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Original Research ajog.

org

GYNECOLOGY
Spectrum of symptoms in women diagnosed
with endometriosis during adolescence vs adulthood
Amy D. DiVasta, MD, MMSc; Allison F. Vitonis, SM; Marc R. Laufer, MD; Stacey A. Missmer, ScD

BACKGROUND: Endometriosis symptoms often start at a young age, RESULTS: Most participants (90%) experienced moderate-severe
and the time between symptom onset and endometriosis diagnosis can be menstrual pain. On average, 3 doctors were seen before diagnosis,
several years. It is not clear whether the symptoms that are experienced by regardless of age at presentation (range, 0-25 years). Time from symp-
adolescents differ from adults. Better understanding may shorten the often toms to diagnosis averaged 2 years for adolescents and 5 years for adults
lengthy delay in diagnosis. (P<.001). More adolescents (50%) than adults (33%) reported pain
OBJECTIVE: The purpose of the study was to further elucidate the starting at menarche (P¼.002) and nausea accompanying pain (69% vs
symptom presentation of adolescents as compared with adults to deter- 53%; P¼.01). Noncyclic, general pelvic pain was prevalent. One-half of
mine whether differences existed, based on age at surgical diagnosis that the participants reported relief of their general pelvic pain after a bowel
could impact time to diagnosis. movement. Pain interfered with work/school, daily activities, exercise, and
STUDY DESIGN: This investigation was a cross-sectional study at sleep to a moderate-extreme degree; difficulties were similar by age at
enrollment within a longitudinal cohort of adolescents and women with diagnosis.
endometriosis. The population-based cohort was recruited from 2 tertiary CONCLUSIONS: Pelvic pain was severe and noncyclic and negatively
care centers and the surrounding communities. Participants included impacted quality of life. At our tertiary care centers, symptoms of endo-
adolescents (diagnosed at 18 years old; n¼295) and adults (diagnosed metriosis did not differ between women surgically diagnosed during
at >18 years old; n¼107) with surgically confirmed endometriosis who adolescence compared with those diagnosed as adults. Adolescents had
were enrolled into The Women’s Health Study: From Adolescence to more nausea and symptom onset at menarche. Multi-year delays in
Adulthood. Participants completed an expanded version of the World diagnosis were common. Clinicians should be aware of these alternate
Endometriosis Research Foundation Endometriosis Phenome and Bio- symptom patterns and include endometriosis in their differential diagnosis
banking Harmonization Project standard clinical questionnaire that for both adolescent and young adult women who experience noncyclic
included items regarding menstrual history, associated symptoms, and pelvic pain and nausea.
pain. Chi-square or Fisher’s exact tests were applied to categoric data;
Wilcoxon rank sum tests were applied to continuous data. Key words: adolescents, diagnosis, endometriosis, pelvic pain

E ndometriosis is an estrogen-
dependent chronic inflammatory
condition that affects 6e10% of
diagnostic delays are common.4-6
Although symptoms usually begin dur-
ing adolescence,7,8 delays frequently
Materials and Methods
This cross-sectional study was set
within an ongoing longitudinal cohort
women during the reproductive result between presentation of symp- study (The Women’s Health Study:
years.1 Although prevalence rates in toms to a clinician and referral to a from Adolescence to Adulthood) that
the general population are unknown gynecologist,6 often including visits with enrolled premenopausal female patients
because of the need for laparoscopic nongynecologic specialists and mis- aged 7 years with and without endo-
diagnosis, 50e60% of women with diagnoses.6,9,10 Diagnostic delays may metriosis. This joint project between
pelvic pain and approximately 50% of lead to central sensitization,11 chronic Boston Children’s Hospital (BCH) and
women with infertility experience pain, scarring, and compromised Brigham and Women’s Hospital (BWH)
endometriosis.2 Nearly two-thirds of fecundability.12 has the overall aim of investigating
adolescents with chronic acyclic pelvic Delays may be due to adolescents endometriosis across the lifespan.
pain have laparoscopic evidence of lacking the experience and influence to Participants are recruited from the 2
endometriosis.3 advocate for their own diagnosis and tertiary care centers and from the sur-
Definitive diagnosis of endometriosis treatment.12 However, we hypothesized rounding community. They complete
requires laparoscopy, and multi-year that delays would also occur if the an extensive baseline questionnaire and
symptoms of adolescents differed from annual follow-up questionnaires. The
Cite this article as: DiVasta AD, Vitonis AF, Laufer MR, those of adults. Small studies suggest initial version of our baseline ques-
et al. Spectrum of symptoms in women diagnosed with that only 9.4% of adolescents experi- tionnaire included questions on
endometriosis during adolescence vs adulthood. Am J ence “classic” symptoms of cyclic pain medical history, lifestyle, medication,
Obstet Gynecol 2018;218:324.e1-11.
only during menses.13 We sought to anthropometric and environmental
0002-9378/$36.00 further elucidate the symptom presen- exposures, symptom experience, and
ª 2017 Elsevier Inc. All rights reserved.
https://doi.org/10.1016/j.ajog.2017.12.007
tation of adolescents as compared with treatments. In January 2014, we adop-
adults. ted an expanded version of the World

