ORIGINAL ARTICLE: REPRODUCTIVE ENDOCRINOLOGY
Utility of ultrasound in the diagnosis of polycystic ovary syndrome in adolescents Michal Youngster, M.D.,a Valerie L. Ward, M.D., M.P.H.,c Emily A. Blood, Ph.D.,a,d Carol E. Barnewolt, M.D.,c S. Jean Emans, M.D.,a and Amy D. Divasta, M.D., M.M.Sc.a,b a
Division of Adolescent/Young Adult Medicine, Department of Medicine, b Division of Gynecology, Department of Surgery, Department of Radiology, and d Department of Pediatrics, Boston Children's Hospital, Harvard Medical School, Boston, Massachusetts c
Objective: To determine the utility of transabdominal pelvic ultrasound in the diagnosis of polycystic ovary syndrome (PCOS) during adolescence. Design: Retrospective case-control study. Setting: Academic tertiary care pediatric hospital. Patient(s): A case group of 54 patients (mean age, 15.2 years) with PCOS based on the National Institutes of Health criteria and a comparison group of 98 patients (mean age, 14.6 years) with acute appendicitis. Intervention(s): Transabdominal ultrasound (TAUS) images were evaluated in the two groups of adolescents, with data collected on quality of the images, ovarian volume, ovarian follicle count, and endometrial thickness. Main Outcome Measure(s): Sonographic modified Rotterdam criteria (volume >10 mL and/or follicle number per section R10) for polycystic ovaries (PCO). Result(s): Among the 54 patients with PCOS and 98 comparison subjects with usable images, the sonographic modified Rotterdam criteria for PCO morphology (PCOM) were met more frequently in the PCOS group than in the comparison group (65% vs. 11%). The vast majority of images were of adequate quality for diagnosis (PCOS ¼ 94% and comparison ¼ 91%), even in the presence of obesity. Conclusion(s): The prevalence of ovarian morphology meeting the sonographic modified Rotterdam criteria by TAUS in girls with PCOS was markedly higher than in the adolescents serving as a comparison group. PCOM findings by the sonographic modified Rotterdam criteria were uncommon in the nongynecologic comparison group, in contrast to previous reports. TAUS may provide useful information in the evaluation of PCOS during adolescence, even in obese adolescents. (Fertil Use your smartphone SterilÒ 2014;-:-–-. Ó2014 by American Society for Reproductive Medicine.) to scan this QR code Key Words: Polycystic ovary syndrome, adolescents, transabdominal ultrasound, Rotterdam and connect to the criteria, endometrial thickness Discuss: You can discuss this article with its authors and with other ASRM members at http:// fertstertforum.com/youngsterm-ultrasonography-diagnosis-pcos-adolescents/
P
olycystic ovary syndrome (PCOS) is the most common endocrine disorder, affecting 6%–15% of women of reproductive age (1). Manifestations of PCOS include irregular menses, hyperandrogenism, and the presence of polycystic ovaries
on pelvic ultrasound (US). Associated conditions include obesity, diabetes, cardiovascular disease, infertility, and increased risk of endometrial hyperplasia and cancer (2, 3). Early diagnosis is important, as awareness can promote lifestyle modifications or medical
Received February 8, 2014; revised July 21, 2014; accepted July 22, 2014. M.Y. has nothing to disclose. V.L.W. has nothing to disclose. E.A.B. has nothing to disclose. C.E.B. has nothing to disclose. S.J.E. has nothing to disclose. A.D.D. has nothing to disclose. This study was supported by the National Institutes of Health grant nos. R01HD066963, R01DA033974, and R34DA030353-01A1 (to E.A.B., not related to this work). Reprint requests: Michal Youngster, M.D., Division of Adolescents/Young Adults, 300 Longwood Avenue, Boston, Massachusetts 02115 (E-mail: [email protected]). Fertility and Sterility® Vol. -, No. -, - 2014 0015-0282/$36.00 Copyright ©2014 American Society for Reproductive Medicine, Published by Elsevier Inc. http://dx.doi.org/10.1016/j.fertnstert.2014.07.1241 VOL. - NO. - / - 2014
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treatments to prevent at least part of the late sequelae (4). Several criteria have been proposed in adults to make a diagnosis of PCOS with the concomitant exclusion of other disorders. The 1990 National Institutes of Health (NIH) criteria require menstrual irregularities and clinical or biochemical hyperandrogenism. The Rotterdam criteria (RC), the product of a consensus workshop held in 2003 by the European Society for Human Reproduction and Embryology (ESHRE) and the American Society for Reproductive Medicine (ASRM), broadened the definition to include two out of three of the following criteria: oligomenorrhea 1
ORIGINAL ARTICLE: REPRODUCTIVE ENDOCRINOLOGY and/or anovulation, hyperandrogenism, and polycystic ovaries (PCO) by transvaginal US (5) (either ovarian volume >10 mL and/or R12 follicles measuring 2–9 mm) (6). The Androgen Excess-PCOS Society criteria require the presence of hyperandrogenism (clinical and/or biochemical) and ovarian dysfunction (oligoanovulation and/or PCO) (7). The application of these diagnostic criteria for PCOS in the adolescent girl is more challenging, given the expected anovulatory menses and hormone changes characteristic of the early postmenarchal years. Menstrual and hormonal fluctuations that occur normally during adolescence may mimic the clinical characteristics included in the adult PCOS diagnostic criteria, making them less reliable as a diagnostic tool in this age group. After menarche, anovulatory cycles are common, may persist for several years (1, 8), and do not necessarily correspond to clinical or biochemical hyperandrogenism (9). Clinical hyperandrogenism is defined primarily by the degree of hirsutism in adolescents because acne is common in this age group and is usually transient (10, 11). Although some studies suggest relying primarily on biochemical markers when making the diagnosis of PCOS (12, 13), measurements of serum androgens can be challenging to interpret owing to the variability among laboratories and the use of different methods of determining free and total T (14). The usefulness of pelvic US in supporting the suspected diagnosis of PCOS has been controversial. The finding of PCO on US has been reported to be nonspecific, overlapping with image findings seen in up to 40% of the normal population (9, 15–17). In addition, most pelvic US exams in adolescents are performed transabdominally rather than transvaginally, resulting in lower resolution and thus less accurate observation of ovarian morphology (6). The prevalence of obesity in the PCOS population may potentially make the transabdominal US (TAUS) even less ideal to define ovarian morphology. Furthermore, the multifollicular appearance characteristically seen during puberty as a result of follicular growth without consistent recruitment of a dominant follicle may also be a source of confusion and misdiagnosis of PCO in this age group (6). As a result, some investigators have proposed replacing ovarian sonographic imaging with ovarian magnetic resonance imaging or serum antim€ ullerian hormone (AMH) levels, especially in the adolescent population (18–21). The most recent Endocrine Society guidelines cautioned against the use of PCO morphology (PCOM) as a diagnostic criteria for adolescents (22). Given the controversies and questions regarding the use of US in an adolescent PCOS population, we analyzed pelvic US images obtained in a cohort of adolescents with PCOS and a comparison adolescent population to assess the prevalence of PCOM by a modified version of the Rotterdam US criteria and to examine whether there were differences in endometrial thickness.
