Accepted Manuscript Treatment of acute abnormal uterine bleeding in adolescents: what are providers doing in various specialties? P.S. Huguelet, MD, E.M. Buyers, MD, J.H. Lange-Liss, MD, S.M. Scott, MD PII:
S1083-3188(15)00373-3
DOI:
10.1016/j.jpag.2015.10.021
Reference:
PEDADO 1922
To appear in:
Journal of Pediatric and Adolescent Gynecology
Received Date: 22 June 2015 Revised Date:
22 October 2015
Accepted Date: 30 October 2015
Please cite this article as: Huguelet P, Buyers E, Lange-Liss J, Scott S, Treatment of acute abnormal uterine bleeding in adolescents: what are providers doing in various specialties?, Journal of Pediatric and Adolescent Gynecology (2015), doi: 10.1016/j.jpag.2015.10.021. This is a PDF file of an unedited manuscript that has been accepted for publication. As a service to our customers we are providing this early version of the manuscript. The manuscript will undergo copyediting, typesetting, and review of the resulting proof before it is published in its final form. Please note that during the production process errors may be discovered which could affect the content, and all legal disclaimers that apply to the journal pertain.
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Treatment of acute abnormal uterine bleeding in adolescents: what are providers doing in various specialties?
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Huguelet PS, MD1; Buyers EM, MD1; Lange-Liss JH, MD2; Scott SM, MD1
1. Pediatric and Adolescent Gynecology, Children’s Hospital Colorado, Department of Obstetrics and Gynecology, University of Colorado School of Medicine, Aurora, CO
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2. Department of Obstetrics and Gynecology, University of Colorado School of Medicine, Aurora,
Corresponding Author and Reprints:
Patricia Huguelet, MD
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Assistant Professor, Department of Obstetrics and Gynecology
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University of Colorado and Children’s Hospital Colorado, Anschutz Medical Campus Academic Office 1, Box B-198-2
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12631 East 17th Avenue, Aurora, CO 80045 [email protected]
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303-724-2038 Phone 303-724-2056 Fax
Disclosure: The authors report no conflicts of interest.
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Abstract
Objectives: The purpose of this study was to assess whether variability exists in the management of
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acute abnormal uterine bleeding (AUB) in adolescents by pediatric emergency department physicians, pediatric gynecologists and adolescent medicine specialists.
Setting: Tertiary care medical center Emergency Department.
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Design: Retrospective chart review.
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Participants: Females aged 9-22 who presented from July 2008 to June 2014 with the complaint of acute AUB. Patients were identified by ICD-9 codes for heavy menstrual bleeding, abnormal uterine bleeding, and irregular menses. Exclusion criteria included pregnancy and current use of hormonal therapy. 150 patients were included.
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Results: Among those evaluated, 61% (n = 92) were prescribed hormonal medication to stop their bleeding by providers from the Emergency Department (ED), Adolescent Medicine, or Pediatric Gynecology.
ED physicians prescribed mostly single dose and multi-dose taper combined oral
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contraceptive pills (COCPs) to patients (85%, n=24), compared to Adolescent medicine (54%, n = 7) and Gynecology (28%, n = 13).
Pediatric gynecologists were more likely than Emergency Department
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physicians to treat patients with norethindrone acetate, either alone or in combination with a single dose COCP (61%, n = 33 versus 7%, n = 2; P < 0.001).
Conclusion: Variations in treatment strategies for adolescents who present with acute AUB exist among pediatric specialties, reflecting lack of standardized care for adolescents. Prospectively evaluating shortest interval to cessation of bleeding, side effects and patient satisfaction are valuable next steps.
Key Words: Acute abnormal uterine bleeding, Adolescents, Treatment
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Introduction
Abnormal uterine bleeding (AUB) may be acute or chronic and is defined as bleeding from the uterine
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corpus that is abnormal in regularity, volume, frequency, or duration and occurs in the absence of pregnancy.1 Acute uterine bleeding is defined as “an episode of bleeding in a woman of reproductive age, who is not pregnant, that, in the opinion of the provider, is of sufficient quantity to require immediate intervention to prevent further blood loss.”2 Intervention in this setting is often initiated
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prior to the completed work up for the specific etiology of AUB.3
Menstrual disorders are common in adolescents. Self-reported surveys have demonstrated that 30% of adolescents report irregular bleeding and 15-40% perceive their bleeding as abnormally heavy.4,5 Numerous studies have shown that 50-80% of menstrual cycles in the first two years after menarche are
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anovulatory, creating dysfunctional endometrial shedding.6,7 Anovulatory cycles create an environment of unopposed estrogen stimulation and endometrial proliferation, without progestin-induced stabilization. The end result is disorderly shedding of the endometrial lining without prostaglandin-
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mediated vasoconstriction and platelet-plugging of arterioles.8 The presence of an underlying bleeding disorder may further exacerbate the situation. Ultimately, these issues may lead to episodes of heavy
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vaginal bleeding, often prompting an emergency room visit.
Medical management is generally considered first-line therapy for acute AUB and may consist of estrogen, progestin, or a combination of both, usually in the form of combined oral contraceptive pills (COCPs). Despite their widespread use, there exists very little information regarding the effectiveness,
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side effects and patient satisfaction associated with these commonly used medical regimens. Even less
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evidence exists in the adolescent medical literature.
Only one study has been reported in the literature that compared medical intervention to placebo.9 In this randomized controlled trial, intravenous conjugated equine estrogen (CEE) resulted in cessation of
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bleeding by 5 hours in 72% of the treatment group versus only 38% of placebo.9 In all other studies, medications have been compared to each other, without a control group. In one randomized controlled
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trial, COCPs were administered with a taper and compared to oral progestin therapy alone, with no difference in efficacy between the two regimens.10
Two additional studies describe the time to
cessation of bleeding using a single oral progestin method, again without control groups participating
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and no difference in efficacy demonstrated.11,12
No studies have evaluated the long-term bleeding patterns of various hormonal regimens. Given the lack of strong evidence to support one medical regimen over another, we sought to understand whether
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variability exists in work up and prescribing methods, and if so, whether it was specialty specific.
Materials and Methods
Research Design and Study Population This retrospective chart review was IRB-approved at a children’s hospital in a large urban academic setting. Females aged 9 – 22 who had been evaluated in the Emergency Department (ED) for acute AUB
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were included. In this study, the term adolescent refers to females up to the age of 22, which reflects
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the upper age-limit set by Children’s Hospital Colorado (CHCO) for routine patient care.