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ajog.org GYNECOLOGY Original Research

Endometriosis Research Foundation Chi-square or Fisher’s exact tests were years old on average (range, 8e18 years
Endometriosis Phenome and Bio- applied to categoric data. Continuous old). These adolescents first saw a
banking Harmonization Project stan- data were compared by Wilcoxon rank clinician because of pain at 14 years old
dard clinical questionnaire.14 Surveys sum test. All hypothesis tests were (9-19; median [min-max]) and received
are collected and managed with the use 2-sided. Data were analyzed with SAS a diagnosis at 16 years old (9-18).
of REDCap electronic data capture tools statistical software (version 9.4; SAS Women diagnosed during adulthood
hosted at BWH.15 The study was Institute Inc, Cary, NC). recalled symptoms beginning at 16 years
approved by the BCH Institutional old(10-36), first saw a clinician at 20
Review Board on behalf of both BCH Results years old (12-37), and received a surgical
and BWH. Informed consent was From November 2012 to March 2016, diagnosis at 22 years old (19-46). On
obtained, with parental consent/ we enrolled 984 participants. Partici- average, adolescents waited 1 year (0-7)
participant assent for girls <18 years old pants were excluded if they never began between symptom onset and first seeing
at enrollment. the baseline questionnaire (n¼225) or if any clinician for complaints of pain and
The endometriosis symptoms they left >20% of it blank after begin- 2 years (0-7) between symptom onset
included in our analysis were self- ning (n¼68). The sample then included and diagnosis of endometriosis. For
reported pain and details of acyclic (not 268 control subjects (no diagnosis of women diagnosed during adulthood,
associated with menses) and/or cyclic endometriosis) and 423 cases (female delays were significantly longer
(associated with menses) pain of the participants who self-reported a diag- (Table 2). Adults waited almost 3 times
abdomen and/or pelvis over the lifetime nosis of endometriosis), among whom longer between first seeing a clinician
and at varying time points over the last 10 were excluded subsequently because and achieving a surgical diagnosis
12 months,14 which included age of pain they did not have an operative report (3.04.0 vs 1.21.4 years; P¼.001).
onset, impact of pain, and care-seeking that confirmed endometriosis diagnosis. Adolescents saw a median of 2 (0-20)
behaviors. Pain severity was graded on We restricted the sample to cases and clinicians before surgical diagnosis;
an 11-point numeric rating scale excluded those who omitted items on adults saw a median of 2.5 (0-25) clini-
anchored with 0¼no pain and 10¼worst cyclic/general pelvic pain (n¼11), for a cians. No significant differences were
imaginable pain. Participants reported final sample of 402 endometriosis cases. found in age, weight status, age at
the severity of typical cramps with Among these participants, 202 menarche, or parity between women
menses (dysmenorrhea), age of completed the first version of the ques- who saw 1e2, 3e4, or >5 clinicians.
dysmenorrhea onset, and associated tionnaire, and 200 completed the Women who saw >5 clinicians before
physician visits and diagnoses. Urinary expanded World Endometriosis diagnosis were more likely to report that
or bowel movement habit changes dur- Research Foundation Endometriosis they “tried to get pregnant for at least 6
ing menses were characterized, which Phenome and Biobanking Harmoniza- months without becoming pregnant”
included gastrointestinal symptoms tion Project standard clinical question- (9.4%) than women who saw 1e2 cli-
experienced over the preceding year, naire. Participants ranged in age from nicians (4.5%) or 3e4 clinicians (1.0%;
activities that worsened or helped pain, 12e49 years old at enrollment (median P¼.04; data not shown).
and medications used to relieve pain. age, 19 years; Table 1). We divided the
Additional exposures included partic- cohort based on age at diagnosis of Menstrual symptoms
ipants’ demographic data and reproduc- endometriosis. “Adolescents” were Most participants (93%) experienced
tive history. Body mass index (BMI) was defined as participants 18 years old at moderate pain (pain usually requiring
calculated from self-reported weight the time of surgical diagnosis; they medication) to severe pain (pain
and height. For women aged  20 years, comprised 73% (295/402) of the total requiring medications and bed rest)
participants were categorized as under- sample. “Adults” were defined as partic- during menses over the lifetime; there
weight (BMI, <18.5 kg/m2), normal- ipants >18 years old at surgical diag- was no appreciable difference between
weight (BMI, 18.5e24.9 kg/m2), nosis. Most participants self-identified as groups (P¼.52; Table 3). One-half of
overweight (BMI, 25e29.9 kg/m2), or white (88%) and non-Hispanic (93%). those diagnosed as adolescents and one-
obese (BMI,  30 kg/m2) per World Most adolescents had menarche from third of adults reported pain starting
Health Organization criteria.16 For ado- 11e14 years old. Twelve adolescents and with their very first period (P¼.002).
lescents, the age-and gender-specific BMI 10 adults were gravid before enrollment; More adults (25%) than adolescents
Z-score was calculated and categorized as 14 of the participants (3%) reported (12%) noted that pain began >2 years
underweight (Z-score,  e2), normal- having tried >6 months to become after menarche. There were no differ-
weight (Z-score, > e2 to <1), over- pregnant without success. ences in birthweight, race, ethnicity, or
weight (Z-score, 1e2), or obese (Z-score, premenarchal somatotype between
>2).17 All self-reports of a diagnosis of Diagnosis those who experienced pain proximal to
endometriosis were verified by review of Participants who had been diagnosed menarche or those without pain until >2
the participants’ operative reports stating surgically with endometriosis during years after (data not shown). Both
that endometriosis had been visualized. adolescence had symptoms start at 13 groups were equally likely to have taken

