Indications for Testing

• Irregular menses, infertility, hirsutism, acne

Criteria for Diagnosis

• Rotterdam criteria [ESHRE/ASRM-sponsored] (2004) – diagnosis requires two of the following three
  • Oligo/anovulation
  • Clinical or biochemical signs of hyperandrogenism (≥12 follicular structures measuring 2-9 mm in diameter or an increased ovarian volume of >10 mL)
  • Polycystic ovaries on ultrasound
  • Exclusion of other etiologies
• NIH/NICHD criteria – diagnosis requires both (Zawadski 1992)
  • Clinical anovulation
  • Clinical or biochemical signs of hyperandrogenism
• Androgen Excess Society (AE/PCOS) guidelines (2009) – diagnosis requires the following
  • Polycystic ovaries
  • Hirsutism and oligoanovulation after other etiologies of androgen excess have been excluded
  • Disorders such as congenital adrenal hyperplasia (CAH) and androgen-secreting tumors are ruled out

Laboratory Testing

• Free testosterone level (gold standard by mass spectrometry) along with dehydroepiandrosterone sulfate (DHEA-S), androstenedione and androstanediol glucuronide – all elevated [testosterone should be >2 standard deviations over the mean for the method used (ie, ~55-58 ng/dL)]
  • Testosterone >200 ng/dL and DHEA-S >700 µg/dL suggest ovarian or adrenal tumor
  • Free testosterone concentration is the single most important androgen measure
• Luteinizing hormone/follicle stimulating hormone (LH/FSH) levels – do not contribute to diagnosis (typically LH is elevated and FSH is normal)
  • LH/FSH ratio >2 suggestive of PCOS but should not be ordered as a routine diagnostic test
• Rule out the following (diagnosis involves exclusion of other etiologies)
  • Late onset CAH – 17-hydroxyprogesterone; morning testing preferred
    • If result is <200 ng/ml, referral is not necessary to rule out CAH
  • Prolactinoma – serum prolactin level
  • Cushing syndrome – 24-hour urine cortisol or 11 p.m. salivary cortisol or overnight low-dose dexamethasone suppression test
  • Hypothyroidism – thyroid-stimulating hormone  

Imaging Studies

• Ultrasound to image polycystic ovaries (often unnecessary)
  • Presence of polycystic ovaries alone does not necessarily indicate PCOS
• MRI/CT – if testosterone level is moderately elevated, use these images to rule out adrenal/ovarian tumors

Differential Diagnosis

• Pregnancy
• Cushing syndrome
• Late onset CAH (present in <5% of hyperandrogenic women)
• Obesity
• Ovarian failure
• Androgen secreting tumors (ovarian, adrenal) (present in 0.2% of hyperandrogenic women)
• Metabolic syndrome
• Prolactinoma
• Idiopathic hirsutism
• Acromegaly
• Thyroid dysfunction
• Drugs
  • Testosterone
  • Danazol
  • Androgenic progestins
  • Valproic acid
  • Acetazolamide
  • Minoxidil
  • High-dose glucocorticosteroids

• Long-term health consequences associated with PCOS
  • Metabolic syndrome
  • Cardiovascular disease
  • Impaired glucose tolerance and diabetes
  • Increased endometrial cancer risk
• Laboratory testing (after diagnosis) to evaluate for metabolic complications of PCOS
  • Fasting 2-hour glucose tolerance test
  • Fasting lipid profile
  • Liver function testing (alanine aminotransferase, aspartate aminotransferase)

Polycystic ovarian syndrome (PCOS) is a common endocrinopathy caused by androgen excess and is the leading cause of anovulatory infertility.

Epidemiology

• Prevalence – 6-8% of adult females worldwide

Inheritance

• Family incidence nears 40%
• Appears to be autosomal dominant

Pathophysiology

• Etiology is unknown
• Excess androgen production (hyperandrogenism); often insulin resistance

Clinical Presentation

• Irregular menses or amenorrhea
• Infertility
• Hirsutism, acne, male pattern baldness
  • Ferriman-Gallwey score – gold standard to measure hirsutism
    • Hirsutism defined by score ≥8
• High rate of diabetes mellitus (DM) type 2, metabolic syndrome, sleep apnea and obesity, which present increased risk for cardiovascular disease

Clinical Background

Epidemiology

• Prevalence – affects 5-10% of adolescent females
• 40% develop DM type 2 or impaired glucose tolerance by age 40

Clinical Presentation

• Hirsutism (moderate to severe = >15 on Ferriman-Gallwey scale)
  • Male pattern baldness
• Acne
• Irregular menses >2 years duration
• Obesity (central or refractory)

Diagnosis

Indications for Testing

• Irregular menses, hirsutism, acne, infertility

Criteria for Diagnosis

• Some authors suggest delaying diagnosis until 18 years; earlier symptoms may represent transient adolescent hormonal changes
• Androgen Excess Society (AE/PCOS) guidelines (Azziz, 2009) – diagnosis requires the following
  • Polycystic ovaries
  • Hirsutism and oligoanovulation after other etiologies of androgen excess have been excluded
  • Disorders such as congenital adrenal hyperplasia (CAH) and androgen-secreting tumors are ruled out

