Original Study

Differences in the Management of Adolescents with Polycystic OvarySyndrome across Pediatric Specialties

Bethany Auble MD1, Deborah Elder MD1, Andrea Gross MD2, Jennifer B. Hillman MD3,*1Division of Pediatric Endocrinology, Cincinnati Children’s Hospital Medical Center and the University of Cincinnati College of Medicine, Cincinnati, OH2Department of Pediatrics, Cincinnati Children’s Hospital Medical Center and the University of Cincinnati College of Medicine, Cincinnati, OH3Division of Adolescent Medicine, Cincinnati Children’s Hospital Medical Center and the University of Cincinnati College of Medicine, Cincinnati, OH

a b s t r a c t

Study Objective: Evaluate for differences in the management of ado

lescents with polycystic ovarian syndrome (PCOS) across 3 pediatricspecialties.Design: Retrospective review of medical records.Setting: Academic children’s hospital.Participants: 181 adolescents seen between July 2008 and June 2010 by providers in Pediatric Endocrinology (PEndo), Adolescent Medicine(AMed), or Pediatric and Adolescent Gynecology (PGyn) identified via billing data (ICD-9 code for PCOS, 256.4).Interventions: None.Main Outcome Measures: (1) Percentage of adolescents with a billing diagnosis of PCOS who met diagnostic criteria; (2) Percentage ofindividuals screened for comorbidities and differences across specialties; (3) Differences in treatment recommendations across specialties;(4) Factors associated with recommendation for metformin and hormonal contraceptives.Results: Thirteen percent of PEndo patients did not meet diagnostic criteria for PCOS; 20% of AMed and PGyn patients did not meet criteria.There were significant differences in rates of screening for obesity, insulin resistance, and Type 2 diabetes. There were significantdifferences in treatment recommendations for lifestyle changes, metformin, and anti-androgen therapy across specialties. Specialty andobesity were significant predictors of metformin recommendation; specifically PEndo predicted metformin recommendation. PGyn andAMed specialties predicted hormonal contraceptive recommendation.Conclusions: The variability observed among specialties may be due to differences in training, accounting for a range of comfort withaspects of PCOS. Formulation of consensus guidelines for diagnosis and management of PCOS are needed, along with broad educationalefforts. By correctly diagnosing, screening for comorbidities, and managing PCOS appropriately during adolescence, providers may reducethe risk for long-term consequences.Key Words: PCOS, Rotterdam criteria, Hirsutism, Metformin

Introduction

Polycystic ovarian syndrome (PCOS) is a complexmedical condition associated with metabolic comorbidities,reproductive health and cosmetic concerns, and psycho-logical distress for young women. Prevalence estimatesrange from 6%-26% of reproductive-aged women, depend-ing largely on whether narrow or more broad diagnosticcriteria are applied.1e4 Symptoms of PCOS often manifestduring adolescence making this an important time forrecognition and intervention to prevent adverse metabolicoutcomes such as insulin resistance and diabetes mellitus.Due to the broad range of symptoms associated with PCOSand the wide age range of women affected, patients seektreatment from a range of medical providers including adultand pediatric primary care providers, endocrinologists, andgynecologists.

The constellation of symptoms that defines PCOSincludes androgen excess (eg, excessive body hair growth,

The authors indicate no conflicts of interest.* Address correspondence to: Jennifer B. Hillman, MD, 3333 Burnett Ave, MLC

4000, Cincinnati, OH 45229; Phone: (513) 636-3539; fax: (513) 636-1129E-mail address: Jennifer.hillman@cchmc.org (J.B. Hillman).

1083-3188/$ - see front matter � 2013 North American Society for Pediatric and Adolehttp://dx.doi.org/10.1016/j.jpag.2013.03.007

male pattern baldness, and acne) and menstrual irregular-ities (eg, anovulatory cycles, missed periods, oligomenor-rhea, or amenorrhea)5 and 3 groups of experts (NationalInstitutes of Health (NIH),6 Rotterdam,7 Androgen ExcessSociety8) have published diagnostic criteria. The NIHConsensus Guidelines indicate the need for both biochem-ical and/or clinical evidence of hyperandrogenism withchronic anovulation, while excluding other causes ofhyperandrogenism (eg, Cushing Syndrome, congenitaladrenal hyperplasia, adrenal tumors). The Rotterdamcriteria utilize not only the 2 NIH criteria but also utilizeultrasonographic findings with 2 out of 3 criteria requiredfor diagnosis. The Androgen Excess Society (AES) requiresonly androgen excess either biochemical and/or clinical)and ovarian dysfunction (ovulation concerns or ultrasono-graphic findings of polycystic ovaries) to diagnose PCOS.However, there is currently no consensus on how to diag-nose PCOS during adolescence; the existing criteria do notapply to adolescents.9

Previous work employed surveys to assess how differentgroups of providers utilized existing diagnostic recom-mendations. The Lawson Wilkins Pediatric EndocrineSociety (LWPES) found that LWPES members use a widerange of practice for diagnosis and treatment.10 In contrast,

scent Gynecology. Published by Elsevier Inc.