Data Collection
The CHCO Research Institute searched the entire electronic medical record (EMR) between July 2008
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and June 2014. The EMR was queried for all female patients between the ages of 9 – 22, presenting to the ED with acute vaginal bleeding. Cases of vaginal bleeding were identified based on the following
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ICD-9 codes: disorders of menstruation (626), excessive or frequent menstruation (626.2), irregular bleeding (626.4), and dysfunctional uterine bleeding (626.8). Patients with a coexisting pregnancy or currently on hormonal medication were excluded. A total of 419 charts were accessed and ultimately
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150 met inclusion criteria.
Once the initial query was performed, the Research Institute uploaded the patient list, including the patient’s medical record number, age, race, and date of ED visit into a secure REDCap database. Four
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gynecologists then independently searched each patient’s medical record for the following information
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pertaining to the ED visit: age at menarche, menstrual history, notes documenting inquiry about personal and family history of a bleeding disorder, relevant physical exam findings, including body mass index (BMI) and vital signs at presentation, laboratory findings including complete blood count (CBC) or hematocrit if a full CBC was not ordered, prothromin time (PT), partial thromboplastin time (PTT) and standard Von Willebrand Disease (VWD) testing, presence or absence of transfusion, diagnosis, medication and dosage prescribed, and finally, specialty of provider who recommended therapy.
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All cases were initially evaluated by the ED provider and then the chart was reviewed to determine whether phone consultation was obtained. The chart was then reviewed for subsequent follow up office visits, recording time to cessation of bleeding, side effects from medication and satisfaction with
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treatment prescribed.
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Throughout the process, regular meetings were held among the reviewers to maintain consistency and discuss any discrepancies in the medical record. Once all charts were reviewed, the principal
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investigator subsequently reviewed all charts to confirm accuracy of data gathering.
The primary outcome was treatment recommended and specialty of the prescribing physician. Secondary outcomes included rates of historical data collection, rates of laboratory evaluation and
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predictors of laboratory studies ordered, criteria for blood transfusion, time to cessation of bleeding,
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side effects from medication and satisfaction with treatment prescribed.
Consistent with previous studies, we defined severe anemia as a hemoglobin < 8mg/dL and tachycardia
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as a heart rate ≥ 100.
Data Analysis
Descriptive statistics are presented for continuous variables using means and ranges for each clinical specialty, with Student t-tests used to compare these variables. The association between two categorical variables was tested using chi-square tests, and ANOVA was used when comparing more
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than two variables. When a chi-square test was invalid due to small sample size, the Fisher exact test
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was used. P < 0.05 was considered significant.
Results
A total of 150 adolescents, not on hormonal medication, presented to CHCO Emergency Department
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complaining of acute AUB. The median age was 14.9 years (range 9 – 22). There was no significant difference in demographic information between patients evaluated by Emergency Medicine, Pediatric
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Gynecology, or Adolescent Medicine (Table 1). Among the faculty providers, there were a total of 77 ED physicians, 3 Pediatric gynecologists and 5 Adolescent medicine physicians caring for these patients.
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All patients were initially evaluated by ED staff, with ED providers subsequently consulting a specialty service in just over 50% of patients. Among the adolescents not treated with medication (39%, n = 58), the ED staff managed all of them alone. Among those who were treated with medication (61%, n = 92),
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the ED consulted primarily Adolescent Medicine and Pediatric Gynecology. 5 patients were managed by other faculty, including Hematology and their Primary Care Physician. Given the small number of other
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providers, this group was not compared to the other specialties to assess for statistical significance (Table 2).
Regarding those adolescents who were ultimately prescribed hormonal medication to stop their bleeding (61%, n = 92), ED providers treated 28 patients and of those, 86% (n = 24) were prescribed single dose and multi-dose taper combined oral contraceptive pills (COCPs). Adolescent Medicine
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providers were consulted on 13 patients, recommending a COCP regimen 54% (n = 7) of the time. Pediatric Gynecologists were consulted on 46 patients, recommending a COCP regimen in 28% (n = 13) of cases (Table 2).
Pediatric Gynecologists were significantly more likely than ED physicians to
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recommend treatment with norethindrone acetate, either alone or in combination with a single dose COCP (72%, n = 33 of 46 versus 7%, n = 2 of 28; P < 0.001). Adolescent Medicine providers did not demonstrate a single preferred medication, with 46% of providers recommending norethindrone alone
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or in combination with a COCP, versus 54% recommending single dose or multi-dose tapered COCPs (Table 2). Only two providers, both from the ED, recommended medroxyprogesterone acetate (MPA).
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In both cases, MPA was prescribed alone. No patients were prescribed tranexamic acid or required surgical intervention.
When looking at secondary outcomes, we also noted wide variation in recorded historical data. BMI
(52%).
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was reported in a third of all patient charts (36%) and providers recorded age at menarche in one half The vast majority of providers attempted to characterize the patient’s bleeding history.
However, less than half of providers (45%) inquired about factors suggestive of a bleeding disorder,
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including history of frequent nosebleeds, bleeding gums, bleeding with surgical or dental procedures, or
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family history of a bleeding disorder.12
Regarding laboratory analysis, the following was noted. Among patients prescribed medication (n = 92), 92% were evaluated with a hemoglobin level. Among those patients not prescribed medication (n = 58), 50% were evaluated with a hemoglobin level. The average hemoglobin level was lower among those who were treated (Hb 11.4, range 4.3 – 15.8) versus those who were untreated (Hb 13.0, range 8.9 –
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15.6). However, this did not meet statistical significance (p = 0.07). The average hemoglobin was significantly lower among patients prescribed norethindrone, either alone or in combination with a COCP: norethindrone = 11.3, norethindrone with COCP = 10.0, COCP single dose = 12.3, COCP multi-
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dose = 12.1 (p = 0.03).
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Based on these observations, we next looked at objective criteria that might have influenced decision to order a CBC. There was no difference in average systolic blood pressure (121 vs 122, p = 0.71), diastolic
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blood pressure (69 vs 70, p = 0.79) or heart rate (87 vs 84, p = 0.38) among those patients who had a CBC drawn versus those who did not. Looking specifically at tachycardic patients, 35 (23%) presented with tachycardia and 115 (77%) presented with a normal heart rate. Among those patients who were
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tachycardic, 86% had a CBC drawn versus 72% who were not tachycardic (p = 0.10).
We also looked at whether vital signs influenced decision to recommend treatment. The average systolic (120 vs 124) and diastolic (69 vs 72) blood pressures were not significantly different among the
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treatment and non-treatment groups (p = 0.10, p = 0.07). The average heart rate was also similar
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among the two groups at 87 (range 44 – 135) and 85 (range 57 – 115), respectively (p= 0.57).