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Original Research GYNECOLOGY ajog.org

(48%) complained of general pelvic pain


TABLE 1
that lasted for days at a time (P¼.18).
Demographics, anthropometrics, and menstrual history of participants with
Participants rated the impact of pain
surgically-confirmed endometriosis, stratified by age at time of surgical
on their normal activities on a contin-
diagnosis (n[402)
uum from 0 (not at all) to 10 (extreme).
Adolescents at Adults at General pelvic pain made it difficult to
Variable diagnosis (n¼295) diagnosis (n¼107) participate in work/school for partici-
Age at enrollment, ya 17 (12e46) 24 (17e49) pants, regardless of age (median score,
Race, n (%)
7.0 for both groups; P¼.95). Pain also
made participation in recreational and
White 260 (88.1) 96 (89.7)
social activities difficult (median score,
Black 6 (2.0) 5 (4.7) 7.0 for both groups; P¼.99). General
Other/unknown 29 (9.8) 6 (5.6) pelvic pain interfered with school or
Ethnicity, n (%)
work “moderately,” “quite a bit,” or
“extremely” for almost two-thirds (61%
Non-Hispanic 270 (94.1) 95 (90.5) in both adolescents and adults). Inter-
Hispanic 17 (5.9) 10 (9.5) estingly, women diagnosed during
In school at study enrollment, n (%) adulthood were more likely to report
either that general pelvic pain interfered
No 43 (14.6) 66 (61.7)
“not at all” with work/school (adults
Yes 252 (85.4) 41 (38.3) 24% vs adolescents 13%) or that general
Height, cm a
162.6 (130e191) 165.1 (142e180) pelvic pain interfered “extremely” with
Weight, kg a
61.2 (43e133) 63.5 (43e110) work/school (adults 32% vs adolescents
2a 13%; P¼.01).
Body mass index, kg/m 23.0 (16e45) 23.5 (18e43)
Overall, general pelvic pain interfered
Body mass index category,b n (%) with daily activities at home, exercise,
Underweight 2 (0.7) 2 (1.9) sleep, and social activities similarly be-
Normal weight 190 (65.3) 65 (61.3) tween the 2 age groups (P¼.07e.41).
However, many differences are still
Overweight 74 (25.4) 22 (20.8)
notable (Table 3). General pelvic pain
Obese 25 (8.6) 17 (16.0) interfered with sleep “not at all” for twice
Age at menarche, y as many participants diagnosed during
Median (min-max) 12.0 (8e15) 12.0 (8e15) adolescence (23.4%) compared with
adults (10%). Exercise was also impacted
Early menarche, <11 y, n (%) 58 (19.7) 11 (10.3)
more severely for adults. General pelvic
Typical menarche, 11-14 y, n (%) 230 (78.0) 89 (83.2) pain interfered with exercise “extremely”
Delayed menarche, >14 y, n (%) 7 (2.4) 7 (6.5) for 36.1% of adults, compared with
Ever pregnant, n (%) 21.3% of adolescents. With social activ-
ities, general pelvic pain interfered “not
No 282 (95.9) 88 (89.8)
at all” or “slightly” for 35.9% of adoles-
Yes 12 (4.1) 10 (10.2) cents and 44.7% of adults. The extent to
a b
Data are given as median (minimumemaximum); Categories were defined with the use of World Health Organization criteria which general pelvic pain interfered with
for participants 20 years old and the use of age-specific Center for Disease Control body mass index z-scores for those
participants <20 years old.
these activities did not differ between
DiVasta et al. Symptoms of endometriosis during adolescence vs adulthood. Am J Obstet Gynecol 2018. patients diagnosed relatively quickly
(1 year between symptom onset and
diagnosis) and those with a protracted
medication for menstrual pain (P¼.99). Acyclic pain time until diagnosis (>5 years from
Over-the-counter pain killers were used General acyclic pelvic pain over the symptom onset to diagnosis; P¼.27e.92;
by 70% of participants. One-third of lifetime was common for adolescents data not shown).
them tried hormone medications for (66%) and adults (77%; P¼.04). Over
pain but did not have an improvement in the previous 1e3 months, general pelvic Urinary and gastrointestinal
symptoms; the proportion did not vary pain severity was severe and similar be- symptoms
by age at diagnosis (P¼.42). Few ado- tween groups, with a median score of 8.0 Nausea was a frequent complaint.
lescents (18%) and adults (13%) took for both (on a 0e10 scale, where 0¼no Within the 12 months before survey
hormones and found that pain “got at pain and 10¼worst imaginable pain). completion, more adolescents (70%)
least somewhat better” (P¼.38). Many adolescents (40%) and adults than adults (51%) reported nausea