MATERIALS AND METHODS We performed a retrospective, case-control cohort study. The protocol was approved by the Boston Children's Hospital Committee on Clinical Investigation. 2
Study Populations US images were evaluated in two cohorts: [1] a sample of adolescent girls who all were diagnosed with PCOS by the 1990 NIH criteria (menstrual irregularities and clinical and/ or biochemical hyperandrogenism) between 2006 and 2008 at the Boston Children's Hospital's Reproductive Endocrine Clinic in the Division of Adolescent/Young Adult Medicine; and [2] a comparison group of adolescents with surgically confirmed appendicitis who had a pelvic TAUS in the Emergency Department (ED) (2005–2013) before the operative procedure. Patients with PCOS taking hormonal medications (such as birth control pills) that could affect ovarian morphology were excluded. Hormonal and physical characteristics of PCOS patients were assessed (Table 1). Hirsutism was considered clinically significant if the Ferriman-Gallwey score was >7. None of the girls had acne as the only sign of hyperandrogenism. The biochemical evaluation included serum concentrations of total T (high-performance liquid chromatography tandem mass spectrometry, Esoterix, Inc.; the upper limit of the normal values ranged between 32 and 55 ng/dL, depending on Tanner stage) and free T (equilibrium dialysis, Esoterix, Inc.; normal 10 mm. Ovarian volume (OV) was calculated using the traditional method of a simplified formula for a prolate ellipse (0.5 length width thickness) (6). The US images were evaluated for the number of antral follicles (2–9 mm) in a single cross-sectional plane (follicle number per section [FNPS]) for each ovary. The RC use an OV cutoff of >10 mL and a follicle number per ovary (FNPO) cutoff of R12 follicles as seen in cineloops or real time US images. Since we reviewed still images obtained by TAUS, we defined PCOM for the purposes of this VOL. - NO. - / - 2014
study using a modified Rotterdam US criteria (mRC), with an OV cutoff of >10 mL and FNPS threshold of 10 follicles, as previously described (23–25). Endometrial thickness was also assessed. In the comparison group, patients were stratified into the following subgroups: US occurring during the first 2 weeks of the cycle (follicular phase) or US occurring during weeks 3 and 4 since LMP (luteal phase). The usability of the US for ovarian imaging was evaluated; the US was excluded if it was technically nonreadable for either ovary. The two clinicians initially reviewed 30 images to ensure similar techniques for measurement and calculations.
Data Analysis Descriptive statistics were used to characterize the participant data. Tests of associations between variables within the PCOS group and comparison group were followed by comparisons between two groups. For participant-level data (age, weight, maximum OV, mRC PCOM, and US usability), tests of association between continuous variables were carried out via correlation coefficients, associations 3
ORIGINAL ARTICLE: REPRODUCTIVE ENDOCRINOLOGY between continuous and binary variables were carried out via nonparametric Wilcoxon rank sum tests, and associations between two categorical variables were carried out via Fisher's exact test. Since data from participants were collected at the ovary level (OV for both right and left ovary) and sagittal versus transverse view level (number of follicles for both views for both right and left ovary) in addition to the participant level, statistical procedures that account for the correlation within person for ovary-level variables and correlation within person and within ovary for view-level variables were used. The associations between age and weight and number of follicles were performed via nonlinear and linear mixed-effects models that included a random individual and ovary random effects. For the PCOS group, associations between age and weight and the dichotomous variable ‘‘number of follicles R10’’ were performed and nonlinear models were used. For the comparison group (in which few participants had 10 or more follicles), the association between age and weight and continuous number of follicles was performed and linear models were used. The ovary-level association between OV and age was tested via generalized estimating equations. These models account for the correlation of volume measurements between the right and left ovary within a participant. All analyses were carried out with SAS version 9.3; P< .05 was considered statistically significant at the two-sided level.
RESULTS Ovarian Data Among 70 girls with PCOS initially identified by the NIH criteria, two US exams were not obtainable. Fourteen girls were excluded from the analyses owing to nondiagnostic quality of the imaging or follicular size >10 mm.
Among the 54 remaining cases (mean age, 15.2 1.8 years; mean weight, 79.0 19.8 kg), 35 met the sonographic mRC for PCOM on TAUS (65%); 14/35 (40%) by number of follicles R10 alone, 5/35 (14%) by volume alone, and 16/35 (46%) by both number and volume (Table 2). Of the 21 cases who met OV criteria, 13 (62%) had enlargement of both ovaries and eight (38%) had unilateral enlargement. There were no associations between age and maximal OV (P¼ .15) or meeting the mRC (P¼ .29). Increased age was not associated with a reduced likelihood of having R10 follicles (P¼ .08). There was no relationship between weight and meeting the sonographic criteria (P¼ .46). Weight was not associated with the likelihood of having R10 follicles (P¼ .11) or with mean OV (P¼ .17). The comparison group included 158 patients who met the criteria for inclusion. After review of the images, 60 patients were excluded from further analysis owing to inadequate ovarian imaging or ovarian follicle greater than 10 mm. Of the 98 girls in the comparison group (mean age, 14.7 1.7 years; mean weight, 56.6 11.7 kg) included in the final analysis, 11 met the criteria for PCOM (11%): four by follicle criteria alone, two by volume alone, and five by both volume and number of follicles. The increased OV was unilateral in all instances. The girls who met the sonographic mRC for PCOM tended to be older (P¼ .04). Older girls had larger maximal OV (P¼ .03) and mean OV (P¼ .01). Age was not significantly associated with an increased number of follicles (P¼ .10). Increased weight was associated with increased OV (P¼ .02) but not with increased follicle number (P¼ .50) or with meeting mRC for PCOM (P¼ .25). The vast majority of images were of adequate quality for diagnosis (PCOS ¼ 94% and comparison ¼ 91%; P¼ .45). Among the 54 PCOS patients and 98 comparisons with usable images, the sonographic mRC for PCOM was significantly
TABLE 2 Physical and US characteristics of girls with PCOS (n [ 54) and comparison group (n [ 98). PCOS Age (y) Weight (kg) Race/ethnicity (%) Non-Hispanic white Non-Hispanic black Hispanic Asian Other No information Meeting mRC for PCOM (%) Volume only (% of PCOM) No. of follicles only (% of PCOM) Both volume and follicle number (% of PCOM) Total meeting mRC by volume (% of PCOM) Total meeting mRC by no. of follicles (% of PCOM) Both ovaries > 10 mL (% of PCOM) Maximal OV (patient's largest ovary, mL) Mean OV (mL) No. of images with a follicle > 10 mm (%)
15.2 1.8 (range, 12–20) 79.0 19.8 (range, 44–122) 31 (57) 4 (7) 6 (11) 4 (7) 1 (2) 8 (15) 35 (65) 5/35 (14) 14/35 (40) 16/35 (46) 21/35 (60) 30/35 (86) 13/35 (37) 9.5 3.9 (range, 2.7–19.7) 8.2 3.9 (range, 1.6–19.7) (n ¼ 110 ovaries) 10/68 (15)
Comparison group 14.7 1.7 (range, 11–18) 56.6 11.7 (range, 31–94) 55 (56) 8 (8) 19 (19) 5 (5) 6 (6) 5 (5) 11 (11) 2/11 (18) 4/11 (36) 5/11 (45) 7/11 (64) 9/11 (82) 0 6.9 2.3 (range, 1.6–13.0) 5.96 2.4 (range, 1.2–13.0) (n ¼ 196 ovaries) 46/158 (29)
P value .09 < .0001 .57
< .0001
< .0001 < .0001 .02
Note: Data are presented as mean SD (continuous variables) or n (%) (categorical variables). Ethnicity was self-reported by the patients at the time of clinic registration. MRC: OV >10 mL and/or FNPS R10 in either ovary. Youngster. US evaluation of PCO morphology in adolescents. Fertil Steril 2014.