Regarding potential criteria to order a bleeding workup, the following was noted. A total of 35 patients (23%) were tested for a bleeding disorder, with testing including PT, PTT, and/or VWD testing. Among those patients who were tested for a bleeding disorder, the average hemoglobin level was 10.4 versus 12.3 in those not tested (p = 0.001). Both average systolic and diastolic blood pressure at presentation
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did not predict bleeding disorder workup (p = 0.07, p = 0.24) but average heart rate was higher, 93
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versus 84, in those patients who ultimately had these labs drawn (p = 0.004).
Charts were next reviewed for the evaluation and management of patients with severe anemia. A total of 16 patients (10.7%) met criteria for severe anemia. There was a significant difference in mean
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hemoglobin level between adolescents who received a blood transfusion (Hb 5.48, Range 4.3 – 6.9
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mg/dL) and those who were not transfused (Hb 6.6, Range 5.0 – 7.1 mg/dL mg/dL, p = 0.02).
In 100% of the patients with severe anemia, ED physicians consulted with a specialist, primarily Pediatric Gynecology. Norethindrone acetate was recommended in the majority of cases, either alone or in combination with a COCP (Table 3). Four patients with severe anemia were treated with IV CEE. In each
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case, this treatment was initiated and within 24 hours of starting CEE therapy, a single dose COCP and norethindrone acetate were added to the patient’s regimen.
Of note, one additional patient in our
study was also treated with IV CEE. This was initiated after an acute vasovagal episode in the ED.
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However, subsequent laboratory analysis revealed a normal hemoglobin level of 12.2 mg/dL.
Only patients with severe anemia were admitted to the hospital, defined in our study by a Hb < 8mg/dL. Among those patients with severe anemia (n = 16), 9 were admitted, with an average hemoglobin of 5.6 versus 6.3 in the non-admission group (p = 0.13). All patients treated with IV CEE required hospital admission.
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Next, we attempted to look at predictors of ED consultation with specialists for treatment recommendation. There was a trend towards younger age at presentation in those patients referred to specialists (14.3) versus those managed by ED providers (15.0), but this did not reach statistical
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significance (p = 0.10). However, the average hemoglobin level was significantly lower in those patients
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referred to specialists (10.8) versus managed solely by ED providers (12.9, p = 0.001).
Finally, charts were reviewed to evaluate whether a difference existed in time to cessation of bleeding
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and patient satisfaction with prescribed medication. Unfortunately, not enough patients presented for outpatient follow up to collect meaningful information regarding these secondary outcomes.
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Discussion
There appears to be wide variation in practice management of acute AUB in adolescents. Among pediatric providers at our institution, ED physicians prescribed single and multi-dose COCPs significantly
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more often than Pediatric Gynecologists. Adolescent Medicine faculty appeared to be evenly divided between COCP use and norethindrone acetate.
There was a significant trend toward use of
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norethindrone acetate by Pediatric Gynecology, particularly in the setting of true anemia. The practice pattern for why one medication was chosen above another was unable to be determined, given the retrospective nature of the study.
We also noted wide variability in the collection of historical information and physical exam findings relevant to the evaluation of acute AUB patients. Both age at menarche and BMI can provide valuable
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clues in deciphering the etiology of an adolescent’s bleeding pattern, including discriminating between normal anovulatory bleeding due to an immature hypothalamic-pituitary-ovarian axis versus bleeding due to polycystic ovarian syndrome (AUB-O) and other ovulatory disorders.
Furthermore, bleeding
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disorders (AUB-C) can often be unmasked at the time of menarche and personal and family history questions can be highly predictive of a bleeding disorder.12 However, this information was not collected
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consistently, with less than half of all patients queried for this information.
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We next attempted to understand the factors that influenced a provider’s decision to order blood work. Given the retrospective study, we were unable to reliably collect patient-reported symptoms of anemia. However, when we analyzed objective data, including blood pressure and heart rate, there were no differences among patients who did and did not have a CBC drawn. Although vital signs did not appear to influence decision to order a CBC, heart rate did appear to influence bleeding disorder evaluation.
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disorder evaluation.
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Furthermore, the hemoglobin level itself also appeared to influence decision to proceed with a bleeding
Finally, we attempted to understand the factors that influenced provider’s decision to initiate
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treatment. Once again, there were no differences in average blood pressure and heart rate among the treatment and non-treatment groups. Furthermore, when we analyzed the average hemoglobin level among these two groups, the hemoglobin level was not significantly lower in the treated group and the total range of values overlapped. Interestingly, the majority of patients who were ultimately treated with medication were evaluated with a hemoglobin level, versus only 50% of the untreated group. These discrepancies in objective evaluation suggest that subjective assessment of acute AUB played a
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strong role in the provider’s evaluation and subsequent treatment of these patients. Simply deciding to draw a hemoglobin level appeared to determine treatment versus the absolute value returned.
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However, historically we know that patient’s report of bleeding is often unreliable.13
There are clearly times when a provider’s subjective assessment of the severity of bleeding may override
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the laboratory data. However, this can lead to both over and under treatment of some patients. The results section describes an individual who received IV estrogen even in the face of a normal
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hemoglobin level. Although generally thought of as safe, the thrombotic risk posed by higher estrogen levels must be considered prior to its initiation. Conversely, among the individuals who were not treated with hormones, several individuals were found to be anemic in an ambulatory setting one week later. Based on ACOG recommendations, all patients being evaluated for acute AUB would benefit from
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CBC analysis.13
Ultimately, the decision to treat acute bleeding may not be based on the provider’s perceived severity of
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active blood loss, but more by patient preference and reported complaints. Functional impairment of daily activities or simply patient preference may influence a provider to initiate hormonal therapy even
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in the absence of any clinic health concerns associated with bleeding. Given the retrospective nature of this study, we were unable to assess for this possibility.
Strengths and Limitations
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Two strengths of this retrospective chart review are the size of the cohort and the attempt to characterize a common problem that has been relatively understudied. A total of 419 charts were
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reviewed, with 150 patients ultimately meeting inclusion criteria.
Given the retrospective nature of the study, however, several limitations exist. Frequently, inconsistent information was recorded in the medical chart, resulting in limited ability to make precise conclusions
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regarding the provider’s decision to order a hemoglobin level, when to initiate therapy, and type of medication prescribed. Furthermore, very few patients followed up in our outpatient clinic setting,
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preventing us from comparing efficacy and side effects of the various medications prescribed.
Conclusion
Wide variability in the evaluation and management of young women with acute AUB exists among
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pediatric specialties. It appears to be specialty-specific, rather than patient-specific and currently is not evidence based, likely due to the lack of good quality studies comparing the different options.
