Close
New

Medscape is available in 5 Language Editions – Choose your Edition here.

 

Polycystic Ovarian Syndrome

  • Author: Richard Scott Lucidi, MD, FACOG; Chief Editor: Richard Scott Lucidi, MD, FACOG  more...
 
Updated: Nov 14, 2015
 

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 Low power, H and E of an ovary containing multiple cystic follicles in a patient with PCOS.

Essential update: AACE/ACE and AES Society release new guidelines

In November 2015, the American Association of Clinical Endocrinologists (AACE), American College of Endocrinology (ACE), and Androgen Excess and PCOS Society (AES) released new guidelines in the evaluation and treatment of PCOS.[1] Among their opinions and recommendations are the following[1] :

  • 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-Müllerian 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.

Signs and symptoms

The major features of PCOS include menstrual dysfunction, anovulation, and signs of hyperandrogenism.[2] Other signs and symptoms of PCOS may include the following:

  • Hirsutism
  • Infertility
  • Obesity and metabolic syndrome
  • Diabetes
  • Obstructive sleep apnea

See Clinical Presentation for more detail.

Diagnosis

On examination, findings in women with PCOS may include the following:

  • 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]

Baseline screening laboratory studies for women suspected of having PCOS include the following:

  • Thyroid function tests [5] (eg, TSH, free thyroxine)
  • Serum prolactin level [5]
  • Total and free testosterone levels
  • Free androgen index [5]
  • Serum hCG level
  • Cosyntropin stimulation test
  • Serum 17-hydroxyprogesterone (17-OHPG) level
  • Urinary free cortisol (UFC) and creatinine levels
  • Low-dose dexamethasone suppression test
  • Serum insulinlike growth factor (IGF)–1 level

Other tests used in the evaluation of PCOS include the following:

  • Androstenedione level
  • FSH and LH levels
  • GnRH stimulation testing
  • Glucose level
  • Insulin level
  • Lipid panel

Imaging tests

The following imaging studies may be used in the evaluation of PCOS:

  • Ovarian ultrasonography, preferably using transvaginal approach
  • Pelvic CT scan or MRI to visualize the adrenals and ovaries

Procedures

An ovarian biopsy may be performed for histologic confirmation of PCOS; however, ultrasonographic diagnosis of PCOS has generally superseded histopathologic diagnosis. An endometrial biopsy may be obtained to evaluate for endometrial disease, such as malignancy.

See Workup for more detail.

Management

Lifestyle modifications are considered first-line treatment for women with PCOS. Such changes include the following[3, 4] :

  • Diet
  • Exercise
  • Weight loss

Pharmacotherapy

Pharmacologic treatments are reserved for so-called metabolic derangements, such as anovulation, hirsutism, and menstrual irregularities. First-line medical therapy usually consists of an oral contraceptive to induce regular menses.

If symptoms such as hirsutism are not sufficiently alleviated, an androgen-blocking agent may be added. First-line treatment for ovulation induction when fertility is desired is clomiphene citrate.[3, 4, 6]

  • Medications used in the management of PCOS include the following:
  • Oral contraceptive agents (eg, ethinyl estradiol, medroxyprogesterone)
  • Antiandrogens (eg, spironolactone, leuprolide, finasteride)
  • Hypoglycemic agents (eg, metformin, insulin)
  • Selective estrogen receptor modulators (eg, clomiphene citrate)
  • Topical hair-removal agents (eg, eflornithine)
  • Topical acne agents (eg, benzoyl peroxide, tretinoin topical cream (0.02–0.1%)/gel (0.01–0.1%)/solution (0.05%), adapalene topical cream (0.1%)/gel (0.1%, 0.3%)/solution (0.1%), erythromycin topical 2%, clindamycin topical 1%, sodium sulfacetamide topical 10%)

Surgery

Surgical management of PCOS is aimed mainly at restoring ovulation. Various laparoscopic methods include the following:

  • Electrocautery
  • Laser drilling
  • Multiple biopsy

See Treatment and Medication for more detail.

Next

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.)

Further biochemical, clinical, and endocrinologic studies revealed an array of underlying abnormalities. As a result, the condition is now referred to as PCOS, although it may occur in women without ovarian cysts and although ovarian morphology is no longer an essential requirement for diagnosis.

A woman is diagnosed with polycystic ovaries (as opposed to PCOS) if she has 12 or more follicles in at least 1 ovary—measuring 2-9 mm in diameter—or a total ovarian volume greater than 10 cm3. (See the image below.) (See Workup.)

