8/11/2019 The diagnosis of polycystic ovary syndrome in adolescents.pdf

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GE NE R AL GY NE C OL OGY

The diagnosis of polycystic ovary syndrome in adolescentsEnrico Carmina, MD; Sharon E. Oberfield, MD; Rogerio A. Lobo, MD

Three criteria allowing for severalphenotypes are currently used to

diagnose polycystic ovary syndrome(PCOS) in adults. During the transitionfrom adolescence to adulthood, severalfeatures may be in evolution or transi-tory.Thus, prematurely assigninga diag-nostic label of PCOS to an adolescentmay result in unnecessary treatments,impose psychological distress, and jeop-ardize clinical andbasicstudies of PCOS,which require greater homogeneity andcertainty about the diagnosis.

We sought to review elements thoughtto encompassthe diagnosis of PCOS thatmay emerge during adolescence and toattempt to establish firm criteria uponwhich to base the diagnosis.

Hyperandrogenism

The use of immunoassays after extractionor ligand chromatography/mass spectom-etry-mass has been suggested for assessingtotal testosterone in children. Routineclinical assays, which use a direct assay

method without organic solvent extrac-tion or chromatography, are often inaccu-rate and imprecise. An early-morningscreening value of 200 ng/dL of serumtestosterone and especially of 17-hydroxprogesterone is sufficient to rule out tu-mors or congenital adrenal hyperplasia asthe cause of oligomenorrhea.

The hormone most commonly agreedupon for identifying PCOS is an elevatedtestosterone (2SDabovethemean)forthe assay used. For an assay performed

after appropriate extraction, an elevatedvalue should be 55-58 ng/dL. Al-

though free testosterone (non-sex hor-mone binding globulin bound or un-bound testosterone) of 15 ng/dL iscommonly used, most commercial as-says have poor validity in females. Webelieve that to diagnose PCOS in adoles-cents, it is more prudent to rely on thepresence of hyperandrogenemia, a clas-sic character of PCOS that generally ap-pears at puberty, than on biologicalsigns.

Chronic anovulation andmenstrual irregularities

Chronic anovulation, generally present-ing with oligomenorrhea or secondaryamenorrhea, is a key element for diag-nosing PCOS in adults. However, in ad-olescence, chronic anovulation andmenstrual irregularities are common;approximately 40-50% of adolescentgirls (gynecologic age, 0.5-5) haveanovulatory cycles. Some girls may havechronic anovulation even with regular

cycles. There is a progression towardsmore ovulatory cycles with increasinggynecologic age; the prevalence of ovula-tory cycles increases from 23-35% dur-ing the first year after menarche to 63-65% in the fifth year after menarche andto 70-80% of women with a gynecologicage of 6-10 years.

It has been suggested that menstrualcycles lasting 40-45 days be considerednormal until 2-3 years after menarche.However, 35 days for an upper limit of

the menstrual interval may be more cor-rect, since prospective studies have

shown that 98% of girls with cycles of21-34 days have normal cycles duringadult age, whereas the same is true foronly 66% of adolescent girls with cycleslasting 35-40 days.

Because half of adolescent girls whohave oligomenorrhea or secondary am-enorrhea are affected by a permanentanovulatory disorder, it would be im-portant to attempt to distinguish thesegirls from those who will eventuallyprogress toward ovulatory cycles. Thus,

although it has been suggested that oli-gomenorrhea persisting 2 years aftermenarche should be used as a criterionfor the diagnosis of PCOS in adolescents,we suggest that this finding, althoughsuggestive, should not be used in isola-tionas a firm criterion.

Ovarian findings on ultrasound

In adolescents, the ultrasound examina-tion is typically carried out abdominallyrather than vaginally, where the resolu-

tion of the scan is significantly improved.Thus there is an inherent level of subjec-tivity to the ultrasound diagnosis. Fur-ther, there is evidence of a fair amount ofoverlap in ovarian morphologic find-ings, which tend to be heterogeneous,between PCOS and normal women.

In adolescents, this problem is furthermagnified by the evolution of ovarianfindings with age. Some girls will befound to have not polycystic ovaries butmultifollicularovaries as a stage of devel-

opment. Although by strict criteria thisshould not be confused with PCOS, it

From the Department of Medicine,

University of Palermo, Palermo, Italy (Dr

Carmina), and the Departments of

Pediatrics (Dr Oberfield) and Obstetrics and

Gynecology (Dr Lobo), College of Physicians

and Surgeons, Columbia University, New

York, NY.

0002-9378/free

2010 Mosby, Inc. All rights reserved.

doi: 10.1016/j.ajog.2010.03.008

In women, the definition of polycystic ovary syndrome (PCOS) has become broad and

includes several possible phenotypes. Because several features of PCOS may be in evo-

lution in adolescents, we suggest that only firm criteria should be used to make a diagnosis

of PCOS during adolescence. Hyperandrogenism, oligomenorrhea, and ovarian morphol-

ogy change during adolescence and are discussed individually. Adolescents with incom-

plete criteria for a firm diagnosis of PCOS should be followed up carefully and may be

diagnosed at a later time.

Cite this article as: Carmina E, Oberfield SE, Lobo RA. The diagnosis of polycystic ovary syndrome in

adolescents. Am J Obstet Gynecol 2010;203:201.e1-5.

