Diagnostic Evaluation of Polycystic Ovary Syndrome in Adolescents

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Diagnostic evaluation of polycystic ovary syndrome in adolescents
Author: Robert L Rosenfield, MD

Section Editors: Mitchell E Geffner, MD, Amy B Middleman, MD, MPH, MS Ed
Deputy Editor: Alison G Hoppin, MD
All topics are updated as new evidence becomes available and our peer review process is complete.
Literature review current through: Apr 2018. | This topic last updated: Apr 13, 2018.
INTRODUCTION — Polycystic ovary syndrome (PCOS) is the most common cause of infertility in women [1],
frequently becomes manifest during adolescence, and is primarily characterized by ovulatory dysfunction and
hyperandrogenism. The syndrome is heterogeneous clinically and biochemically. The diagnosis of PCOS has
lifelong implications with increased risk for metabolic syndrome, type 2 diabetes mellitus, and possibly
cardiovascular disease and endometrial carcinoma. PCOS should be considered in any adolescent girl with a
chief complaint of hirsutism, treatment-resistant acne, menstrual irregularity, or obesity.
The diagnostic evaluation of an adolescent with suspected PCOS is described here. Other aspects of PCOS in
adolescents are reviewed separately:
● (See "Definition, clinical features and differential diagnosis of polycystic ovary syndrome in adolescents".)
● (See "Treatment of polycystic ovary syndrome in adolescents".)
● (See "Etiology and pathophysiology of polycystic ovary syndrome in adolescents".)
INDICATIONS FOR EVALUATION — Evaluation for polycystic ovary syndrome (PCOS) is recommended for
adolescent girls with one or more of the following characteristics:
● An abnormal degree of hirsutism or a hirsutism equivalent, such as inflammatory acne vulgaris, that is poorly
responsive to topical therapies
● Menstrual abnormality (persistent amenorrhea or oligomenorrhea, or excessive uterine bleeding)
● Obesity or focal hirsutism accompanied by menstrual abnormality
EVALUATION OVERVIEW — We suggest a stepwise approach to the evaluation that addresses the diagnostic
criteria (table 1). This approach is first outlined here and then detailed in the sections below.
● Basic evaluation – The evaluation begins with a focused clinical evaluation for the presence of hirsutism (or
hirsutism equivalents) and menstrual abnormality. This is followed by laboratory testing for
hyperandrogenemia by measuring total or free testosterone (algorithm 1). Patients with elevated
testosterone levels are likely to have polycystic ovary syndrome (PCOS). I advise further evaluating these
patients to rule-out the most common non-PCOS causes of hyperandrogenemia with ovarian
ultrasonography and a screening panel of laboratory tests (algorithm 2) [2]. This evaluation excludes the
vast majority of disorders that mimic PCOS. Some other experts reserve the ultrasonographic screening for
those patients with atypical features, such as those with features suggestive of virilization, such as rapidly
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progressive hirsutism, or failure to respond to therapy. (See 'History and physical examination' below and
'Testing for hyperandrogenemia' below and 'Exclusion of non-PCOS causes of hyperandrogenemia' below.)
• Demonstration of persistent hyperandrogenism in a patient with a persistently abnormal degree of

menstrual irregularity fulfills the diagnostic criteria for PCOS if the endocrine screening tests are
negative for the most common disorders that mimic PCOS. This minimalist approach is approximately
99 percent specific for PCOS in young women and meets international consensus criteria for the
diagnosis of PCOS in adolescents [3-5].
• Lack of hyperandrogenism effectively rules out the diagnosis of PCOS in adolescents. However, the
ovarian hyperandrogenism of PCOS may not become demonstrable until a few years after menarche
[6]. Thus, young patients with menstrual irregularity should be followed, and the diagnosis of PCOS
should not be dismissed until their menses normalize and androgen levels remain persistently normal.
● Further endocrine evaluation – The basic evaluation described above does not exclude rare virilizing
disorders (table 2) [7-9]. In the presence of concern about the possibility of a rare virilizing disorder, such as
a tumor or rare congenital disorders, a more comprehensive evaluation is suggested, including
dexamethasone suppression testing and cosyntropin testing, which determine the source of androgen
(algorithm 3). These tests also help to exclude the possibility that a mild PCOS picture is simply due to
obesity. This approach is consistent with the hirsutism clinical practice guidelines from the Endocrine Society
[9]. (See 'Further endocrine evaluation for rare disorders mimicking PCOS' below.)
● Additional evaluation after the diagnosis of PCOS – Girls diagnosed with PCOS should have additional
evaluations for glucose intolerance and other features of the metabolic syndrome, particularly if they are
obese. Primary relatives of PCOS patients may also benefit from screening for these disorders. (See
'Additional evaluation of PCOS patients' below and 'Evaluation of family members' below.)
BASIC DIAGNOSTIC APPROACH
History and physical examination — The evaluation starts with a thorough assessment of the clinical
symptoms and signs suggestive of polycystic ovary syndrome (PCOS) and for disorders that mimic it (algorithm
1). The cutaneous manifestations of hyperandrogenism (particularly hirsutism or acne, which occur in
approximately three-quarters of PCOS cases) provide clinical evidence of hyperandrogenism. An abnormal
menstrual pattern constitutes evidence of oligo-anovulation. Assessment includes a history of medications that
may either mask the symptoms (eg, oral contraceptives and topical or systemic acne medications) or cause the
symptoms (eg, androgenic steroids, antiepileptic drugs).
● Hirsutism – The degree and distribution of sexual hair growth should be identified (eg, using the Ferriman-
Gallwey score (figure 1)) and interpreted in the context of norms for the patient's age and ethnicity. Moderate
or severe hirsutism (hirsutism score >15) constitutes clinical evidence of hyperandrogenism in an adolescent
[3-5]. The history should specifically explore whether the patient shaves excess hair or uses depilatory
agents, which may obscure the physical findings, and whether the patient is taking medications that cause
hirsutism (eg, anabolic steroids, valproate). (See "Definition, clinical features and differential diagnosis of
polycystic ovary syndrome in adolescents", section on 'Hirsutism'.)
● Acne – The degree of acne should be evaluated in the context of the patient's gynecologic age. The
possibility of hyperandrogenism is suggested by moderate or severe inflammatory acne (>10 lesions in any
area, eg, face, chest, back (table 3)) through the perimenarcheal years or acne that is persistent and poorly
responsive to topical dermatologic therapy [3-5]. (See "Definition, clinical features and differential diagnosis
of polycystic ovary syndrome in adolescents", section on 'Acne'.)
● Menses – The age of menarche and subsequent menstrual patterns should be described and interpreted in
the context of the patient's gynecologic age. The menstrual dysfunctions that suggest abnormal degrees of
anovulation in adolescence are detailed in the table (table 4) [4]. A menstrual pattern that is outside of these
bounds for two years (or one year with supporting evidence for PCOS) can be considered a "persistent"
abnormality and fulfills one of the two criteria for the diagnosis of PCOS [3-5]. Note that normal menstrual
regularity does not necessarily mean that ovulatory function is normal. (See "Definition, clinical features and
differential diagnosis of polycystic ovary syndrome in adolescents", section on 'Anovulation'.)
The assessment also includes addressing the differential diagnosis of PCOS for familial hyperandrogenic
disorders, medication usage, virilization (eg, rapidly progressive hirsutism), galactorrhea, Cushingoid or
acromegaloid changes, or evidence of thyroid dysfunction (algorithm 1). (See "Definition, clinical features and
differential diagnosis of polycystic ovary syndrome in adolescents", section on 'Differential diagnosis'.)
Testing for hyperandrogenemia — Persistent serum testosterone elevation above adult norms in a reliable
reference laboratory is the best evidence of hyperandrogenism [3-5]. Therefore, in the presence of clinical risk
factors for PCOS, the routine evaluation should begin with measuring serum testosterone concentrations
(algorithm 1). The choice between initiating workup with assay of total or free testosterone depends on assay
reliability and cost-effectiveness considerations discussed below [9]. If a reliable measurement of total
testosterone is easily available, this can be used as an initial test, but should be followed by measurement of free
testosterone if the results are not consistent with the patient's clinical course. If a reliable method for measuring
serum free (or bioavailable) testosterone is available to the practitioner and cost is not an issue, this test is the
preferred choice for initial testing. Measurement of dehydroepiandrosterone sulfate (DHEAS) should be included
for those with severe or rapidly progressive hyperandrogenism to screen for a primary adrenal source.
Hyperandrogenemia is present in most cases of moderate or severe hirsutism, but only about one-half of cases
of mild hirsutism [9]. Therefore, moderate or severe hirsutism can constitute clinical evidence of
hyperandrogenism, but should only be used as a diagnostic criterion when a reliable assay for
hyperandrogenemia is not available [3-5].
Testosterone assays: choices and pitfalls — There are many pitfalls in testosterone assays at the low
levels found in women, and reliable testosterone assays are not available to many physicians. For these and
other reasons discussed below, assessment may be best deferred to a specialist.
● Total testosterone – A reliable total testosterone assay is critical to accurate assessment for biochemical
evidence of hyperandrogenism. The automated assays that are used to measure serum total testosterone in
most laboratories are not suitable to accurately measure levels in females [10,11]. Results by the best
available assays vary by an average of approximately 6 to 26 percent [8,12]. The interpretation of the
laboratory results is further complicated by systematic differences between assays and excessively broad
normal ranges derived from populations of apparently normal women with unrecognized androgen excess.
Liquid chromatography mass spectrometry methods are becoming the preferred method, but their
availability is limited to major specialty laboratories [13]. Where this technology is not available, high quality
post-chromatographic radioimmunoassay is the method of choice [5].
● Free testosterone – An elevation of serum (or plasma) free testosterone is the single most sensitive test to
establish the presence of hyperandrogenemia [3,9,11,14,15]. The combination of an upper-normal total
testosterone and a lower-normal sex hormone-binding globulin (SHBG) yields a high free testosterone
concentration. The serum free testosterone concentration is about 50 percent more sensitive for the
detection of hyperandrogenemia than the total testosterone concentration. This is because PCOS is
characterized by low levels of SHBG, which is the main determinant of the fraction of serum testosterone
that is free, and thus bioactive, and the fraction that is weakly bound to albumin [16,17]. SHBG production by
the liver is raised by estrogen and suppressed by androgen, insulin-resistant obesity, and hypothyroidism
[18]. Although the low SHBG in obese individuals has been attributed to hyperinsulinemia [19], evidence
suggests that monosaccharide excess itself and inflammatory cytokines mediate the SHBG response to
obesity [20].
Despite these advantages, assaying the free testosterone level introduces other potential sources of error. In
part, this is because of systematic differences between assays and because there is no uniform standard.
The most accurate androgen determinations come from specialty laboratories using established, validated
assays in well-characterized control women.
The only reliable methods report free testosterone that is calculated as the product of the total testosterone
and a function of SHBG (free testosterone = total testosterone x percent free testosterone) [21]. The most
common methods calculate percent free testosterone from the SHBG concentration or determine the
percent free testosterone by equilibrium dialysis. An alternative reliable method is to instead calculate
"bioavailable testosterone" by determining the percent of serum testosterone not precipitated with globulins
by ammonium sulfate (the supernatant includes both the fraction free and that weakly bound to albumin, the
latter being bioactive to the extent that it dissociates to free in a given tissue space dependent upon the local
interstitial albumin concentration) [21]. Direct assays of the free testosterone serum concentration are
inaccurate and should be avoided.
Interpretation of testosterone levels — The normal upper limit for serum total testosterone in adult women
is approximately 40 to 60 ng/dL (1.4 to 2.1 nmol/L) when using most validated assays [11,14,15]. The adult norm
is the appropriate reference range for adolescents [3,4]. Most patients with PCOS have serum testosterone
concentrations 29 to 150 ng/dL (1.0 to 5.2 nmol/L). A total testosterone >200 ng/dL (6.9 nmol/L) increases the
likelihood of a virilizing neoplasm.
For practical purposes, an elevated serum total and free testosterone at any time of day provides evidence of
hyperandrogenism in an anovulatory cycle. However, a normal level in the afternoon does not exclude
hyperandrogenemia. Partly this is because serum testosterone undergoes episodic changes of about twofold
(trough-to-peak). Partly it is because norms are standardized for early morning on days 4 through 10 of the
menstrual cycle in regularly cycling women because normal testosterone levels fall 10 percent from 8:00 AM to
4:00 PM and rise transiently during midcycle [22,23].
Patients who have clinical features consistent with PCOS but have an initial normal total testosterone should
have repeat testing, preferably an early morning serum free testosterone level calculated from SHBG in a reliable
specialty laboratory.
The estrogen and progestin contents of combined oral contraceptive pills (COCs) interfere with the assessment
of androgens. They suppress gonadotropins, elevate SHBG, and directly inhibit steroidogenic enzymes such as
3ß-hydroxysteroid dehydrogenase (3ß-HSD). They normalize androgens in PCOS and also have been reported
to normalize androgens in some virilizing tumors [24]. After discontinuing COCs, normal women may transiently
have a slightly high total testosterone level but a normal free testosterone level because SHBG turnover is
slower than testosterone turnover.
Adolescents with PCOS or with features of PCOS that do not fulfill diagnostic criteria should be followed to
determine that hyperandrogenemia and symptoms persist, since data are limited on the natural history of
adolescent PCOS. The diagnosis of PCOS should not be fully dismissed until menses normalize and androgen
levels remain persistently normal.
Exclusion of non-PCOS causes of hyperandrogenemia — The hyperandrogenic patient should be further