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

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:

  • Oligo-ovulation or anovulation manifested by oligomenorrhea or amenorrhea
  • Hyperandrogenism (clinical evidence of androgen excess) or hyperandrogenemia (biochemical evidence of androgen excess)
  • Exclusion of other disorders that can result in menstrual irregularity and hyperandrogenism

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] :

  • Oligo-ovulation or anovulation manifested as oligomenorrhea or amenorrhea
  • Hyperandrogenism (clinical evidence of androgen excess) or hyperandrogenemia (biochemical evidence of androgen excess)
  • Polycystic ovaries (as defined on ultrasonography)

The Androgen Excess and PCOS Society (AE-PCOS) published a position statement in 2006[11] and its criteria in 2009[12] emphasizing that, in the society’s opinion, PCOS should be considered a disorder of androgen excess, as defined by the following:

  • Clinical/biochemical evidence of hyperandrogenism
  • Evidence of ovarian dysfunction (oligo-ovulation and/or polycystic ovaries)
  • Exclusion of related disorders

The Society of Obstetricians and Gynaecologists of Canada (SOGC) indicated that a diagnosis of polycystic ovarian syndrome (PCOS) is made in the presence of at least 2 of the following 3 criteria, when congenital adrenal hyperplasia, androgen-secreting tumors, or Cushing syndrome have been excluded[3] :

  • Oligo-ovulation or anovulation
  • Clinical/biochemical evidence of hyperandrogenism
  • Polycystic ovaries on ultrasonograms (>12 small antral follicles in an ovary)
Previous
Next

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.

PCOS is also associated with peripheral insulin resistance and hyperinsulinemia, and obesity amplifies the degree of both abnormalities. Insulin resistance in PCOS can be secondary to a postbinding defect in insulin receptor signaling pathways, and elevated insulin levels may have gonadotropin-augmenting effects on ovarian function. Hyperinsulinemia may also result in suppression of hepatic generation of sex hormone–binding globulin (SHBG), which in turn may increase androgenicity.[13]

In addition, insulin resistance in PCOS has been associated with adiponectin, a hormone secreted by adipocytes that regulates lipid metabolism and glucose levels. Lean and obese women with PCOS have lower adiponectin levels than do women without PCOS.[14]

A proposed mechanism for anovulation and elevated androgen levels suggests that, under the increased stimulatory effect of luteinizing hormone (LH) secreted by the anterior pituitary, stimulation of the ovarian theca cells is increased. These cells, in turn, increase the production of androgens (eg, testosterone, androstenedione). Because of a decreased level of follicle-stimulating hormone (FSH) relative to LH, the ovarian granulosa cells cannot aromatize the androgens to estrogens, which leads to decreased estrogen levels and consequent anovulation. Growth hormone (GH) and insulin-like growth factor–1 (IGF-1) may also augment the effect on ovarian function.[15]

Hyperinsulinemia is also responsible for dyslipidemia and for elevated levels of plasminogen activator inhibitor-1 (PAI-1) in patients with PCOS. Elevated PAI-1 levels are a risk factor for intravascular thrombosis.

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.

Some evidence suggests that patients have a functional abnormality of cytochrome P450c17, the 17-hydroxylase, which is the rate-limiting enzyme in androgen biosynthesis.[14]

PCOS is a genetically heterogeneous syndrome in which the genetic contributions remain incompletely described. PCOS is an inherently difficult condition to study genetically because of its heterogeneity, difficulty with retrospective diagnosis in postmenopausal women, associated subfertility, incompletely understood etiology, and gene effect size.[7] Many published genetics studies in PCOS have been underpowered, and the results of published candidate gene studies have been disappointing.

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.

Wickenheisser et al reported that CYP17 promoter activity was 4-fold greater in cells of patients with PCOS. This research suggests that the pathogenesis of PCOS may be in part related to the gene regulation of CYP17.[19] However, in a study that assessed candidate genes for PCOS using microsatellite markers to look for association in 4 genes— CYP19, CYP17, FST, and INSR —only 1 marker 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]

Subsequent studies have found additional associations, such as those of 15 regions in 11 genes previously described to influence insulin resistance, obesity, or type 2 diabetes.[21] Individuals with PCOS were found more likely to be homozygous for a variant upstream of the PON1 gene and homozygous for an allele of interest in IGF2. Interestingly, the PON1 gene variant resulted in decreased gene expression, which could increase oxidative stress. The exact result of the IGF2 variant is unclear, but IGF2 stimulates androgen secretion in the ovaries and adrenal glands.[21]

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]

In a genome-wide association study for PCOS in a Han Chinese population, 3 strong regions of association were identified, at 2p16.3, 2p21, and 9q33.3.[24] The polymorphism most strongly associated with PCOS at the 2p16 locus was near several genes involved in proper formation of the testis, as well as a gene that encodes a receptor for luteinizing hormone (LH) and human chorionic gonadotropin (HCG). This polymorphism was also located 211kb upstream from the FSHR gene, which encodes the follicle-stimulating hormone (FSH) receptor.[24]

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]

Previous
Next

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]

Previous
Next

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]

Approximately 40% of patients with PCOS have insulin resistance that is independent of body weight. These women are at increased risk for type 2 diabetes mellitus and consequent cardiovascular complications.