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Based on our observations, we have created an algorithm that we believe will lead to quality improvement with more standardized evaluation of these patients (Figure 1). Once this goal is achieved,
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we can then begin to conduct valuable prospective research to identify the optimal medication to treat acute AUB in adolescents.
Acknowledgements We would like to thank Jeanelle Sheeder, PhD, for her help with statistical analysis for this project.
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References
1. Management of acute abnormal uterine bleeding in nonpregnant reproductive-aged
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women. ACOG Committee Opinion No. 557. Obstet Gynecol 2013; 121:891 2. Munro MG, Critchley H, Broder MS, et al: FIGO classification system (PALM-COEIN) for causes of abnormal uterine bleeding in nongravid women of reproductive age. Int J
3. James AH, Kouides PA, Abdul-Kadir R, et al:
Evaluation and management of acute
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Gynaecol Obstet 2011; 113:3
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menorrhagia in women with and without underlying bleeding disorders: consensus from an international expert panel. Eur J Obstet Gynecol Reprod Biol 2011; 158:124 4. Agarwal A, Venkat A: Questionnaire study on menstrual disorders in adolescent girls in Singapore. J Pediatr Adolesc Gynecol 2009; 22:365 5. Friberg B, Orno AK, Lindgren A, et al:
Bleeding disorders among young women: a
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population-based prevalence study. Acta Obstet et Gynecol Scand 2006; 85:200 6. Apter D, Viinikka L, Vihko R: Hormonal pattern of adolescent cycles. J Clin Endocrinol Metab 1978; 47:944
816:9
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7. Apter D: Development of the Hypothalamic-Pituitary-Ovarian Axis. Ann N Y Acad Sci 1997;
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8. Cowan BD, Morrison JC: Current Concepts: Management of abnormal genital bleeding in girls and women. N Engl J Med 1991; 324:1710
9. DeVore GR, Owens O, Kase N:
Use of intravenous premarin in the treatment of
dysfunctional uterine bleeding – a double-blind randomized control study. Obstet Gynecol 1982; 59:285
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10. Munro MG, Mainor N, Basu R, et al: Oral medroxyprogesterone acetate and combination oral contraceptives for acute uterine bleeding, a randomized controlled trial.
Obstet
Gynecol 2006; 108:924 High-dose medroxyprogesterone acetate for the
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11. Aksu F, Madazli R, Budak E, et al:
treatment of dysfunctional uterine bleeding in 24 adolescents. Aust NZ J Obstet Gynaecol 1997; 37:228
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12. Santos M, Hendry D, Sangi-Haghpeykar H, et al: Retrospective review of norethindrone use in adolescents. J Pediatr Adolesc Gynecol 2014; 27:41
Hemostasis and menstruation: appropriate
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13. Kouides PA, Conard J, Peyvandi F, et al:
investigation for underlying disorders of hemostasis in women with excessive menstrual bleeding. Fertil Steril 2005; 84:1345
14. Menstruation in girls and adolescents: using the menstrual cycle as a vital sign. ACOG
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Committee Opinion No. 349. Obstet Gynecol 2006; 108:1323
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Table 1 Demographics of Patients Evaluated for Acute AUB in Emergency Department by Specialty Pediatric Gynecology
Adolescent Medicine
N
86
46
13
Age, mean (range)
15.3 (9-22)
14.1 ( 10-19)
15.3 (11-20)
Other
5
Ethnicity, n (%)
13.6 (10-18)
0.170 0.112
20 (23)
15 (33)
4 (31)
2 (40)
African American
15 (17)
9 (20)
1 (8)
0 (0)
Hispanic
46 (53)
16 (35)
7 (54)
2 (40)
5 (6)
6 (13)
1 (8)
1 (20)
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Caucasian
Other
P Value
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Emergency Medicine
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Table 2 Recommended Treatment of Acute AUB by Specialty
N (%)
Pediatric Gynecology
28
NA +/- COCP
2 (7)
MPA
2 (7)
46
Adolescent Medicine
13
33 (72) 0
Other
5
6 (46) 0
P Value
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Emergency Medicine
< 0.001
1 (20) 0
13 (45)
11 (24)
3 (23)
3 (60)
COCP taper
11 (39)
2 (4)
4 (31)
1 (20)
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COCP single dose
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NA, Norethindrone acetate; MA, Medroxyprogesterone acetate; COCP, Combined oral contraceptive pill
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Table 3 Management of Patients with Severe Anemia, by Specialty Adolescent Medicine
Other
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Pediatric Gynecology
N
0
12
1
IV CEE
0
4
0
NA
0
6
0
NA + COCP
0
6
0
COCP taper
0
0
1
COCP daily
0
0
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Emergency Medicine
0
3
0
1
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0
0
2
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NA, Norethindrone acetate; COCP, Combined oral contraceptive pill; IV CEE, Intravenous conjugated equine estrogen
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Figure 1. Algorithm for ED Evaluation of Acute AUB not due to Trauma or Pregnancy
Laboratory analysis for all adolescents: • HCG • CBC
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Physical examination • Vital signs and BMI • General examination
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Clinical History including: • Age at menarche • Family history of bleeding • Easy bruising, epistaxis, frequent gum bleeding, surgery-related bleeding • Sexual activity
If sexually active: Gonorrhea/Chlamydia NAAT If history suggestive of bleeding, include Tier 1 Testing: • VWF Ag, VWF Activity, Factor VIII Assay, PT/PTT
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Imaging usually not needed. Consider if bleeding or pain not controlled.
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No anemia • Offer outpatient regimen • Follow-up with outpatient provider in next 7 days.
Hemodynamically unstable
Complete lab assessment including Type and Screen
IV Conjugated Equine Estrogen 25mg IV q 4hours, up to 6 doses
Initiate outpatient regimen once stabilized
+ Anemia • Start outpatient regimen; counsel that bleeding should slow or stop within 1-2 days of treatment. • Follow-up with outpatient provider in next 7 days, sooner if bleeding persists.
