of chemotaxis and apoptosis. Hum Reprod Update 2013;19:406–18.
20. Ballard K, Lowton K, Wright J. What's the delay? A qualitative study of women’s experiences of reaching a diagnosis of endometriosis. Fertil Steril 2006;86:1296–301.
2. Kennedy S, Bergqvist A, Chapron C, et al. ESHRE guideline for the diagnosis and treatment of endometriosis. Hum Reprod 2005;20:2698– 704.
21. Levy AR, Osenenko KM, Lozano-Ortega G, et al. Economic burden of surgically confirmed endometriosis in Canada. J Obstet Gynaecol Can 2011;33:830–7.
3. Bulletti C, Coccia ME, Battistoni S, et al. Endometriosis and infertility. J Assist Reprod Genet 2010;27:441–7.
22. Simoens S, Dunselman G, Dirksen C, et al. The burden of endometriosis: costs and quality of life of women with endometriosis and treated in referral centres. Hum Reprod 2012;27:1292–9.
4. Soliman AM, Coyne KS, Zaiser E, et al. The burden of endometriosis symptoms on health-related quality of life in women in the United States: a cross-sectional study. J Psychosom Obstet Gynaecol 2017;38:238–48.
23. Soliman AM, Coyne KS, Gries KS, et al. The effect of endometriosis symptoms on absenteeism and presenteeism in the workplace and at home. J Manag Care Spec Pharm 2017;23:745–54.
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24. Hudelist G, Fritzer N, Thomas A, et al. Diagnostic delay for endometriosis in Austria and Germany: causes and possible consequences. Hum Reprod 2012;27:3412–6.
27. van der Zanden M, Nap AW. Knowledge of, and treatment strategies for, endometriosis among general practitioners. Reprod Biomed Online 2016;32:527–31.
25. As-Sanie S, Harris RE, Harte SE, et al. Increased pressure pain sensitivity in women with chronic pelvic pain. Obstet Gynecol 2013;122:1047–55.
28. Bush D, Brick E, East MC, et al. Endometriosis education in schools: a New Zealand model examining the impact of an education program in schools on early recognition of symptoms suggesting endometriosis. Aust N Z J Obstet Gynaecol 2017;57:452–7.
26. As-Sanie S, Black R, Giudice LC, et al. Assessing research gaps and unmet needs in endometriosis. Am J Obstet Gynecol 2019;221:86–94.
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Prevalence, Symptomatic Burden, and Diagnosis of Endometriosis in Canada: Cross-Sectional Survey of 30 000 Women Sukhbir Singh, MD;1,2 Ahmed M. Soliman, MS, PhD;3 Yasmine Rahal, MSc;4 Catherine Robert, MBA;4 Isabelle Defoy, PhD;4 Paul Nisbet, PhD;5 Nicholas Leyland, MHCM, MD6 1
Clinical Epidemiology Program, Ottawa Hospital Research Institute, Ottawa, ON
2
Department of Obstetrics and Gynecology, University of Ottawa, Ottawa, ON
3
AbbVie, Inc., North Chicago, IL
4
AbbVie Corporation, Saint-Laurent, QC
5
S. Singh
One Research LLC, Mt. Pleasant, SC
6
McMaster University, Hamilton, ON
Abstract Objective: This study sought to estimate the prevalence of diagnosis of endometriosis (DxE) in Canada and to assess the symptomatic and diagnostic experience of Canadian women with DxE. Method: A cross-sectional, online survey of women in Canada aged 18 to 49 was conducted from December 7, 2018 through January 24, 2019. Survey data were weighted by Canadian population statistics to estimate the prevalence, symptomatic burden, and diagnostic experience of DxE. Logistic regressions were used to assess differences in symptom burden between women with and without DxE. Result: The estimated prevalence of DxE was 7.0% (2004 women of 28 532 women surveyed). Almost half (47.5%) of women with DxE were aged 18 to 29 when they received an endometriosis diagnosis, and 84.1% experienced symptoms before diagnosis. More women with versus without DxE experienced menstrual pelvic pain or cramping (70.3% vs. 50.7%), non-menstrual pelvic pain or cramping (49.5% vs. 18.7%), dyspareunia (52.5% vs. 28.0%), and Key Words: Endometriosis, prevalence, symptoms, diagnosis, clinical practice Corresponding author. Dr. Sukhbir Singh, Clinical Epidemiology Program, Ottawa Hospital Research Institute; Department of Obstetrics and Gynecology, University of Ottawa, Ottawa, ON. [email protected] Competing interests: See Acknowledgements. Each author has indicated that they meet the journal’s requirements for authorship. Data, in part, were presented at the Fourth Annual Conference of the Canadian Society for the Advancement of Gynecologic Excellence (CanSAGE4), September 26−28, 2019, Ottawa, ON [ePoster 119]. Received on August 9, 2019 Accepted on October 29, 2019
infertility (22.3% vs. 6.3%). Women with DxE were more likely to report severe menstrual pelvic pain or cramping (odds ratio [OR] 2.9; 95% confidence interval [CI] 2.5−3.3), non-menstrual pelvic pain or cramping (OR 3.4; 95% CI 2.8−4.2), general abdominal pain (OR 3.0; 95% CI 2.5−3.6), and pelvic pressure (OR 3.0; 95% CI 2.3−3.8). Women with DxE reported an average 5.4-year diagnostic delay, with a 3.1-year delay from onset of symptoms to physician consultation and a 2.3-year delay between physician consultation and diagnosis. Conclusion: Self-reported DxE is prevalent among Canadian women and is associated with a substantial symptomatic burden. The 5.4-year diagnostic delay reported here indicates an important unmet need for more timely diagnosis of endometriosis in Canada.