evaluated to screen for an underlying cause of androgen excess. The diagnosis of PCOS is made when other
hyperandrogenic disorders are excluded (table 2) (see "Definition, clinical features and differential diagnosis of
polycystic ovary syndrome in adolescents", section on 'Clinical features' and "Definition, clinical features and
differential diagnosis of polycystic ovary syndrome in adolescents", section on 'Anovulation' and "Definition,
clinical features and differential diagnosis of polycystic ovary syndrome in adolescents", section on 'Differential
diagnosis'). For practical purposes, the endocrine screening panel is often performed at the same time as the
initial testing for hyperandrogenemia (above), particularly in patients with a high clinical suspicion for PCOS (eg,
oligomenorrheic girls with moderate or severe hirsutism).
In my pediatric endocrinology practice, I have performed basic screening for all patients with confirmed
hyperandrogenemia, consisting of a panel of serum endocrine studies as described below (algorithm 2). This
screening evaluation excludes most of the non-PCOS causes of hyperandrogenism and is consistent with the
American College of Obstetricians and Gynecologists (ACOG), Endocrine Society, and adolescent guidelines for
the diagnosis of PCOS [3,25,26]. I also generally perform ultrasonography at this stage, primarily to exclude rare
tumors. Other experts reserve ultrasonography for patients with atypical features, as outlined below. (See
'Ultrasonography' below and 'Endocrine screening panel' below.)
However, this exclusionary approach to the differential diagnosis will miss a few patients with rare disorders.
Therefore, patients must at the least be followed closely to be sure they respond to therapy as expected.
Patients with abnormal results of the endocrine studies, or with unusual features on history or physical
examination suggesting rare causes of hyperandrogenism other than PCOS, may warrant further testing by a
subspecialist (algorithm 3).
Ultrasonography — Ultrasonography is not recommended or required for the diagnosis of PCOS in

adolescents, because the high frequency of polycystic-appearing ovaries in this age group makes this an
unreliable criterion for the diagnosis of PCOS. The primary purpose of ultrasonography in the
hyperandrogenemic adolescent is to exclude causes other than PCOS. A secondary benefit is to identify the few
individuals with very large ovaries, for whom it simply provides further evidence of PCOS severity and diagnostic
specificity, as discussed below.
● Ultrasonographic criteria for polycystic ovary morphology – International consensus criteria for adults
define polycystic ovary morphology (PCOM) on the basis of either excessive size or follicle number (or
both), in the absence of a dominant-size follicle (>1.0 mL) or a corpus luteum, as evaluated by transvaginal
ultrasonography (image 1) [27,28] (see "Diagnosis of polycystic ovary syndrome in adults", section on
'Transvaginal ultrasound'). On the one hand, PCOM are most prevalent in the most clinically severe PCOS
cases [29] (see "Definition, clinical features and differential diagnosis of polycystic ovary syndrome in
adolescents", section on 'Definition'). On the other hand, PCOM are a common normal variant in
asymptomatic women that may predict a slightly longer period of fertility [29]. Furthermore, it has become
apparent that these criteria are problematic in young adults because normal young adults have slightly
larger ovaries [30], and the newer high-definition vaginal imaging techniques show that small antral follicle
counts up to 24 are normal [31].
Adult PCOM criteria are especially problematic when applied to adolescents [3,4]. For one thing, an
accurate antral follicle count cannot be defined by the abdominal ultrasonographic approach necessary in
virginal adolescents [31,32]. For another, even if an accurate follicle count is obtained by magnetic
resonance imaging (MRI), the adult criteria for PCOM overlap with criteria for a multifollicular ovary, which is
defined by the presence of ≥6 follicles of 4 to 10 mm diameter without increase in ovarian volume and is
known to be a normal variant unrelated to hyperandrogenism [3]. Additionally, studies suggest that ovarian
volume is slightly larger in adolescents than in adults, though data vary considerably [3,29,32].
Consequently, one-quarter to one-half of normal adolescents meet adult criteria for PCOM [32,33]. In 2015,
an international consensus group proposed using an ovarian volume >12 mL to constitute PCOM in
adolescence [3]. However, this threshold may be too low, since a study of 102 adolescents with normal
cycles found that 13 percent had PCOM by this criterion [34]. These findings are consistent with the
evidence that a mean ovarian volume (average of both ovaries) up to 12 mL or a single ovarian volume up
to 14 to 15 mL may be normal in adolescents [4,29,32,33].
Because of these uncertainties about definitive criteria for PCOM and the wide range of findings in
adolescents, PCOM is not included in the 2015 consensus diagnostic criteria for PCOS in adolescents [3-5].
However, there is reason to believe that the presence of clear PCOM, in combination with symptomatic
hyperandrogenism in the absence of anovulatory symptoms, poses a risk for PCOS in an adolescent [29],
so that we suggest careful follow-up of girls with PCOM. In adults, these same features would meet a
somewhat nonspecific PCOS criterion. (See "Definition, clinical features and differential diagnosis of
polycystic ovary syndrome in adolescents", section on 'Adults'.)
● The role of ultrasonography in the differential diagnosis of PCOS – Practice varies as to the indications
for ultrasonography in girls with confirmed hyperandrogenemia, since ultrasonography is not recommended
for the diagnosis of PCOS. In my pediatric endocrinology practice, I have recommended adrenal and ovarian
ultrasonography for all patients with anovulatory symptoms and documented hyperandrogenemia, to
exclude rare but serious androgen-producing tumors, as described below. Other experts perform
ultrasonography only for selected patients with features that are atypical for PCOS, such as very high
testosterone levels (eg, >200 ng/dL), clitoromegaly, rapidly progressive hirsutism, or poor response to
treatment [35].
The primary purpose of ultrasonography is to exclude the rare but serious adrenal or ovarian tumor and
ovarian pathology not related to PCOS (algorithm 2). In addition, other pelvic pathology, including an
ovotesticular disorder of sex development and the functional hyperandrogenism of pregnancy, may be
detected by ultrasonography. On rare occasions, ultrasonography has been insensitive in detecting a
virilizing ovarian tumor in adults [36,37], and it must be remembered that one-half of virilizing tumors are
adrenocortical. Girls who have an ultrasound that shows an ovarian tumor or other explanation for
hyperandrogenism should be referred for further evaluation and treatment of the underlying disorder.
Otherwise, hyperandrogenic girls need further endocrine studies irrespective of whether the ovaries are
polycystic, as discussed in the following section. (See 'Endocrine screening panel' below.)
Ultrasonography also provides the opportunity for patient reassurance and education. For many women, the
diagnosis of ovarian "cysts" raises a concern about tumors, so it is reassuring to know that a tumor has been
ruled out by the ultrasound. The clinician can explain to the PCOS patient with a polycystic ovary that these
are numerous small egg sacs that are not ovulating properly. Conversely, if a polycystic ovary is not
visualized in a PCOS patient, the clinician can explain that the ovarian dysfunction is "too mild to be seen on
the ultrasound."
Endocrine screening panel — Exclusion of disorders that commonly mimic PCOS is an integral part of the
diagnostic process. All clinical guidelines recommend screening for congenital adrenal hyperplasia, Cushing's
syndrome, prolactin excess, thyroid dysfunction, and acromegaly [3,25-27,38]. However, the guidelines vary in
which tests are recommended for universal screening, and which are recommended only for patients with
symptoms suggestive of one of these disorders. These guidelines are based on expert opinion and no cost-
effectiveness analyses have been performed. Therefore, the actual range of practice varies considerably among
expert clinicians in this field.
In my pediatric endocrinology practice, I have typically performed the full range of screening tests outlined below
for all patients presenting with suspected PCOS. I have taken this approach because I consider it to be both
simple and an economic use of time for patients, and it permits a thorough screening workup within two visits.
Some other experts select among these tests based on clinical symptoms and signs that raise concerns for a
particular disorder. This approach considers the costs of the laboratory tests themselves, and recognizes that
most of these disorders are rare in adolescents and usually can be identified by specific symptoms. PCOS is by
far the most common cause of hyperandrogenic anovulation, and the most common of the disorders mimicking
PCOS is nonclassic congenital adrenal hyperplasia (CAH), which occurs in only about 3 percent of women in the
United States. In the absence of a cost-effectiveness analysis, the optimal approach to the workup would seem
to be an individualized one.
In my practice, I begin the specific work-up for PCOS by ordering a random serum free testosterone at the initial
evaluation for hyperandrogenemia (algorithm 1). At the same time, I generally include the most clinically relevant
of the simple screening tests in the initial blood draw: prolactin, thyroid stimulating hormone (TSH), insulin-like
growth factor I (IGF-I), and, if the patient is centrally obese, cortisol (algorithm 2). For practical reasons, after
documentation of hyperandrogenemia, I ordinarily schedule the serum 17- hydroxyprogesterone (17-OHP)
(algorithm 2) for early morning of the day of the ultrasound examination, since this test requires early morning
sampling to be highly discriminatory in detecting nonclassic CAH. It is best to perform these tests in the
untreated state because hormonal medications (eg, COCs, corticosteroids) affect these results.
Pregnancy should be excluded in all amenorrheic patients. My initial general evaluation of patients presenting
with anovulatory symptoms also ordinarily includes ancillary evaluations of serum levels of luteinizing hormone
(LH), follicle-stimulating hormone (FSH), and estradiol, as well as a focused dietary history. The purpose of these
tests is to screen for other causes of amenorrhea (see "Evaluation and management of secondary amenorrhea");
LH and FSH (and their ratio) are not useful in establishing the diagnosis of PCOS. (See "Etiology and
pathophysiology of polycystic ovary syndrome in adolescents", section on 'Gonadotropin abnormalities'.)
It is important to confirm the persistence of hyperandrogenism in order to avoid labeling as PCOS adolescents
who have the transient hyperandrogenemia of physiologic adolescent anovulation (see "Definition, clinical
features and differential diagnosis of polycystic ovary syndrome in adolescents", section on 'Differential
diagnosis'). About one-quarter of adolescents with an abnormal degree of menstrual irregularity will have an
elevated androgen level, but no clinical manifestations of hyperandrogenism, and neither the menstrual
abnormality nor the hyperandrogenemia will persist. In the absence of clinical signs of hyperandrogenism (eg,
hirsutism or an abnormal degree of acne), a diagnosis of PCOS is not warranted in an adolescent with
anovulatory symptoms and an elevated androgen level without other clinical manifestations of PCOS, unless
both of these features are documented to persist for two years [3,4].
In patients with PCOS, hyperandrogenism will be persistent, and the following endocrine studies will be normal.
An abnormal result for any of these tests suggests another cause of hyperandrogenism (see "Definition, clinical
features and differential diagnosis of polycystic ovary syndrome in adolescents", section on 'Differential
diagnosis') and should be further evaluated as suggested in the linked topic reviews.
● Early-morning 17-hydroxyprogesterone – An 8 AM 17-OHP level is a good screening test for nonclassical