Options for Outpatient Regimen Not anemic, no contraindications to COCPs: • Single dose monophasic COCP
Anemic, no contraindications to COCPs. Also consider if bleeding prolonged or otherwise difficult to manage: • Single dose monophasic COCP combined with norethindrone acetate 5mg daily • Multi-dose taper monophasic COCP, TID for 7 days, followed by daily therapy Alternatives if COCPs are contraindicated or non-hormonal treatment indicated: • Norethindrone Acetate 5-15mg daily • Medroxyprogesterone acetate 10-20mg daily • Norethindrone acetate 0.35mg daily (POP); can use BID or TID if needed to stop bleeding • Tranexamic acid 1300mg TID for 5 days
S1083-3188(15)00373-3
DOI:
10.1016/j.jpag.2015.10.021
Reference:
PEDADO 1922
To appear in:
Journal of Pediatric and Adolescent Gynecology
Received Date: 22 June 2015 Revised Date:
22 October 2015
Accepted Date: 30 October 2015
Please cite this article as: Huguelet P, Buyers E, Lange-Liss J, Scott S, Treatment of acute abnormal uterine bleeding in adolescents: what are providers doing in various specialties?, Journal of Pediatric and Adolescent Gynecology (2015), doi: 10.1016/j.jpag.2015.10.021. This is a PDF file of an unedited manuscript that has been accepted for publication. As a service to our customers we are providing this early version of the manuscript. The manuscript will undergo copyediting, typesetting, and review of the resulting proof before it is published in its final form. Please note that during the production process errors may be discovered which could affect the content, and all legal disclaimers that apply to the journal pertain.
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Treatment of acute abnormal uterine bleeding in adolescents: what are providers doing in various specialties?
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Huguelet PS, MD1; Buyers EM, MD1; Lange-Liss JH, MD2; Scott SM, MD1
1. Pediatric and Adolescent Gynecology, Children’s Hospital Colorado, Department of Obstetrics and Gynecology, University of Colorado School of Medicine, Aurora, CO
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2. Department of Obstetrics and Gynecology, University of Colorado School of Medicine, Aurora,
Corresponding Author and Reprints:
Patricia Huguelet, MD
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Assistant Professor, Department of Obstetrics and Gynecology
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University of Colorado and Children’s Hospital Colorado, Anschutz Medical Campus Academic Office 1, Box B-198-2
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12631 East 17th Avenue, Aurora, CO 80045 [email protected]
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303-724-2038 Phone 303-724-2056 Fax
Disclosure: The authors report no conflicts of interest.
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Abstract
Objectives: The purpose of this study was to assess whether variability exists in the management of
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acute abnormal uterine bleeding (AUB) in adolescents by pediatric emergency department physicians, pediatric gynecologists and adolescent medicine specialists.
Setting: Tertiary care medical center Emergency Department.
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Design: Retrospective chart review.
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Participants: Females aged 9-22 who presented from July 2008 to June 2014 with the complaint of acute AUB. Patients were identified by ICD-9 codes for heavy menstrual bleeding, abnormal uterine bleeding, and irregular menses. Exclusion criteria included pregnancy and current use of hormonal therapy. 150 patients were included.
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Results: Among those evaluated, 61% (n = 92) were prescribed hormonal medication to stop their bleeding by providers from the Emergency Department (ED), Adolescent Medicine, or Pediatric Gynecology.
ED physicians prescribed mostly single dose and multi-dose taper combined oral
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contraceptive pills (COCPs) to patients (85%, n=24), compared to Adolescent medicine (54%, n = 7) and Gynecology (28%, n = 13).
Pediatric gynecologists were more likely than Emergency Department
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physicians to treat patients with norethindrone acetate, either alone or in combination with a single dose COCP (61%, n = 33 versus 7%, n = 2; P < 0.001).
Conclusion: Variations in treatment strategies for adolescents who present with acute AUB exist among pediatric specialties, reflecting lack of standardized care for adolescents. Prospectively evaluating shortest interval to cessation of bleeding, side effects and patient satisfaction are valuable next steps.
Key Words: Acute abnormal uterine bleeding, Adolescents, Treatment
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Introduction
Abnormal uterine bleeding (AUB) may be acute or chronic and is defined as bleeding from the uterine
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corpus that is abnormal in regularity, volume, frequency, or duration and occurs in the absence of pregnancy.1 Acute uterine bleeding is defined as “an episode of bleeding in a woman of reproductive age, who is not pregnant, that, in the opinion of the provider, is of sufficient quantity to require immediate intervention to prevent further blood loss.”2 Intervention in this setting is often initiated
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prior to the completed work up for the specific etiology of AUB.3
Menstrual disorders are common in adolescents. Self-reported surveys have demonstrated that 30% of adolescents report irregular bleeding and 15-40% perceive their bleeding as abnormally heavy.4,5 Numerous studies have shown that 50-80% of menstrual cycles in the first two years after menarche are
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anovulatory, creating dysfunctional endometrial shedding.6,7 Anovulatory cycles create an environment of unopposed estrogen stimulation and endometrial proliferation, without progestin-induced stabilization. The end result is disorderly shedding of the endometrial lining without prostaglandin-
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mediated vasoconstriction and platelet-plugging of arterioles.8 The presence of an underlying bleeding disorder may further exacerbate the situation. Ultimately, these issues may lead to episodes of heavy
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vaginal bleeding, often prompting an emergency room visit.
Medical management is generally considered first-line therapy for acute AUB and may consist of estrogen, progestin, or a combination of both, usually in the form of combined oral contraceptive pills (COCPs). Despite their widespread use, there exists very little information regarding the effectiveness,
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side effects and patient satisfaction associated with these commonly used medical regimens. Even less
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evidence exists in the adolescent medical literature.
Only one study has been reported in the literature that compared medical intervention to placebo.9 In this randomized controlled trial, intravenous conjugated equine estrogen (CEE) resulted in cessation of
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bleeding by 5 hours in 72% of the treatment group versus only 38% of placebo.9 In all other studies, medications have been compared to each other, without a control group. In one randomized controlled
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trial, COCPs were administered with a taper and compared to oral progestin therapy alone, with no difference in efficacy between the two regimens.10
Two additional studies describe the time to
cessation of bleeding using a single oral progestin method, again without control groups participating
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and no difference in efficacy demonstrated.11,12
No studies have evaluated the long-term bleeding patterns of various hormonal regimens. Given the lack of strong evidence to support one medical regimen over another, we sought to understand whether
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variability exists in work up and prescribing methods, and if so, whether it was specialty specific.
Materials and Methods
Research Design and Study Population This retrospective chart review was IRB-approved at a children’s hospital in a large urban academic setting. Females aged 9 – 22 who had been evaluated in the Emergency Department (ED) for acute AUB
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were included. In this study, the term adolescent refers to females up to the age of 22, which reflects
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the upper age-limit set by Children’s Hospital Colorado (CHCO) for routine patient care.