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ajog.org GYNECOLOGY Original Research

TABLE 2
Pathways to surgical diagnosis of endometriosis for female participants diagnosed during adolescence (£18 years old)
and during adulthood (>18 years old)
Adolescents at Adults at
Variable diagnosis (n¼270a) diagnosis (n¼101a) P valueb
Symptoms prompting the diagnosis of endometriosis
Pain 259 (95.9) 95 (94.1) .85
Infertility 1 (0.4) 4 (4.0) .02
Age at first symptoms, y c
13 (8e18) 16 (10e36) <.0001
Age when first saw any clinician about symptoms, y cd
14 (9e19) 20 (12e37) <.0001
d
Time between symptom onset and clinician visit, y
Median (minimumemaximum) 1.0 (0e7) 1.0 (0e17) .007
0 69 (41.1) 27 (34.6) <.0001
1 41 (24.4) 15 (19.2)
>1e3 45 (26.8) 12 (15.4)
>3 13 (7.7) 24 (30.8)
Time between symptom onset and surgical diagnosis, y
Median (minimumemaximum) 2.0 (0e7) 5.0 (0e26) <.0001
0 37 (14.0) 8 (8.0) <.0001
1 66 (25.0) 8 (8.0)
>1e3 86 (32.6) 19 (18.0)
>3 75 (28.4) 65 (65.0)
Age surgically diagnosed with endometriosis, y c
16 (9e18) 22 (19e46) <.0001
No. of clinicians seen for symptoms before surgical diagnosis of endometriosisc 2.0 (0e20) 2.5 (0e25) .37
a
Thirty-one participants who completed the questionnaire before their surgical diagnosis did not answer questions regarding diagnosis and symptom onset and are excluded from this Table; b Two-
sided probability values from Chi-square or Fisher’s exact tests for categoric variables and from Wilcoxon rank sum tests for continuous variables; c Data are given as median (minimumemaximum);
d
One hundred twenty-four participants completed the earliest version of the questionnaire (participants enrolled from 11/2012 to 6/2013) where age when first saw clinician about symptoms was
not queried.
DiVasta et al. Symptoms of endometriosis during adolescence vs adulthood. Am J Obstet Gynecol 2018.

accompanying general pelvic pain Participants who were diagnosed as with endometriosis during adolescence
(P¼.004). Only 20% reported vomiting adults were more likely to report more compared with adulthood. Pain signifi-
in conjunction with pain; no difference frequent urination when experiencing cantly impaired the women’s daily lives,
between groups occurred (P¼.15). menstrual pain (57%) compared with was frequently associated with nausea,
Bowel symptoms were less frequent adolescents (32%; P¼.05; Table 4). Pain and frequently improved after a bowel
(Table 4). One-third of participants re- with urination during menstrual pain movement.
ported more frequent bowel movements occurred in one-half the sample and was Unlike adult endometriosis that is
when period pain started (P¼.74); 21% similar between the 2 groups (P¼.38). diagnosed typically on the basis of
reported less frequent bowel movements The prevalence of pain with urination either pelvic pain or infertility, adoles-
when the period pain started (P¼.62). was slightly less with general pelvic pain cents are driven to seek medical care
Looser stools accompanying pain onset (adolescents 37% vs adults 40%; P¼.56). almost solely through life-impacting
were more common with dysmenorrhea pain symptoms. Dysmenorrhea and
than general pelvic pain (Table 4). Comment the pattern of pelvic pain in adolescents
Although changes in bowel habits did Dysmenorrhea and acyclic general pelvic with endometriosis were thought to
not often accompany the onset of general pain are common symptoms of endo- differ from adults.12,18 In a previous
pelvic pain, one-half of participants had metriosis, regardless of age at diagnosis. small case series of 46 adolescents with
general pelvic pain relief “sometimes,” Contrary to our original hypothesis, endometriosis, 9.4% had solely cyclic
“often,” “most of the time,” or “always” pain patterns were similar between pain with menses, whereas 62.5% had
after a bowel movement. female participants who were diagnosed both acyclic and cyclic pain and 28.1%

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Original Research GYNECOLOGY ajog.org

