Pediatric Polycystic Ovarian Syndrome 

  • Author: Robert J Ferry Jr, MD; Chief Editor: Stephen Kemp, MD, PhD   more...
 
Updated: Apr 27, 2010
 

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.

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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.

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Epidemiology

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 have also 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.

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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 Hospital; Professor, Department of Pediatrics, University of Tennessee Health Science Center at Memphis; St. Jude Children's Research Hospital, Memphis, TN; Brigade Surgeon, 36th Sustainment Brigade, U.S. Army; Adjunct Professor, Pediatric Surgery Department, King Saud University, Riyadh, Saudi Arabia

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; NovoNordisk SA Grant/research funds Independent contractor; Diamyd Independent contractor

Specialty Editor Board

Phyllis W Speiser, MD  Chief, Division of Pediatric Endocrinology, The Children's Hospital, North Shore LIJ Health System; 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.

Mary L Windle, PharmD  Adjunct Associate Professor, University of Nebraska Medical Center College of Pharmacy; Pharmacy Editor, eMedicine

Disclosure: Nothing to disclose.

Lynne Lipton Levitsky, MD  Chief, Pediatric Endocrine Unit, Massachusetts General Hospital; Associate Professor of Pediatrics, Harvard 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

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: Nothing to disclose.

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Longitudinal transabdominal ultrasonogram of an ovary. This image reveals multiple peripheral follicles.
 
 
 
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