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Fertility and Sterility® more prevalent in the PCOS group than in the comparison group (65% vs. 11%; P< .0001). Similarly, maximal OV was greater in the PCOS group (P< .0001). Mean weight in the PCOS group was higher than in the comparison cohort (79.0 kg vs. 56.6 kg; P< .0001), but there was no significant association between weight and US usability in either group (P¼ .52 for the PCOS group and .66 for the comparison group).
Endometrial Thickness Endometrial thickness was greater in the comparison group than in the PCOS group (P¼ .005; Table 3). In the comparison group, 80 patients had documentation of their LMP; these patients had their US further stratified as occurring during the follicular phase or luteal phase. Girls in the follicular phase had a thinner endometrium compared with girls in the PCOS group (P¼ .05), while girls in the luteal phase had a thicker endometrium than girls in the PCOS group (P< .0001). No association was found between endometrial thickness and PCOM by US criteria in either group (P¼ .99 and P¼ .12 for the PCOS and comparison group, respectively).
DISCUSSION In the current study, we found that most adolescents with PCOS diagnosed by the 1990 NIH criteria did meet the sonographic mRC for PCOM using TAUS. In our sample, the comparison cohort had a lower prevalence of PCOM than in previous studies (15, 17). The incidence of PCOM was significantly higher in adolescents with PCOS than in the comparison group. Although the evaluation of ovarian morphology continues to be part of the diagnostic criteria for adults, the utility of TAUS has been widely debated for adolescents. The results of our study suggest that TAUS may be a useful diagnostic tool and that OV >10 mL and follicle number R10 using FNPS can be determined using TA imaging even in overweight patients. The measurement of endometrial thickness did not yield additional diagnostic information. Recent guidelines for the evaluation of PCOS in adolescents have questioned the usefulness of TAUS. The recently published Australian evidence-based guidelines for assessment and management of PCOS recommended against using US as a first-line diagnostic tool in the adolescent patient. This recommendation was based on expert opinion, as the investigators found insufficient data generated from controlled studies to support its use (26). Another recent publication
from the Endocrine Society similarly suggested that while basing the diagnosis of PCOS in adult women on the RC is recommended, the workup of the adolescent should be approached differently and the diagnosis should be based on hyperandrogenism and amenorrhea, while limiting the use of US (22). The reluctance to include the use of US as a diagnostic tool for PCOS in adolescence is based on three assumptions that our study was structured to address: the prevalence of PCOM in the general adolescent population; the evolution of ovarian morphology; and the imaging quality of TAUS, particularly in obese adolescents. First, studies have demonstrated that PCOM is found in up to 40% of the healthy adult and adolescent population and thus questioned the validity of the diagnosis of PCOS using the revised RC (15, 27). A recent Australian study found a prevalence of PCOM of 35% in 244 unselected adolescents aged 14–16 years, mainly attributed to increased OV rather than an increased number of follicles (9). Whether a proportion of the study populations had a variant of PCOS is unknown (16). Moreover, women presenting with isolated PCOM have higher levels of AMH compared with control subjects, suggesting the presence of a granulosa cell abnormality in PCO similar to that observed in PCOS (28). In contrast, using a comparison group with a proven surgical diagnosis and no documentation of irregular menses or clinical signs of hyperandrogenism, we found the prevalence of PCO in the general adolescent population to be only 11%, which is compatible with the data presented in several other studies (2, 29). Because we do not have laboratory data available for the control subjects, we cannot exclude the possibility of biochemical hyperandrogenism in this cohort; thus the percentage of PCOM in the control population may be lower. Second, investigators have raised concerns about the utility of sonography as ovarian morphology may evolve during adolescence and early adulthood (30), specifically the finding of a multifollicular appearance. In our study, no association was found between age and PCOM in girls with PCOS. In the comparison cohort, which had a young mean age of 14.6 years, older age was associated with the presence of PCOM. This result was attributed to the increase in OV, as expected with increased age, and not to an increase in the number of follicles. We found no association between older age and the likelihood of having a reduced number of follicles. If a patient is evaluated in early adolescence and does not have features of PCO on imaging, she may be reevaluated at
TABLE 3 Endometrial thickness in the PCOS group and comparison group. Endometrial thickness (mm) 10
PCOS (n [ 53) (%)
Comparison group (n [ 94) (%)
Comparison follicular phase group (n [ 47) (%)
Comparison luteal phase group (n [ 33) (%)
28 (53) 17 (32) 8 (15)
29 (31) 56 (60) 9 (10)
23 (51) 21 (47) 1 (2)
3 (9) 24 (73) 6 (18)
Note: One patient in the PCOS group and four patients in the comparison group were missing data on endometrial thickness. Fourteen patients in the comparison group did not have the date of the LMP documented. Youngster. US evaluation of PCO morphology in adolescents. Fertil Steril 2014.