TABLE 3
Dysmenorrhea and general pelvic pain among female participants with endometriosis diagnosed during adolescence
(£18 years old) or during adulthood (>18 years old)
Adolescents at Adults at
Variable diagnosis (n¼295) diagnosis (n¼107) P valuea
Menstrual pain
Do you experience pain with periods? n (%)
No pain 3 (1.0) 2 (1.9) .52
Mild cramps (medication seldom needed) 20 (6.8) 5 (4.7)
Moderate cramps (medication usually needed) 86 (29.2) 26 (24.3)
Severe cramps (medication and bed rest needed) 186 (63.1) 74 (69.2)
When did you start having pain with your periods? n (%)
With my very first period 144 (49.7) 35 (34.0) .002
Within 2 years of my first period 111 (38.3) 42 (40.8)
>2 years after my first period 35 (12.1) 26 (25.2)
How long has it been since your last period? n (%)
3 Mo 159 (57.8) 62 (61.4) .49
4-6 Mo 34 (12.4) 13 (12.9)
7-12 Mo 20 (7.3) 3 (3.0)
>12 Mo 62 (22.5) 23 (22.8)
b
During the time in life when menstrual pain was the worst..., n (%)
Did you take any medication for the pain?
No 8 (5.7) 3 (5.0) .99
Yes 133 (94.3) 57 (95.0)
Did you take prescription pain-killers?
No 98 (69.5) 41 (68.3) .87
Yes 43 (30.5) 19 (31.7)
Did you take over-the-counter pain-killers?
No 41 (29.1) 17 (28.3) .92
Yes 100 (70.9) 43 (71.7)
Did you take hormonal medication, but the pain did not get better?
No 88 (62.4) 41 (68.3) .42
Yes 53 (37.6) 19 (31.7)
Did you take hormonal medication, and the pain got
at least somewhat better?
No 115 (81.6) 52 (86.7) .38
Yes 26 (18.4) 8 (13.3)
Acyclic pelvic pain
Did you ever experience general pelvic pain? n (%)
No 101 (34.2) 25 (23.4) .04
Yes 194 (65.8) 82 (76.6)
DiVasta et al. Symptoms of endometriosis during adolescence vs adulthood. Am J Obstet Gynecol 2018. (continued)

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ajog.org GYNECOLOGY Original Research

TABLE 3
Dysmenorrhea and general pelvic pain among female participants with endometriosis diagnosed during adolescence
(£18 years old) or during adulthood (>18 years old) (continued)
Adolescents at Adults at
Variable diagnosis (n¼295) diagnosis (n¼107) P valuea
How long did this pelvic pain last? n (%)
Minutes 20 (10.5) 13 (16.0) .18
Up to 1 hour 29 (15.3) 8 (9.9)
Hours 64 (34.2) 21 (25.9)
Days 74 (40.0) 39 (48.1)
How difficult did the pain make it to participate in school/work?c 7.0 (0e10) 7.0 (0e10) .95
c
How difficult did the pain make it to participate in recreational/social activities? 7.0 (0e10) 7.0 (0e10) .99
c
How severe was the pain in the last 1-3 months? 8.0 (0e10) 8.0 (0e10) .75
Did you experience nausea with your pain? n (%)
No 57 (30.5) 40 (48.8) .004
Yes 130 (69.5) 42 (51.2)
Did you experience vomiting with your pain? n (%)
No 138 (75.4) 66 (83.5) .15
Yes 45 (24.6) 13 (16.5)
b
During the time in life when the general pelvic pain was the worst..., n (%)
Did you take any medication for the pain?
No 13 (14.3) 5 (10.9) .58
Yes 78 (85.7) 41 (89.1)
Did you take prescription pain-killers?
No 58 (63.7) 33 (71.7) .35
Yes 33 (36.3) 13 (28.3)
Did you take over-the-counter pain-killers?
No 28 (30.8) 13 (28.3) .76
Yes 63 (69.2) 33 (71.4)
Did you take hormonal medication, but the pain did not get better?
No 55 (60.4) 34 (73.9) .12
Yes 36 (39.6) 12 (26.1)
Did you take hormonal medication, and the pain got
at least somewhat better?
No 82 (90.1) 40 (87.0) .58
Yes 9 (9.9) 6 (13.0)
If you had pelvic pain in the last 3 months, to what extent did the
general pelvic pain interfere with., n (%)b
Work or school?
Not at all 10 (13.0) 9 (23.7) .01
Slightly 20 (26.0) 6 (15.8)
Moderately 12 (15.6) 7 (18.4)
Quite a bit 25 (32.5) 4 (10.5)
Extremely 10 (13.0) 12 (31.6)
DiVasta et al. Symptoms of endometriosis during adolescence vs adulthood. Am J Obstet Gynecol 2018. (continued)

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Original Research GYNECOLOGY ajog.org

