eMedicine Specialties > Pediatrics: General Medicine > Endocrinology

Polycystic Ovarian Syndrome

Author: Robert J Ferry Jr, MD,, Chief, Division of Pediatric Endocrinology and Metabolism, Le Bonheur Children's Medical Center, University of Tennessee Health Science Center at Memphis, and St. Jude Children's Research Hospital; Brigade Surgeon, 36th Sustainment Brigade, 13th Expeditionary Sustainment Command, U.S. Army
Contributor Information and Disclosures

Updated: Oct 21, 2009

Introduction

Background

In 1935, Stein and Leventhal first described the association of polycystic ovaries, amenorrhea, hirsutism, and obesity.1 However, the key features necessary for the diagnosis of polycystic ovarian syndrome (PCOS) were not detailed until 1990 at a conference convened by the National Institutes of Health (NIH). These key features included hyperandrogenism, menstrual dysfunction, and exclusion of other causes of hyperandrogenism (eg, congenital adrenal hyperplasia, androgen-secreting tumors, hyperprolactinemia). Probable criteria included insulin resistance, perimenarchal onset, elevated ratio of luteinizing hormone (LH) to follicle stimulating hormone (FSH) ratio, and polycystic ovaries identified using ultrasonography.

The hyperandrogenic effects observed in polycystic ovarian syndrome most commonly include hirsutism, acne, or androgen-dependent alopecia. Obesity is also common. Endocrine abnormalities include elevated serum concentrations of androgens (particularly testosterone and androstenedione), increased LH levels, and normal or decreased FSH levels. Polycystic ovarian syndrome is also associated with insulin resistance and changes in lipid metabolism. A common mnemonic acronym for the clinical association of hyperandrogenism, insulin resistance, and acanthosis nigricans is the HAIRAN syndrome.

Beyond the NIH criteria of hyperandrogenism and menstrual dysfunction, other manifestations vary; polycystic ovarian syndrome is a clinically, histologically, and biochemically heterogeneous condition. For example, many women with the syndrome do not have evidence of polycystic ovaries. Although earlier descriptions of the syndrome were based on ovarian morphology, approximately 20% of regularly ovulating normal women have polycystic ovaries. Therefore, ovarian morphology is no longer an essential requirement for diagnosis.

Pathophysiology

Major features of polycystic ovarian syndrome include menstrual dysfunction, anovulation, and signs of hyperandrogenism.2 Although the exact etiopathophysiology is unclear, polycystic ovarian syndrome can result from abnormal function of the hypothalamic-pituitary-ovarian (HPO) axis. A key characteristic of polycystic ovarian syndrome is inappropriate gonadotropin secretion, which is more likely a result of, rather than a cause of, ovarian dysfunction. LH levels are tonically elevated throughout the menstrual cycle, whereas FSH levels are within the reference range or low. The LH-to-FSH ratio is often more than 3, and pituitary LH release is exaggerated after exogenous gonadotropin-releasing hormone (GnRH) stimulation.

Androgens such as testosterone, free testosterone, and dehydroepiandrosterone sulfate (DHEAS)may or may not be measurably elevated in the peripheral circulation; however, these hormones and their metabolites account for the physical characteristics of the syndrome. The source of androgens may be from the ovaries, adrenals, or both. Other contributing factors to androgen excess in women with polycystic ovarian syndrome (compared with women who do not have polycystic ovarian syndrome) include an elevated serum level of androstenedione (which is converted within adipose tissue to testosterone) and a greater percentage of unbound active testosterone circulating in the peripheral blood.

In the early phase of the menstrual cycle, circulating estradiol levels in women with polycystic ovarian syndrome are equal to those of normal women. However, mid cycle elevations of estrogen and progesterone that normally occur after ovulation are absent. Because of the lack of cyclical progesterone secretion, the action of estradiol on both the hypothalamic-pituitary axis and the endometrium is unopposed. Both progesterone deficiency and acyclic estrogen production contribute to increased LH release. The effects of unopposed estrogen on the endometrium may cause it to become hyperplastic, which may cause intermittent and heavy uterine bleeding and may increase the long-term risk of endometrial cancer. These effects may be compounded by increased levels of estrone converted from androstenedione in adipose tissue, especially in patients who are obese.

Frequency

United States

Polycystic ovarian syndrome affects approximately 5-7% of premenopausal women.