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ORIGINAL ARTICLE: REPRODUCTIVE ENDOCRINOLOGY a later time. However, if PCOM is present, specifically based on OV, then studies suggest this finding is unlikely to regress (30, 31). A third concern repeatedly raised about the use of sonography as a criterion for PCOS is the technical challenge associated with accurately visualizing the ovaries on TAUS in this frequently obese population. In our study, we were able to visualize and calculate the ovarian and endometrial values for the vast majority of our patients regardless of weight, consistent with other studies (9, 15, 29). When the ovaries are adequately visualized, OV can reliably be assessed (32, 33). The similarity between the prevalence of PCOM in our case group and previous studies (16) strengthens the validity of our results and underscores the high usability of TAUS in our study. Recent advances in technology have improved detection rates of antral follicles, especially when using endovaginal sonography with FNPO count (25, 34, 35), leading to the suggestion that follicle count cutoffs be increased. However, in adolescents, most imaging is performed transabdominally, and despite the improvement in US machine resolution, several studies have demonstrated a remarkably similar threshold for OV and FNPS when comparing new versus older reports using a single cross-sectional view of the ovary (25, 36). The investigators concluded that a combined metric of FNPS (using a cutoff of nine to 10 follicles) and OV provides significant predictive power in detecting PCOS comparable with that of FNPO alone (25). In situations in which image quality is reduced, the investigators suggest using the volume criterion alone (sensitivity of 81% and specificity of 84% in distinguishing between PCOS and non-PCOS patients) (36). These studies suggest that the use of TAUS in obese girls, even with concerns for suboptimal image quality, has a significant predictive value in the diagnosis of PCOS using the OV and FNPS, as was used in our study. Endometrial thickness did not add diagnostic information. Most girls in the PCOS group had an endometrial thickness 10 mm. In adulthood, PCOS and anovulation are risk factors for endometrial hyperplasia and cancer (38, 39), which typically occur in cases in which the endometrium is thick and heterogeneous (40). Unopposed estrogen secretion and anovulation should be treated to limit endometrial overgrowth and prevent this increased risk in the future. Study limitations should be acknowledged. This study was a single-center review of imaging, laboratory, and clinical data. However, the study group was selected based on clinical criteria ascertained in real time, and the imaging was reviewed specifically for these analyses. The comparison group was carefully selected to include adolescents who were evaluated for a nongynecological diagnosis. As their main complaint was acute abdominal pain, the evaluation was performed to exclude any ovarian pathology according to a unified pelvic exam protocol used in our institution. As expected, more US studies were excluded from analysis for the presence of a dominant follicle >10 mm from the comparison group. In addition, menstrual history and the use of contraceptives
6
were addressed in the vast majority of cases as these factors have implications for the differential diagnosis of abdominal pain in adolescents. We were able to compare weights between the two groups. Obesity is a prevalent clinical feature in PCOS patients, and the mean weight was higher in the PCOS group than in the comparison group. We did not find a correlation between weight and US usability in terms of image quality; thus, weight did not affect our ability to review the images. We did not have a sufficient number of height measurements for the comparison group as this is not a part of the routine evaluation in the ED, thus a comparison of body mass index between the groups was not presented. It is still possible that some findings of PCOS, such as the presence of hirsutism or high androgen levels, could have been present and not documented in the 11 patients with PCOM in the comparison group; however, exclusion of any patient included in that group would only further decrease the percentage of PCOM identified in the normal comparison group. It is also possible that relevant patient medical history including recent past medical use of oral contraceptives that might affect ovarian morphology was not documented. Sonographic interpretation was performed by review of previously obtained still frames; both clinicians remeasured all relevant parameters and recalculated all volumes. It is possible that prospective assessment of real-time images and/or cine clips might be more precise. A recent task force recommended using FNPO on transvaginal US with a higher threshold as the most accurate diagnostic criteria for PCOM when using advanced US equipment (41). With older US equipment, the task force recommended using the volume criteria. As noted above, an evaluation based on a combined metric of FNPS and OV can provide predictive power in detecting PCOM comparable with that of FNPO alone (25). Most pelvic US exams in adolescent girls are performed with a lower resolution TA transducer and use FNPS counts, emphasizing the need to develop targeted criteria for this age group. In the current study, we used a combined metric of FNPS and OV measured transabdominally that requires further validation in future investigations. Images were reviewed independently by two different clinicians with a high level of interobserver agreement for follicle number and OV. In conclusion, the prevalence of ovarian morphology meeting the mRC by TAUS in girls diagnosed with PCOS according to the NIH criteria, in our study, was markedly higher than that in adolescents who served as a comparison group. Our study found the prevalence of PCOM using a sonographic mRC in a nongynecologic cohort to be lower than previously reported, supporting the usefulness of US in adolescents as part of the diagnosis of PCOS. Based on our results, TAUS may provide useful information in the evaluation of PCOM, even in obese girls. Studies have indicated that adolescence may be the most appropriate time to intervene in PCOS patients, as many cardiovascular risk factors are present in early adulthood (42). Continued efforts to define diagnostic criteria in adolescents that potentially include TAUS are warranted so that patient-specific early interventions can be initiated. VOL. - NO. - / - 2014