B. Auble et al. / J Pediatr Adolesc Gynecol 26 (2013) 234e238 235

the North American Society for Pediatric and AdolescentGynecology (NASPAG)11 showed that its members weresomewhat discordant in their diagnostic evaluation, butconcordant regarding treatment. Furthermore, a survey ofreproductive endocrinologists and gynecologists designedto assess the frequency of screening for diabetes in PCOSfound a higher rate of screening for diabetes by reproduc-tive endocrinologists than by gynecologists.12 No study hasreviewed primary sources to assess potential differences inthe use of diagnostic and therapeutic interventions acrosssubspecialties.

To address these issues, we obtained primary source datafrom medical records of adolescents diagnosed with PCOSfollowed at a large academic pediatric hospital by one ofthe following 3 pediatric specialties: Pediatric Endocri-nology, Adolescent Medicine, or Pediatric and AdolescentGynecology. Our goals were to establish within and thencompare across the 3 pediatric specialties: (1) thepercentage of individuals identified with an ICD-9 diagnosisof PCOS who met diagnostic criteria; (2) the percentage ofindividuals who were screened for comorbidities; (3) thetreatment recommendations; (4) factors associated withspecific treatment recommendations (eg, metformin,hormonal contraceptives). We hypothesized significantdifferences in management practices exist among thedifferent specialties. For example, endocrinologists may bemore likely to screen for insulin resistance and diabetesthan Adolescent Medicine or Pediatric and AdolescentGynecology providers.

Methods and Materials

After receiving the approval of the Institutional ReviewBoard at Cincinnati Children’s Hospital, we performeda systematic retrospective review of the medical records ofpatients with PCOS in the Divisions of Pediatric Endocri-nology (PEndo), Pediatric and Adolescent Gynecology(PGyn), and Adolescent Medicine (AMed).

Participants

Adolescent girls with PCOS were identified using billingdata. All girls seen within a 2-year period (July 2008 to June2010) with the ICD-9 code for PCOS (256.4) were identified.This time frame was chosen because it was the most recent2-year period prior to any of the divisions converting to anelectronic medical record. Therefore, all 3 divisions wereusing a similar process for medical documentation (ie,paper chart).

Procedures

We employed written, standardized abstraction rulesand data abstraction forms. Three members of the researchteam abstracted the data (BA, AG, and JH). In addition, 8% ofthe charts were reviewed by 2 researchers to ensureagreement in approach and method of data abstraction. Foreach patient record, we identified the first visit inwhich thediagnosis or evaluation of PCOS was recorded. Up to 3subsequent provider visits (ie, follow-up visits) were also

reviewed for a total of up to 4 visits. Age, race, insurancestatus, height, weight, and age at menarche were collected.In addition, the presence or absence of symptoms of PCOSin the history and examination were recorded (such asirregular menstrual bleeding, missed periods, oligomenor-rhea, amenorrhea, acne, hair loss, excessive hair growth,hirsutism, and acanthosis nigricans). Information from theprovider’s evaluation was also abstracted, including docu-mentation of blood pressure, BMI/BMI percentile, labora-tory, and ultrasonographic assessment. The provider’srecommendations for lifestyle changes, hormonal contra-ceptives, metformin, referral to a dietician, use of anti-androgens, and other treatment options were collected.

Medical records were reviewed by random numbergeneration within each division. Initially, 20 charts wererandomly selected and abstracted for each division toconduct a power analysis. Results of the power analysisdetermined that approximately 57 charts from each divi-sionwere needed to detect a difference in the screening andtreatment recommendations among the 3 pediatricspecialties, taking into account the need for multiplecomparisons. Sixty charts from both PEndo and PGyn and61 charts from AMed were reviewed. Six patient chartswere excluded: 3 charts were missing significant data(eg, no record of the initial evaluation), 2 patients wereincorrectly identified as having PCOS (ie, the patient chartdid not indicate any evaluation or mention of PCOS), andone patient identified as an AMed patient was seen only byPGyn.

Data were entered in duplicate into the REDCap data-base. The double-data entry comparison tool was used toidentify discrepancies in the data. Any discrepancy wasverified on the data abstraction tool and reconciled.