CAH secondary to 21-hydroxylase deficiency, when performed under properly controlled circumstances:
• Early morning sampling is critical to detect the 17-OHP elevation of non-classical CAH because it
wanes rapidly thereafter due to the diurnal variation of adrenal steroid secretion.
• It is important to obtain the screening sample when the patient is amenorrheic, or within the first 10 days
after the start of a menstrual cycle in regularly cycling patients because 17-OHP rises during the
preovulatory and luteal phases of the cycle. A 17-OHP value of >200 ng/dL (6.0 nmol/L) is suggestive of
nonclassical CAH in an anovulatory cycle, but is also compatible with recent ovulation. This cut-off
displayed 92 to 98 percent sensitivity in detecting nonclassical CAH [39,40], but only 12 to 25 percent
specificity in discriminating it from PCOS (>20 percent of patients with PCOS have elevated baseline
17-OHP concentrations) and tumoral hyperandrogenism [41-43]. An abnormal screening test is not
diagnostic, but requires a cosyntropin (ACTH) stimulation test to confirm the diagnosis of CAH [40],
unless the 17-OHP level is >1000 ng/dL (30 nmol/L) [40]. (See 'Further endocrine evaluation for rare
disorders mimicking PCOS' below.)
• I also measure serum progesterone at the same time as the 17-OHP measurement, to rule out the
possibility that the patient has unexpectedly ovulated (which occurs in about 10 percent of oligo-
amenorrheic PCOS patients) and is unexpectedly being tested in the luteal phase of her cycle. The
luteal phase is indicated by a serum progesterone >400 ng/dL (12.7 nmol/L) and can be accompanied
by 17-OHP levels up to 350 ng/dL (10.5 nmol/L).
• In those patients with known CAH that is complicated by PCOS (see "Etiology and pathophysiology of
polycystic ovary syndrome in adolescents", section on 'Congenital virilization'), full glucocorticoid
replacement treatment will suppress the 17-OHP level to normal, but androgen levels will remain slightly
elevated. (See "Etiology and pathophysiology of polycystic ovary syndrome in adolescents", section on
'Congenital virilization'.)
● Dehydroepiandrosterone sulfate (DHEAS) – DHEAS is a marker for adrenal hyperandrogenism; it has

little diurnal variation. While the most common cause of DHEAS elevation is the functional adrenal
hyperandrogenism of PCOS, the main purpose of measuring DHEAS levels is to rapidly identify an unusual
virilizing adrenal disorder, such as cortisone reductase deficiency [44,45] or an adrenal tumor. Girls with a
virilizing tumor usually present with a rapid onset of virilizing features, and DHEAS levels are often, but not
necessarily, markedly elevated (>700 mcg/dL, 13.6 mmol/L) if the tumor is of adrenal origin. However, in a
substantial minority of patients with virilizing tumors the symptoms are indolent in onset and mimic PCOS in
presentation (see "Definition, clinical features and differential diagnosis of polycystic ovary syndrome in
adolescents", section on 'Differential diagnosis' and "Adrenal hyperandrogenism"). COCs have equivocal
effects on the DHEAS level. (See "Normal adrenarche".)
● Serum cortisol – I include this in the initial evaluation of centrally obese patients. Although the normal
range for serum cortisol is wide (5 to 25 mcg/dL), a serum cortisol concentration of <10 mcg/dL (276 nmol/L)
is reassuring evidence against endogenous Cushing's syndrome in a hyperandrogenic girl with central
obesity. A mid-day or afternoon sample is more optimal for this screening than an early morning sample.
Patients with markedly elevated serum cortisol levels, or those with clinical features suggestive of Cushing's
disease, warrant further evaluation (eg, with 24-hour urine collection for free cortisol and creatinine).
Estrogen raises total serum cortisol levels by increasing cortisol binding globulin, but low-dose COCs do not
generally cause falsely abnormal results. (See "Establishing the diagnosis of Cushing's syndrome".)
● Prolactin – Hyperprolactinemia usually can be identified by galactorrhea, but about 15 percent of

hyperandrogenemic hyperprolactinemic women lack galactorrhea. Estrogen-containing medications
increase prolactin secretion, but the amount of estrogen in low-dose COCs generally does not cause
hyperprolactinemia. Prolactin elevation is unusual in PCOS, occurring in less than one percent of subjects,
and marginal elevation in the absence of specific clinical evidence does not necessitate a prolactinoma
workup [38,46]. Serum prolactin values more than 25 ng/mL usually have an identifiable cause, rather than
PCOS [46]. (See "Definition, clinical features and differential diagnosis of polycystic ovary syndrome in
adolescents", section on 'Differential diagnosis' and "Clinical manifestations and evaluation of
hyperprolactinemia".)
● Thyroid function tests – Normal serum thyroid stimulating hormone (TSH) is ordinarily adequate to rule out
thyroid dysfunction. High-dose estrogenic medications raise total serum T4 by elevating thyroxine binding
globulin levels, but low-dose COCs do not generally cause falsely abnormal results for these tests. Of note,
mildly elevated levels of TSH are more often found in obese children as compared with normal-weight
children, but this is a consequence rather than a cause of the obesity. (See "Acquired hypothyroidism in
childhood and adolescence".)
● Insulin-like growth factor-I (IGF-I) – Growth hormone excess usually can be identified by clinical
symptoms (gigantism in growing children or acromegaly after epiphysial fusion). However, the disorder
occasionally first presents with PCOS-like symptoms. Serum IGF-I concentrations are elevated in virtually all
patients with untreated acromegaly and provide excellent discrimination from normal individuals. The oral
estrogen of COCs may lower IGF-I levels sufficiently to obscure the diagnosis of acromegaly. (See
"Diagnosis of acromegaly".)
FURTHER ENDOCRINE EVALUATION FOR RARE DISORDERS MIMICKING PCOS — Some endocrinologists
perform additional testing in hyperandrogenemic patients to detect disorders that mimic polycystic ovary
syndrome (PCOS) and would go undetected by the above basic screening approach. These disorders include
the approximately one percent or less who have a rare virilizing disorder that may be encountered no more than
a few times in an endocrinologist's career (table 2), and the eight percent in whom simple obesity may account
for a mild PCOS picture in the absence of ovarian androgenic dysfunction [8]. This diagnostic approach is
consistent with that recommended by hirsutism guidelines from the Endocrine Society for evaluation of hirsute
women with hyperandrogenemia [9], but the cost-effectiveness is unknown. (See "Definition, clinical features and
differential diagnosis of polycystic ovary syndrome in adolescents", section on 'Differential diagnosis'.)
This more comprehensive diagnostic evaluation is typically performed only in selected patients during an
evaluation by a subspecialist (eg, a pediatric or reproductive endocrinologist). This evaluation may be particularly
helpful in patients with atypical features such as virilization (eg, rapidly progressive hirsutism), unexplained
congenital or familial hyperandrogenism, or unresponsiveness to standard therapy. Our approach augments the
initial evaluation by starting with a dexamethasone androgen-suppression test to distinguish an
adrenocorticotropic hormone (ACTH)-dependent adrenal source of androgen excess from other sources of
androgen (algorithm 3) [7]. (See "Definition, clinical features and differential diagnosis of polycystic ovary
syndrome in adolescents", section on 'Other'.)
Dexamethasone androgen suppression test (DAST) — The responses of androgens (testosterone and
dehydroepiandrosterone sulfate [DHEAS] are the primary outcome measures) and corticoids to dexamethasone
suppression establish the underlying cause of hyperandrogenism (algorithm 3).
● Baseline levels of steroid intermediates, such as 17-hydroxypregnenolone, 11-deoxycortisol, and