TABLE 3
Dysmenorrhea and general pelvic pain among female participants with endometriosis diagnosed during adolescence
(£18 years old) or during adulthood (>18 years old) (continued)
Adolescents at Adults at
Variable diagnosis (n¼295) diagnosis (n¼107) P valuea
Daily activities at home?
Not at all 8 (10.3) 9 (22.5) .07
Slightly 20 (25.6) 5 (12.5)
Moderately 21 (26.9) 8 (20.0)
Quite a bit 20 (25.6) 8 (20.0)
Extremely 9 (11.5) 10 (25.0)
Sleep?
Not at all 18 (23.4) 4 (10.0) .41
Slightly 15 (19.5) 11 (27.5)
Moderately 16 (20.8) 11 (27.5)
Quite a bit 16 (20.8) 7 (17.5)
Extremely 12 (15.6) 7 (17.5)
Exercise?
Not at all 7 (9.3) 3 (8.3) .09
Slightly 16 (21.3) 12 (33.3)
Moderately 17 (22.7) 5 (13.9)
Quite a bit 19 (25.3) 3 (8.3)
Extremely 16 (21.3) 13 (36.1)
Social activities?
Not at all 8 (10.3) 6 (15.8) .18
Slightly 20 (25.6) 11 (28.9)
Moderately 17 (21.8) 3 (7.9)
Quite a bit 22 (28.2) 8 (21.1)
Extremely 11 (14.1) 10 (26.3)
a
Two-sided probability values from Chi-square or Fisher’s exact tests for categoric variables and from Wilcoxon rank sum tests for severity ratings; b These questions were asked only on the final
version of the questionnaire implemented January 2014; c Rated on a scale ranging from 0¼no difficulty to 10¼extreme difficulty.
DiVasta et al. Symptoms of endometriosis during adolescence vs adulthood. Am J Obstet Gynecol 2018.

had acyclic pain only.19 We similarly cohort included a large proportion of reported >6 months of moderate-severe
found a high prevalence of acyclic pain adolescents and young women who had cramping during menstruation not
(66%) during adolescence and in the symptoms of pain and at surgical relieved by over-the-counter medica-
adult cohort (76%), which suggests that diagnosis were observed to have stage I tions. One-third of participants took
endometriosis-associated pain may and II endometriosis and is positioned hormone medications for pain without
remain acyclic and perhaps even to compare symptoms of adults and symptom improvement, regardless of
become more acyclic as patients get adolescents. The sample does not reflect age at diagnosis. This result likely reflects
older. Symptom patterns may change the adults with infertility or more the lowered responsiveness of
over time because of changes in the type advanced American Society for Repro- endometriosis-associated pain to hor-
of endometriosis lesions found at lap- ductive Medicine stage disease.6,20 monal therapies. These historical details
aroscopy that differ between adoles- Dysmenorrhea not responding to should be considered markers of poten-
cents and adults or because of the medical therapy with nonsteroidal anti- tial endometriosis and prompt clinicians
increased prevalence of deep infiltrating inflammatory drugs and/or combined to consider further evaluation. How-
endometriosis as women age.19 Our oral contraceptive pills is suggestive of ever, the higher risk of endometri-
findings may also be related to the endometriosis among adolescents.3,13 osis being observed at diagnostic
population that was studied. Our More than 90% of our participants surgery among women with acyclic or

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TABLE 4
Urinary and bowel symptoms associated with menstrual pain and general pelvic pain in females with endometriosis
diagnosed during adolescence (£ 18 years old) or during adulthood (>18 years old)
Pelvic pain with periods General pelvic pain
Adolescents at Adolescents at
diagnosis Adults at diagnosis diagnosis Adults at diagnosis
Variable (n¼82), n (%) (n¼35), n (%) P valuea (n¼78), n (%) (n¼40), n (%) P valuea
Urinary symptoms among those with
pain in the past 3 monthsb
Urinated more frequently than
usual
Never/rarely 23 (28.0) 6 (17.1) .05 32 (41.6) 12 (30.0) .35
Sometimes 33 (40.2) 9 (25.7) 24 (31.2) 11 (27.5)
Often 15 (18.3) 8 (22.9) 15 (19.5) 10 (25.0)
Most of the time 5 (6.1) 8 (22.9) 3 (3.9) 5 (12.5)
Always 6 (7.3) 4 (11.4) 3 (3.9) 2 (5.0)
Pain with urination
Never/rarely 41 (50.0) 17 (50.0) .38 49 (62.8) 24 (60.0) .56
Sometimes 25 (30.5) 7 (20.6) 18 (23.1) 9 (22.5)
Often 6 (7.3) 4 (11.8) 6 (7.7) 4 (10.0)
Most of the time 3 (3.7) 4 (11.8) 2 (2.6) 3 (7.5)
Always 7 (8.5) 2 (5.9) 3 (3.8) 0
Bowel symptoms among those with
pain in the past 3 monthsb
Pain got better or stopped after
bowel movement
Never/rarely 42 (51.9) 16 (47.1) .16 39 (50.0) 14 (36.8) .38
Sometimes 24 (29.6) 12 (35.3) 23 (29.5) 17 (44.7)
Often 11 (13.6) 1 (2.9) 6 (7.7) 1 (2.6)
Most of the time 3 (3.7) 4 (11.8) 7 (9.0) 5 (13.2)
Always 1 (1.2) 1 (2.9) 3 (3.8) 1 (2.6)
Pain got worse after bowel
movement
Never/rarely 48 (58.5) 18 (52.9) .88 48 (62.3) 24 (61.5) .94
Sometimes 22 (26.8) 10 (29.4) 21 (27.3) 10 (25.6)
Often 6 (7.3) 2 (5.9) 3 (3.9) 2 (5.1)
Most of the time 2 (2.4) 1 (2.9) 2 (2.6) 2 (5.1)
Always 4 (4.9) 3 (8.8) 3 (3.9) 1 (2.6)
More frequent bowel movements
when the pain started
Never/rarely 38 (46.9) 18 (52.9) .74 44 (57.1) 22 (55.0) .35
Sometimes 15 (18.5) 4 (11.8) 19 (24.7) 6 (15.0)
Often 10 (12.3) 4 (11.8) 5 (6.5) 7 (17.5)
Most of the time 11 (13.6) 3 (8.8) 6 (7.8) 3 (7.5)
Always 7 (8.6) 5 (14.7) 3 (3.9) 2 (5.0)
DiVasta et al. Symptoms of endometriosis during adolescence vs adulthood. Am J Obstet Gynecol 2018. (continued)