Measures

Providers were credited with meeting diagnostic criteriawhen there was documented evidence of 2 of the following3 symptoms: androgen excess, anovulatory menstrualcycles, or polycystic ovaries on ultrasonography. Thesecriteria were chosen because they encompass the broadestapproach to defining of PCOS.7 The Rotterdam criteria arenot widely endorsed for use among adolescent populationsdue to the potential for overdiagnosis (ie, some of thecriteria are common among healthy adolescents). Authorschose to use these criteria for this retrospective review inorder to be optimally inclusive of the provider’s diagnoses.Androgen excess was evidenced by acne, hirsutism, hairloss, male pattern baldness, or elevated serum androgens(ie, elevated total or free testosterone concentration) asnoted by the provider in the medical record. Anovulatorymenstrual cycles were defined by report of irregularmenstrual bleeding, “missed periods,” irregular cycles, oli-gomenorrhea, primary amenorrhea, or secondary amenor-rhea. Presence of polycystic ovaries was defined as greaterthan 12 follicles in the periphery of the ovary as seen onpelvic ultrasonography or use of the term “consistent withPCOS” in the radiology report.

To determine and compare the percentage of patientsscreened for PCOS-associated comorbidities, approaches to

Table 1Demographic and Descriptive Characteristics of the Sample by Pediatric Specialty

PediatricEndocrinology

(n 5 60)

AdolescentMedicine(n 5 61)

Pediatric andAdolescentGynecology(n 5 60)

P Value

Mean age, y (SD) 15.3 (1.7) 15.9 (1.7) 15.9 (2.7) .22Mean age at menarche,

y (SD)11.8 (1.5) 12.0 (1.5) 11.6 (1.6) .44

Race, n (%) !.0001Black 10 (17) 39 (64) 5 (8)White 45 (75) 18 (30) 53 (88)Other 5 (8) 4 (7) 2 (3)

Insurance, n (%) .007None/self-pay 2 (3) 9 (15) 4 (7)Medicaid 19 (32) 27 (44) 14 (23)Commercial 39 (65) 25 (41) 42 (70)

Mean BMI (kg/m2) (SD) 35.2 (�6.9) 34.5 (�7.8) 30.6 (�8.0) .0025Weight status, n (%) .0014Normal 4 (7) 12 (20) 16 (27)Overweight 3 (5) 8 (13) 12 (20)Obese 53 (88) 41 (67) 32 (53)

BMI, Body mass indexComparison across pediatric specialties was analyzed by chi-square.Normal weight 5 BMI # 85th percentile; Overweight 5 BMI percentile O 85th and# 95th percentile; Obese 5 BMI percentile O 95th percentile.

B. Auble et al. / J Pediatr Adolesc Gynecol 26 (2013) 234e238236

screening for obesity, diabetes, hyperlipidemia, and insulinresistance were initially defined. Obesity screening requiredthe provider to document a body mass index (BMI) or BMIpercentile at any of the visits. Screening for insulin resis-tance required the provider to order a fasting insulin levelor to document the presence or absence of acanthosis nig-ricans. Screening for type 2 diabetes mellitus requiredproviders to order either a fasting glucose, hemoglobin A1C,or oral glucose tolerance test (OGTT). Finally, screening forhyperlipidemia required providers to order either totalcholesterol (non-fasting) or fasting lipid profile. Providerswere considered to have screened for a comorbidity if theyordered a test, even if the patient did not comply.

To describe treatment recommendations for adolescentswith PCOS and compare rates by specialty, definitions foreach treatment recommendation were formulated.Providers were noted to recommend “lifestyle changes” ifthey included any of the following in their assessment:“weight loss,” “exercise,” “nutrition counseling,” or anybehavioral change that would promote weight loss, such aselimination of sugar-sweetened beverages or decreasedsedentary activity, etc. Abstractors were instructed to beinclusive about any documentation that suggested theprovider discussed healthy lifestyle as a treatment option.Treatment recommendation for the use of hormonal

Table 2Comparison of Screening for PCOS-associated Comorbidities across 3 PediatricSpecialties

PediatricEndocrinology

(n 5 60)n (%)

AdolescentMedicine(n 5 61)n (%)

Pediatric andAdolescentGynecology(n 5 60)n (%)

P Value*

Obesity 28 (47) 13 (21) 24 (40) .011Insulin resistance 58 (97) 46 (75) 53 (88) .001Type 2 diabetes 58 (97) 43 (70) 50 (83) .006Hyperlipidemia 48 (80) 41 (67) 41 (68) .224

* Comparison across specialties was analyzed by chi-square testing. Significancedefined as P ! .0125 due to multiple comparisons.

contraceptives was noted if the provider counseled thepatient on this option or prescribed any hormonal contra-ceptive, including progestin-only pills, the transdermalpatch, or the intravaginal ring. A recommendation formetformin was noted if a provider documented discussionabout the use of metformin or prescribed metformin. Areferral to a dietician was credited by provider documen-tation of referral in the provider’s progress note. Recom-mendation for use of an anti-androgen medication wasnoted if a provider discussed or prescribed medicationssuch as spironolactone. Other treatment recommendationswere recorded but not analyzed, including referral totertiary care programs for weight loss or bariatric surgery.

