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Study Objective: To evaluate whether ovulatory dysfunction due to polycystic ovary syndrome (PCOS) is a common underlying etiology of
abnormal uterine bleeding (AUB) in adolescents who require hospitalization and to explore etiology, treatment, and complications of AUB
with severe anemia in adolescents.
Design, Setting, Participants, Interventions, and Main Outcome Measures: We identied female patients aged 8-20 years admitted to a
children's hospital for treatment of AUB from January 2000 to December 2014. Our hospital protocol advises hormonal testing for PCOS
and other disorders before treatment for AUB. We reviewed medical records and recorded laboratory evaluations, treatments, and nal
underlying diagnoses as well as recurrences of AUB and readmissions in the subsequent year.
Results: Of the 125 subjects, the mean age was 16.5 2.9 years; mean hemoglobin level was 7.0 1.8 g/dL; 54% were overweight/obese;
and 41% sexually active. PCOS accounted for 33% of admissions; hypothalamic pituitary ovarian axis immaturity 31%; endometritis 13%;
bleeding disorders 10%. Girls with PCOS were more likely to be overweight/obese (74% vs 46%; P ! .01) and girls with hypothalamic
pituitary ovarian axis immaturity had lower hemoglobin levels (6.4 g/dL vs 7.4 g/dL; P ! .05), than girls with all other etiologies of AUB.
Treating physicians failed to diagnose endometritis as the etiology for AUB in 4 of 8 girls with positive tests for sexually transmitted
infection and no other etiology.
Conclusion: PCOS was the most common underlying etiology in adolescents hospitalized with AUB. Screening for hyperandrogenemia is
important for early diagnosis of PCOS to allow ongoing management and prevention of comorbidities. Endometritis was frequently
underestimated as an etiology for AUB.
Key Words: Abnormal uterine bleeding, Menorrhagia, Anemia, Polycystic Ovary Syndrome, Adolescent, Endometritis
emergency department physicians, in consultation with acute menorrhagia and anemia from January 1, 2000 to
adolescent medicine specialists who manage the patients December 31, 2014. CLG integrates demographic, clinical,
during their hospitalization (Fig. 1). In addition to recom- and administrative data sets from the electronic medical
mending appropriate assessment and treatment regimens, records (EMRs) of all patients seen in inpatient hospitals
the protocol advises that certain blood tests to assess for and ambulatory clinics in our extensive health system and
bleeding disorders, and hormonal dysfunction including allows them to be reproduced in a programmable format for
polycystic ovary syndrome (PCOS) should be sent to the statistical access.13 Specically, we queried CLG for all fe-
laboratory before beginning treatment with any hormonal male patients aged 8-20 years discharged from the hospital
medication or blood transfusion. Thus, for our cohort of ad- with primary or secondary International Classication of
olescents, we have the opportunity to differentiate ovulatory Diseases, Ninth Revision diagnosis codes for menorrhagia,
dysfunction secondary to PCOS from that due to other causes. menstrual disorders, acute and chronic anemia, thrombo-
In this study, we aimed to describe the underlying eti- cytopenia and other bleeding disorders, and who were
ologies, treatments, and complications of AUB in a large treated with estrogens, progestins, or antibrinolytics dur-
sample of adolescents admitted to a single quaternary care ing the hospital admission.
children's hospital. We hypothesized that ovulatory
dysfunction related to PCOS would be a common underly- Subjects
ing etiology because we frequently diagnose PCOS in ado-
lescents in the outpatient setting.12 The CLG search produced a total of 335 patient records
that we screened for inclusion in the cohort. We excluded a
Materials and Methods total of 210 adolescents; most with pregnancy-related
uterine bleeding admitted to a hospital other than the
The study was approved by the institutional review children's hospital in our health system. In addition, we
board of the Albert Einstein College of Medicine/Children's excluded a few adolescents admitted to the children's
Hospital at Monteore. hospital who did not meet inclusion criteria because they
did not have active uterine bleeding during the hospitali-
Procedure zation. A total of 125 subjects were included in the study.
data extraction tool created for this study. The 5 physicians Table 1
Characteristics of Adolescents Admitted to a Children's Hospital with AUB (N 5 125)
met in person after reviewing 3-5 medical records each to
discuss and resolve areas of confusion and amend the data Characteristic Value
Statistical Analyses For our 125 adolescent subjects we determined the un-
derlying etiology of AUB for a total of 102 (Fig. 2). For 84
Descriptive statistics were used to characterize de- subjects the treating physician documented the etiology in
mographic characteristics, age at menarche, gynecologic the medical record. For 18 subjects the etiology was deter-
age, etiology of AUB, and types of treatment. To compare mined in our medical record review. Ovulatory dysfunction
etiologies, hemoglobin measurement at the time of related to PCOS accounted for 33% (34 out of 102) of the
admission and patient characteristics we used the Student t admissions and was the most common underlying etiology
test for continuous variables and c2 for categorical vari- of AUB. Ovulatory dysfunction related to HPO axis imma-
ables. STATA version 11.0 (StataCorp, College Station, TX) turity accounted for 31% (32 out of 102) of admissions,
4 S. Maslyanskaya et al. / J Pediatr Adolesc Gynecol xxx (2016) 1e7
Endometritis
13% Treatment of AUB and Anemia during the Index Hospital Admission
anfibrinolycs
anbiocs
intravenous estrogens
0% 10% 20% 30% 40% 50% 60% 70% 80% 90% 100%
Fig. 3. Inpatient management of abnormal uterine bleeding (AUB) with severe anemia according to frequency of therapeutic use (N 5 125).