androstenedione are very elevated in rare forms of congenital adrenal hyperplasia (CAH) and some virilizing
tumors. Baseline urine corticoids (ie, free cortisol and 17α-hydroxycorticoids with creatinine) are helpful for
the unusual case of Cushing's syndrome and the rare case of cortisone reductase deficiency. The latter is
characterized by elevated urinary corticoid excretion that is comprised predominantly of cortisone rather
than cortisol metabolites [44].
● A short (four-hour) DAST can be used to screen for an ovarian source of androgen in obese women [8]. This
consists of a noontime 0.5 mg oral dose of dexamethasone followed by blood sampling four hours later for
cortisol, DHEAS, and testosterone. A short DAST is 95 percent sensitive for detecting the functional ovarian
hyperandrogenism of PCOS. Therefore, normal suppression of plasma testosterone by a short DAST rules
out PCOS with high probability. However, subnormal testosterone suppression in response to a short DAST
cannot be expected to distinguish virilizing disorders or Cushing syndrome from PCOS.
● A long (four-day) DAST is the definitive form of dexamethasone suppression test for the differential
diagnosis of hyperandrogenic disorders.
● The DAST is interpreted as follows:
• If testosterone excess is not suppressed by dexamethasone, but cortisol and DHEAS are suppressed
normally, the diagnosis of PCOS is virtually assured. However, virilizing tumor and adrenal rests must
still be considered in the presence of suggestive clinical factors.
• If neither androgen (testosterone and DHEAS) excess nor corticoids are suppressed normally by
dexamethasone, then disorders other than PCOS must be considered, such as Cushing's syndrome,
adrenal tumors, and glucocorticoid resistance (or dexamethasone was not taken properly). If the levels
of androgens suggest an adrenal tumor, further imaging, such as computed tomography, is indicated.
• If both androgens (testosterone and DHEAS) and corticoids are suppressed normally, an ovarian
source for androgen is unlikely, so further evaluation for adrenal disorders is indicated with a
cosyntropin (ACTH) test for CAH.
Cosyntropin (ACTH) stimulation test — The responses of steroid intermediates on the pathway to cortisol and
androgens distinguish adrenal steroidogenic disorders that mimic PCOS (algorithm 3).
● The cosyntropin (ACTH) stimulation test (using a 250-mcg dose, with samples drawn 30 to 60 minutes later)
is interpreted as follows:
• A 17-OHP value >1000 ng/dL (30 nmol/L) is highly suggestive, and >1500 ng/dL is definitive for the 21-
hydroxylase deficiency form of nonclassic CAH [39]. Intermediate 17-OHP levels (1000 to 1500 ng/dL)
require genetic confirmation to make a definitive diagnosis of nonclassic CAH [47,48]. (See "Diagnosis
and treatment of nonclassic (late-onset) congenital adrenal hyperplasia due to 21-hydroxylase
deficiency".)
• Mildly elevated responses of 17-hydroxypregnenolone and DHEA are characteristic of the primary
functional adrenal hyperandrogenism of PCOS and are often confused with nonclassic 3ß-
hydroxysteroid dehydrogenase deficiency [49]. Only when the 17-hydroxypregnenolone response to
ACTH is >10 SD above the normal mean (ie, >4500 ng/dL [150 nmol/L]) has nonclassic 3ß-
hydroxysteroid dehydrogenase deficiency (3βHSD) been documented by mutation analysis in hirsute
females [50]. (See "Definition, clinical features and differential diagnosis of polycystic ovary syndrome in
adolescents", section on 'Differential diagnosis' and "Etiology and pathophysiology of polycystic ovary
syndrome in adolescents", section on 'Functional adrenal hyperandrogenism (FAH)'.)
• Nonclassic 11ß-hydroxylase deficiency is a rare mime of PCOS [51]. Only an 11-deoxycortisol response
to ACTH >5 times greater than the upper limit of normal (>4000 ng/dl/116 nmol/L) has been shown to
be specific for mutation detection. (See "Definition, clinical features and differential diagnosis of
polycystic ovary syndrome in adolescents", section on 'Differential diagnosis'.)
If both the DAST and the ACTH stimulation test are normal, obesity or idiopathic hyperandrogenism are most
likely. The most common cause of this may be the pseudo-PCOS of obesity [8] (see "Definition, clinical features
and differential diagnosis of polycystic ovary syndrome in adolescents", section on 'Differential diagnosis'). The
rare possibility of cortisone reductase deficiency should be considered on the basis of the clinical picture. (See
"Dexamethasone suppression tests" and "Evaluation of the response to ACTH in adrenal insufficiency".)
Ancillary tests
● Serum levels of anti-müllerian hormone (AMH), a product of the granulosa cells of small growing follicles,
are mildly increased in many asymptomatic adolescents and young women with polycystic ovaries
[33,52,53]. Consequently, it has been suggested as a surrogate for ovarian ultrasonography, but this is
controversial. While this may result from androgen excess, it usually seems to indicate an enlarged follicle
pool ("increased ovarian reserve"), which in turn prognosticates a slightly lengthened reproductive lifespan
[52,54]. Serum AMH elevation of twofold or more is highly specific for PCOS [52]. (See "Etiology and
pathophysiology of polycystic ovary syndrome in adolescents", section on 'Primary functional ovarian

hyperandrogenism (FOH)'.)
● Gonadotropin-releasing hormone agonist test – In patients with PCOS, administration of a gonadotropin