Résumé tude visait a estimer la pre valence des diagnostics Objectif : Cette e triose au Canada et a e valuer l’expe rience des d’endome triose relativement Canadiennes ayant re¸c u un diagnostic d’endome leurs sympto ^mes et au processus diagnostique. a ^te transversale en ligne a e te mene e du Méthodologie : Une enque cembre 2018 au 24 janvier 2019 aupre s de Canadiennes 7 de es de 18 a 49 ans. Les donne es de l’enque ^ te ont e te ponde re es âge mographiques canadiennes pour au moyen des statistiques de valence, le fardeau des sympto ^mes et l’expe rience du estimer la pre triose. Des re gressions processus diagnostique de l’endome te utilise es pour e valuer les diffe rences par rapport logistiques ont e ^mes entre les femmes qui ont ou non re¸c u au fardeau des sympto triose. un diagnostic d’endome valence estime e du diagnostic d’endome triose e tait Résultats : La pre a l’enque ^te). de 7,0% (2004 des 28 532 femmes ayant participe s de la moitie (47,5%) des femmes ayant re¸c u un diagnostic Pre triose avaient entre 18 et 29 ans au moment du diagnostic d’endome prouve des sympto ^mes avant le diagnostic. Par et 84,1% ont e rapport aux autres femmes, celles ayant re¸c u un diagnostic triose ont e te plus nombreuses a e prouver des crampes d’endome
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ou des douleurs pelviennes menstruelles (70,3% par rapport a e prouver des crampes ou des douleurs pelviennes non 50,7%), a 18,7%), a souffrir de dyspareunie menstruelles (49,5% par rapport a 28,0%) et a e ^tre infertiles (22,3% par rapport a (52,5% par rapport a 6,3%). Toujours par rapport aux autres femmes, celles ayant re¸c u triose e taient plus susceptibles; d’affirmer un diagnostic d’endome prouver des crampes ou douleurs pelviennes menstruelles e importantes (rapport de cotes [RC] 2,9; intervalle de confiance [IC] 95% 2,5–3,3), des crampes ou douleurs pelviennes non a menstruelles (RC 3,4; IC de 95% 2,8–4,2), des douleurs ne rales (RC 3,0; IC de 95% 2,5–3,6) et de la abdominales ge e sur le pelvis (RC 3,0; IC de 95% 2,3–3,8). En pression exerce triose ont moyenne, les femmes ayant re¸c u un diagnostic d’endome un temps moyen de 5,4 ans avant d’obtenir un diagnostic rapporte lai de 3,1 ans de l’apparition des sympto ^mes a la avec un de decin et un de lai de 2,3 ans entre la consultation avec un me consultation et le diagnostic. triose autode clare est pre valent Conclusion : Le diagnostic d’endome a un important fardeau des chez les Canadiennes et est associe ^ mes. Le temps de 5,4 ans avant l’obtention d’un diagnostic sympto ci-dessus indique d’importantes lacunes quant a la rapporte cessite d’ame liorer le de lai d’obtention du diagnostic de ne triose au Canada. l’endome © 2019 The Society of Obstetricians and Gynaecologists of Canada/La Société des obstétriciens et gynécologues du Canada. Published by Elsevier Inc. This is an open access article under the CC BY-NC-ND license. (http://creativecommons.org/licenses/by-nc-nd/4.0/)
J Obstet Gynaecol Can 2019;000(000):1−10 https://doi.org/10.1016/j.jogc.2019.10.038
INTRODUCTION
ndometriosis is a chronic inflammatory disease that predominantly affects women of reproductive age and is characterized by the growth of endometrial-like tissue outside of the uterus.1,2 Women with endometriosis experience a range of symptoms, including pelvic pain and cramping during menstruation, non-menstrual pelvic pain, painful intercourse (dyspareunia), heavy menstrual bleeding, and chronic fatigue.2 Subfertility or infertility is also commonly associated with endometriosis.3 The chronicity and severity of endometriosis-related symptoms considerably affect all aspects of women’s quality of life.4,5
E
Although the prevalence of endometriosis in women of reproductive age is commonly cited as 10%,6 global estimates vary widely, ranging from 2% to 45%7−12 and anywhere from 2% to 77% in women with infertility.7 Historically, prevalence estimates have been based on studies of women who were hospitalized or undergoing surgery and were not necessarily representative of the general female population.7,9 Differences in the populations of women included in studies (e.g., surgical cases), the definition of disease, and the diagnostic method used contribute to the substantial variability among prevalence estimates.7,13