Laboratory Testing

• Initial testing
  • Urine hCG – rule out pregnancy
  • Serum free testosterone – single most important androgen measure
  • Serum prolactin – rule out hyperprolactinemia
  • Luteinizing hormone/follicle stimulating hormone (LH/FSH) – do not contribute to diagnosis (typically LH is elevated and FSH is normal)
  • DHEA-S – may not be necessary
• Rule out the following (diagnosis involves exclusion of other etiologies)
  • Late onset congenital adrenal hyperplasia (CAH) – 17-hydroxyprogesterone; morning testing preferred
    • If result is <200 ng/dL, referral is not necessary to rule out CAH
  • Cushing syndrome – 24-hour urine cortisol or 11 p.m. salivary cortisol or overnight low-dose dexamethasone suppression test
    • Fasting blood glucose and fasting lipid panel if patient is overweight and meets criteria for metabolic syndrome

Imaging Studies

• Ultrasound to image polycystic ovaries (often unnecessary)

Differential Diagnosis

• Late-onset CAH
• Androgen secreting tumors (ovarian, adrenal)
• Thyroid dysfunction
• Prolactinoma
• Pregnancy

Tests generally appear in the order most useful for common clinical situations

Guidelines

• Azziz R, Carmina E, Dewailly D, amanti-Kandarakis E, Escobar-Morreale HF, Futterweit W, Janssen OE, Legro RS, Norman RJ, Taylor AE, Witchel SF. Positions statement: criteria for defining polycystic ovary syndrome as a predominantly hyperandrogenic syndrome: an Androgen Excess Society guideline. J Clin Endocrinol Metab. 2006; 91 (11) :4237-4245.PubMed
• Polycystic ovary syndrome. American College of Obstetricians and Gynecologists - Medical Specialty Society. 2009 October. NGC:007458
• 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 (1) :19-25.PubMed

General

• Azziz R, Carmina E, Dewailly D, amanti-Kandarakis E, Escobar-Morreale HF, Futterweit W, Janssen OE, Legro RS, Norman RJ, Taylor AE, Witchel SF. The Androgen Excess and PCOS Society criteria for the polycystic ovary syndrome: the complete task force report. Fertil Steril. 2009; 91 (2) :456-488.PubMed
• Baldwin CY, Witchel SF. Polycystic ovary syndrome. Pediatr Ann. 2006; 35 (12) :888-896.PubMed
• Benjamins LJ, Barratt MS. Evaluation and management of polycystic ovary syndrome. J Pediatr Health Care. 2009; 23 (5) :337-343.PubMed
• Broekmans FJ, Fauser BC. Diagnostic criteria for polycystic ovarian syndrome. Endocrine. 2006; 30 (1) :3-11.PubMed
• Bruni V, Dei M, Nannini S, Balzi D, Nuvolone D. Polycystic ovary syndrome in adolescence. Ann N Y Acad Sci. 2010; 1205 :175-184.PubMed
• Carmina E, Oberfield SE, Lobo RA. The diagnosis of polycystic ovary syndrome in adolescents. Am J Obstet Gynecol. 2010; 203 (3) :201-205.PubMed
• Hassan A, Gordon CM. Polycystic ovary syndrome update in adolescence. Curr Opin Pediatr. 2007; 19 (4) :389-397.PubMed
• Lorenz LB, Wild RA. Polycystic ovarian syndrome: an evidence-based approach to evaluation and management of diabetes and cardiovascular risks for today's clinician. Clin Obstet Gynecol. 2007; 50 (1) :226-243.PubMed
• Lujan ME, Chizen DR, Pierson RA. Diagnostic criteria for polycystic ovary syndrome: pitfalls and controversies. J Obstet Gynaecol Can. 2008; 30 (8) :671-679.PubMed
• Oliveira A, Sampaio B, Teixeira A, Castro-Correia C, Fontoura M, Luis Medina J. Polycystic ovary syndrome: challenges in adolescence. Endocrinol Nutr. 2010; 57 (7) :328-336.PubMed
• Setji TL, Brown AJ. Polycystic ovary syndrome: diagnosis and treatment. Am J Med. 2007; 120 (2) :128-132.PubMed
• Somani N, Harrison S, Bergfeld WF. The clinical evaluation of hirsutism. Dermatol Ther. 2008; 21 (5) :376-391.PubMed
• Yii MF, Lim CE, Luo X, Wong WS, Cheng NC, Zhan X. Polycystic ovarian syndrome in adolescence. Gynecol Endocrinol. 2009; 25 (10) :634-639.PubMed

Adrenal Hyperfunction
Amenorrhea
Cardiovascular Disease (Non-traditional Risk Markers)
Cardiovascular Disease (Traditional Risk Markers)
Diabetes Mellitus
Infertility
Metabolic Syndrome