Diagnosis
Indications for Testing
Irregular menses, infertility, hirsutism, acne
Criteria for Diagnosis
Two of 3 of the following criteria in the absence of other etiology (American Association of Clinical Endocrinologists [AACE]/American College of Endocrinology [ACE]/Androgen Excess and Polycystic Ovarian Syndrome Society, 2015).
Menstrual irregularities
Hyperandrogenism (clinical or biological)
Polycystic ovaries
Criteria for Defining Polycystic Ovarian Syndrome (PCOS)
Androgen Excess and PCOS Society Guidelines (developed in 2006, reaffirmed in 2015 [Goodwin, 2015])
Amsterdam European Society of Human Reproduction and Embryology (ESHRE)/American Society for Reproductive Medicine ( ASRM) Consensus (3rd PCOS Consensus 2012 ) – reaffirmed use of Rotterdam 2003 criteria
PCOS is a disorder of androgen excess or hyperandrogenism
Diagnosis requires all 3 of the following elements
Hyperandrogenisma Clinical (hirsutism) and/or biochemical signs (elevated levels of total or free testosterone)
Ovarian dysfunction and/or polycystic ovaries (prominent but not universal feature of PCOS)
Polycystic ovarian morphology defined as per guidelines (Dewailey, 2014)
≥25 follicles/ovary – recommended criterion over ovarian volume
≥10 mL ovarian volume
Exclusion of other androgen excess disorders
Adult female
PCOS is a disorder of androgen excess or hyperandrogenism
Presence of 2 of the following 3 elements confirms PCOS
Hyperandrogenisma Clinical (hirsutism) or biochemical signs
Oligo-ovulation and/or anovulation
Polycystic ovaries on ultrasound
Presence of ≥12 follicles in each ovary measuring 2-9 mm in diameter and/or increased ovarian volume >10 cm3
Exclusion of other androgen excess disorders
Adolescent female
Risk of overdiagnosis of PCOS in this population
All 3 of the following elements must be present to confirm diagnosis
Oligomenorrhea or amenorrhea for ≥2 years after menarche (or primary amenorrhea at 16 years)
Polycystic ovaries on ultrasound (size >10 cm3 )
Hyperandrogenemia
a Hyperandrogenism
Usually defined as >2.5 standard deviations above mean for assay
Measure between day 4 and 10 of menstrual cycle
Lab testing to confirm
Testosterone is the hormone usually measured
May have poor validity in some labs
Assay should measure testosterone levels for female and children
Androstenedione and dehydroepiandrosterone sulfate (DHEA-S) are informative markers but not necessary in most cases
Laboratory Testing
Initial testing
Serum free testosterone
Mass spectrometry – gold standard
Mass spectrometry with liquid chromatography (LC-MS/MS) – acceptable
Radioimmunoassay (RIA) that includes purification – acceptable
Assay that measures levels for females and children should be used
Sample should be collected between day 4 and 10 of menstrual cycle
Testosterone is elevated if >2.5 standard deviations above the mean
Value >200 ng/dL should prompt evaluation for androgen-secreting tumor
Testing should be performed by laboratories that use appropriate methods
Additional testing
Serum 17-hydroxyprogesterone
Test for nonclassic 21-hydroxylase deficiency – patients with this deficiency will present with same clinical signs and symptoms as those with PCOS
Anti-Mullerian hormone (AMH)
AMH testing can be used in place of ovarian morphology assessment
AMH reference intervals for females (age dependent)
AMH Reference Intervals for Females
Age
Reference Interval (ng/mL)
6 mos-14 yrs
0.256-6.345
15-17 yrs
0.861-10.451
18-29 yrs
0.401-16.015
30-39 yrs
0.176-11.705
40-45 yrs
≤6.282
46-50 yrs
≤0.064
Postmenopausal
≤0.003
Progesterone
Test midcycle to confirm anovulation
Not required for diagnosis
Other hormone testing not indicated
