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Practice Essentials
Women with polycystic ovarian syndrome (PCOS) have abnormalities in the
metabolism of androgens and estrogen and in the control of androgen production.
PCOS can result from abnormal function of the hypothalamic-pituitary-ovarian
(HPO) axis. A woman is diagnosed with polycystic ovaries (as opposed to PCOS) if
she has 12 or more follicles in at least 1 ovary (see the image below).
Low power, H and E of an ovary containing multiple cystic follicles in a patient with PCOS.
The diagnostic criteria for PCOS should include two of the following three
criteria: chronic anovulation, hyperandrogenism (clinical/biologic), and
polycystic ovaries
In addition to clinical findings, obtain levels of serum 17-
hydroxyprogesterone and anti-Mllerian hormone to aid the diagnosis of
PCOS.
Free testosterone levels are more sensitive for determining androgen
excess than total T levels and should be obtained with equilibrium dialysis
techniques
Women with PCOS should also be evaluated and/or treated for reproductive
function, hirsutism, alopecia, and acne.
Adolescent girls with PCOS remain a diagnostic and therapeutic challenge.
Girls whose oligomenorrhea persists 2-3 years past menarche typically
have ongoing menstrual anomalies and are at higher risk for having an
underlying ovarian or adrenal dysfunction. First-line monotherapy in this age
group includes metformin monotherapy and/or combination therapy with
oral contraceptive agents and antiandrogen agents.
Hirsutism
Infertility
Obesity and metabolic syndrome
Diabetes
Obstructive sleep apnea
Diagnosis
On examination, findings in women with PCOS may include the following:
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Virilizing signs
Acanthosis nigricans
Hypertension
Enlarged ovaries: May or may not be present; evaluate for an ovarian mass
Testing
Exclude all other disorders that can result in menstrual irregularity and
hyperandrogenism, including adrenal or ovarian tumors, thyroid dysfunction,
congenital adrenal hyperplasia, hyperprolactinemia, acromegaly, and Cushing
syndrome.[3, 4, 5]
Androstenedione level
FSH and LH levels
GnRH stimulation testing
Glucose level
Insulin level
Lipid panel
Imaging tests
Procedures
Management
Lifestyle modifications are considered first-line treatment for women with PCOS.
Such changes include the following[3, 4] :
Diet
Exercise
Weight loss
Pharmacotherapy
Surgery
Electrocautery
Laser drilling
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Multiple biopsy
Background
The major features of polycystic ovarian syndrome (PCOS) include menstrual
dysfunction, anovulation, and signs of hyperandrogenism.[2] Although the exact
etiopathophysiology of this condition is unclear, PCOS can result from abnormal
function of the hypothalamic-pituitary-ovarian (HPO) axis. A key characteristic of
PCOS is inappropriate gonadotropin secretion, which is more likely a result of,
rather than a cause of, ovarian dysfunction. In addition, one of the most consistent
biochemical features of PCOS is a raised plasma testosterone level.[7] (See
Etiology and Workup.)
Stein and Leventhal were the first to recognize an association between the
presence of polycystic ovaries and signs of hirsutism and amenorrhea (eg,
oligomenorrhea, obesity).[8] After women diagnosed with Stein-Leventhal
syndrome underwent successful wedge resection of the ovaries, their menstrual
cycles became regular, and they were able to conceive.[9] As a consequence, a
primary ovarian defect was thought to be the main culprit, and the disorder came to
be known as polycystic ovarian disease. (See Etiology and Treatment.)
A woman is diagnosed with polycystic ovaries (as opposed to PCOS) if she has 12
or more follicles in at least 1 ovarymeasuring 2-9 mm in diameteror a total
ovarian volume greater than 10 cm3. (See the image below.) (See Workup.)
Diagnostic criteria
A 1990 expert conference sponsored by the National Institute of Child Health and
Human Disease (NICHD) of the United States National Institutes of Health (NIH)
proposed the following criteria for the diagnosis of PCOS:
In 2003, the European Society for Human Reproduction and Embryology (ESHRE)
and the American Society for Reproductive Medicine (ASRM) recommended that
at least 2 of the following 3 features are required for PCOS to be diagnosed[10] :
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Oligo-ovulation or anovulation
Clinical/biochemical evidence of hyperandrogenism
Polycystic ovaries on ultrasonograms (>12 small antral follicles in an ovary)
Etiology
Women with polycystic ovarian syndrome (PCOS) have abnormalities in the
metabolism of androgens and estrogen and in the control of androgen production.
High serum concentrations of androgenic hormones, such as testosterone,
androstenedione, and dehydroepiandrosterone sulfate (DHEA-S), may be
encountered in these patients. However, individual variation is considerable, and a
particular patient might have normal androgen levels.