Data Collection
The CHCO Research Institute searched the entire electronic medical record (EMR) between July 2008
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and June 2014. The EMR was queried for all female patients between the ages of 9 – 22, presenting to the ED with acute vaginal bleeding. Cases of vaginal bleeding were identified based on the following
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ICD-9 codes: disorders of menstruation (626), excessive or frequent menstruation (626.2), irregular bleeding (626.4), and dysfunctional uterine bleeding (626.8). Patients with a coexisting pregnancy or currently on hormonal medication were excluded. A total of 419 charts were accessed and ultimately
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150 met inclusion criteria.
Once the initial query was performed, the Research Institute uploaded the patient list, including the patient’s medical record number, age, race, and date of ED visit into a secure REDCap database. Four
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gynecologists then independently searched each patient’s medical record for the following information
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pertaining to the ED visit: age at menarche, menstrual history, notes documenting inquiry about personal and family history of a bleeding disorder, relevant physical exam findings, including body mass index (BMI) and vital signs at presentation, laboratory findings including complete blood count (CBC) or hematocrit if a full CBC was not ordered, prothromin time (PT), partial thromboplastin time (PTT) and standard Von Willebrand Disease (VWD) testing, presence or absence of transfusion, diagnosis, medication and dosage prescribed, and finally, specialty of provider who recommended therapy.
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All cases were initially evaluated by the ED provider and then the chart was reviewed to determine whether phone consultation was obtained. The chart was then reviewed for subsequent follow up office visits, recording time to cessation of bleeding, side effects from medication and satisfaction with
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treatment prescribed.
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Throughout the process, regular meetings were held among the reviewers to maintain consistency and discuss any discrepancies in the medical record. Once all charts were reviewed, the principal
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investigator subsequently reviewed all charts to confirm accuracy of data gathering.
The primary outcome was treatment recommended and specialty of the prescribing physician. Secondary outcomes included rates of historical data collection, rates of laboratory evaluation and
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predictors of laboratory studies ordered, criteria for blood transfusion, time to cessation of bleeding,
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side effects from medication and satisfaction with treatment prescribed.
Consistent with previous studies, we defined severe anemia as a hemoglobin < 8mg/dL and tachycardia
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as a heart rate ≥ 100.
Data Analysis
Descriptive statistics are presented for continuous variables using means and ranges for each clinical specialty, with Student t-tests used to compare these variables. The association between two categorical variables was tested using chi-square tests, and ANOVA was used when comparing more
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than two variables. When a chi-square test was invalid due to small sample size, the Fisher exact test
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was used. P < 0.05 was considered significant.
Results
A total of 150 adolescents, not on hormonal medication, presented to CHCO Emergency Department
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complaining of acute AUB. The median age was 14.9 years (range 9 – 22). There was no significant difference in demographic information between patients evaluated by Emergency Medicine, Pediatric
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Gynecology, or Adolescent Medicine (Table 1). Among the faculty providers, there were a total of 77 ED physicians, 3 Pediatric gynecologists and 5 Adolescent medicine physicians caring for these patients.
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All patients were initially evaluated by ED staff, with ED providers subsequently consulting a specialty service in just over 50% of patients. Among the adolescents not treated with medication (39%, n = 58), the ED staff managed all of them alone. Among those who were treated with medication (61%, n = 92),
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the ED consulted primarily Adolescent Medicine and Pediatric Gynecology. 5 patients were managed by other faculty, including Hematology and their Primary Care Physician. Given the small number of other
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providers, this group was not compared to the other specialties to assess for statistical significance (Table 2).
Regarding those adolescents who were ultimately prescribed hormonal medication to stop their bleeding (61%, n = 92), ED providers treated 28 patients and of those, 86% (n = 24) were prescribed single dose and multi-dose taper combined oral contraceptive pills (COCPs). Adolescent Medicine
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providers were consulted on 13 patients, recommending a COCP regimen 54% (n = 7) of the time. Pediatric Gynecologists were consulted on 46 patients, recommending a COCP regimen in 28% (n = 13) of cases (Table 2).
Pediatric Gynecologists were significantly more likely than ED physicians to
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recommend treatment with norethindrone acetate, either alone or in combination with a single dose COCP (72%, n = 33 of 46 versus 7%, n = 2 of 28; P < 0.001). Adolescent Medicine providers did not demonstrate a single preferred medication, with 46% of providers recommending norethindrone alone
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or in combination with a COCP, versus 54% recommending single dose or multi-dose tapered COCPs (Table 2). Only two providers, both from the ED, recommended medroxyprogesterone acetate (MPA).
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In both cases, MPA was prescribed alone. No patients were prescribed tranexamic acid or required surgical intervention.
When looking at secondary outcomes, we also noted wide variation in recorded historical data. BMI
(52%).
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was reported in a third of all patient charts (36%) and providers recorded age at menarche in one half The vast majority of providers attempted to characterize the patient’s bleeding history.
However, less than half of providers (45%) inquired about factors suggestive of a bleeding disorder,
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including history of frequent nosebleeds, bleeding gums, bleeding with surgical or dental procedures, or
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family history of a bleeding disorder.12
Regarding laboratory analysis, the following was noted. Among patients prescribed medication (n = 92), 92% were evaluated with a hemoglobin level. Among those patients not prescribed medication (n = 58), 50% were evaluated with a hemoglobin level. The average hemoglobin level was lower among those who were treated (Hb 11.4, range 4.3 – 15.8) versus those who were untreated (Hb 13.0, range 8.9 –
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15.6). However, this did not meet statistical significance (p = 0.07). The average hemoglobin was significantly lower among patients prescribed norethindrone, either alone or in combination with a COCP: norethindrone = 11.3, norethindrone with COCP = 10.0, COCP single dose = 12.3, COCP multi-
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dose = 12.1 (p = 0.03).
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Based on these observations, we next looked at objective criteria that might have influenced decision to order a CBC. There was no difference in average systolic blood pressure (121 vs 122, p = 0.71), diastolic
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blood pressure (69 vs 70, p = 0.79) or heart rate (87 vs 84, p = 0.38) among those patients who had a CBC drawn versus those who did not. Looking specifically at tachycardic patients, 35 (23%) presented with tachycardia and 115 (77%) presented with a normal heart rate. Among those patients who were
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tachycardic, 86% had a CBC drawn versus 72% who were not tachycardic (p = 0.10).
We also looked at whether vital signs influenced decision to recommend treatment. The average systolic (120 vs 124) and diastolic (69 vs 72) blood pressures were not significantly different among the
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treatment and non-treatment groups (p = 0.10, p = 0.07). The average heart rate was also similar
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among the two groups at 87 (range 44 – 135) and 85 (range 57 – 115), respectively (p= 0.57).