releasing hormone (GnRH) agonist induces a hyper-responsive elevation of 17-OHP without evidence of a
steroidogenic block. The steroid pattern in response to the test distinguishes PCOS from other causes,
particularly rare hyperandrogenic disorders of steroidogenesis such as non-classic 3ß-hydroxysteroid
dehydrogenase deficiency. The test is performed by administering leuprolide acetate 10 mcg/kg
subcutaneously and checking steroid levels 20 to 24 hours later; the test can be performed in conjunction
with dexamethasone administration (as part of the DAST described above) to suppress coincidental adrenal
secretion that might interfere in the interpretation [55,56]. This test may facilitate the early diagnosis of
PCOS in adolescents [57]. It also helps in determining if mild PCOS is simply due to obesity, which is
suggested when hyperandrogenemia is mild, and serum LH, AMH, and DHEAS, along with ovarian
morphology, are normal [8]. (See "Definition, clinical features and differential diagnosis of polycystic ovary
syndrome in adolescents", section on 'Differential diagnosis' and "Uncommon congenital adrenal
hyperplasias", section on '3-beta-hydroxysteroid dehydrogenase type 2 deficiency'.)
ADDITIONAL EVALUATION OF PCOS PATIENTS — Once a diagnosis of polycystic ovary syndrome (PCOS)
has been established, the possibility of insulin resistance manifestations and quality of life issues should be
considered. This is because PCOS is a risk factor for the early development of type 2 diabetes mellitus,
metabolic syndrome, and their associated risks for sleep-disordered breathing, and possibly cardiovascular
disease [58,59]. About a quarter of adolescents with PCOS meet proposed adolescent criteria for the metabolic
syndrome. (See "Definition, clinical features and differential diagnosis of polycystic ovary syndrome in
adolescents", section on 'Manifestations of insulin resistance'.)
We advise screening for type 2 diabetes mellitus in adolescents with PCOS and obesity or other risk factors for
diabetes mellitus. At the least, a fasting plasma glucose or hemoglobin A1C should be advised. However, an oral
glucose tolerance test (OGTT) is preferable because it is the most sensitive and specific measure of glucose
tolerance (see "Epidemiology, presentation, and diagnosis of type 2 diabetes mellitus in children and
adolescents", section on 'Screening'). This recommendation is consistent with the recommendations made by
international reproductive endocrinology consensus [60], the American Association of Clinical Endocrinologists
(AACE), and the minority position of the Androgen Excess and PCOS Society (AES) in adult women with PCOS
[61,62]. The prevalence of diabetes was reported to be 2 percent based on the fasting blood sugar in one series,
and 8 percent when based on OGTT criteria in another series of adolescents [63,64]. In both series, almost all of
the adolescents had no symptoms of diabetes. Impaired glucose tolerance suggests insulin resistance and is a
risk factor for type 2 diabetes mellitus and cardiovascular disease. Thus, an abnormal OGTT has important
therapeutic implications. (See "Treatment of polycystic ovary syndrome in adolescents", section on 'Obesity and
insulin resistance'.)
Glucose tolerance should be monitored regularly because a substantial number of women with PCOS will
experience deterioration in glucose tolerance. As an example, among 25 adolescent and young women followed
for a mean of 34 months, the two-hour blood glucose increased at an average rate of 9 mg/dL (0.5 mmol/L) per
year [65]. Among the 14 women with PCOS and normal glucose tolerance at baseline, 55 percent experienced
deterioration of glucose tolerance when they were retested with an OGTT. Among the 14 women with PCOS and
impaired glucose tolerance at baseline, 29 percent progressed to diabetes.
PCOS is a risk factor for endometrial carcinoma in young women [66]. The basis of the risk is multifactorial: it is
related to the endometrial hyperplasia that arises from persistent estrogen stimulation without the progesterone-
induced inhibition of proliferation and differentiation to secretory endometrium that occurs after ovulation.
Hyperandrogenism, insulin-resistant hyperinsulinism, and the inflammatory changes of obesity appear to be
aggravating factors in PCOS; risk also seems related to body mass index (BMI)-independent proto-oncogenic
changes in endometrial cells [67].
Mood, anxiety disorders, and emotional distress are increased in prevalence in PCOS [68,69]. They contribute to
sleep disturbance. Adolescents with PCOS should be screened for these important factors affecting quality of
life.
EVALUATION OF FAMILY MEMBERS — Parents and siblings of PCOS patients are at increased risk for
metabolic syndrome and diabetes mellitus, particularly if they are obese. Screening can be accomplished by
measurement of hemoglobin A1c or oral glucose tolerance testing in first-degree relatives of either sex.
Premenopausal mothers and sisters are at risk for polycystic ovary syndrome (PCOS) and should be screened
for those features.
These recommendations are prompted by the high prevalence of PCOS and metabolic syndrome among
immediate relatives of individuals with PCOS (see "Etiology and pathophysiology of polycystic ovary syndrome in
adolescents", section on 'Heritable traits'). According to one study, approximately one-half of sisters of PCOS
probands have an elevated serum testosterone level, and one-half of these (one-quarter of the total) in turn have
menstrual irregularity and thus meet National Institutes of Health (NIH) criteria for PCOS [70]. In another study,
about one-quarter of sisters met Androgen Excess Society (AES) criteria for PCOS, having hyperandrogenism
and a polycystic ovary, although menses were ovulatory [71]. The likelihood of a mother having PCOS seems
similar, 22 percent in our series [63].
The prevalence of metabolic syndrome or diabetes mellitus in parents of women with PCOS is higher than in
parents of women without PCOS. In our series, one-third or more of mothers and the great majority of fathers
had metabolic syndrome and diabetes mellitus [63]. Notably, the diabetes was asymptomatic in half and was
uncovered by glucose tolerance testing. In another series, fathers had a 42 percent prevalence and brothers had
a 22 percent prevalence of metabolic syndrome; glucose tolerance testing was not performed, so this is likely an
underestimate [72].
OTHER RESOURCES — The following online resources are available to patients with PCOS and their families:
● PCOS resources for a healthier you – From the Center for Young Women's Health of Boston Children's
Hospital [73].
● Polycystic ovary syndrome: A guide for patients and parents – From the Pediatric Endocrine Society and the
American Academy of Pediatrics [74].
SOCIETY GUIDELINE LINKS — Links to society and government-sponsored guidelines from selected countries
and regions around the world are provided separately. (See "Society guideline links: Polycystic ovary syndrome"
and "Society guideline links: Hirsutism".)
INFORMATION FOR PATIENTS — UpToDate offers two types of patient education materials, "The Basics" and
"Beyond the Basics." The Basics patient education pieces are written in plain language, at the 5th to 6th grade
reading level, and they answer the four or five key questions a patient might have about a given condition. These
articles are best for patients who want a general overview and who prefer short, easy-to-read materials. Beyond
the Basics patient education pieces are longer, more sophisticated, and more detailed. These articles are written
at the 10th to 12th grade reading level and are best for patients who want in-depth information and are
comfortable with some medical jargon.
Here are the patient education articles that are relevant to this topic. We encourage you to print or e-mail these
topics to your patients. (You can also locate patient education articles on a variety of subjects by searching on
"patient info" and the keyword(s) of interest.)
● Basics topic (See "Patient education: Polycystic ovary syndrome (The Basics)".)
● Beyond the Basics topic (See "Patient education: Polycystic ovary syndrome (PCOS) (Beyond the Basics)".)
SUMMARY
● Evaluation for polycystic ovary syndrome (PCOS) is recommended for adolescent girls with an abnormal
degree of hirsutism or menstrual abnormality (eg, persistently irregular menses or severe anovulatory
abnormal uterine bleeding). Evaluation is also appropriate for girls with multiple minor characteristics
suggestive of PCOS, such as obesity or focal hirsutism, particularly if associated with menstrual
abnormalities. (See 'Indications for evaluation' above.)
● The evaluation begins with a focused clinical evaluation for the presence of hirsutism (or hirsutism
equivalents) and menstrual abnormality (table 4). This is followed by laboratory testing for androgen excess,
measuring total or free testosterone. (algorithm 1). (See 'History and physical examination' above and
'Testing for hyperandrogenemia' above.)
● If serum free testosterone levels are normal (in the absence of oral contraceptives), the diagnosis of PCOS
is unlikely. However, the possibility of PCOS in an adolescent should not be fully dismissed until menses
normalize and androgen levels are persistently normal. (See 'Interpretation of testosterone levels' above.)
● If serum levels of total and free testosterone are elevated, a focused history and physical examination
should be performed to exclude other hyperandrogenic disorders. In my practice, I also perform
ultrasonography and a simple screening battery of endocrine tests at this stage (algorithm 2 and table 2).
(See 'Exclusion of non-PCOS causes of hyperandrogenemia' above.)
• The primary purpose of ultrasonography is to exclude the rare but serious adrenal or ovarian tumor and
ovarian pathology not related to PCOS. Determining whether the ovaries are polycystic is not helpful for
the diagnosis of PCOS because of the high frequency of polycystic-appearing ovaries in adolescents
with or without PCOS. (See 'Ultrasonography' above.)
• If the results of the endocrine screening panel are normal, the diagnosis of PCOS is confirmed with a
high level of certainty. Any abnormal results suggest that the hyperandrogenism is caused by a disorder
other than PCOS. (See 'Endocrine screening panel' above.)
● Patients with atypical features such as virilization, unexplained congenital or familial hyperandrogenism, or
unresponsiveness to standard PCOS therapy may have a rare virilizing disorder rather than PCOS. In such
cases, we suggest evaluation for rare disorders mimicking PCOS, starting with a dexamethasone androgen-
suppression test (DAST) (algorithm 3). (See 'Further endocrine evaluation for rare disorders mimicking
PCOS' above.)
● Once a diagnosis of PCOS has been established, it is important to identify and monitor for abnormal glucose
tolerance, type 2 diabetes, and other features of the metabolic syndrome. This is because PCOS is a risk
factor for the early development of these disorders. Immediate family members are also at risk for these
metabolic dysfunctions, and premenopausal mothers and sisters are at risk for PCOS. (See 'Additional
evaluation of PCOS patients' above and 'Evaluation of family members' above.)
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REFERENCES
1. Azziz R, Woods KS, Reyna R, et al. The prevalence and features of the polycystic ovary syndrome in an
unselected population. J Clin Endocrinol Metab 2004; 89:2745.
2. Rosenfield RL. What every physician should know about polycystic ovary syndrome. Dermatol Ther 2008;
21:354.
3. Witchel SF, Oberfield S, Rosenfield RL, et al. The Diagnosis of Polycystic Ovary Syndrome during
Adolescence. Horm Res Paediatr 2015.
4. Rosenfield RL. The Diagnosis of Polycystic Ovary Syndrome in Adolescents. Pediatrics 2015; 136:1154.
5. Ibáñez L, Oberfield SE, Witchel S, et al. An International Consortium Update: Pathophysiology, Diagnosis,
and Treatment of Polycystic Ovarian Syndrome in Adolescence. Horm Res Paediatr 2017; 88:371.
6. Ibáñez L, de Zegher F, Potau N. Anovulation after precocious pubarche: early markers and time course in
adolescence. J Clin Endocrinol Metab 1999; 84:2691.
7. Buggs C, Rosenfield RL. Polycystic ovary syndrome in adolescence. Endocrinol Metab Clin North Am
2005; 34:677.
8. Rosenfield RL, Mortensen M, Wroblewski K, et al. Determination of the source of androgen excess in
functionally atypical polycystic ovary syndrome by a short dexamethasone androgen-suppression test and
a low-dose ACTH test. Hum Reprod 2011; 26:3138.
9. Martin KA, Anderson RR, Chang RJ, et al. Evaluation and Treatment of Hirsutism in Premenopausal
Women: An Endocrine Society Clinical Practice Guideline. J Clin Endocrinol Metab 2018.