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TABLE 4
Urinary and bowel symptoms associated with menstrual pain and general pelvic pain in females with endometriosis
diagnosed during adolescence (£ 18 years old) or during adulthood (>18 years old) (continued)
Pelvic pain with periods General pelvic pain
Adolescents at Adolescents at
diagnosis Adults at diagnosis diagnosis Adults at diagnosis
Variable (n¼82), n (%) (n¼35), n (%) P valuea (n¼78), n (%) (n¼40), n (%) P valuea
Less frequent bowel movements
when the pain started
Never/rarely 46 (56.8) 22 (64.7) .62 42 (53.8) 26 (66.7) .52
Sometimes 18 (22.2) 5 (14.7) 18 (23.1) 9 (23.1)
Often 9 (11.1) 2 (5.9) 12 (15.4) 4 (10.3)
Most of the time 5 (6.2) 2 (5.9) 3 (3.8) 0
Always 3 (3.7) 3 (8.8) 3 (3.8) 0
Stools looser when the pain
started
Never/rarely 34 (42.0) 16 (47.1) .19 40 (51.3) 14 (35.0) .34
Sometimes 22 (27.2) 7 (20.6) 21 (26.9) 15 (37.5)
Often 11 (13.6) 1 (2.9) 12 (16.4) 6 (15.0)
Most of the time 10 (12.3) 9 (26.5) 3 (3.8) 4 (10.0)
Always 4 (4.9) 1 (2.9) 2 (2.6) 1 (2.5)
Stools harder when the pain
started
Never/rarely 48 (59.3) 21 (63.6) .34 43 (55.8) 22 (55.0) .84
Sometimes 24 (29.6) 7 (21.2) 19 (24.7) 13 (32.5)
Often 2 (2.5) 2 (6.1) 12 (15.6) 5 (12.5)
Most of the time 4 (4.9) 0 2 (2.6) 0
Always 3 (3.7) 3 (9.1) 1 (1.3) 0
a
Two-sided probability values from Fisher’s exact tests; b These questions were asked only on the final version of the questionnaire implemented January 2014.
DiVasta et al. Symptoms of endometriosis during adolescence vs adulthood. Am J Obstet Gynecol 2018.

hormone-resistant pain may also be Because endometriosis is a progressive treatment of endometriosis were com-
confounding by indication. If symptoms disease, early diagnosis and treatment mon. Female patients who were diag-
had been treated satisfactorily by are particularly important for younger nosed during adolescence experienced
hormones or if pain negatively impacted patients,18,23 particularly because endo- pain for a year on average before seeing a
quality of life solely during menses, these metriosis is a major cause of disability clinician and for 2 years between symp-
women may have never undergone sur- and compromised quality of life.12 In tom onset and diagnosis. It took almost 3
gery to obtain a laparoscopic diagnosis. our sample, participants described in- times longer for women diagnosed dur-
Our data regarding response to hormonal hibition of normal daily activities ing adulthood to receive their diagnosis.
treatment reflect this likelihood as well. because of pain and a substantial nega- Adults experienced longer time from
Early onset of dysmenorrhea is tive impact on academic or work success, symptom onset to first seeing a clinician
another characteristic of endometriosis exercise, and sleep. Recreational/social and then again from first seeing a clini-
among adolescents.8,21,22 Pain most activities were slightly less impacted than cian to a diagnosis. This “double delay”
commonly started within 2 years after these other areas, hypothesized to implies that it is not a delay in
menarche. Twice as many women who perhaps be due to the potential inactive/ care-seeking that prolongs the time to
were diagnosed during adulthood than passive nature of many social activities diagnosis but that other factors are
during adolescence did not start having and the more physical/active nature of contributing. We speculate that these
pain until >2 years after menarche. the others. factors may include normalization of
These women did not differ on Despite the enormous impact of these menstrual pain,24 fear of stigmatization
measured premenarchal characteristics. symptoms, delays in diagnosis and regarding a gynecologic complaint,25