Polycystic ovaries are enlarged bilaterally and have a smooth, thickened capsule
that is avascular. On cut sections, subcapsular follicles in various stages of atresia
are seen in the peripheral part of the ovary. The most striking ovarian feature of
PCOS is hyperplasia of the theca stromal cells surrounding arrested follicles. On
microscopic examination, luteinized theca cells are seen.
Studies of family members with PCOS indicate that an autosomal dominant mode
of inheritance occurs for many families with this disease. The fathers of women
with PCOS can be abnormally hairy; female siblings may have hirsutism and
oligomenorrhea; and mothers may have oligomenorrhea.[16] Research has
suggested that in a large cohort of women with PCOS, a family history of type 2
diabetes in a first-degree family member is associated with an increased risk of
metabolic abnormality, impaired glucose tolerance, and type II diabetes.[16] In
addition, a Dutch twin-family study showed a PCOS heritability of 0.71 in
monozygotic twin sisters, versus 0.38 in dizygotic twins and other sisters.[17]
An important link between PCOS and obesity was corroborated genetically for the
first time by data from a case-control study in the United Kingdom that involved
463 patients with PCOS and more than 1300 female controls.[18] The investigators
demonstrated that a variant within the FTO gene (rs9939609, which has been
shown to predispose to common obesity) was significantly associated with
susceptibility to the development of PCOS.
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near the INSR gene was found to be significantly associated with PCOS.[20] The
authors concluded that a susceptibility locus for PCOS (designated PCOS1) exists
in 19p13.3 in the INSR region, but it cannot be concluded that the INSR gene itself
is responsible.[20]
In study by Goodarzi et al, the leucine allele was found to be associated with
protection against PCOS, as compared to the valine allele at position 89 in
SRD5A2.[22] The leucine allele is associated with a lower enzyme activity.[22] When
the results of this study are combined with those of an observational study by
Vassiliadi et al, based on urinary steroid profiles in women with PCOS, further
support can be found for an important role for 5-alpha reductase in the
pathogenesis of this syndrome.[23]
The polymorphisms most strongly associated with PCOS at the 2q21 locus encode
a number of genes, including the THADA gene, which has previously been
associated with type 2 diabetes. In addition, 6 significant polymorphisms were
identified as being associated with PCOS at the 9q33.3 locus near the DENND1A
gene, which interacts with the ERAP1 gene. Elevation in serum ERAP1 has been
previously associated with PCOS and obesity.[24]
Epidemiology
In the United States, polycystic ovarian syndrome (PCOS) is one of the most
common endocrine disorders of reproductive-age women, with a prevalence of 4-
12%.[25, 26] Up to 10% of women are diagnosed with PCOS during gynecologic
visits.[27] In some European studies, the prevalence of PCOS has been reported to
be 6.5-8%.[28, 29]
A great deal of ethnic variability in hirsutism is observed. For example, Asian (East
and Southeast Asia) women have less hirsutism than white women given the same
serum androgen values. In a study that assessed hirsutism in southern Chinese
women, investigators found a prevalence of 10.5%.[30] In hirsute women, there was
a significant increase in the incidence of acne, menstrual irregularities, polycystic
ovaries, and acanthosis nigricans.[30]
PCOS 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 PCOS findings
with normal physiologic maturation during the 2 years after menarche. In lean
women with a genetic predisposition to PCOS, the syndrome may be unmasked
when they subsequently gain weight.[13]
Prognosis
Evidence suggest that women with polycystic ovarian syndrome (PCOS) may be at
increased risk for cardiovascular and cerebrovascular disease. Women with
hyperandrogenism have elevated serum lipoprotein levels similar to those of men.
[31, 32, 33, 34]
Patients with PCOS are also at an increased risk for endometrial hyperplasia and
carcinoma.[5, 36] The chronic anovulation in PCOS leads to constant endometrial
stimulation with estrogen without progesterone, and this increases the risk of
endometrial hyperplasia and carcinoma. The Royal College of Obstetricians and
Gynaecologists (RCOG) recommends induction of withdrawal bleeding with
progestogens a minimum of every 3-4 months.[5]
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No known association with breast or ovarian cancer has been found; thus, no
additional surveillance is needed.[5]
Patient Education
Discuss with patients the symptoms of polycystic ovarian syndrome (PCOS) as
well as their increased risk for cardiovascular and cerebrovascular disease.
Educate women with this condition regarding lifestyle modifications such as weight
reduction, increased exercise, and dietary modifications.[3, 4, 5] (See Diet and
Activity.)
For more information, see Women's Health Center, as well as Ovarian Cysts,
Amenorrhea, and Female Sexual Problems.