10. Rosner W, Vesper H, Endocrine Society, et al. Toward excellence in testosterone testing: a consensus
statement. J Clin Endocrinol Metab 2010; 95:4542.
11. Goodman NF, Cobin RH, Futterweit W, et al. AMERICAN ASSOCIATION OF CLINICAL
ENDOCRINOLOGISTS, AMERICAN COLLEGE OF ENDOCRINOLOGY, AND ANDROGEN EXCESS AND
PCOS SOCIETY DISEASE STATE CLINICAL REVIEW: GUIDE TO THE BEST PRACTICES IN THE
EVALUATION AND TREATMENT OF POLYCYSTIC OVARY SYNDROME--PART 1. Endocr Pract 2015;
21:1291.
12. Legro RS, Schlaff WD, Diamond MP, et al. Total testosterone assays in women with polycystic ovary
syndrome: precision and correlation with hirsutism. J Clin Endocrinol Metab 2010; 95:5305.
13. Auchus RJ. Steroid assays and endocrinology: best practices for basic scientists. Endocrinology 2014;
155:2049.
14. Salameh WA, Redor-Goldman MM, Clarke NJ, et al. Specificity and predictive value of circulating
testosterone assessed by tandem mass spectrometry for the diagnosis of polycystic ovary syndrome by the
National Institutes of Health 1990 criteria. Fertil Steril 2014; 101:1135.
15. Tosi F, Fiers T, Kaufman JM, et al. Implications of Androgen Assay Accuracy in the Phenotyping of Women
With Polycystic Ovary Syndrome. J Clin Endocrinol Metab 2016; 101:610.
16. Moll GW Jr, Rosenfield RL. Testosterone binding and free plasma androgen concentrations under
physiological conditons: chararacterization by flow dialysis technique. J Clin Endocrinol Metab 1979;
49:730.
17. Rosenfield RL, Moll GW. The role of proteins in the distribution of plasma androgens and estradiol. In: Andr
ogenization in women, Molinatti G, Martini L, James V (Eds), Raven Press, New York 1983. p.25-45.
18. Pugeat M, Nader N, Hogeveen K, et al. Sex hormone-binding globulin gene expression in the liver: drugs
and the metabolic syndrome. Mol Cell Endocrinol 2010; 316:53.
19. Nestler JE, Powers LP, Matt DW, et al. A direct effect of hyperinsulinemia on serum sex hormone-binding
globulin levels in obese women with the polycystic ovary syndrome. J Clin Endocrinol Metab 1991; 72:83.
20. Simó R, Barbosa-Desongles A, Lecube A, et al. Potential role of tumor necrosis factor-α in downregulating
sex hormone-binding globulin. Diabetes 2012; 61:372.
21. Vermeulen A, Verdonck L, Kaufman JM. A critical evaluation of simple methods for the estimation of free
testosterone in serum. J Clin Endocrinol Metab 1999; 84:3666.
22. Abraham GE. Ovarian and adrenal contribution to peripheral androgens during the menstrual cycle. J Clin
Endocrinol Metab 1974; 39:340.
23. Rosenfield RL, Helke JC. Small diurnal and episodic fluctuations of the plasma free testosterone level in
normal women. Am J Obstet Gynecol 1974; 120:461.
24. Hatch R, Rosenfield RL, Kim MH, Tredway D. Hirsutism: implications, etiology, and management. Am J
Obstet Gynecol 1981; 140:815.
25. ACOG Committee on Practice Bulletins--Gynecology. ACOG Practice Bulletin No. 108: Polycystic ovary
syndrome. Obstet Gynecol 2009; 114:936.
26. Legro RS, Arslanian SA, Ehrmann DA, et al. Diagnosis and treatment of polycystic ovary syndrome: an
Endocrine Society clinical practice guideline. J Clin Endocrinol Metab 2013; 98:4565.
27. Rotterdam ESHRE/ASRM-Sponsored PCOS Consensus Workshop Group. Revised 2003 consensus on
diagnostic criteria and long-term health risks related to polycystic ovary syndrome. Fertil Steril 2004; 81:19.
28. Balen AH, Laven JS, Tan SL, Dewailly D. Ultrasound assessment of the polycystic ovary: international
consensus definitions. Hum Reprod Update 2003; 9:505.
29. Rosenfield RL. The Polycystic Ovary Morphology-Polycystic Ovary Syndrome Spectrum. J Pediatr Adolesc
Gynecol 2015; 28:412.
30. Bentzen JG, Forman JL, Johannsen TH, et al. Ovarian antral follicle subclasses and anti-mullerian
hormone during normal reproductive aging. J Clin Endocrinol Metab 2013; 98:1602.
31. Dewailly D, Lujan ME, Carmina E, 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.
32. Kenigsberg LE, Agarwal C, Sin S, et al. Clinical utility of magnetic resonance imaging and ultrasonography
for diagnosis of polycystic ovary syndrome in adolescent girls. Fertil Steril 2015; 104:1302.
33. Villarroel C, Merino PM, López P, et al. Polycystic ovarian morphology in adolescents with regular
menstrual cycles is associated with elevated anti-Mullerian hormone. Hum Reprod 2011; 26:2861.
34. Merino PM, Villarroel C, Jesam C, et al. New Diagnostic Criteria of Polycystic Ovarian Morphology for
Adolescents: Impact on Prevalence and Hormonal Profile. Horm Res Paediatr 2017; 88:401.
35. Bremer AA. Polycystic ovary syndrome in the pediatric population. Metab Syndr Relat Disord 2010; 8:375.
36. Pascale MM, Pugeat M, Roberts M, et al. Androgen suppressive effect of GnRH agonist in ovarian
hyperthecosis and virilizing tumours. Clin Endocrinol (Oxf) 1994; 41:571.
37. Prassopoulos V, Laspas F, Vlachou F, et al. Leydig cell tumour of the ovary localised with positron emission
tomography/computed tomography. Gynecol Endocrinol 2011; 27:837.
38. Azziz R, Carmina E, Dewailly D, et al. The Androgen Excess and PCOS Society criteria for the polycystic
ovary syndrome: the complete task force report. Fertil Steril 2009; 91:456.
39. Bidet M, Bellanné-Chantelot C, Galand-Portier MB, et al. Clinical and molecular characterization of a cohort
of 161 unrelated women with nonclassical congenital adrenal hyperplasia due to 21-hydroxylase deficiency
and 330 family members. J Clin Endocrinol Metab 2009; 94:1570.
40. Livadas S, Dracopoulou M, Dastamani A, et al. The spectrum of clinical, hormonal and molecular findings
in 280 individuals with nonclassical congenital adrenal hyperplasia caused by mutations of the CYP21A2
gene. Clin Endocrinol (Oxf) 2015; 82:543.
41. Rosenfield RL, Cohen RM, Talerman A. Lipid cell tumor of the ovary in reference to adult-onset congenital
adrenal hyperplasia and polycystic ovary syndrome. A case report. J Reprod Med 1987; 32:363.
42. Escobar-Morreale HF, Sanchón R, San Millán JL. A prospective study of the prevalence of nonclassical
congenital adrenal hyperplasia among women presenting with hyperandrogenic symptoms and signs. J
Clin Endocrinol Metab 2008; 93:527.
43. Pall M, Azziz R, Beires J, Pignatelli D. The phenotype of hirsute women: a comparison of polycystic ovary
syndrome and 21-hydroxylase-deficient nonclassic adrenal hyperplasia. Fertil Steril 2010; 94:684.
44. Lavery GG, Walker EA, Tiganescu A, et al. Steroid biomarkers and genetic studies reveal inactivating
mutations in hexose-6-phosphate dehydrogenase in patients with cortisone reductase deficiency. J Clin
45. Lawson AJ, Walker EA, Lavery GG, et al. Cortisone-reductase deficiency associated with heterozygous
mutations in 11beta-hydroxysteroid dehydrogenase type 1. Proc Natl Acad Sci U S A 2011; 108:4111.
46. Filho RB, Domingues L, Naves L, et al. Polycystic ovary syndrome and hyperprolactinemia are distinct
entities. Gynecol Endocrinol 2007; 23:267.
47. Ambroziak U, Kępczyńska-Nyk A, Kuryłowicz A, et al. The diagnosis of nonclassic congenital adrenal
hyperplasia due to 21-hydroxylase deficiency, based on serum basal or post-ACTH stimulation 17-
hydroxyprogesterone, can lead to false-positive diagnosis. Clin Endocrinol (Oxf) 2016; 84:23.
48. Carmina E, Dewailly D, Escobar-Morreale HF, et al. Non-classic congenital adrenal hyperplasia due to 21-
hydroxylase deficiency revisited: an update with a special focus on adolescent and adult women. Hum
Reprod Update 2017; 23:580.
49. Ehrmann DA, Barnes RB, Rosenfield RL. Polycystic ovary syndrome as a form of functional ovarian
hyperandrogenism due to dysregulation of androgen secretion. Endocr Rev 1995; 16:322.
50. Lutfallah C, Wang W, Mason JI, et al. Newly proposed hormonal criteria via genotypic proof for type II
3beta-hydroxysteroid dehydrogenase deficiency. J Clin Endocrinol Metab 2002; 87:2611.
51. Joehrer K, Geley S, Strasser-Wozak EM, et al. CYP11B1 mutations causing non-classic adrenal
hyperplasia due to 11 beta-hydroxylase deficiency. Hum Mol Genet 1997; 6:1829.
52. Rosenfield RL, Wroblewski K, Padmanabhan V, et al. Antimüllerian hormone levels are independently
related to ovarian hyperandrogenism and polycystic ovaries. Fertil Steril 2012; 98:242.
53. Hart R, Doherty DA, Norman RJ, et al. Serum antimullerian hormone (AMH) levels are elevated in
adolescent girls with polycystic ovaries and the polycystic ovarian syndrome (PCOS). Fertil Steril 2010;
94:1118.
54. Freeman EW, Sammel MD, Lin H, Gracia CR. Anti-mullerian hormone as a predictor of time to menopause
in late reproductive age women. J Clin Endocrinol Metab 2012; 97:1673.
55. Barnes RB, Rosenfield RL, Burstein S, Ehrmann DA. Pituitary-ovarian responses to nafarelin testing in the
polycystic ovary syndrome. N Engl J Med 1989; 320:559.
56. Barnes RB, Ehrmann DA, Brigell DF, Rosenfield RL. Ovarian steroidogenic responses to gonadotropin-
releasing hormone agonist testing with nafarelin in hirsute women with adrenal responses to
adrenocorticotropin suggestive of 3 beta-hydroxy-delta 5-steroid dehydrogenase deficiency. J Clin
57. Rosenfield RL, Ehrmann DA, Littlejohn EE. Adolescent polycystic ovary syndrome due to functional ovarian
hyperandrogenism persists into adulthood. J Clin Endocrinol Metab 2015; 100:1537.
58. Shaw LJ, Bairey Merz CN, Azziz R, et al. Postmenopausal women with a history of irregular menses and
elevated androgen measurements at high risk for worsening cardiovascular event-free survival: results from
the National Institutes of Health--National Heart, Lung, and Blood Institute sponsored Women's Ischemia
Syndrome Evaluation. J Clin Endocrinol Metab 2008; 93:1276.
59. Fauser BC, Bouchard P. Uncertainty remains in women with PCOS regarding the increased incidence of
cardiovascular disease later in life, despite the indisputable presence of multiple cardiovascular risk factors
at a young age. J Clin Endocrinol Metab 2011; 96:3675.
60. Fauser BC, Tarlatzis BC, Rebar RW, et al. Consensus on women's health aspects of polycystic ovary
syndrome (PCOS): the Amsterdam ESHRE/ASRM-Sponsored 3rd PCOS Consensus Workshop Group.
Fertil Steril 2012; 97:28.
61. American Association of Clinical Endocrinologists Polycystic Ovary Syndrome Writing Committee.
American Association of Clinical Endocrinologists Position Statement on Metabolic and Cardiovascular
Consequences of Polycystic Ovary Syndrome. Endocr Pract 2005; 11:126.
62. Salley KE, Wickham EP, Cheang KI, et al. Glucose intolerance in polycystic ovary syndrome--a position
statement of the Androgen Excess Society. J Clin Endocrinol Metab 2007; 92:4546.
63. Leibel NI, Baumann EE, Kocherginsky M, Rosenfield RL. Relationship of adolescent polycystic ovary
syndrome to parental metabolic syndrome. J Clin Endocrinol Metab 2006; 91:1275.
64. Coviello AD, Legro RS, Dunaif A. Adolescent girls with polycystic ovary syndrome have an increased risk of
the metabolic syndrome associated with increasing androgen levels independent of obesity and insulin
resistance. J Clin Endocrinol Metab 2006; 91:492.
65. Ehrmann DA, Barnes RB, Rosenfield RL, et al. Prevalence of impaired glucose tolerance and diabetes in
women with polycystic ovary syndrome. Diabetes Care 1999; 22:141.
66. Farhi DC, Nosanchuk J, Silverberg SG. Endometrial adenocarcinoma in women under 25 years of age.
Obstet Gynecol 1986; 68:741.
67. Piltonen TT, Chen J, Erikson DW, et al. Mesenchymal stem/progenitors and other endometrial cell types
from women with polycystic ovary syndrome (PCOS) display inflammatory and oncogenic potential. J Clin
68. Dokras A. Mood and anxiety disorders in women with PCOS. Steroids 2012; 77:338.
69. Veltman-Verhulst SM, Boivin J, Eijkemans MJ, Fauser BJ. Emotional distress is a common risk in women
with polycystic ovary syndrome: a systematic review and meta-analysis of 28 studies. Hum Reprod Update
2012; 18:638.
70. Legro RS, Driscoll D, Strauss JF 3rd, et al. Evidence for a genetic basis for hyperandrogenemia in
polycystic ovary syndrome. Proc Natl Acad Sci U S A 1998; 95:14956.
71. Franks S, Webber LJ, Goh M, et al. Ovarian morphology is a marker of heritable biochemical traits in
sisters with polycystic ovaries. J Clin Endocrinol Metab 2008; 93:3396.
72. Coviello AD, Sam S, Legro RS, Dunaif A. High prevalence of metabolic syndrome in first-degree male
relatives of women with polycystic ovary syndrome is related to high rates of obesity. J Clin Endocrinol
Metab 2009; 94:4361.
73. Center for Young Women's Health. PCOS (polycystic ovary syndrome). Available at: https://youngwomensh
ealth.org/2014/02/25/polycystic-ovary-syndrome/ (Accessed on March 15, 2018).
74. Pediatric Endocrine Society and the American Academy of Pediatrics: Polycystic Ovary Syndrome: A guide
for Patients and Parents. Available at: https://www.pedsendo.org/assets/patients_families/Educational_Mat
erials/PolycysticOvarySyndrome.pdf (Accessed on March 15, 2018).
Topic 94182 Version 15.0
GRAPHICS
International consensus diagnostic criteria for polycystic ovary syndrome in