Mortality/Morbidity

Prolonged, unopposed estrogen stimulation of the endometrium increases the risk of endometrial cancer in patients with polycystic ovarian syndrome. Approximately 40% of patients with polycystic ovarian syndrome have insulin resistance that is independent of body weight. These women are at increased risk for type 2 diabetes mellitus and consequent cardiovascular complications compared with healthy women. Women with hyperandrogenism also have elevated serum lipoprotein levels similar to men, which may increase their risk of cardiovascular disease.

Race

A great deal of ethnic variability in hirsutism is observed. For instance, Asian women have less hirsutism given the same serum androgen values as white women. On the other hand, southern Mediterranean women more often are hirsute.

Sex

Polycystic ovarian syndrome affects females of reproductive age. Studies of family members with polycystic ovarian syndrome indicate that an autosomal dominant mode of inheritance with premature male pattern baldness as the male phenotype may occur.

Age

Polycystic ovarian syndrome affects premenopausal women, and the age of onset is most often perimenarchal (before bone age reaches 16 y). However, clinical recognition of the syndrome may be delayed by failure of the patient to become concerned by irregular menses, hirsutism, or other symptoms or by the overlap of polycystic ovarian syndrome findings with normal physiologic maturation during the 2 years after menarche.

Clinical

History

  • Family history
    • Hirsutism
    • Adrenal enzyme deficiencies
    • Menstrual disorders
    • Polycystic ovarian syndrome (PCOS)
    • Diabetes
    • Infertility
  • Menstrual disturbance
    • The patient usually has a history of menstrual disturbance dating back to menarche. Irregular menses during the initial 2 years after menarche are most often physiologic, requiring no special evaluation. Persistent clinical symptoms beyond this time, especially in the presence of other signs of polycystic ovarian syndrome, warrant further evaluation.
    • Because of anovulation or oligo-ovulation, patients may present with amenorrhea, oligomenorrhea, dysfunctional uterine bleeding, or infertility. Menarche may be delayed, and primary amenorrhea, although uncommon, does occur.
  • Hyperandrogenism
    • Hyperandrogenism presents as hirsutism, acne, and male pattern alopecia.
    • Rapid progression of virilization is characteristic of adrenal or ovarian androgen-producing tumors.
    • Other signs of hyperandrogenism (eg, clitoromegaly, increased muscle mass, voice deepening) are more characteristic of an extreme form of polycystic ovarian syndrome termed hyperthecosis. These signs and symptoms could also be consistent with androgen-producing tumors, exogenous androgen administration, or virilizing congenital adrenal hyperplasia.
    • Premature adrenarche is a common occurrence and, in some cases, may represent a precursor to polycystic ovarian syndrome. Both hirsutism and obesity may be present in premenarchal adolescent girls with polycystic ovarian syndrome.
  • Acanthosis nigricans
    • Another cutaneous manifestation is acanthosis nigricans.
    • Patients may have a dark and thickened area of skin behind the neck and in skin folds. Acanthosis nigricans is staged according to the scoring system below. Among sites where severity is taken into consideration, the neck showed the highest agreement and the least variation between a pediatric endocrinologist's examination (the gold standard) and individual observers, and between the individual observers themselves. Texture should be noted as smooth, rough, or rugated.
    • Staging acanthosis (neck severity)
      • Absent (0) - Not detectable on close inspection
      • Present (1) - Clearly present on close visual inspection, not visible to the casual observer, extent not measurable
      • Mild (2) - Limited to the base of the skull, usually does not extend to the lateral margins of the neck
      • Moderate (3) - Extends to lateral margins of neck, but not visible anteriorly
      • Severe (4) - Visible anteriorly
      • Severe (5) - Circumferential
  • Obesity
    • Obesity, although common, is not universal.
    • Obesity is not usually the presenting complaint.

Physical

  • Hirsutism: The modified Ferriman-Gallwey score grades 11 body areas from 0 (no hair) to 4 (frankly virile), including the upper lip, chin, chest, upper and lower abdomen, thighs, upper and lower back, arm, forearm, and buttocks. A total score of 8 or more is considered abnormal for an white adult woman; a score of 44 is the most severe.
  • Other cutaneous findings
    • Acne
    • Acanthosis nigricans (marker for insulin resistance)
  • Other possible physical examination findings
    • Increased upper body mass
    • Obesity (increased body mass index >85%)
    • Male pattern baldness
    • Clitoromegaly
    • Enlarged ovaries (not always present): Evaluate for ovarian mass.
    • Elevated prolactin levels and galactorrhea
    • Endometrial hyperplasia

Causes

  • Enzyme abnormality
    • The cause is unknown, although some evidence suggests that patients have a functional abnormality of cytochrome P450c17, the 17-hydroxylase, which is the rate-limiting enzyme in androgen biosynthesis.3
    • Cytochrome P450c17 is active in the adrenals and ovaries, and excess activity of this enzyme could explain the increased androgen production from both sources in polycystic ovarian syndrome.
  • Genetic causes
    • Polycystic ovarian syndrome is, in some cases, a familial disorder, but the genetic basis of the syndrome remains unclear. One study revealed evidence of an autosomal dominant mode of inheritance.4
    • Full expression of the syndrome may require an insulin abnormality and a defect in androgen biosynthesis, but no gene (or genes) has been identified.