Dehydroepiandrosterone (DHEA) – measurement does not add significantly to diagnosis
11β-hydroxyandrostenedione and androstenedione – generally not needed to assist with diagnosis
Luteinizing hormone (LH)/follicle-stimulating hormone (FSH) – not indicated
Imaging Studies
Transvaginal ultrasound
Presence of polycystic ovaries alone is not sufficient to establish diagnosis
Magnetic resonance imaging (MRI)/computed tomography (CT) – most useful to rule out adrenal/ovarian tumors if testosterone level is moderately elevated
Differential Diagnosis
Pregnancy
Measure beta human chorionic gonadotropin (β-hCG) level
Adrenal hyperfunction (Cushing syndrome )
Late onset congenital adrenal hyperplasia (CAH)
Present in <5% of hyperandrogenic women
Measure 17-hydroxyprogesterone
Morning testing preferred
If result is >200 ng/mL, further assessment is necessary to rule out CAH
Androgen-secreting tumors (ovarian, adrenal)
Present in 0.2% of hyperandrogenic women
Testosterone >200 ng/dL combined with dehydroepiandrosterone sulfate (DHEA-S) >700 µg/dL suggests ovarian or adrenal tumor
Metabolic syndrome
Prolactinoma
Idiopathic hirsutism
Acromegaly
Thyroid dysfunction /hypothyroidism
Measure thyroid-stimulating hormone (TSH)
Drug related
Testosterone
Danazol
Androgenic progestins
Valproic acid
Acetazolamide
Minoxidil
High-dose glucocorticosteroids
Monitoring
Monitoring is recommended for long-term health consequences associated with polycystic ovarian syndrome (PCOS)
Laboratory testing (after diagnosis) to evaluate for metabolic complications of PCOS
Background
Epidemiology
Prevalence – 10-15% of adult females worldwide (Azziz, Androgen Excess and Polycystic Ovarian Syndrome Society, 2009).
Genetics
Family incidence nearly 40%
Appears to be autosomal dominant
Pathophysiology
Etiology is unknown
Excess androgen production (hyperandrogenism) and insulin resistance play a role in disease pathogenesis
Clinical Presentation
Irregular menses or amenorrhea
Infertility
Signs of hyperandrogenism, including
Acne
Hirsutism
Increased number of terminal hairs
Hatch modification of the Ferriman-Gallwey scale should be used to evaluate
Alopecia – similar to male pattern baldness
High rate of type 2 diabetes mellitus (T2DM), metabolic syndrome , sleep apnea, and obesity
Pediatrics
Epidemiology
Prevalence – affects 5-10% of adolescent females
40% develop type 2 diabetes mellitus (T2DM) or impaired glucose tolerance by age 40
Clinical Presentation
Hirsutism
Increased number of terminal hairs
Hatch modification of the Ferriman-Gallwey scale should be used to evaluate
Ethnic differences affect hirsutism
Alopecia – similar to male pattern baldness
Acne – consider diagnosis of polycystic ovarian syndrome (PCOS) if acne is severe or does not respond to standard therapies
Irregular menses of >2 years duration
Obesity (central or refractory)
Indications for Testing
Irregular menses, hirsutism, acne, infertility
Laboratory Testing
Initial testing
Diagnosis may be more difficult in adolescents, but PCOS is important to be aware of and address early due to the risks associated with nontreatment
Symptoms in patients <18 years may represent transient adolescent hormonal changes
Serum or urine human chorionic gonadotropin (hCG) should be measured to rule out pregnancy
Refer to main Laboratory Testing subsection within Diagnosis
Refer to Secondary Amenorrhea Testing Algorithm
Imaging Studies
Transvaginal ultrasound to evaluate ovaries
Complicated by increased number of cysts normally occurring in adolescents
Required by Amsterdam criteria, but not by Androgen Excess and Polycystic Ovarian Syndrome Society criteria
Differential Diagnosis