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The overlap between endometriosis-related pelvic-abdominal pain symptoms and other chronic pain conditions contributes to difficulty in diagnosing endometriosis.2,14 Furthermore, clinical examination findings in women with endometriosis may often be normal.2 The traditional gold standard for definitively diagnosing endometriosis is laparoscopic visualization of lesions and histologic confirmation, and only recently has there been a push towards nonsurgical methods of diagnosis in Canada.15 For these and other reasons, many women experience a significant delay from the time of symptom onset to diagnosis. Worldwide, estimates of diagnostic delay range from 4 to 11 years.16−19 This lengthy delay in diagnosis may result in prolonged suffering, reduced productivity, and worse health-related quality of life for women with endometriosis.20 Importantly, there have been no studies on the prevalence of endometriosis in Canada. In fact, Levy et al. sought to evaluate the economic burden of endometriosis in Canada but relied on prevalence estimates from a study of women in the United States.21 Moreover, information about the symptom burden and diagnostic experience of Canadian women with endometriosis is lacking. Therefore, in this study, data were collected from a nationally representative, large-scale, cross-sectional survey of women in Canada with the goals of (1) estimating the prevalence of selfreported diagnosis of endometriosis (DxE) in Canada, (2) comparing the symptom experience with that of women without endometriosis, and (3) evaluating the diagnostic experience (e.g., diagnostic methods, diagnosing physician’s specialty, and time to diagnosis) of women with DxE in Canada. METHODS Study Design and Participants
This comprehensive cross-sectional survey was undertaken to determine the prevalence and symptomatic burden of DxE among the general population of women in Canada and to characterize the diagnostic experience of Canadian women with DxE. Three independent response panels were used as sampling frames for this research to maximize the response rate and ensure adequate representation of the Canadian female population: the Survey Sampling International (SSI) panel (now Dynata, Shelton, CT; http://www.dynata.com), the Leger panel (Toronto, ON; https://leger360.com), and the Lightspeed panel (now Kantar, Vancouver, BC; http://www.lightspeedresearch. com/). Panel members were invited to participate in the survey via an email stating that the latest SSI survey was open and directing those interested to the survey website. Female Canadian residents aged 18 to 49 who completed
Prevalence, Symptomatic Burden, and Diagnosis of Endometriosis in Canada
the study consent form were eligible to participate. Survey responses from 30 000 Canadian women were collected from December 7, 2018 through January 24, 2019. To ensure the survey sample was representative of the national Canadian population of women, survey data were weighted on the basis of the 2016 Canada Census data22 on distributions of age, education, geographic region, and household income by using a random iterative method. The survey contained two sections. The first section, a prevalence screener, included questions on demographics, whether respondents had received a DxE and, if so, the diagnostic method or methods used, and questions regarding symptom experience. DxE was self-reported, and no cross-referencing or verification was possible. For diagnostic methods, respondents were asked to select all methods that applied, and methods were grouped into four broader categories during analysis. Surgical methods included laparoscopy, laparotomy, and other surgical procedures. Empirical methods included patient description of pain, confirmed diagnosis that was based on response to medication, and physician suspects endometriosis but has not confirmed with surgery. Diagnostic methods leading physician to suspect endometriosis (physician-suspected methods) included ultrasound or sonogram, other imaging testing (e.g., magnetic resonance imaging), physical or pelvic examination, patient description of heavy or irregular bleeding, family history, blood test for anemia, hysterectomy, and infertility. The other or unsure category included the responses “other” or “unsure” and patients who declined to answer. Respondents were asked to select symptoms they had ever experienced from an extensive list of endometriosis-related symptoms, to select symptoms currently being experienced (within 4 weeks before the survey), to indicate symptom severity (mild, moderate, or severe), and to describe how bothersome symptoms were (not at all, somewhat, or extremely bothersome). The second part of the survey asked participants about endometriosis-specific information such as diagnostic experience, treatment patterns, health-related quality of life, health-related productivity losses, and health care resource use. This report focuses on prevalence, symptom burden, and diagnostic experience. Data Analyses
Data for each survey question were reported only for respondents who answered the question; participants with missing responses about a symptom were assigned to the “no symptom” category for that specific question or symptom. Continuous variables were summarized by means, and categorical variables were reported as percentages.