Statistical Analyses

The percentage of girls meeting criteria for PCOS basedon the Rotterdam criteria7 was calculated for each specialty.This study was not designed with the power to evaluate fordifferences between pediatric specialties for the percentageof girls who met criteria for PCOS. Chi-square testing wasused to compare the percentage of patients who werescreened for a PCOS-associated comorbidity by specialty.Level of significance was set at P! .0125 using a Bonferronicorrection due to multiple (ie, 4) comparisons.13 Nearly allpatients were screened for hypertension with a bloodpressure reading, therefore it was not necessary or feasibleto evaluate for differences. Chi-square testing compared thepercentage of patients whowere recommended a particulartreatment across specialties. Level of significance was set atP! .01 using a Bonferroni correction due to multiple (ie, 5)comparisons.13 Finally, stepwise logistic regression wasused to determine those factors that were associated withmetformin and hormonal contraceptives as treatmentrecommendations.

Results

One hundred eighty-one patient records were reviewed(60 PEndo, 61 AMed, and 60 PGyn). There was a significantdifference across specialties for race, insurance status, BMI,and weight status (see Table 1). Significant differences werealso found in the presenting symptoms across specialties.Hirsutism was often found in patients presenting to PEndo(P ! .0001), while acne was frequently encountered inPGyn (P 5 .006). There was no difference in menstrualirregularities across specialties (Table 1).

Based on abstracted clinical documentation, 13% ofpatients in PEndo did not meet diagnostic PCOS standardsusing Rotterdam criteria; in both AMed and PGyn, 20% ofpatients did not meet criteria for PCOS. For screening ofcomorbidities, there were significant differences across the3 divisions in rates screening for obesity, insulin resistance,and Type 2 Diabetes. There were no statistically significantdifferences in screening for hypertension or hyperlipidemia(Table 2).

Treatment recommendations were statistically differentby specialty (Table 3). There were statistically significantdifferences across the 3 divisions for recommendations oflifestyle modification, metformin, and anti-androgen

Table 3Comparison of Treatment Recommendations for PCOS across 3 Pediatric Specialties

PediatricEndocrinology

(n 5 60)n (%)

AdolescentMedicine(n 5 61)n (%)

Pediatric andAdolescentGynecology(n 5 60)n (%)

P Value*

Lifestyle changes 51 (85) 38 (62) 24 (40) !.0001Hormonal

contraceptives50 (83) 58 (95) 58 (97) .015

Metformin 54 (90) 15 (25) 23 (38) !.0001Dietician 34 (57) 28 (46) 18 (30) .013Anti-androgen 12 (20) 1 (2) 6 (10) .001

* Comparison across specialties was analyzed by chi-square testing. Significancedefined as P ! .01 due to multiple comparisons.

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therapy (P ! .0001, P ! .0001, and P 5 .001, respectively).There was no statistically significant difference acrossdivisions for the recommendation of hormonal contracep-tives (P 5 .015).

Results of stepwise logistic regression revealed thatspecialty (ie, PEndo) and obesity were significant predictorsof metformin use (Table 4). Patients seen by a provider ineither AMed or PGyn were less likely than patients seen bya PEndo to be receive recommendation for metformin(Table 4). All other variables tested were not significant butincluded age, race, insurance status, primary or secondaryamenorrhea, irregular menstural bleeding, and presence ofhirsutism. Likewise, being seen by a provider in the Divi-sions of PGyn and AMed predicted hormonal contraceptiverecommendation. All other variables mentioned abovefor metformin models were tested but were not signifi-cantly associated with recommendation for hormonalcontraceptives.