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Adams J, Franks S, Polson DW, Mason HD, Abdulwahid N, Tucker M, et al. Multifollicular ovaries: clinical and endocrine features and response to pulsatile gonadotropin releasing hormone. Lancet 1985;2:1375–9. Atiomo WU, Pearson S, Shaw S, Prentice A, Dubbins P. Ultrasound criteria in the diagnosis of polycystic ovary syndrome (PCOS). Ultrasound Med Biol 2000;26:977–80. Christ JP, Willis AD, Brooks ED, Vanden Brink H, Jarrett BY, Pierson RA, et al. Follicle number, not assessments of the ovarian stroma, represents the best ultrasonographic marker of polycystic ovary syndrome. Fertil Steril 2014;101:280–7.e1. Boyle J, Teede HJ. Polycystic ovary syndrome—an update. Aust Fam Physician 2012;41:752–6. Mortensen M, Rosenfield RL, Littlejohn E. Functional significance of polycystic-size ovaries in healthy adolescents. J Clin Endocrinol Metab 2006;91:3786–90. Catteau-Jonard S, Bancquart J, Poncelet E, Lefebvre-Maunoury C, Robin G, Dewailly D. Polycystic ovaries at ultrasound: normal variant or silent polycystic ovary syndrome? Ultrasound Obstet Gynecol 2012;40:223–9. Van Hooff MH, Voorhorst FJ, Kaptein MB, Hirasing RA, Koppenaal C, Schoemaker J. Hyperandrogenism: polycystic ovaries in adolescents and the relationship with menstrual cycle patterns, luteinizing hormone, androgens, and insulin. Fertil Steril 2000;74:49. Venturoli S, Porcu E, Fabbri R, Pluchinotta V, Ruggeri S, Macrelli S, et al. Longitudinal change of sonographic ovarian aspects and endocrine parameters in irregular cycles of adolescence. Pediatr Res 1995;38:974–80. Panidis D, Tziomalos K, Macut D, Delkos D, Betsas G, Misichronis G, et al. Cross-sectional analysis of the effects of age on the hormonal, metabolic, and ultrasonographic features and the prevalence of the different phenotypes of polycystic ovary syndrome. Fertil Steril 2012;97:494–500. Chen Y, Yang D, Li L, Chen X. The role of ovarian volume as a diagnostic criterion for Chinese adolescents with polycystic ovary syndrome. J Pediatr Adolesc Gynecol 2008;21:347–50. Herter LD, Magalhaes JA, Spritzer PM. Relevance of the determination of ovarian volume in adolescent girls with menstrual disorders. J Clin Ultrasound 1996;24:243–8. Dewailly D, Gronier H, Poncelet E, Robin G, Leroy M, Pigny P, et al. Diagnosis of polycystic ovary syndrome (PCOS): revisiting the threshold values of follicle count on ultrasound and of the serum AMH level for the definition of polycystic ovaries. Hum Reprod 2011;26:3123–9. Kristensen SL, Ramlau-Hansen CH, Ernst E, Olsen SF, Bonde JP, Vested A, et al. A very large proportion of young Danish women have polycystic ovaries: is a revision of the Rotterdam criteria needed? Hum Reprod 2010; 25:3117–22. Lujan ME, Jarrett BY, Brooks ED, Reines JK, Peppin AK, Muhn N, et al. Updated ultrasound criteria for polycystic ovary syndrome: reliable thresholds for elevated follicle population and ovarian volume. Hum Reprod 2013; 28:1361–8. Shah B, Parnell L, Milla S, Kessler M, David R. Endometrial thickness, uterine, and ovarian ultrasonographic features in adolescents with polycystic ovarian syndrome. J Pediatr Adolesc Gynecol 2010;23:146–52. Cheung AP. Ultrasound and menstrual history in predicting endometrial hyperplasia in polycystic ovary syndrome. Obstet Gynecol 2001;98:325–31. Wild S, Pierpoint T, Jacobs H, McKeigue P. Long-term consequences of polycystic ovary syndrome: results of a 31 year follow-up study. Hum Fertil (Camb) 2000;3:101–5. Peri N, Levine D. Sonographic evaluation of the endometrium in patients with a history or an appearance of polycystic ovarian syndrome. J Ultrasound Med 2007;26:55–8. quiz 59–60. Dewailly D, Lujan ME, Carmina E, Cedars MI, Laven J, Norman RJ, et al. Definition and significance of polycystic ovarian morphology: a task force report from the Androgen Excess and Polycystic Ovary Syndrome Society. Hum Reprod Update 2014;20:334–52. Vural B, Caliskan E, Turkoz E, Kilic T, Demirci A. Evaluation of metabolic syndrome frequency and premature carotid atherosclerosis in young women with polycystic ovary syndrome. Hum Reprod 2005;20:2409–13.
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Utility of ultrasound in the diagnosis of polycystic ovary syndrome in adolescents Michal Youngster, M.D.,a Valerie L. Ward, M.D., M.P.H.,c Emily A. Blood, Ph.D.,a,d Carol E. Barnewolt, M.D.,c S. Jean Emans, M.D.,a and Amy D. Divasta, M.D., M.M.Sc.a,b a
Division of Adolescent/Young Adult Medicine, Department of Medicine, b Division of Gynecology, Department of Surgery, Department of Radiology, and d Department of Pediatrics, Boston Children's Hospital, Harvard Medical School, Boston, Massachusetts c
Objective: To determine the utility of transabdominal pelvic ultrasound in the diagnosis of polycystic ovary syndrome (PCOS) during adolescence. Design: Retrospective case-control study. Setting: Academic tertiary care pediatric hospital. Patient(s): A case group of 54 patients (mean age, 15.2 years) with PCOS based on the National Institutes of Health criteria and a comparison group of 98 patients (mean age, 14.6 years) with acute appendicitis. Intervention(s): Transabdominal ultrasound (TAUS) images were evaluated in the two groups of adolescents, with data collected on quality of the images, ovarian volume, ovarian follicle count, and endometrial thickness. Main Outcome Measure(s): Sonographic modified Rotterdam criteria (volume >10 mL and/or follicle number per section R10) for polycystic ovaries (PCO). Result(s): Among the 54 patients with PCOS and 98 comparison subjects with usable images, the sonographic modified Rotterdam criteria for PCO morphology (PCOM) were met more frequently in the PCOS group than in the comparison group (65% vs. 11%). The vast majority of images were of adequate quality for diagnosis (PCOS ¼ 94% and comparison ¼ 91%), even in the presence of obesity. Conclusion(s): The prevalence of ovarian morphology meeting the sonographic modified Rotterdam criteria by TAUS in girls with PCOS was markedly higher than in the adolescents serving as a comparison group. PCOM findings by the sonographic modified Rotterdam criteria were uncommon in the nongynecologic comparison group, in contrast to previous reports. TAUS may provide useful information in the evaluation of PCOS during adolescence, even in obese adolescents. (Fertil Use your smartphone SterilÒ 2014;-:-–-. Ó2014 by American Society for Reproductive Medicine.) to scan this QR code Key Words: Polycystic ovary syndrome, adolescents, transabdominal ultrasound, Rotterdam and connect to the criteria, endometrial thickness Discuss: You can discuss this article with its authors and with other ASRM members at http:// fertstertforum.com/youngsterm-ultrasonography-diagnosis-pcos-adolescents/
P
olycystic ovary syndrome (PCOS) is the most common endocrine disorder, affecting 6%–15% of women of reproductive age (1). Manifestations of PCOS include irregular menses, hyperandrogenism, and the presence of polycystic ovaries
on pelvic ultrasound (US). Associated conditions include obesity, diabetes, cardiovascular disease, infertility, and increased risk of endometrial hyperplasia and cancer (2, 3). Early diagnosis is important, as awareness can promote lifestyle modifications or medical
Received February 8, 2014; revised July 21, 2014; accepted July 22, 2014. M.Y. has nothing to disclose. V.L.W. has nothing to disclose. E.A.B. has nothing to disclose. C.E.B. has nothing to disclose. S.J.E. has nothing to disclose. A.D.D. has nothing to disclose. This study was supported by the National Institutes of Health grant nos. R01HD066963, R01DA033974, and R34DA030353-01A1 (to E.A.B., not related to this work). Reprint requests: Michal Youngster, M.D., Division of Adolescents/Young Adults, 300 Longwood Avenue, Boston, Massachusetts 02115 (E-mail: [email protected]). Fertility and Sterility® Vol. -, No. -, - 2014 0015-0282/$36.00 Copyright ©2014 American Society for Reproductive Medicine, Published by Elsevier Inc. http://dx.doi.org/10.1016/j.fertnstert.2014.07.1241 VOL. - NO. - / - 2014
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treatments to prevent at least part of the late sequelae (4). Several criteria have been proposed in adults to make a diagnosis of PCOS with the concomitant exclusion of other disorders. The 1990 National Institutes of Health (NIH) criteria require menstrual irregularities and clinical or biochemical hyperandrogenism. The Rotterdam criteria (RC), the product of a consensus workshop held in 2003 by the European Society for Human Reproduction and Embryology (ESHRE) and the American Society for Reproductive Medicine (ASRM), broadened the definition to include two out of three of the following criteria: oligomenorrhea 1