adolescents
Otherwise unexplained combination of:

1. Abnormal uterine bleeding pattern
a. Abnormal for age or gynecologic age
b. Persistent symptoms for one to two years
2. Evidence of hyperandrogenism
a. Persistent testosterone elevation above adult norms in a reliable reference laboratory is the best evidence
b. Moderate-severe hirsutism is clinical evidence of hyperandrogenism
c. Moderate-severe inflammatory acne vulgaris is an indication to test for hyperandrogenemia
Reproduced with permission from Pediatrics, Vol 136, Pages 1154-65, Copyright © 2015 by the AAP.
Graphic 107842 Version 4.0
Initial evaluation for the presence of hyperandrogenism
Suggested algorithm for the initial evaluation of young women for hyperandrogenism, based on The
Endocrine Society clinical practice guidelines for the evaluation of hirsutism. Risk assessment
includes more than the degree of hirsutism. Focal hirsutism that is not accompanied by
hyperandrogenism risk factors does not require an endocrine workup. If hirsutism is of an abnormal
degree (Ferriman-Gallwey score ≥8 in the general US population) or if a risk factor assessment
suggests an underlying disorder, elevated androgen levels should be ruled out. Disorders to be
considered, as shown, include neoplasm and various endocrinopathies, of which PCOS is the most
common; if an abdominal or pelvic mass is palpable, a prompt screening ultrasound is advisable.
Drugs that cause hirsutism include anabolic or androgenic steroids (consider in athletes), most of
which are not detected by testosterone assays, and valproic acid (consider in neurologic disorders),
which elevates serum testosterone. Serum testosterone is best assessed by an analytically specific
method, such as mass spectrometry, preferably in the early morning. Females with mild hirsutism
(score 8 to 15 in the general US population), normal total testosterone level, and no risk factors
probably have idiopathic hirsutism, which may be responsive to oral contraceptive therapy. The
calculated free testosterone level is the most clinically sensitive marker of androgen excess and
should be assayed in a reference laboratory if the total testosterone is normal in the presence of risk
factors or if signs or symptoms progress on therapy. Simultaneous assay of 17-hydroxyprogesterone
may be indicated in subjects at risk for congenital adrenal hyperplasia, eg, Ashkenazi Jews.
PCOS: polycystic ovary syndrome; SHBG: sex hormone binding globulin.

* The free testosterone level in blood is ordinarily calculated as the product of the total testosterone level
and the percent free testosterone, which may be computed from the SHBG level. Norms are standardized
for early morning in the early follicular phase (days 4 to 10) of the menstrual cycle.
¶ Progression of hyperandrogenism in the presence of a normal serum free testosterone is very unusual.
Such patients should be thoroughly re-evaluated.
Adapted and expanded from: Martin KA, Change J, Ehrmann DA, et al. Evaluation and treatment of
hirsutism in premenopausal women: an Endocrine Society clinical practice guideline. J Clin Endocrinol Metab
2008; 93:1105.
Initial evaluation of hyperandrogenemia
This algorithm outlines the author's initial workup for causes of hyperandrogenism. The most common
cause of hyperandrogenism in women is polycystic ovary syndrome (PCOS). The algorithm outlines an
approach to exclude most other causes of hyperandrogenism, using the combination of ultrasonography
and an endocrine screening workup. Other experts select among these tests based on clinical
symptoms and signs or laboratory data such as very high androgen levels that raise concerns for one of
the disorders listed above (refer to UpToDate topic text).
* Ultrasonography is the initial study that excludes ovarian pathology other than polycystic ovaries. The
abdominal ultrasound that is indicated for pelvic ultrasonographic imaging in virginal adolescents can be used
to screen for adrenal enlargement or mass. The more current consensus criteria for polycystic ovary
morphology in adults is an ovary with a volume >10 cc and/or containing ≥12 follicles 2 to 9 mm in diameter,
in the absence of a dominant follicle (≥10 mm diameter) or corpus luteum. One-third to one-half of normal
adolescents meet these adult criteria. Until further research establishes definitive criteria, evidence suggests
that a mean ovarian volume >12cc (or single ovary >15 cc) be considered enlarged in adolescents. The
normal range for follicle number in adolescents remains to be defined. Unless the ultrasound reveals an
abnormality other than polycystic ovary morphology, further workup for hyperandrogenism is indicated.
¶ Ovotesticular disorder of sex development (DSD) was formerly termed true hermaphroditism.
Δ Virilization during pregnancy may be due to androgen hypersecretion by a luteoma or hyper-reactio
luteinalis.
◊ The presence of a polycystic ovary supports the diagnosis of PCOS in hyperandrogenic adolescents.
However, the presence of a polycystic ovary is not necessary - nor does it suffice - for the diagnosis of PCOS in
a patient with hyperandrogenic anovulation.
§ In an eumenorrheic symptomatically hyperandrogenic adolescent with normal menses, the presence of a
polycystic ovary (which meets Rotterdam-AES diagnostic criteria in adults) is a risk factor for a subsequent
diagnosis of PCOS.
¥ A polycystic ovary is not specific for PCOS; it has been reported in several specific endocrinopathies (eg,
hypothyroidism and Cushing's syndrome) and is also common in asymptomatic individuals.
‡ Further evaluation should include levels of serum prolactin, thyroid stimulating hormone (TSH), insulin-like
growth factor I (IGF-I), cortisol, 17-hydroxyprogesterone and dehydroepiandrosterone sulfate (DHEAS). An
abnormality of any of these endocrine tests is suggestive of one of the disorders that most commonly mimic
PCOS.
† 8AM 17-hydroxyprogesterone >170 to 200 ng/dL is approximately 95% sensitive and 90% specific for
detecting common type (21-hydroxylase deficient) nonclassic congenital adrenal hyperplasia (CAH) in
anovulatory or follicular phase women; it is often found in virilizing neoplasms. DHEAS >700 mcg/dL suggests
adrenal virilizing tumor or a rare type of CAH (3-beta-hydroxysteroid dehydrogenase deficiency).
** Plasma cortisol <10 mcg/dL essentially rules out endogenous Cushing's syndrome, unless the clinical index
of suspicion is high.
¶¶ Exclusion of the preceding disorders in a hyperandrogenic patient with menstrual dysfunction meets
standard diagnostic criteria for PCOS with approximately 95% reliability. However, this workup does not
identify rare adrenal disorders (eg, some types of CAH and related types of congenital adrenal steroid
metabolic disorders), the rare testosterone-secreting adrenal tumor, or, most commonly, idiopathic
hyperandrogenism (hyperandrogenism of unknown origin, which can arise from obesity or possibly metabolic
abnormalities).
ΔΔ Computed tomographic scanning of the adrenal gland is a more definitive study for identifying adrenal
tumor than is ultrasound.
Original figure modified for this publication. Buggs C, Rosenfield RL. Polycystic ovary syndrome in adolescence.
Endocrinol Metab Clin North Am 2005; 34:677. Illustration used with the permission of Elsevier Inc. All rights
reserved.
Differential diagnosis of hyperandrogenism in adolescents
Physiologic adolescent anovulation
Functional gonadal hyperandrogenism

PCOS: primary functional ovarian hyperandrogenism (common form of polycystic ovary syndrome)
Secondary functional ovarian hyperandrogenism

Virilizing congenital adrenal hyperplasia
Adrenal rests of the ovary
Syndromes of severe insulin resistance
Acromegaly
Epilepsy ± valproic acid therapy
Ovarian steroidogenic blocks
Disorders of sex development
Pregnancy-related hyperandrogenism
Functional adrenal hyperandrogenism

PCOS: primary functional adrenal hyperandrogenism (uncommon form of polycystic ovary syndrome)
Virilizing congenital adrenal hyperplasia
Other glucocorticoid-suppressible functional adrenal hyperandrogenism

Prolactin excess
Cortisone reductase deficiency (and apparent cortisone reductase deficiency)
Dehydroepiandrosterone sulfotransferase deficiency, apparent
Glucocorticoid-nonsuppressible functional adrenal hyperandrogenism

Cushing syndrome
Glucocorticoid resistance
Peripheral androgen overproduction

Obesity
Idiopathic hyperandrogenism
Portohepatic shunting
Virilizing tumors (adrenal or ovarian)
Androgenic drugs (eg, exogenous androgenic steroids or valproic acid)
PCOS: polycystic ovary syndrome.
Original figure modified for this publication. Buggs C, Rosenfield RL. Polycystic ovary syndrome in adolescence. Endocrinol
Metab Clin North Am 2005; 34:677. Illustration used with the permission of Elsevier Inc. All rights reserved.
Updates reflected in the version published in: Rosenfield RL. The diagnosis of polycystic ovary syndrome in adolescents.
Pediatrics 2015; 136:1154.
Determining source of androgen excess
The dexamethasone androgen-suppression test (DAST) often permits a positive diagnosis of the
characteristic ovarian and adrenal dysfunction of polycystic ovary syndrome (PCOS) and will elucidate
rare disorders that mimic PCOS. The responses to dexamethasone of serum androgens (testosterone and
DHEAS) and serum cortisol are the primary outcome measures.
PCOS: polycystic ovary syndrome; ACTH: adrenocorticotropic hormone; SD: standard deviations; CAH:
congenital adrenal hyperplasia; FAH: functional adrenal hyperandrogenism; DHEAS: dehydroepiandrosterone
sulfate.
* After obtaining an early morning blood sample for baseline steroid intermediates (eg, 17-
hydroxypregnenolone, 17-hydroxyprogesterone, 11-deoxycortisol, dehydroepiandrosterone, androstenedione)
and a 24-hour urine for corticoids (ie, free cortisol and 17α-hydroxycorticoids, as well as creatinine to control for
completeness of collection), a dexamethasone androgen-suppression test (DAST) is performed.
¶ A long DAST is a definitive test. This consists of a four-day course of dexamethasone 0.5 mg four times daily
prior to an early morning post-test blood sample on day five after a final dexamethasone dose. A short DAST
(sampling blood four hours after a single noon-time 0.5 mg dexamethasone dose) maximally suppresses total
and free testosterone and 17-hydroxyprogesterone, but DHEAS and cortisol are not maximally suppressed in
comparison with the four-day DAST.
Δ Normal androgen suppression in response to the four-day DAST is indicated in our laboratory (95 percent cut-
off levels) by total testosterone <28 ng/dL (1.0 nmol/L), free testosterone <8 pg/mL (28 pmol/L), DHEAS <40
mcg/dL (1.0 micromol/L) (>75 percent fall), and 17-hydroxyprogesterone <26 ng/dL (0.8 nmol/L).
◊ Normal corticoid suppression is indicated by serum cortisol <1.5 µg/dL (40 nmol/L) and urinary cortisol <10
mcg (27 nmol) per 24 hours by the second day of dexamethasone administration.
§ If androgen excess is suppressed by dexamethasone, further evaluation with a cosyntropin (ACTH) stimulation
test is indicated. To perform the ACTH test, cosyntropin 250 micrograms is given, and blood is drawn for steroid
measurements 30 to 60 minutes later.
¥ Subnormal suppression of testosterone (as well as androstenedione and 17-hydroxyprogesterone) and a
normal suppression of cortisol and DHEAS is characteristic of PCOS, but the rare virilizing tumor or adrenal rests
should be considered on the basis of clinical factors.
‡ If androgen and cortisol are both not normally suppressed, Cushing syndrome and cortisol resistance should be
considered. Poor suppression can also result from non-compliance with the dexamethasone regimen.
† Steroid levels are assessed 30 to 60 minutes after ACTH administration. A post-ACTH 17-OHP value >1000
ng/dL (30 nmol/L) is highly suggestive, and >1500 ng/dL is definitive for nonclassical CAH due to 21-
hydroxylase deficiency. A post-ACTH value of 17-hydroxypregnenolone >4500 ng/dL (150 nmol/L) suggests
nonclassical 3ß-hydroxysteroid dehydrogenase deficiency, and a post-ACTH value of 11-deoxycortisol >4000
ng/dL (116 nmol/L) suggests nonclassical 11ß-hydroxylase deficiency. A serum cortisol level ≥18 mcg/dL (500
nmol/L) validates the administration of ACTH.