Trends in the prevalence of DxE across age groups and geographic regions were assessed. Comparisons were made between the percentages of women with DxE and women without DxE who ever experienced symptoms, those currently experiencing symptoms, those currently experiencing severe symptoms, and the degree to which symptoms bothered women. Logistic regression models controlling for age were used to assess differences in the frequencies of symptoms experienced by women with DxE versus women without DxE. The likelihood (odds ratio [OR]) of experiencing symptoms, along with the corresponding 95% confidence interval (CI), were determined. Logistic models that controlled for age were used to determine the odds of a respondent reporting a severe symptom or an extremely bothersome symptom as a function of whether the respondent had DxE. All data analyses were performed using IBM SPSS Statistics software version 25 (IBM Corp., Armonk, NY). This study was reviewed and approved by the Copernicus Group Institutional Review Board. RESULTS Prevalence
A total of 30 000 women in Canada met the inclusion criteria and completed the survey prevalence screener. Sampling weights were applied to survey data according to Canada population statistics.22 After weighting, a total of 2004 women (7.0%) reported receiving a DxE (Figure A). Demographics of the study population are shown in Table 1. All Canadian provinces and territories were represented by respondents of the survey. Extrapolating these results to the overall population projects that an estimated 516 327 women in Canada aged 18 to 49 have a selfreported DxE. The average age at the time of DxE was 27.9 years, and approximately half (47.5%) of women with DxE were in the 18 to 29 age group when they received a DxE. The majority (84.1%) of women with DxE experienced symptoms before diagnosis. The prevalence of selfreported DxE was highest among women in the 35 to 39 age group (9.6%), followed by the 30 to 34 age group (8.4%) (Figure A). Similar prevalence rates were reported for women in Ontario, the Prairies, the Atlantic, and Quebec, with the highest prevalence in western Canada (Figure B). Symptom Burden
Canadian women with self-reported DxE were more likely to have ever experienced endometriosis-related symptoms than women without DxE, according to ageadjusted ORs (Table 2). Women with DxE had the
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Figure. Total population prevalence of endometriosis by age group and geographic region. (A) Total population prevalence of endometriosis: overall and by age group. (B) Total population prevalence of endometriosis by Canada geographic region.
BC: British Columbia; NB: New Brunswick; NL: Newfoundland and Labrador; NS: Nova Scotia; PEI: Prince Edward Island.
highest odds of experiencing non-menstrual pelvic pain or cramping (OR 4.4; 95% CI 4.0−4.9), infertility (OR 4.1; 95% CI 3.6−4.6), pelvic pressure (OR 3.9; 95% CI 3.5−4.3), and dyspareunia (OR 3.0; 95% CI 2.7−3.3) compared with women without DxE. A greater percentage of women with DxE were experiencing “typical” endometriosis symptoms in the 4 weeks before the survey than women without DxE: menstrual pelvic pain or cramping (54.0% vs. 39.3%), non-menstrual pelvic pain or cramping (39.4% vs. 14.2%), and dyspareunia (38.3% vs. 17.7%) (Table 3). Although all endometriosis-related symptoms were reported with greater prevalence by women with DxE than by those without DxE, the age-adjusted OR was highest for infertility
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(OR 4.4; 95% CI 3.8−5.1), non-menstrual pelvic pain or cramping (OR 4.2; 95% CI 3.8−4.6), and pelvic pressure (OR 4.1; 95% CI 3.7−4.6). In addition to a higher prevalence of endometriosis symptoms, women with DxE were also more likely to experience severe symptoms than women without DxE. For example, 37.3% of women with DxE versus 17.6% of women without DxE were experiencing severe menstrual pelvic pain or cramping (OR 2.9; 95% CI 2.5−3.3) in the 4 weeks before the survey. Other severe symptoms with high age-adjusted ORs included non-menstrual pelvic pain or cramping (OR 3.4; 95% CI 2.8−4.2), general abdominal pain (OR 3.0; 95% CI 2.5−3.6), and pelvic pressure (OR
Prevalence, Symptomatic Burden, and Diagnosis of Endometriosis in Canada
Table 1. Demographics of study population Women with DxE (n = 2004)
Women without DxE (n = 26 528)
35.5 § 8.1
33.6 § 9.2
18−29
25.6
37.2
30−34