More on Polycystic Ovarian Syndrome

Overview: Polycystic Ovarian Syndrome
Differential Diagnoses & Workup: Polycystic Ovarian Syndrome
Treatment & Medication: Polycystic Ovarian Syndrome
Follow-up: Polycystic Ovarian Syndrome
Multimedia: Polycystic Ovarian Syndrome
References
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Further Reading

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Keywords

polycystic ovarian syndrome, PCOS, Stein-Leventhal syndrome, hyperandrogenism, functional ovarian hyperandrogenism, sclerocystic disease of the ovary, insulin resistance, perimenarchal onset, amenorrhea, obesity, menstrual dysfunction, HAIR-AN syndrome, treatment, diagnosis

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Contributor Information and Disclosures

Author

Robert J Ferry Jr, MD,, Chief, Division of Pediatric Endocrinology and Metabolism, Le Bonheur Children's Medical Center, University of Tennessee Health Science Center at Memphis, and St. Jude Children's Research Hospital; Brigade Surgeon, 36th Sustainment Brigade, 13th Expeditionary Sustainment Command, U.S. Army
Robert J Ferry Jr, MD, is a member of the following medical societies: American Academy of Pediatrics, American Diabetes Association, American Medical Association, Endocrine Society, Lawson-Wilkins Pediatric Endocrine Society, Society for Pediatric Research, and Texas Pediatric Society
Disclosure: Nutropin Speakers Bureau Honoraria Speaking and teaching; Genotropin Speakers Bureau Honoraria Speaking and teaching; Eli Lilly & Co. Grant/research funds Independent contractor; MacroGenics, Inc. Grant/research funds Independent contractor; Ipsen, S.A. (formerly Tercica, Inc.) Grant/research funds Independent contractor

Medical Editor

Phyllis W Speiser, MD, Chief of Pediatric Endocrinology, Schneider Children's Hospital; Professor of Pediatrics, New York University School of Medicine
Phyllis W Speiser, MD is a member of the following medical societies: American Association of Clinical Endocrinologists, Endocrine Society, Lawson-Wilkins Pediatric Endocrine Society, and Society for Pediatric Research
Disclosure: Nothing to disclose.

Pharmacy Editor

Mary L Windle, PharmD, Adjunct Assistant Professor, University of Nebraska Medical Center College of Pharmacy, Pharmacy Editor, eMedicine
Disclosure: Pfizer Inc Stock Investment from financial planner; Avanir Pharma Stock Investment from financial planner ; WebMD Salary and stock Employment and investment from financial planner

Managing Editor

Lynne Lipton Levitsky, MD, Chief, Pediatric Endocrine Unit, Massachusetts General Hospital; Associate Professor, Department of Pediatrics, Harvard University Medical School
Lynne Lipton Levitsky, MD is a member of the following medical societies: Alpha Omega Alpha, American Academy of Pediatrics, American Diabetes Association, American Pediatric Society, Endocrine Society, Lawson-Wilkins Pediatric Endocrine Society, and Society for Pediatric Research
Disclosure: Pfizer Grant/research funds P.I.; Tercica Grant/research funds PI, also occasional consultant

CME Editor

Merrily P M Poth, MD, Professor, Department of Pediatrics and Neuroscience, Uniformed Services University of the Health Sciences
Merrily P M Poth, MD is a member of the following medical societies: American Academy of Pediatrics, Endocrine Society, and Lawson-Wilkins Pediatric Endocrine Society
Disclosure: Nothing to disclose.

Chief Editor

Stephen Kemp, MD, PhD, Professor, Department of Pediatrics, Section of Pediatric Endocrinology, University of Arkansas and Arkansas Children's Hospital
Stephen Kemp, MD, PhD is a member of the following medical societies: American Academy of Pediatrics, American Association of Clinical Endocrinologists, American Pediatric Society, Endocrine Society, Phi Beta Kappa, Southern Medical Association, and Southern Society for Pediatric Research
Disclosure: Genentech, Inc. Honoraria Speaking and teaching; Pfizer, Inc. Honoraria Consulting

 
 
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