Clinical Presentation
Richard Scott Lucidi, MD, FACOG is a member of the following medical societies: American College of
Obstetricians and Gynecologists, American Society for Reproductive Medicine
Frances E Casey, MD, MPH is a member of the following medical societies: American College of Obstetricians
and Gynecologists, Association of Reproductive Health Professionals, Society of Family Planning, National
Abortion Federation, Physicians for Reproductive Health
Chief Editor
Richard Scott Lucidi, MD, FACOG Associate Professor of Reproductive Endocrinology and Infertility,
Department of Obstetrics and Gynecology, Virginia Commonwealth University School of Medicine
Richard Scott Lucidi, MD, FACOG is a member of the following medical societies: American College of
Obstetricians and Gynecologists, American Society for Reproductive Medicine
Acknowledgements
Elizabeth Alderman, MD Director of Fellowship Training Program, Director of Adolescent Ambulatory Service,
Professor of Clinical Pediatrics, Department of Pediatrics, Division of Adolescent Medicine, Albert Einstein
College of Medicine and Children's Hospital at Montefiore
Elizabeth Alderman, MD is a member of the following medical societies: American Academy of Pediatrics,
American Pediatric Society, North American Society for Pediatric and Adolescent Gynecology, and Society for
Adolescent Medicine
A David Barnes, MD, PhD, MPH, FACOG Consulting Staff, Department of Obstetrics and Gynecology,
Mammoth Hospital (Mammoth Lakes, California), Pioneer Valley Hospital (Salt Lake City, Utah), Warren
General Hospital (Warren, Pennsylvania), and Mountain West Hospital (Tooele, Utah)
A David Barnes, MD, PhD, MPH, FACOG is a member of the following medical societies: American College of
Forensic Examiners, American College of Obstetricians and Gynecologists, American Medical Association,
Association of Military Surgeons of the US, and Utah Medical Association
Robert J Ferry Jr, MD Le Bonheur Chair of Excellence in Endocrinology, Professor and Chief, Division of
Pediatric Endocrinology and Metabolism, Department of Pediatrics, University of Tennessee Health Science
Center
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, Pediatric Endocrine Society,
Society for Pediatric Research, and Texas Pediatric Society
Disclosure: Eli Lilly & Co Grant/research funds Investigator; MacroGenics, Inc Grant/research funds
Investigator; Ipsen, SA (formerly Tercica, Inc) Grant/research funds Investigator; NovoNordisk SA
Grant/research funds Investigator; Diamyd Grant/research funds Investigator; Bristol-Myers-Squibb
Grant/research funds Other; Amylin Other; Pfizer Grant/research funds Other; Takeda Grant/research funds
Other
Stephen Kemp, MD, PhD Professor, Department of Pediatrics, Section of Pediatric Endocrinology, University of
Arkansas for Medical Sciences College of Medicine, 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
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Polycystic Ovarian Syndrome: Practice Essentials, Background, Etiology 27/07/2016, 10:57 PM
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,
Pediatric Endocrine Society, and Society for Pediatric Research
Disclosure: Pfizer Grant/research funds P.I.; Tercica Grant/research funds Other; Eli Lily Grant/research funds
PI; NovoNordisk Grant/research funds PI; NovoNordisk Consulting fee Consulting; Onyx Heart Valve Consulting
fee Consulting
Jordan G Pritzker, MD, MBA, FACOG Assistant Professor of Obstetrics/Gynecology and Women's Health,
Women's Comprehensive Health Center, Hofstra University School of Medicine; Attending Physician,
Department of Obstetrics and Gynecology, Long Island Jewish Medical Center
Kathy Silverman, DO Albert Einstein College of Medicine and Montefiore Medical Center
Phyllis W Speiser, MD Chief, Division of Pediatric Endocrinology, Steven and Alexandra Cohen Children's
Medical Center of New York; Professor of Pediatrics, Hofstra-North Shore LIJ School of Medicine at Hofstra
University
Phyllis W Speiser, MD is a member of the following medical societies: American Association of Clinical
Endocrinologists, Endocrine Society, Pediatric Endocrine Society, and Society for Pediatric Research
Francisco Talavera, PharmD, PhD Adjunct Assistant Professor, University of Nebraska Medical Center
College of Pharmacy; Editor-in-Chief, Medscape Drug Reference
Mary L Windle, PharmD Adjunct Associate Professor, University of Nebraska Medical Center College of
Pharmacy; Editor-in-Chief, Medscape Drug Reference
Andrea Leigh Zaenglein, MD Associate Professor of Dermatology and Pediatrics, Department of Dermatology,
Milton S Hershey Medical Center, Pennsylvania State University College of Medicine
Andrea Leigh Zaenglein, MD is a member of the following medical societies: American Academy of
Dermatology, American Acne and Rosacea Society, and Society for Pediatric Dermatology
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