19.5
16.0
35−39
21.4
15.3
40−44
16.0
15.5
45−49
17.6
16.1
27.9 § 8.1
—
<18
8.4
—
18−29
47.5
—
30−34
25.9
—
35−39
11.8
—
40−44
5.3
—
45−49
1.0
—
White
88.8
78.0
Black
1.0
3.1
Hispanic
1.0
1.1
Other
8.4
16.3
Before diagnosis
84.1
—
At time of diagnosis
3.7
—
After diagnosis
6.0
—
Unsure
6.2
—
29.4
3.7
Ontario
37.5
39.1
bec Que
18.6
24.0
British Columbia
16.7
12.7
Alberta
15.3
10.4
Parameter Average age, years, mean § SD Age group, years, %
Average age at diagnosis, years, mean § SD Age group at diagnosis, years, %
Ethnicity, %
When patients began experiencing symptoms, %
Had hysterectomy, %
3.0; 95% CI 2.3−3.8). A substantial percentage of women with DxE indicated that endometriosis-related symptoms were extremely bothersome, compared with women without DxE (Table 4). Women with DxE were most likely to report extremely bothersome menstrual pelvic pain or cramping (OR 2.3; 95% CI 2.0−2.6), non-menstrual pelvic pain or cramping (OR 2.6; 95% CI 2.2−3.1), general abdominal pain (OR 2.6; 95% CI 2.2−3.0), and pelvic pressure (OR 2.3; 95% CI 1.8−2.9). Diagnostic Experience
Among 1686 women with DxE who reported experiencing symptoms before DxE, the mean overall delay from symptom onset to diagnosis was 5.4 years. The mean patient-related delay (time from symptom onset to the first consultation with a physician) was 3.1 years, and the mean physician-related delay (time from the first consultation with a physician to receiving a diagnosis) was 2.3 years. More than half (53.0%) of women with DxE were diagnosed by an obstetriciangynaecologist. Approximately 19.0% of women with DxE reported receiving a diagnosis from a primary care physician, 17.0% from a general surgeon, 7.3% from an infertility specialist, 1.1% from a urologist, and 2.5% from an “other” specialist. On average, women with DxE reported consulting three physicians about endometriosis. As part of the survey, women with DxE indicated the method or methods used to confirm the DxE, with the option to select multiple methods. Surgical diagnostic methods were reported by 30.8% of women, whereas empirical and physician-suspected diagnostic methods were reported by 32.7% and 56.4% of women, respectively. Approximately 2% of women with DxE selected response options in the “other or unsure” category.
Canadian province, %
Manitoba
3.3
3.5
Nova Scotia
3.2
2.8
Saskatchewan
2.5
3.0
Newfoundland and Labrador
1.4
1.5
New Brunswick
1.1
2.4
Prince Edward Island
0.3
0.4
Northwest Territories
0
0.1
Nunavut
0
0.1
Yukon
0
0.1
DxE: diagnosis of endometriosis.
DISCUSSION
The current study is the first to estimate the prevalence of self-reported DxE among women in Canada on the basis of a large survey and to characterize the symptomatic burden and diagnostic experience of Canadian women with DxE. The prevalence of DxE among Canadian women was 7.0% in this survey, which is greater than that reported by a small, population-based study of Canadian women aged 15 to 49 (5.2%)12 and similar to prevalence estimates of DxE among women in the United States (6.1%−6.6%).10,12 In this survey, at least 65% of Canadian women with DxE reported ever experiencing menstrual pelvic pain or cramping; fatigue, weariness, or anemia; heavy menstrual
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Table 2. Endometriosis symptoms ever experienced Symptom
Women with DxE (n = 2 004), %
Women without DxE (n = 26 528), %
Odds ratio (95% CI)
Menstrual pelvic pain or cramping
70.3
50.7
2.4 (2.1−2.6)
Non-menstrual pelvic pain or cramping
49.5
18.7
4.4 (4.0−4.9)
Dyspareunia
52.5
28.0
3.0 (2.7−3.3)
Fatigue, weariness, or anemia
67.4
56.3
1.6 (1.5−1.8)
Heavy menstrual bleeding
68.7
47.1
2.5 (2.2−2.7)
Excessive or irregular bleeding (e.g., spotting between periods)
47.6
25.7
2.7 (2.4−2.9)
Passage of clots
43.5
23.5
2.4 (2.2−2.6)
Irregular periods (timing and/or duration)
61.4
47.6
1.8 (1.7−2.0)
Pelvic pressure
32.7
11.3
3.9 (3.5−4.3)
Lower back pain
66.5
63.4
1.1 (1.0−1.3)
General abdominal pain
52.2
33.7
2.2 (2.0−2.5)
Constipation, bloating, or diarrhea
66.5
62.6
1.2 (1.1−1.3)
Difficulty having bowel movement
47.6
36.1
1.6 (1.5−1.8)
Frequent urination or urinary urgency
40.5
27.1
1.8 (1.7−2.0)
Infertility
22.3
6.3
4.1 (3.6−4.6)
Depressed feelings or mood swings
64.2
62.8
1.1 (1.0−1.2)
Dizziness during period
44.6
26.3
2.5 (2.2−2.7)
Anxiety or stress
74.1
73.8
1.1 (1.0−1.2)
Complications during pregnancy and labour
25.3
14.1
1.9 (1.7−2.1)
DxE: diagnosis of endometriosis.