Regarding potential criteria to order a bleeding workup, the following was noted. A total of 35 patients (23%) were tested for a bleeding disorder, with testing including PT, PTT, and/or VWD testing. Among those patients who were tested for a bleeding disorder, the average hemoglobin level was 10.4 versus 12.3 in those not tested (p = 0.001). Both average systolic and diastolic blood pressure at presentation
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did not predict bleeding disorder workup (p = 0.07, p = 0.24) but average heart rate was higher, 93
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versus 84, in those patients who ultimately had these labs drawn (p = 0.004).
Charts were next reviewed for the evaluation and management of patients with severe anemia. A total of 16 patients (10.7%) met criteria for severe anemia. There was a significant difference in mean
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hemoglobin level between adolescents who received a blood transfusion (Hb 5.48, Range 4.3 – 6.9
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mg/dL) and those who were not transfused (Hb 6.6, Range 5.0 – 7.1 mg/dL mg/dL, p = 0.02).
In 100% of the patients with severe anemia, ED physicians consulted with a specialist, primarily Pediatric Gynecology. Norethindrone acetate was recommended in the majority of cases, either alone or in combination with a COCP (Table 3). Four patients with severe anemia were treated with IV CEE. In each
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case, this treatment was initiated and within 24 hours of starting CEE therapy, a single dose COCP and norethindrone acetate were added to the patient’s regimen.
Of note, one additional patient in our
study was also treated with IV CEE. This was initiated after an acute vasovagal episode in the ED.
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However, subsequent laboratory analysis revealed a normal hemoglobin level of 12.2 mg/dL.
Only patients with severe anemia were admitted to the hospital, defined in our study by a Hb < 8mg/dL. Among those patients with severe anemia (n = 16), 9 were admitted, with an average hemoglobin of 5.6 versus 6.3 in the non-admission group (p = 0.13). All patients treated with IV CEE required hospital admission.
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Next, we attempted to look at predictors of ED consultation with specialists for treatment recommendation. There was a trend towards younger age at presentation in those patients referred to specialists (14.3) versus those managed by ED providers (15.0), but this did not reach statistical
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significance (p = 0.10). However, the average hemoglobin level was significantly lower in those patients
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referred to specialists (10.8) versus managed solely by ED providers (12.9, p = 0.001).
Finally, charts were reviewed to evaluate whether a difference existed in time to cessation of bleeding
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and patient satisfaction with prescribed medication. Unfortunately, not enough patients presented for outpatient follow up to collect meaningful information regarding these secondary outcomes.
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Discussion
There appears to be wide variation in practice management of acute AUB in adolescents. Among pediatric providers at our institution, ED physicians prescribed single and multi-dose COCPs significantly
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more often than Pediatric Gynecologists. Adolescent Medicine faculty appeared to be evenly divided between COCP use and norethindrone acetate.
There was a significant trend toward use of
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norethindrone acetate by Pediatric Gynecology, particularly in the setting of true anemia. The practice pattern for why one medication was chosen above another was unable to be determined, given the retrospective nature of the study.
We also noted wide variability in the collection of historical information and physical exam findings relevant to the evaluation of acute AUB patients. Both age at menarche and BMI can provide valuable
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clues in deciphering the etiology of an adolescent’s bleeding pattern, including discriminating between normal anovulatory bleeding due to an immature hypothalamic-pituitary-ovarian axis versus bleeding due to polycystic ovarian syndrome (AUB-O) and other ovulatory disorders.
Furthermore, bleeding
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disorders (AUB-C) can often be unmasked at the time of menarche and personal and family history questions can be highly predictive of a bleeding disorder.12 However, this information was not collected
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consistently, with less than half of all patients queried for this information.
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We next attempted to understand the factors that influenced a provider’s decision to order blood work. Given the retrospective study, we were unable to reliably collect patient-reported symptoms of anemia. However, when we analyzed objective data, including blood pressure and heart rate, there were no differences among patients who did and did not have a CBC drawn. Although vital signs did not appear to influence decision to order a CBC, heart rate did appear to influence bleeding disorder evaluation.
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disorder evaluation.
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Furthermore, the hemoglobin level itself also appeared to influence decision to proceed with a bleeding
Finally, we attempted to understand the factors that influenced provider’s decision to initiate
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treatment. Once again, there were no differences in average blood pressure and heart rate among the treatment and non-treatment groups. Furthermore, when we analyzed the average hemoglobin level among these two groups, the hemoglobin level was not significantly lower in the treated group and the total range of values overlapped. Interestingly, the majority of patients who were ultimately treated with medication were evaluated with a hemoglobin level, versus only 50% of the untreated group. These discrepancies in objective evaluation suggest that subjective assessment of acute AUB played a
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strong role in the provider’s evaluation and subsequent treatment of these patients. Simply deciding to draw a hemoglobin level appeared to determine treatment versus the absolute value returned.
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However, historically we know that patient’s report of bleeding is often unreliable.13
There are clearly times when a provider’s subjective assessment of the severity of bleeding may override
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the laboratory data. However, this can lead to both over and under treatment of some patients. The results section describes an individual who received IV estrogen even in the face of a normal
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hemoglobin level. Although generally thought of as safe, the thrombotic risk posed by higher estrogen levels must be considered prior to its initiation. Conversely, among the individuals who were not treated with hormones, several individuals were found to be anemic in an ambulatory setting one week later. Based on ACOG recommendations, all patients being evaluated for acute AUB would benefit from
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CBC analysis.13
Ultimately, the decision to treat acute bleeding may not be based on the provider’s perceived severity of
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active blood loss, but more by patient preference and reported complaints. Functional impairment of daily activities or simply patient preference may influence a provider to initiate hormonal therapy even
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in the absence of any clinic health concerns associated with bleeding. Given the retrospective nature of this study, we were unable to assess for this possibility.
Strengths and Limitations
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Two strengths of this retrospective chart review are the size of the cohort and the attempt to characterize a common problem that has been relatively understudied. A total of 419 charts were
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reviewed, with 150 patients ultimately meeting inclusion criteria.
Given the retrospective nature of the study, however, several limitations exist. Frequently, inconsistent information was recorded in the medical chart, resulting in limited ability to make precise conclusions
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regarding the provider’s decision to order a hemoglobin level, when to initiate therapy, and type of medication prescribed. Furthermore, very few patients followed up in our outpatient clinic setting,
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preventing us from comparing efficacy and side effects of the various medications prescribed.
Conclusion
Wide variability in the evaluation and management of young women with acute AUB exists among
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pediatric specialties. It appears to be specialty-specific, rather than patient-specific and currently is not evidence based, likely due to the lack of good quality studies comparing the different options.