ORIGINAL ARTICLE: REPRODUCTIVE ENDOCRINOLOGY and/or anovulation, hyperandrogenism, and polycystic ovaries (PCO) by transvaginal US (5) (either ovarian volume >10 mL and/or R12 follicles measuring 2–9 mm) (6). The Androgen Excess-PCOS Society criteria require the presence of hyperandrogenism (clinical and/or biochemical) and ovarian dysfunction (oligoanovulation and/or PCO) (7). The application of these diagnostic criteria for PCOS in the adolescent girl is more challenging, given the expected anovulatory menses and hormone changes characteristic of the early postmenarchal years. Menstrual and hormonal fluctuations that occur normally during adolescence may mimic the clinical characteristics included in the adult PCOS diagnostic criteria, making them less reliable as a diagnostic tool in this age group. After menarche, anovulatory cycles are common, may persist for several years (1, 8), and do not necessarily correspond to clinical or biochemical hyperandrogenism (9). Clinical hyperandrogenism is defined primarily by the degree of hirsutism in adolescents because acne is common in this age group and is usually transient (10, 11). Although some studies suggest relying primarily on biochemical markers when making the diagnosis of PCOS (12, 13), measurements of serum androgens can be challenging to interpret owing to the variability among laboratories and the use of different methods of determining free and total T (14). The usefulness of pelvic US in supporting the suspected diagnosis of PCOS has been controversial. The finding of PCO on US has been reported to be nonspecific, overlapping with image findings seen in up to 40% of the normal population (9, 15–17). In addition, most pelvic US exams in adolescents are performed transabdominally rather than transvaginally, resulting in lower resolution and thus less accurate observation of ovarian morphology (6). The prevalence of obesity in the PCOS population may potentially make the transabdominal US (TAUS) even less ideal to define ovarian morphology. Furthermore, the multifollicular appearance characteristically seen during puberty as a result of follicular growth without consistent recruitment of a dominant follicle may also be a source of confusion and misdiagnosis of PCO in this age group (6). As a result, some investigators have proposed replacing ovarian sonographic imaging with ovarian magnetic resonance imaging or serum antim€ ullerian hormone (AMH) levels, especially in the adolescent population (18–21). The most recent Endocrine Society guidelines cautioned against the use of PCO morphology (PCOM) as a diagnostic criteria for adolescents (22). Given the controversies and questions regarding the use of US in an adolescent PCOS population, we analyzed pelvic US images obtained in a cohort of adolescents with PCOS and a comparison adolescent population to assess the prevalence of PCOM by a modified version of the Rotterdam US criteria and to examine whether there were differences in endometrial thickness.
MATERIALS AND METHODS We performed a retrospective, case-control cohort study. The protocol was approved by the Boston Children's Hospital Committee on Clinical Investigation. 2
Study Populations US images were evaluated in two cohorts: [1] a sample of adolescent girls who all were diagnosed with PCOS by the 1990 NIH criteria (menstrual irregularities and clinical and/ or biochemical hyperandrogenism) between 2006 and 2008 at the Boston Children's Hospital's Reproductive Endocrine Clinic in the Division of Adolescent/Young Adult Medicine; and [2] a comparison group of adolescents with surgically confirmed appendicitis who had a pelvic TAUS in the Emergency Department (ED) (2005–2013) before the operative procedure. Patients with PCOS taking hormonal medications (such as birth control pills) that could affect ovarian morphology were excluded. Hormonal and physical characteristics of PCOS patients were assessed (Table 1). Hirsutism was considered clinically significant if the Ferriman-Gallwey score was >7. None of the girls had acne as the only sign of hyperandrogenism. The biochemical evaluation included serum concentrations of total T (high-performance liquid chromatography tandem mass spectrometry, Esoterix, Inc.; the upper limit of the normal values ranged between 32 and 55 ng/dL, depending on Tanner stage) and free T (equilibrium dialysis, Esoterix, Inc.; normal 10 mm. Ovarian volume (OV) was calculated using the traditional method of a simplified formula for a prolate ellipse (0.5 length width thickness) (6). The US images were evaluated for the number of antral follicles (2–9 mm) in a single cross-sectional plane (follicle number per section [FNPS]) for each ovary. The RC use an OV cutoff of >10 mL and a follicle number per ovary (FNPO) cutoff of R12 follicles as seen in cineloops or real time US images. Since we reviewed still images obtained by TAUS, we defined PCOM for the purposes of this VOL. - NO. - / - 2014
study using a modified Rotterdam US criteria (mRC), with an OV cutoff of >10 mL and FNPS threshold of 10 follicles, as previously described (23–25). Endometrial thickness was also assessed. In the comparison group, patients were stratified into the following subgroups: US occurring during the first 2 weeks of the cycle (follicular phase) or US occurring during weeks 3 and 4 since LMP (luteal phase). The usability of the US for ovarian imaging was evaluated; the US was excluded if it was technically nonreadable for either ovary. The two clinicians initially reviewed 30 images to ensure similar techniques for measurement and calculations.
Data Analysis Descriptive statistics were used to characterize the participant data. Tests of associations between variables within the PCOS group and comparison group were followed by comparisons between two groups. For participant-level data (age, weight, maximum OV, mRC PCOM, and US usability), tests of association between continuous variables were carried out via correlation coefficients, associations 3
ORIGINAL ARTICLE: REPRODUCTIVE ENDOCRINOLOGY between continuous and binary variables were carried out via nonparametric Wilcoxon rank sum tests, and associations between two categorical variables were carried out via Fisher's exact test. Since data from participants were collected at the ovary level (OV for both right and left ovary) and sagittal versus transverse view level (number of follicles for both views for both right and left ovary) in addition to the participant level, statistical procedures that account for the correlation within person for ovary-level variables and correlation within person and within ovary for view-level variables were used. The associations between age and weight and number of follicles were performed via nonlinear and linear mixed-effects models that included a random individual and ovary random effects. For the PCOS group, associations between age and weight and the dichotomous variable ‘‘number of follicles R10’’ were performed and nonlinear models were used. For the comparison group (in which few participants had 10 or more follicles), the association between age and weight and continuous number of follicles was performed and linear models were used. The ovary-level association between OV and age was tested via generalized estimating equations. These models account for the correlation of volume measurements between the right and left ovary within a participant. All analyses were carried out with SAS version 9.3; P< .05 was considered statistically significant at the two-sided level.
RESULTS Ovarian Data Among 70 girls with PCOS initially identified by the NIH criteria, two US exams were not obtainable. Fourteen girls were excluded from the analyses owing to nondiagnostic quality of the imaging or follicular size >10 mm.