bleeding; lower back pain; constipation, bloating, or diarrhea; and anxiety or stress. In contrast, the only symptom ever experienced by at least 65% of women without DxE was anxiety or stress. These findings are consistent with symptomatology of women with DxE in the United States.4 The high odds of Canadian women with DxE experiencing infertility in the month before the survey is in line with the strong association between infertility and endometriosis.3 For most endometriosis-related symptoms, two to three times as many women with DxE experienced severe symptoms as women without DxE, and the most frequently severe symptoms (non-menstrual pelvic pain, general abdominal pain, pelvic pressure, menstrual pelvic pain or cramping) were also most often reported as extremely bothersome. These results suggest that Canadian women with DxE have a substantial disease burden. Understanding the frequency and severity of endometriosis symptoms lays the foundation for assessing the impact of endometriosis on Canadian women’s health-related quality of life because previous studies have shown a correlation between a greater number and severity of symptoms and worse health-related quality of life.4,23 Canadian women with DxE reported an average diagnostic delay of approximately 5 years from the time of
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symptom onset. Delayed diagnosis contributes to the disease burden of endometriosis by prolonging pain symptoms and preventing women from receiving appropriate treatment.20 Previous studies have reported an average endometriosis diagnostic delay of 6.8 years12 and 10 years in Canadian women.21 The latter study surveyed only a small number of women with surgically confirmed endometriosis, a factor that could increase reported time to diagnosis.21 Furthermore, 53% of women in this study were diagnosed by obstetriciangynaecologists, which may account for a shorter time to diagnosis than previously reported for Canadian women.16 Only 31% of women here reported a surgical diagnosis, a finding suggesting that other non-invasive methods were used to evaluate suspected endometriosis. The influence of diagnostic method on time to DxE remains to be determined. Various factors contribute to diagnostic delay of endometriosis on the part of both patients and physicians. Women may be unable to distinguish “normal” from “abnormal” menstrual experiences or may normalize pain symptoms as a result of embarrassment, thereby delaying consultation with a physician after onset of symptoms.20 Physicians may also normalize pain symptoms reported by patients or
Prevalence, Symptomatic Burden, and Diagnosis of Endometriosis in Canada
Table 3. Endometriosis-related symptoms and severity Currently experiencing symptoms
Currently experiencing severe symptoms
Women with DxE (n = 2004), %
Women without DxE (n = 26 528), %
Odds ratio (95% CI)
Women with DxE (n = 2004), %
Women without DxE (n = 26 528), %
Odds ratio (95% CI)
Menstrual pelvic pain or cramping
54.0
39.3
1.9 (1.7−2.1)
37.3
17.6
2.9 (2.5−3.3)
Non-menstrual pelvic pain or cramping
39.4
14.2
4.2 (3.8−4.6)
25.3
9.3
3.4 (2.8−4.2)
Dyspareunia
38.3
17.7
3.1 (2.8−3.4)
17.3
9.2
2.1 (1.7−2.6)
Heavy menstrual bleeding
48.0
33.3
2.0 (1.8−2.2)
38.3
22.8
2.1 (1.8−2.4)
Excessive or irregular bleeding (e.g., spotting between periods)
31.8
15.6
2.6 (2.4−2.9)
24.8
12.3
2.3 (1.9−2.9)
Passage of clots
26.4
14.9
2.0 (1.8−2.2)
22.7
11.3
2.3 (1.8−2.8)
Irregular periods (timing and/or duration)
41.7
31.3
1.7 (1.5−1.8)
30.0
17.6
2.1 (1.8−2.4)
Pelvic pressure
27.6
8.7
4.1 (3.7−4.6)
20.2
7.9
3.0 (2.3−3.8)
Symptom
Lower back pain
61.6
56.2
1.2 (1.1−1.4)
26.9
16.9
1.8 (1.6−2.1)
General abdominal pain
44.9
27.4
2.3 (2.1−2.5)
22.4
9.1
3.0 (2.5−3.6)
Constipation, bloating, or diarrhea
60.1
52.2
1.4 (1.3−1.5)
18.5
10.2
2.0 (1.7−2.4)
Difficulty having bowel movement
41.8
28.8
1.8 (1.6−2.0)
16.8
10.8
1.7 (1.4−2.0)
Fatigue, weariness, or anemia
61.7
51.7
1.5 (1.4−1.7)
31.7
20.0
1.9 (1.7−2.2)
Frequent urination or urinary urgency
34.8
20.7
2.0 (1.8−2.2)
23.5
15.2
1.7 (1.4−2.1)
Infertility
15.0
3.8
4.4 (3.8−5.1)
55.3
54.4
1.0 (0.8−1.3)
Depressed feelings or mood swings
60.4
55.8
1.3 (1.2−1.4)
27.7
22.7
1.5 (1.3−1.7)
Dizziness during period
32.3
19.3
2.2 (2.0−2.4)
19.3
8.8
2.7 (2.1−3.3)
Anxiety or stress
70.9
69.5
1.1 (1.0−1.3)
31.0
26.8
1.4 (1.2−1.5)
Complications during pregnancy and labour
10.0
3.9
2.6 (2.2−3.1)
43.8
34.6
1.5 (1.1−2.0)
DxE: diagnosis of endometriosis.