324.e9 American Journal of Obstetrics & Gynecology MARCH 2018


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ajog.org GYNECOLOGY Original Research

lack of parental advocacy as young limitations should also be acknowl-


among adolescents. Interference with
women transition into adulthood, and edged. The analytic group includes
school or work, daily activities, exercise,
issues with health insurance coverage.26 women who were evaluated primarily
and sleep is common, as are associated
Additional reasons may include comor- with pain symptoms; this cohort is
gastroenterologic symptoms. Pediatri-
bidities or false diagnoses that lead to undersampled for women presenting
cians and gynecologists should be aware
confusion regarding the endometriosis with infertility, American Society for
of these important and common symp-
diagnosis.24 Although our sample rep- Reproductive Medicine stage III/IV dis-
toms to avoid unnecessary diagnostic
resents the experience of women with ease, or deep infiltrating endometriosis.6
delays and include endometriosis in the
pain symptoms, our data are consistent This selection bias may have led to our
differential diagnosis for both adolescents
with previous reports of adults who were findings of similar clinical symptoms
and adults who experience such pain. A
diagnosed on the basis of either pelvic between the 2 groups. Participants in our
more complete understanding of the
pain or subfertility.26 Educating not only cohort were enrolled from BCH, BWH,
presentation of endometriosis will enable
medical professionals but also patients and the surrounding communities; our
clinicians to improve care and treatment
and their caregivers regarding the nature patient population and clinical practices
for these young women with chronic
of adolescent pathologic pelvic pain is may not be generalizable to patients not
pain. n
critical to promote appropriate care- evaluated in a tertiary care center, to
seeking behaviors and to decrease diag- other geographic areas, or to patients
nostic delays in endometriosis.12,13,27-29 from different racial and ethnic or eco- Acknowledgments
Endometriosis has been associated nomic backgrounds. However, both age The authors thank our patients and their families,
consistently with dyspareunia, dysuria, groups were recruited from the same who made this research possible. Data collec-
and gastrointestinal symptoms.2,3,13,27 geographic and demographic catchment tion was facilitated by and conducted in
compliance with the World Endometriosis
We similarly observed that these symp- population, making the comparison be- Research Foundation Endometriosis Phenome
toms were prevalent. However, contrary tween these 2 age groups internally valid. and Biobanking Harmonization Project (WERF
to our hypothesis, we demonstrated no Additionally, we designated those pa- EPHect).
appreciable differences in the prevalence tients who were diagnosed by age 18
of vomiting, constipation, frequent years as “adolescents.” Based on this References
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MARCH 2018 American Journal of Obstetrics & Gynecology 324.e10


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2026-31. Waikato region of New Zealand: a comparative Ms Vitonis); the Division of Adolescent and Young Adult
13. Laufer MR, Sanfilippo J, Rose G. Adolescent cohort study with a mean follow-up time of 2.6 Medicine, Department of Medicine (Drs DiVasta and
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for providing translational research infor- Pediatric and adolescent gynecologic laparos- Supported by the J. Willard and Alice S. Marriott
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377-81. 26. Shadbolt NA, Parker MA, Orthia LA. Medicine at Boston Children’s Hospital, Boston, MA.
16. World Health Organization Expert Commit- Communicating endometriosis with young The sponsor had no role in the study design, conduct
tee. Physical Status: The use and interpretation women to decrease diagnosis time. Health of the study or data analysis, writing of the report, or
of anthropometry: report of a WHO Expert Promot J Austr 2013;24:151-4. decision to submit the article for publication.
Committee. Geneva: World Health Organization; 27. Shah DK, Missmer SA. Scientific investigation The authors report no conflict of interest.
1995. of endometriosis among adolescents. J Pediatr Presented as an oral platform presentation at the
17. Barlow SE. Expert committee recommen- Adolesc Gynecol 2011;24(suppl5):S18-9. North American Society of Pediatric and Adolescent
dations regarding the prevention, assessment, 28. O’Connell K, Davis AR, Westhoff C. Self- Gynecology Annual Meeting, Toronto, Canada, April
and treatment of child and adolescent over- treatment patterns among adolescent girls with 7-9, 2016.
weight and obesity: summary report. Pediatrics dysmenorrhea. J Pediatr Adolesc Gynecol Corresponding author: Amy D. DiVasta, MD, MMSc.
2007;1209(suppl):S164-92. 2006;19:285-9. amy.divasta@childrens.harvard.edu

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