ClinicalOpinion www.AJOG.org

SEPTEMBER 2010 American Journal of Obstetrics &Gynecology 201

8/11/2019 The diagnosis of polycystic ovary syndrome in adolescents.pdf

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may be misinterpreted because of the re-duced resolution of some abdominalscans.

Because of the scarcity of availabledata,and with theappreciation that mostultrasound scans will be carried out ab-dominally rather than vaginally in ado-lescents, we suggest that the cutoff valuefor maximum ovarian volume should re-main at 10 mL. We further suggest that ifan adolescent meets other strict criteriafor the diagnosis of PCOS, and has on

ultrasound the characteristic peripheralfollicular appearance and a volume 10mL as determined with high-resolutionultrasound, she has polycystic ovaries,which may be used as confirmation ofthe diagnosis. In isolation, however, thisfinding should not be used to diagnosePCOS. Further, if the ovary has featuresof polycystic morphology, but does notmeet the volumetric criteria notedabove, the diagnosis should not be as-cribed on this basis.

Basis of diagnosis of PCOS

in adolescents

Some experts believe that it is importantto make the diagnosis of PCOS at anearly age. In our view, since the possibil-ityof incorrectly diagnosing PCOS in ad-olescents is strong, it is best to limit thediagnosis to situations with the greatestprobability of accuracy. This will avoidany unnecessary label that may be dis-tressing to the teenager. Further, there is

no harm, in our view, in starting treat-ment for milder forms of PCOS at age 18

years rather than at age 15 years, for ex-

ample. In milder PCOS phenotypes,

where the diagnosis is more difficult to

establish, there is good evidence that the

cardiovascular and metabolic risk pro-

files are much lower.

The Table shows our suggestedcriteria

for the diagnosis of PCOS in adolescents.

While using these criteria will miss some

patients with PCOS, they may permit the

diagnosis in the vast majority of adoles-cents who have the severe (classic) phe-

notype. In others, the issue may resolve

with time, and we suggest closely follow-

ing up adolescents who have incomplete

criteria for a firm diagnosis.

During adolescence, a definitive diag-

nosis of PCOS should require all ele-

ments of Rotterdam, not just 2 out of 3.

In addition, we prefer to define hyperan-

drogenism as hyperandrogenemia (ele-

vated blood androgen[s] using sensitive

assays) and to discount clinical findings

such as acne and alopecia, with the ex-

ception of documented progressive hir-

sutism. Oligomenorrhea must have been

present for at least 2 years and the diag-

nosis of polycystic ovaries by abdominal

ultrasound must include increased ovar-

ian size (10 cm3). Further, the diagno-

sis should be considered only in girls

who are at least 2 years postmenarche.

The diagnosis may be confirmed in ado-

lescents with hyperandrogenism, oligo-menorrhea, and polycystic ovaries on

ultrasound.

PCOS may be considered but not con-

firmedin adolescents who havehyperan-

drogenism and persistent oligomenor-

rhea, but no polycystic ovaries (by strict

definition). The diagnosis cannot be

confirmed in any adolescent who has an

isolated finding of any 1 of the 3 vari-

ables; in any adolescent with oligomen-

orrhea and polycystic ovaries, but no hy-

perandrogenism; or in adolescents withhyperandrogenism and polycystic ova-

ries but not persistent oligomenorrhea.

When the diagnosis cannot be con-

firmed, the patient should be followed

up carefully into adulthood and the di-

agnosis reconsidered whenever symp-

toms persist.

CLINICAL IMPLICATIONS

The wide spectrum of phenotypes

possible for the diagnosis of polycystic

ovary syndrome is not appropriate to

use for the diagnosis in adolescents.

Several criteria for the diagnosis of

polycystic ovary syndrome may vary

during adolescence.

Only strict criteria should be used,

with the knowledge that some teenag-

ers may be diagnosed later and should

be followed up closely. f

TABLE

Diagnostic criteria for polycystic ovary syndrome in adolescents

Criterion Hyperandrogenisma Chronic anovulationb Polycystic ovariesc

Diagnosis of PCOS ................................................................................................................................................................................................................................................................................................................................................................................

Diagnosis of PCOS probable but not confirmed ................................................................................................................................................................................................................................................................................................................................................................................

Diagnosis of PCOS not possible during adolescence ................................................................................................................................................................................................................................................................................................................................................................................

Diagnosis of PCOS not possible during adolescence ................................................................................................................................................................................................................................................................................................................................................................................

Not PCOS ................................................................................................................................................................................................................................................................................................................................................................................

Not PCOS ................................................................................................................................................................................................................................................................................................................................................................................

Not PCOS ................................................................................................................................................................................................................................................................................................................................................................................

PCOS, polycystic ovary syndrome.

a Hyperandrogenemia is primary criterionacne and alopecia are not considered as evidence for hyperandrogenismhirsutism may be considered sign of hyperandrogenism only when it has beendocumented to be progressive; b Oligoamenorrhea(or documented anovulation)has to bepresentfor atleast 2 years; c Diagnosisof polycystic ovariesby abdominalultrasoundhas to includeincreasedovarian size (10 cm3).

Carmina. Thediagnosis ofPCOSin adolescents.Am J ObstetGynecol2010.

ClinicalOpinion General Gynecology www.AJOG.org

202 American Journal of Obstetrics &Gynecology SEPTEMBER 2010