Among the 54 remaining cases (mean age, 15.2 1.8 years; mean weight, 79.0 19.8 kg), 35 met the sonographic mRC for PCOM on TAUS (65%); 14/35 (40%) by number of follicles R10 alone, 5/35 (14%) by volume alone, and 16/35 (46%) by both number and volume (Table 2). Of the 21 cases who met OV criteria, 13 (62%) had enlargement of both ovaries and eight (38%) had unilateral enlargement. There were no associations between age and maximal OV (P¼ .15) or meeting the mRC (P¼ .29). Increased age was not associated with a reduced likelihood of having R10 follicles (P¼ .08). There was no relationship between weight and meeting the sonographic criteria (P¼ .46). Weight was not associated with the likelihood of having R10 follicles (P¼ .11) or with mean OV (P¼ .17). The comparison group included 158 patients who met the criteria for inclusion. After review of the images, 60 patients were excluded from further analysis owing to inadequate ovarian imaging or ovarian follicle greater than 10 mm. Of the 98 girls in the comparison group (mean age, 14.7 1.7 years; mean weight, 56.6 11.7 kg) included in the final analysis, 11 met the criteria for PCOM (11%): four by follicle criteria alone, two by volume alone, and five by both volume and number of follicles. The increased OV was unilateral in all instances. The girls who met the sonographic mRC for PCOM tended to be older (P¼ .04). Older girls had larger maximal OV (P¼ .03) and mean OV (P¼ .01). Age was not significantly associated with an increased number of follicles (P¼ .10). Increased weight was associated with increased OV (P¼ .02) but not with increased follicle number (P¼ .50) or with meeting mRC for PCOM (P¼ .25). The vast majority of images were of adequate quality for diagnosis (PCOS ¼ 94% and comparison ¼ 91%; P¼ .45). Among the 54 PCOS patients and 98 comparisons with usable images, the sonographic mRC for PCOM was significantly
TABLE 2 Physical and US characteristics of girls with PCOS (n [ 54) and comparison group (n [ 98). PCOS Age (y) Weight (kg) Race/ethnicity (%) Non-Hispanic white Non-Hispanic black Hispanic Asian Other No information Meeting mRC for PCOM (%) Volume only (% of PCOM) No. of follicles only (% of PCOM) Both volume and follicle number (% of PCOM) Total meeting mRC by volume (% of PCOM) Total meeting mRC by no. of follicles (% of PCOM) Both ovaries > 10 mL (% of PCOM) Maximal OV (patient's largest ovary, mL) Mean OV (mL) No. of images with a follicle > 10 mm (%)
15.2 1.8 (range, 12–20) 79.0 19.8 (range, 44–122) 31 (57) 4 (7) 6 (11) 4 (7) 1 (2) 8 (15) 35 (65) 5/35 (14) 14/35 (40) 16/35 (46) 21/35 (60) 30/35 (86) 13/35 (37) 9.5 3.9 (range, 2.7–19.7) 8.2 3.9 (range, 1.6–19.7) (n ¼ 110 ovaries) 10/68 (15)
Comparison group 14.7 1.7 (range, 11–18) 56.6 11.7 (range, 31–94) 55 (56) 8 (8) 19 (19) 5 (5) 6 (6) 5 (5) 11 (11) 2/11 (18) 4/11 (36) 5/11 (45) 7/11 (64) 9/11 (82) 0 6.9 2.3 (range, 1.6–13.0) 5.96 2.4 (range, 1.2–13.0) (n ¼ 196 ovaries) 46/158 (29)
P value .09 < .0001 .57
< .0001
< .0001 < .0001 .02
Note: Data are presented as mean SD (continuous variables) or n (%) (categorical variables). Ethnicity was self-reported by the patients at the time of clinic registration. MRC: OV >10 mL and/or FNPS R10 in either ovary. Youngster. US evaluation of PCO morphology in adolescents. Fertil Steril 2014.
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Fertility and Sterility® more prevalent in the PCOS group than in the comparison group (65% vs. 11%; P< .0001). Similarly, maximal OV was greater in the PCOS group (P< .0001). Mean weight in the PCOS group was higher than in the comparison cohort (79.0 kg vs. 56.6 kg; P< .0001), but there was no significant association between weight and US usability in either group (P¼ .52 for the PCOS group and .66 for the comparison group).
Endometrial Thickness Endometrial thickness was greater in the comparison group than in the PCOS group (P¼ .005; Table 3). In the comparison group, 80 patients had documentation of their LMP; these patients had their US further stratified as occurring during the follicular phase or luteal phase. Girls in the follicular phase had a thinner endometrium compared with girls in the PCOS group (P¼ .05), while girls in the luteal phase had a thicker endometrium than girls in the PCOS group (P< .0001). No association was found between endometrial thickness and PCOM by US criteria in either group (P¼ .99 and P¼ .12 for the PCOS and comparison group, respectively).
DISCUSSION In the current study, we found that most adolescents with PCOS diagnosed by the 1990 NIH criteria did meet the sonographic mRC for PCOM using TAUS. In our sample, the comparison cohort had a lower prevalence of PCOM than in previous studies (15, 17). The incidence of PCOM was significantly higher in adolescents with PCOS than in the comparison group. Although the evaluation of ovarian morphology continues to be part of the diagnostic criteria for adults, the utility of TAUS has been widely debated for adolescents. The results of our study suggest that TAUS may be a useful diagnostic tool and that OV >10 mL and follicle number R10 using FNPS can be determined using TA imaging even in overweight patients. The measurement of endometrial thickness did not yield additional diagnostic information. Recent guidelines for the evaluation of PCOS in adolescents have questioned the usefulness of TAUS. The recently published Australian evidence-based guidelines for assessment and management of PCOS recommended against using US as a first-line diagnostic tool in the adolescent patient. This recommendation was based on expert opinion, as the investigators found insufficient data generated from controlled studies to support its use (26). Another recent publication
from the Endocrine Society similarly suggested that while basing the diagnosis of PCOS in adult women on the RC is recommended, the workup of the adolescent should be approached differently and the diagnosis should be based on hyperandrogenism and amenorrhea, while limiting the use of US (22). The reluctance to include the use of US as a diagnostic tool for PCOS in adolescence is based on three assumptions that our study was structured to address: the prevalence of PCOM in the general adolescent population; the evolution of ovarian morphology; and the imaging quality of TAUS, particularly in obese adolescents. First, studies have demonstrated that PCOM is found in up to 40% of the healthy adult and adolescent population and thus questioned the validity of the diagnosis of PCOS using the revised RC (15, 27). A recent Australian study found a prevalence of PCOM of 35% in 244 unselected adolescents aged 14–16 years, mainly attributed to increased OV rather than an increased number of follicles (9). Whether a proportion of the study populations had a variant of PCOS is unknown (16). Moreover, women presenting with isolated PCOM have higher levels of AMH compared with control subjects, suggesting the presence of a granulosa cell abnormality in PCO similar to that observed in PCOS (28). In contrast, using a comparison group with a proven surgical diagnosis and no documentation of irregular menses or clinical signs of hyperandrogenism, we found the prevalence of PCO in the general adolescent population to be only 11%, which is compatible with the data presented in several other studies (2, 29). Because we do not have laboratory data available for the control subjects, we cannot exclude the possibility of biochemical hyperandrogenism in this cohort; thus the percentage of PCOM in the control population may be lower. Second, investigators have raised concerns about the utility of sonography as ovarian morphology may evolve during adolescence and early adulthood (30), specifically the finding of a multifollicular appearance. In our study, no association was found between age and PCOM in girls with PCOS. In the comparison cohort, which had a young mean age of 14.6 years, older age was associated with the presence of PCOM. This result was attributed to the increase in OV, as expected with increased age, and not to an increase in the number of follicles. We found no association between older age and the likelihood of having a reduced number of follicles. If a patient is evaluated in early adolescence and does not have features of PCO on imaging, she may be reevaluated at
TABLE 3 Endometrial thickness in the PCOS group and comparison group. Endometrial thickness (mm) 10
PCOS (n [ 53) (%)
Comparison group (n [ 94) (%)
Comparison follicular phase group (n [ 47) (%)
Comparison luteal phase group (n [ 33) (%)
28 (53) 17 (32) 8 (15)
29 (31) 56 (60) 9 (10)
23 (51) 21 (47) 1 (2)
3 (9) 24 (73) 6 (18)
Note: One patient in the PCOS group and four patients in the comparison group were missing data on endometrial thickness. Fourteen patients in the comparison group did not have the date of the LMP documented. Youngster. US evaluation of PCO morphology in adolescents. Fertil Steril 2014.