may misdiagnose conditions.20,24 In this survey, the average time from symptom onset to physician consultation was slightly longer than the delay between consulting a physician and receiving a diagnosis. Additional research is needed to better understand factors contributing to diagnostic delay to reduce the overall time to diagnosis. Further studies are also needed to determine the impact of delayed pain symptom management on the development of chronic pain syndromes that are resistant to endometriosis therapy.25 Initiatives to raise awareness about endometriosis and programs that educate young women about menstrual health may improve symptom recognition and reduce the stigma associated with menstrual irregularities, thus prompting patients to seek care earlier.20,26−28 Similarly, education of health care providers regarding endometriosis symptoms and diagnostic strategies may help reduce the time to diagnosis.26,27 The large sample size and weighting of data to accurately represent the Canadian general population reinforce the generalizability of these findings. The limitations of the current study are common to cross-sectional surveys.
Non-response bias may arise from the exclusion of women not registered with the online panels used. Respondents may have received a DxE several years before the survey, and this could introduce recall bias regarding diagnostic experience. The accuracy of DxE and disease severity could not be confirmed because this study relied on patient reports not substantiated by medical records or clinical evaluations. Therefore, a similar patient survey study with use of electronic medical records databases to confirm DxE against patient-reported diagnoses would provide useful information. Given the frequency with which women reported non-surgical diagnostic methods, which can be less precise than surgical diagnosis, the prevalence reported here may be an underestimate or overestimate. It is important to note that women without DxE in this study may have included women with symptomatic but undiagnosed or unsuspected endometriosis; therefore, the prevalence and symptomatic differences between groups may be underestimated. This analysis did not control for potential impacts of prior or current treatments on symptomatic burden. Finally, surveys are needed to determine the perceptions of health care providers regarding DxE and
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Table 4. Degree to which survey respondents were bothered by endometriosis-related symptoms Not at all bothersome
Symptom
Women Women with DxE without DxE (n = 2004), % (n = 26 528), %
Somewhat bothersome Odds ratio (95% CI)
Women Women with DxE without DxE (n = 2004), % (n = 26 528), %
Odds ratio (95% CI)
Extremely bothersome Women Women with DxE without DxE (n = 2004), % (n = 26 528), %
Odds ratio (95% CI)
Menstrual pelvic pain or cramping
11.9
18.1
0.6 (0.5−0.7)
47.1
57.2
0.7 (0.6−0.7)
41.0
24.7
2.3 (2.0−2.6)
Non-menstrual pelvic pain or cramping
12.4
23.4
0.5 (0.4−0.6)
53.6
59.4
0.8 (0.7−0.9)
34.0
17.2
2.6 (2.2−3.1)
Dyspareunia
13.3
20.6
0.6 (0.5−0.7)
50.2
57.0
0.7 (0.6−0.9)
36.5
22.4
2.1 (1.8−2.4)
Heavy menstrual bleeding
8.6
15.7
0.5 (0.4−0.6)
43.9
49.0
0.8 (0.7−0.9)
47.5
35.3
1.7 (1.4−1.9)
Excessive or irregular bleeding (e.g., spotting between periods)
15.7
24.8
0.6 (0.5−0.7)
47.1
50.8
0.9 (0.7−1.0)
37.2
24.5
1.8 (1.5−2.2)
Passage of clots
30.9
44.1
0.6 (0.5−0.7)
44.8
41.3
1.1 (0.9−1.4)
24.3
14.6
1.8 (1.5−2.3)