Individual patients may have been treated with more than 1 therapeutic agent.
S. Maslyanskaya et al. / J Pediatr Adolesc Gynecol xxx (2016) 1e7 5
about the etiology of AUB, risk of recurrence of AUB if index hospitalization. This highlights the importance of
treatment is discontinued, and prevention of comorbidities. determining the etiology of AUB and providing anticipatory
Thus, making a diagnosis of PCOS as the etiology for AUB guidance for adolescent girls and their families regarding
allows for intensive intervention to assist in improving the the need for ongoing monitoring and adherence to treat-
lifetime health of these adolescents. ment after the initial episode. Many adolescents and their
We found that adolescent girls in our sample whose AUB parents are ambivalent about taking birth control pills,
with severe anemia was related to ovulatory dysfunction the treatment most often used to prevent recurrences of
due to HPO axis immaturity had a signicantly lower he- AUB, and poor adherence is common. Cost utility analysis of
moglobin level on admission to hospital than girls admitted screening for von Willebrand disease in women with
with all other etiologies of AUB. This is a surprising nding menorrhagia was found to be cost-effective,29 and we pro-
and suggests to us that for perimenarchal girls whose pose that screening adolescent girls with AUB for PCOS as
relative inexperience in judging normal quantities of men- our protocol suggests might also be cost-effective. Finally
strual blood loss coupled with embarrassment and reluc- our ndings reafrm the importance of having a clinical
tance to bring attention to their menstrual bleeding likely protocol or guideline to standardize practice and ensure
delays their presentation for needed health care and puts that girls with AUB and severe anemia are tested for
them at risk for life-threatening anemia.26 We suggest that hyperandrogenemia before treatment with hormones is
pediatricians and other clinicians caring for perimenarchal begun and that those who are sexually active are examined
girls document detailed menstrual histories and monitor and tested for STIs.30
hemoglobin levels if prolonged or frequent uterine bleeding A limitation of this study is that it was performed in a
is uncovered so that treatment can be instituted before the single center and the subjects were a diverse ethnic/racial
development of severe anemia and the necessity for hos- mix with very few white adolescents. Our results might not
pital admission.10 be generalizable to primarily Caucasian or other pop-
Another nding of this study that is different from ulations of adolescents. In addition, because of the medical
ndings reported in older published studies of adolescents record review study design, there were missing data and we
admitted to hospital for AUB and severe anemia is that more were limited in obtaining long-term follow up data on all
than 10% of the AUB episodes that required hospitalization subjects. Despite these limitations, the ndings of this study
in our subjects were related to sexually transmitted endo- highlight the importance of considering gynecologic age,
metritis. Studies of adult women suggest that AUB sec- ethnicity, weight status, and sexual activity when deter-
ondary to infectious endometritis is frequently mining the etiology of AUB with severe anemia in the
underestimated.27,28 Toth et al examined endometrial bi- adolescent population. For populations similar to ours, we
opsies from premenopausal women hospitalized with AUB recommend screening for biochemical markers of hyper-
to nd antibodies against Chlamydia trachomatis as well as androgenemia to aid in the diagnosis of PCOS before
histopathology associated with inammation.27 They found beginning treatment with estrogens and/or progestins that
that Chlamydia trachomatis was detected in 48% of speci- suppress ovarian androgens and preclude making the
mens and was signicantly associated with endometrial diagnosis. In addition, all adolescents with AUB and signif-
inammation, suggesting that chlamydia infection of the icant anemia should have a condential sexual history
endometrium might result in chronic inammation causing taken and STIs should be considered in the etiology of AUB
AUB. In our sample of adolescents, more than 40% were at in adolescents.
risk for STIs because they were sexually active and 8% had a
history of a previous STI. Infectious endometritis is a known Acknowledgments
cause of AUB but unless a condential sexual history, pelvic
examination, and tests for STIs are obtained the diagnosis The authors thank Tamara Freiden, MD, 2016 graduate of
might be missed in adolescent girls and appropriate anti- the Albert Einstein College of Medicine, for her assistance
biotic treatment might not be given. Indeed, in our cohort, with review of medical records.
cases of endometritis might have been missed because we
found several adolescents who tested positive for STIs
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