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ORIGINAL ARTICLE: REPRODUCTIVE ENDOCRINOLOGY a later time. However, if PCOM is present, specifically based on OV, then studies suggest this finding is unlikely to regress (30, 31). A third concern repeatedly raised about the use of sonography as a criterion for PCOS is the technical challenge associated with accurately visualizing the ovaries on TAUS in this frequently obese population. In our study, we were able to visualize and calculate the ovarian and endometrial values for the vast majority of our patients regardless of weight, consistent with other studies (9, 15, 29). When the ovaries are adequately visualized, OV can reliably be assessed (32, 33). The similarity between the prevalence of PCOM in our case group and previous studies (16) strengthens the validity of our results and underscores the high usability of TAUS in our study. Recent advances in technology have improved detection rates of antral follicles, especially when using endovaginal sonography with FNPO count (25, 34, 35), leading to the suggestion that follicle count cutoffs be increased. However, in adolescents, most imaging is performed transabdominally, and despite the improvement in US machine resolution, several studies have demonstrated a remarkably similar threshold for OV and FNPS when comparing new versus older reports using a single cross-sectional view of the ovary (25, 36). The investigators concluded that a combined metric of FNPS (using a cutoff of nine to 10 follicles) and OV provides significant predictive power in detecting PCOS comparable with that of FNPO alone (25). In situations in which image quality is reduced, the investigators suggest using the volume criterion alone (sensitivity of 81% and specificity of 84% in distinguishing between PCOS and non-PCOS patients) (36). These studies suggest that the use of TAUS in obese girls, even with concerns for suboptimal image quality, has a significant predictive value in the diagnosis of PCOS using the OV and FNPS, as was used in our study. Endometrial thickness did not add diagnostic information. Most girls in the PCOS group had an endometrial thickness 10 mm. In adulthood, PCOS and anovulation are risk factors for endometrial hyperplasia and cancer (38, 39), which typically occur in cases in which the endometrium is thick and heterogeneous (40). Unopposed estrogen secretion and anovulation should be treated to limit endometrial overgrowth and prevent this increased risk in the future. Study limitations should be acknowledged. This study was a single-center review of imaging, laboratory, and clinical data. However, the study group was selected based on clinical criteria ascertained in real time, and the imaging was reviewed specifically for these analyses. The comparison group was carefully selected to include adolescents who were evaluated for a nongynecological diagnosis. As their main complaint was acute abdominal pain, the evaluation was performed to exclude any ovarian pathology according to a unified pelvic exam protocol used in our institution. As expected, more US studies were excluded from analysis for the presence of a dominant follicle >10 mm from the comparison group. In addition, menstrual history and the use of contraceptives
6
were addressed in the vast majority of cases as these factors have implications for the differential diagnosis of abdominal pain in adolescents. We were able to compare weights between the two groups. Obesity is a prevalent clinical feature in PCOS patients, and the mean weight was higher in the PCOS group than in the comparison group. We did not find a correlation between weight and US usability in terms of image quality; thus, weight did not affect our ability to review the images. We did not have a sufficient number of height measurements for the comparison group as this is not a part of the routine evaluation in the ED, thus a comparison of body mass index between the groups was not presented. It is still possible that some findings of PCOS, such as the presence of hirsutism or high androgen levels, could have been present and not documented in the 11 patients with PCOM in the comparison group; however, exclusion of any patient included in that group would only further decrease the percentage of PCOM identified in the normal comparison group. It is also possible that relevant patient medical history including recent past medical use of oral contraceptives that might affect ovarian morphology was not documented. Sonographic interpretation was performed by review of previously obtained still frames; both clinicians remeasured all relevant parameters and recalculated all volumes. It is possible that prospective assessment of real-time images and/or cine clips might be more precise. A recent task force recommended using FNPO on transvaginal US with a higher threshold as the most accurate diagnostic criteria for PCOM when using advanced US equipment (41). With older US equipment, the task force recommended using the volume criteria. As noted above, an evaluation based on a combined metric of FNPS and OV can provide predictive power in detecting PCOM comparable with that of FNPO alone (25). Most pelvic US exams in adolescent girls are performed with a lower resolution TA transducer and use FNPS counts, emphasizing the need to develop targeted criteria for this age group. In the current study, we used a combined metric of FNPS and OV measured transabdominally that requires further validation in future investigations. Images were reviewed independently by two different clinicians with a high level of interobserver agreement for follicle number and OV. In conclusion, the prevalence of ovarian morphology meeting the mRC by TAUS in girls diagnosed with PCOS according to the NIH criteria, in our study, was markedly higher than that in adolescents who served as a comparison group. Our study found the prevalence of PCOM using a sonographic mRC in a nongynecologic cohort to be lower than previously reported, supporting the usefulness of US in adolescents as part of the diagnosis of PCOS. Based on our results, TAUS may provide useful information in the evaluation of PCOM, even in obese girls. Studies have indicated that adolescence may be the most appropriate time to intervene in PCOS patients, as many cardiovascular risk factors are present in early adulthood (42). Continued efforts to define diagnostic criteria in adolescents that potentially include TAUS are warranted so that patient-specific early interventions can be initiated. VOL. - NO. - / - 2014
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