Irregular periods (timing and/or duration)
18.1
29.4
0.5 (0.4−0.6)
46.5
50.5
0.9 (0.7−1.0)
35.4
20.0
2.2 (1.9−2.6)
Pelvic pressure
10.9
26.2
0.3 (0.3−0.5)
61.1
59.2
1.1 (0.9−1.3)
28.0
14.6
2.3 (1.8−2.9)
Lower back pain
11.2
17.4
0.6 (0.5−0.7)
51.7
57.0
0.8 (0.7−0.9)
37.1
25.7
1.8 (1.6−2.0)
General abdominal pain
10.9
22.3
0.4 (0.3−0.5)
57.8
61.7
0.8 (0.7−1.0)
31.3
16.1
2.6 (2.2−3.0)
Constipation, bloating, or diarrhea
13.1
20.4
0.6 (0.5−0.7)
58.0
59.9
0.9 (0.8−1.0)
28.9
19.7
1.7 (1.5−2.0)
Difficulty having bowel movement
16.0
20.6
0.7 (0.6−0.9)
54.3
58.8
0.8 (0.7−0.9)
29.7
20.6
1.7 (1.4−2.0)
8.3
13.6
0.6 (0.5−0.7)
51.8
56.3
0.8 (0.7−0.9)
39.8
30.2
1.6 (1.4−1.8)
Frequent urination or urinary urgency
11.6
15.7
0.7 (0.6−0.9)
52.5
56.7
0.8 (0.7−1.0)
35.9
27.7
1.5 (1.2−1.7)
Infertility
18.6
21.5
0.8 (0.6−1.2)
31.6
24.8
1.4 (1.1−1.9)
49.8
53.7
0.9 (0.7−1.1)
9.6
10.6
0.8 (0.7−1.0)
44.4
50.8
0.7 (0.6−0.8)
46.0
38.7
1.5 (1.3−1.7)
15.6
20.4
0.7 (0.6−0.9)
55.0
60.9
0.8 (0.7−0.9)
29.4
18.7
1.9 (1.5−2.2)
Fatigue, weariness, or anemia
Depressed feelings or mood swings Dizziness during period Anxiety or stress Complications during pregnancy and labour CI: confidence interval; DxE: diagnosis of endometriosis.
8.6
11.6
0.7 (0.5−0.8)
45.5
49.4
0.8 (0.7−0.9)
45.9
38.9
1.5 (1.3−1.7)
14.5
26.7
0.5 (0.3−0.7)
40.5
32.9
1.4 (1.0−1.9)
45.0
40.4
1.2 (0.9−1.6)
Prevalence, Symptomatic Burden, and Diagnosis of Endometriosis in Canada
disease burden and whether these reflect patient-reported experiences.
5. Culley L, Law C, Hudson N, et al. The social and psychological impact of endometriosis on women’s lives: a critical narrative review. Hum Reprod Update 2013;19:625–39.
CONCLUSION
6. Wheeler JM. Epidemiology of endometriosis-associated infertility. J Reprod Med 1989;34:41–6.
In this large, cross-sectional survey, there was a 7.0% prevalence of self-reported DxE in Canada, which equates to over half a million Canadian women affected by endometriosis. Similar prevalence rates were reported across all provinces, except for slightly higher rates in western Canada. Moreover, women with DxE reported a substantial symptomatic burden and an average diagnostic delay of 5 years. These findings indicate that further research is needed to examine the impact of symptomatic burden on women’s health-related quality of life and to establish the direct and indirect costs of endometriosis in Canada. Future studies are required to ascertain factors contributing to diagnostic delay and to identify steps to reduce time to diagnosis. Acknowledgements
This study was funded by AbbVie, Inc. AbbVie sponsored the study; contributed to the design; participated in collection, analysis, and interpretation of data; and participated in writing, reviewing, and approval of the final version. Medical writing assistance was provided by Dr. Emily Mercadante of JK Associates, Inc., a member of the Fishawack Group of Companies, and was funded by AbbVie, Inc. Dr. Singh was a study investigator in therapeutic trials for endometriosis and fibroids sponsored by Allergan, AbbVie, and Bayer; and served as a speaker and advisor for Allergan, AbbVie, Bayer, Hologic, and Cooper Surgical. Dr. Soliman, Ms. Rahal, Ms. Robert, and Dr. Defoy are AbbVie employees and have stock or stock options. Dr. Nisbet is the president of One Research. Dr. Leyland has received grant support and lecture fees from AbbVie, Bayer, and Allergan and lecture fees from Johnson & Johnson. REFERENCES
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