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Based on our observations, we have created an algorithm that we believe will lead to quality improvement with more standardized evaluation of these patients (Figure 1). Once this goal is achieved,
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we can then begin to conduct valuable prospective research to identify the optimal medication to treat acute AUB in adolescents.
Acknowledgements We would like to thank Jeanelle Sheeder, PhD, for her help with statistical analysis for this project.
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References
1. Management of acute abnormal uterine bleeding in nonpregnant reproductive-aged
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women. ACOG Committee Opinion No. 557. Obstet Gynecol 2013; 121:891 2. Munro MG, Critchley H, Broder MS, et al: FIGO classification system (PALM-COEIN) for causes of abnormal uterine bleeding in nongravid women of reproductive age. Int J
3. James AH, Kouides PA, Abdul-Kadir R, et al:
Evaluation and management of acute
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Gynaecol Obstet 2011; 113:3
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menorrhagia in women with and without underlying bleeding disorders: consensus from an international expert panel. Eur J Obstet Gynecol Reprod Biol 2011; 158:124 4. Agarwal A, Venkat A: Questionnaire study on menstrual disorders in adolescent girls in Singapore. J Pediatr Adolesc Gynecol 2009; 22:365 5. Friberg B, Orno AK, Lindgren A, et al:
Bleeding disorders among young women: a
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population-based prevalence study. Acta Obstet et Gynecol Scand 2006; 85:200 6. Apter D, Viinikka L, Vihko R: Hormonal pattern of adolescent cycles. J Clin Endocrinol Metab 1978; 47:944
816:9
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7. Apter D: Development of the Hypothalamic-Pituitary-Ovarian Axis. Ann N Y Acad Sci 1997;
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8. Cowan BD, Morrison JC: Current Concepts: Management of abnormal genital bleeding in girls and women. N Engl J Med 1991; 324:1710
9. DeVore GR, Owens O, Kase N:
Use of intravenous premarin in the treatment of
dysfunctional uterine bleeding – a double-blind randomized control study. Obstet Gynecol 1982; 59:285
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10. Munro MG, Mainor N, Basu R, et al: Oral medroxyprogesterone acetate and combination oral contraceptives for acute uterine bleeding, a randomized controlled trial.
Obstet
Gynecol 2006; 108:924 High-dose medroxyprogesterone acetate for the
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11. Aksu F, Madazli R, Budak E, et al:
treatment of dysfunctional uterine bleeding in 24 adolescents. Aust NZ J Obstet Gynaecol 1997; 37:228
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12. Santos M, Hendry D, Sangi-Haghpeykar H, et al: Retrospective review of norethindrone use in adolescents. J Pediatr Adolesc Gynecol 2014; 27:41
Hemostasis and menstruation: appropriate
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13. Kouides PA, Conard J, Peyvandi F, et al:
investigation for underlying disorders of hemostasis in women with excessive menstrual bleeding. Fertil Steril 2005; 84:1345
14. Menstruation in girls and adolescents: using the menstrual cycle as a vital sign. ACOG
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Committee Opinion No. 349. Obstet Gynecol 2006; 108:1323
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Table 1 Demographics of Patients Evaluated for Acute AUB in Emergency Department by Specialty Pediatric Gynecology
Adolescent Medicine
N
86
46
13
Age, mean (range)
15.3 (9-22)
14.1 ( 10-19)
15.3 (11-20)
Other
5
Ethnicity, n (%)
13.6 (10-18)
0.170 0.112
20 (23)
15 (33)
4 (31)
2 (40)
African American
15 (17)
9 (20)
1 (8)
0 (0)
Hispanic
46 (53)
16 (35)
7 (54)
2 (40)
5 (6)
6 (13)
1 (8)
1 (20)
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Caucasian
Other
P Value
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Emergency Medicine
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Table 2 Recommended Treatment of Acute AUB by Specialty
N (%)
Pediatric Gynecology
28
NA +/- COCP
2 (7)
MPA
2 (7)
46
Adolescent Medicine
13
33 (72) 0
Other
5
6 (46) 0
P Value
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Emergency Medicine
< 0.001
1 (20) 0
13 (45)
11 (24)
3 (23)
3 (60)
COCP taper
11 (39)
2 (4)
4 (31)
1 (20)
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COCP single dose
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NA, Norethindrone acetate; MA, Medroxyprogesterone acetate; COCP, Combined oral contraceptive pill
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Table 3 Management of Patients with Severe Anemia, by Specialty Adolescent Medicine
Other
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Pediatric Gynecology
N
0
12
1
IV CEE
0
4
0
NA
0
6
0
NA + COCP
0
6
0
COCP taper
0
0
1
COCP daily
0
0
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Emergency Medicine
0
3
0
1
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0
0
2
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NA, Norethindrone acetate; COCP, Combined oral contraceptive pill; IV CEE, Intravenous conjugated equine estrogen
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Figure 1. Algorithm for ED Evaluation of Acute AUB not due to Trauma or Pregnancy
Laboratory analysis for all adolescents: • HCG • CBC
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Physical examination • Vital signs and BMI • General examination
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Clinical History including: • Age at menarche • Family history of bleeding • Easy bruising, epistaxis, frequent gum bleeding, surgery-related bleeding • Sexual activity
If sexually active: Gonorrhea/Chlamydia NAAT If history suggestive of bleeding, include Tier 1 Testing: • VWF Ag, VWF Activity, Factor VIII Assay, PT/PTT
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Imaging usually not needed. Consider if bleeding or pain not controlled.
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No anemia • Offer outpatient regimen • Follow-up with outpatient provider in next 7 days.
Hemodynamically unstable
Complete lab assessment including Type and Screen
IV Conjugated Equine Estrogen 25mg IV q 4hours, up to 6 doses
Initiate outpatient regimen once stabilized
+ Anemia • Start outpatient regimen; counsel that bleeding should slow or stop within 1-2 days of treatment. • Follow-up with outpatient provider in next 7 days, sooner if bleeding persists.
Options for Outpatient Regimen Not anemic, no contraindications to COCPs: • Single dose monophasic COCP
Anemic, no contraindications to COCPs. Also consider if bleeding prolonged or otherwise difficult to manage: • Single dose monophasic COCP combined with norethindrone acetate 5mg daily • Multi-dose taper monophasic COCP, TID for 7 days, followed by daily therapy Alternatives if COCPs are contraindicated or non-hormonal treatment indicated: • Norethindrone Acetate 5-15mg daily • Medroxyprogesterone acetate 10-20mg daily • Norethindrone acetate 0.35mg daily (POP); can use BID or TID if needed to stop bleeding • Tranexamic acid 1300mg TID for 5 days