** Primary functional adrenal hyperandrogenism (FAH) (suggested by a modest rise in 17-hydroxypregnenolone
or 17-hydroxyprogesterone that does not meet the criteria for the diagnosis of CAH) is sometimes the only
demonstrable source of androgen excess in PCOS. (Apparent) cortisone reductase deficiency is a rare mime of
FAH and idiopathic hyperandrogenemia; baseline urinary corticoids consist primarily of cortisone metabolites
rather than cortisol metabolites, so 17α-hydroxycorticoid excretion is elevated, but cortisol excretion is normal.
¶¶ When the source of hyperandrogenemia remains unexplained after intensive investigation (approximately 10
percent of cases), it usually appears to be due to obesity. Otherwise, the diagnosis is idiopathic
hyperandrogenism (distinct from idiopathic hirsutism), if (apparent) cortisone reductase deficiency has been
excluded.
Modified with permission from: Buggs C, Rosenfield RL. Polycystic ovary syndrome in adolescence. Endocrinol
Metab Clin North Am 2005; 34:677.
Grading of severity of hirsutism in women
Ferriman-Gallwey hirsutism scoring system. Each of the nine body areas that is most sensitive to
androgen is assigned a score from 0 (no hair) to 4 (frankly virile), and these are summed to provide a
hormonal hirsutism score. "Focal" hirsutism (score 1 to 7) is a common normal variant, whereas
generalized hirsutism (score of 8 or more) is abnormal in the general United States population. The
normal score is lower in Asian populations and higher in Mediterranean populations.
Reproduced with permission from: Hatch R, Rosenfield RS, Kim MH, Tredway D. Hirsutism: implications, etiology,
and management. Am J Obstet Gynecol 1981; 140:815. Copyright © 1981 Elsevier.
An acne scoring system for adolescents*
Comedonal Inflammatory
Severity Lesions ¶ Lesions Δ
Mild 1-10 1-10
Moderate 11-25 11-25
Severe >25 >25
* Face, chest, shoulders, and back may be graded separately.

¶ Open ("blackheads") or closed ("whiteheads") comedones (>1 mm diameter).
Δ Pustules, papules (≤5 mm), and nodules (>5 mm). Scarring should be noted separately.
Reproduced with permission from Pediatrics, Vol 136, Pages 1154-65, Copyright © 2015 by the AAP.
Types of abnormal uterine bleeding (AUB) suggestive of abnormal degree of

anovulation in adolescent PCOS
Symptom Definition
Primary amenorrhea Lack of menarche by 15 years of age or by three years after the onset of breast development.*
Secondary More than 90 days without a menstrual period, after previously menstruating.
amenorrhea
Oligomenorrhea Postmenarcheal year one:

(infrequent AUB) Average cycle length >90 days (fewer than four periods per year).
Postmenarcheal year two:
Average cycle length >60 days (fewer than six periods per year).
Postmenarcheal years three to five:
Average cycle length >45 days (fewer than eight periods per year).
Postmenarcheal year six and after:
Average cycle length >38 to 40 days (fewer than nine periods per year).
Excessive uterine Bleeding more frequently than every 21 days or is heavy or prolonged (lasts more than seven
bleeding ¶ days or soaks more than one pad or tampon every one to two hours).
AUB: abnormal uterine bleeding; PCOS: polycystic ovary syndrome; DUB: dysfunctional uterine bleeding.
* Bone age of 15 years may be substituted for chronological age in girls with earlier than average age at puberty onset.
¶ Encompasses frequent intermenstrual, heavy, and/or prolonged AUB, "polymenorrhea" and "menometrorrhagia." Formerly
termed "dysfunctional uterine bleeding" (DUB).
Modified from: Rosenfield RL. Adolescent anovulation: Maturational mechanisms and implications. J Clin Endocrinol Metab
2013; 98:3572.
Updates reflected in the version published in: Rosenfield RL. The diagnosis of polycystic ovary syndrome in adolescents.
Pediatrics 2015; 136:1154.
Ultrasonographic appearance of a polycystic ovary in a

15-year-old with PCOS
Ultrasonographic appearance of a polycystic ovary in a 15-year-old with

polycystic ovary syndrome (PCOS). Note that in the maximal diameter the ovary
is enlarged due to excessive central stroma. In addition, it is polycystic,
containing over 10 follicles that are approximately 3 to 8 mm in diameter.
Courtesy of Robert L. Rosenfield, MD.
Contributor Disclosures
Robert L Rosenfield, MD Nothing to disclose Mitchell E Geffner, MD Grant/Research/Clinical Trial Support:
Versartis [Growth (Somatropin)]. Consultant/Advisory Boards: Abbvie [Puberty (Leuprolide)]; Daiichi-Sankyo
[Type 2 diabetes (Colesevelam)]; Diurnal [Congenital adrenal hyperplasia (Hydrocortisone)]; Endo [Puberty
(Histrelin)]; Ipsen [Growth (Mecasermin)]; Millendo [Congenital adrenal hyperplasia]; NovoNordisk [Growth
(Somatropin)]; Nutritional Growth Solutions [Growth]; Pfizer [Growth (Somatropin)]; Sandoz [Growth
(Somatropin)]; Versartis [Growth (Somatropin)]. Other Financial Interest: McGraw-Hill [Pediatric endocrinology
(Textbook royalties)]. Amy B Middleman, MD, MPH, MS Ed Nothing to disclose Alison G Hoppin, MD Nothing
to disclose
Contributor disclosures are reviewed for conflicts of interest by the editorial group. When found, these are
addressed by vetting through a multi-level review process, and through requirements for references to be
provided to support the content. Appropriately referenced content is required of all authors and must conform to
UpToDate standards of evidence.
Conflict of interest policy

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Official reprint from UpToDate®

Author: Robert L Rosenfield, MD

● (See "Treatment of polycystic ovary syndrome in adolescents".)

● (See "Etiology and pathophysiology of polycystic ovary syndrome in adolescents".)

● Menstrual abnormality (persistent amenorrhea or oligomenorrhea, or excessive uterine bleeding)

● Obesity or focal hirsutism accompanied by menstrual abnormality

• Demonstration of persistent hyperandrogenism in a patient with a persistently abnormal degree of

BASIC DIAGNOSTIC APPROACH

Exclusion of non-PCOS causes of hyperandrogenemia — The hyperandrogenic patient should be further

Ultrasonography — Ultrasonography is not recommended or required for the diagnosis of PCOS in

● Early-morning 17-hydroxyprogesterone – An 8 AM 17-OHP level is a good screening test for nonclassical

● Dehydroepiandrosterone sulfate (DHEAS) – DHEAS is a marker for adrenal hyperandrogenism; it has

● Prolactin – Hyperprolactinemia usually can be identified by galactorrhea, but about 15 percent of

● Baseline levels of steroid intermediates, such as 17-hydroxypregnenolone, 11-deoxycortisol, and

● The DAST is interpreted as follows:

still be considered in the presence of suggestive clinical factors.

pathophysiology of polycystic ovary syndrome in adolescents", section on 'Primary functional ovarian

● Gonadotropin-releasing hormone agonist test – In patients with PCOS, administration of a gonadotropin

Use of UpToDate is subject to the Subscription and License Agreement.

Topic 94182 Version 15.0

International consensus diagnostic criteria for polycystic ovary syndrome in

Otherwise unexplained combination of:

a. Abnormal for age or gynecologic age

b. Persistent symptoms for one to two years

b. Moderate-severe hirsutism is clinical evidence of hyperandrogenism

c. Moderate-severe inflammatory acne vulgaris is an indication to test for hyperandrogenemia

Graphic 107842 Version 4.0

Initial evaluation for the presence of hyperandrogenism

PCOS: polycystic ovary syndrome; SHBG: sex hormone binding globulin.

Graphic 59954 Version 8.0

Initial evaluation of hyperandrogenemia

Graphic 85781 Version 11.0

Differential diagnosis of hyperandrogenism in adolescents

Physiologic adolescent anovulation

Functional gonadal hyperandrogenism

Secondary functional ovarian hyperandrogenism

Ovarian steroidogenic blocks

Disorders of sex development

Functional adrenal hyperandrogenism

Virilizing congenital adrenal hyperplasia

Other glucocorticoid-suppressible functional adrenal hyperandrogenism

Glucocorticoid-nonsuppressible functional adrenal hyperandrogenism

Peripheral androgen overproduction

Virilizing tumors (adrenal or ovarian)

Androgenic drugs (eg, exogenous androgenic steroids or valproic acid)

PCOS: polycystic ovary syndrome.

Graphic 91894 Version 6.0

Determining source of androgen excess

nmol/L) validates the administration of ACTH.

Graphic 65682 Version 13.0

Grading of severity of hirsutism in women

Graphic 66629 Version 8.0

An acne scoring system for adolescents*

Severity Lesions ¶ Lesions Δ

Mild 1-10 1-10

Moderate 11-25 11-25

Severe >25 >25

* Face, chest, shoulders, and back may be graded separately.

Graphic 107843 Version 3.0

Types of abnormal uterine bleeding (AUB) suggestive of abnormal degree of

Oligomenorrhea Postmenarcheal year one:

Graphic 93199 Version 6.0