Discussion

This study found that in all 3 pediatric specialties, despiteall adolescents being billed as having PCOS, a moderateportion (13%-20%) of adolescent patients did not meet thebroadest available diagnostic criteria (ie, Rotterdamcriteria). This study also demonstrated differences acrossspecialties in screening rates for obesity, Type 2 DM, andinsulin resistance. Significant differences across specialtieswere also noted for some treatment recommendations,despite that all girls were seen at the same academicinstitution. These data provide a glimpse into the diagnosisand management of adolescent girls with PCOS at a large

Table 4Factors Associated with Recommendation for Metformin and HormonalContraceptives

Odds Ratio 95% CI

MetforminSpecialtyPGyn vs PEndo 0.10 0.04, 0.30AMed vs PEndo 0.04 0.01, 0.12

Obesity (O95th percentile BMI) 4.20 1.79, 9.86Hormonal contraceptivesSpecialtyPGyn vs PEndo 5.80 1.20, 27.73AMed vs PEndo 3.87 1.01, 14.83

CI, Confidence interval; AMed, Adolescent Medicine; BMI, Body mass index; PEndo,Pediatric Endocrinology; PGyn, Pediatric and Adolescent Gynecology

academic center which includes training programs for eachpediatric specialty studied.

Insulin resistance, hyperlipidemia, Type 2 Diabetes,infertility, metabolic syndrome, and early cardiovasculardisease are associated with PCOS.14,15 In adults, the Amer-ican College of Obstetricians and Gynecologists (ACOG),16

American Association of Clinical Endocrinologists,17 andEndocrine Society18 have established treatment screeningguidelines. Despite clear guidelines for adults, very littleresearch has evaluated the management practices for PCOSduring the adolescent period.12 Several surveys have sug-gested that, even among the same specialty, there is noconsensus for the evaluation and management of adoles-cents with PCOS.10e12 Our data correspond with priorresearch and extend this beyond a single specialty todemonstrate that across specialties there are also differ-ences in the management of PCOS. Some of these differ-ences may be driven by greater comfort levels withmetabolic concerns versus reproductive health concernsamong PEndo providers compared to other types ofproviders. These differences are likely reflective of priortraining experiences and a lack of consensus guidelines.

Differences among clinic populations were evident.There were no differences among the disciplines regardingage of the patient or age at menarche, but there weredifferences in insurance status and race, which is reflectiveof the differences in the patient populations served and thetype of practice. The AMed clinic is a primary care clinic thatmanages a primarily underserved population. Both PGynand PEndo are specialty referral clinics that allow forheightened focus on a specific clinical finding or patientconcern. Finally, there was a statistically significant differ-ence in the mean BMI across the different disciplines thatmay also be reflective of differences in the patient pop-ulations served or related to reason for referral. For example,overweight or obese adolescents may be more likely to bereferred to PEndo and leaner girls referred to PGyn.

Limitations to our study include aspects of a medicalrecord review. Documentation among providers variedgreatly, and we were only able to abstract data that werenoted in the medical record (eg, lifestyle recommendations,treatment suggestions). Our findings revealed differences inthe patient populations seen by each specialty, reflectingdifferent referral bases. These differences in referral basesmay explain some of the differences we observed in thetreatment and management across specialties. Anotherlimitation is that data were not included on whether thepatients were sexually active or not and this may haveimpacted the provider’s management and treatmentrecommendations. Our data were not powered to finda difference between specialties but rather across special-ties. In other words, we were unable to evaluate whetherPEndo providers compared to AMed providers recom-mended lifestyle recommendations more often. The find-ings of this study are generalizable to patients and providersin an academic setting, but may not be as relevant to thegeneral pediatric community.

This study highlights the current lack of consensusregarding the diagnosis, treatment, and screening forcomorbidities in adolescents with PCOS. It would be

B. Auble et al. / J Pediatr Adolesc Gynecol 26 (2013) 234e238238

extremely beneficial if experts in the field came togetherto develop adolescent-specific diagnostic criteria andmanagement guidelines. Thiswould allow for consistency indiagnosis and current management practices which wouldpromote research efforts to move the field forward and gainmuch-needed understanding about PCOS during the criticalperiod of adolescence. Once guidelines for adolescents areavailable, extensive educational efforts can be launched toupdate providers in the field at national meetings that crossall 3 specialties and also in the community for primary carepediatricians. It would also be important for providerstreating PCOS to communicate across specialties more, co-manage, or create a multidisciplinary clinic in academicsettings when feasible. By recognizing, correctly diagnosing,screening for comorbidities, and managing this syndromeappropriately in adolescence, providers may reduce the riskfor long-term consequences related to the comorbidities ofPCOS in young women.

Acknowledgments

We would like to thank Mekibib Altaye, PhD for hissupport in the data analyses. Funding was provided byK12HD051953; Building Interdisciplinary Careers inWomen’s Health (J. Hillman) and in part by USPHS Grant #UL1RR026314 from the National Center for ResearchResources, NIH.

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