The American Association of Clinical Endocrinologists and the American College of Endocrinology recommend screening for diabetes by age 30 years in all patients with PCOS, including obese and nonobese women.[35] In patients at particularly elevated risk, testing before 30 years of age may be indicated. Patients who initially test negative for diabetes should be periodically reassessed throughout their lifetime.

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]

No known association with breast or ovarian cancer has been found; thus, no additional surveillance is needed.[5]

Previous
Next

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.

Previous
 
 
Contributor Information and Disclosures
Author

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

Disclosure: Nothing to disclose.

Specialty Editor Board

Frances E Casey, MD, MPH Director of Family Planning Services, Department of Obstetrics and Gynecology, VCU Medical Center

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

Disclosure: Nothing to disclose.

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

Disclosure: Nothing to disclose.

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

Disclosure: Merck Honoraria Speaking and teaching

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

Disclosure: Nothing to disclose.

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

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, 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

Disclosure: Nothing to disclose.

Kathy Silverman, DO Albert Einstein College of Medicine and Montefiore Medical Center

Disclosure: Nothing to disclose.

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

Disclosure: Nothing to disclose.

Francisco Talavera, PharmD, PhD Adjunct Assistant Professor, University of Nebraska Medical Center College of Pharmacy; Editor-in-Chief, Medscape Drug Reference

Disclosure: Medscape Salary Employment

Mary L Windle, PharmD Adjunct Associate Professor, University of Nebraska Medical Center College of Pharmacy; Editor-in-Chief, Medscape Drug Reference

Disclosure: Nothing to disclose.

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

Disclosure: Nothing to disclose.

References
  1. Goodman NF, Cobin RH, Futterweit W, Glueck JS, Legro RS, Carmina E. American Association of Clinical Endocrinologists, American College of Endocrinology, and Androgen Excess and PCOS Society disease state clinical review: guide to the best practices in the evaluation and treatment of polycystic ovary syndrome - part 1. Endocr Pract. 2015 Nov. 21 (11):1291-300. [Medline].

  2. Azziz R, Carmina E, Dewailly D, et al; Task Force on the Phenotype of the Polycystic Ovary Syndrome of The Androgen Excess and PCOS Society. The Androgen Excess and PCOS Society criteria for the polycystic ovary syndrome: the complete task force report. Fertil Steril. 2009 Feb. 91(2):456-88. [Medline].

  3. Vause TD, Cheung AP, Sierra S, et al. Ovulation induction in polycystic ovary syndrome. J Obstet Gynaecol Can. 2010 May. 32(5):495-502. [Medline].

  4. American College of Obstetricians and Gynecologists. Polycystic ovary syndrome. Washington, DC: American College of Obstetricians and Gynecologists; 2009. ACOG practice bulletin; no. 108. [Full Text].

  5. Royal College of Obstetricians and Gynaecologists. Long-term consequences of polycystic ovary syndrome. London, UK: Royal College of Obstetricians and Gynaecologists; 2007. Green-top guideline; no. 33. [Full Text].

  6. Consensus on infertility treatment related to polycystic ovary syndrome. Fertil Steril. 2008 Mar. 89(3):505-22. [Medline].

  7. Barber TM, Franks S. Genetic basis of polycystic ovary syndrome. Expert Review of Endocrinology & Metabolism. 2010. 5(4):549-61.

  8. Stein I, Leventhal M. Amenorrhea associated with bilateralpolycystic ovaries. Am J Obstet Gynecol. 1935. 29:181.

  9. Stein IF. Duration of infertility following ovarian wedge resection. West J Surg. 1964. 72:237.

  10. PCOS Consensus Workshop Group. 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 Jan. 81(1):19-25. [Medline].

  11. Azziz R, Carmina E, Dewailly D, et al. Positions statement: criteria for defining polycystic ovary syndrome as a predominantly hyperandrogenic syndrome: an Androgen Excess Society guideline. J Clin Endocrinol Metab. 2006 Nov. 91(11):4237-45. [Medline].

  12. Azziz R, Carmina E, Dewailly D, et al. The Androgen Excess and PCOS Society criteria for the polycystic ovary syndrome: the complete task force report. Fertil Steril. 2009 Feb. 91(2):456-88. [Medline].

  13. Barber TM, McCarthy MI, Wass JA, Franks S. Obesity and polycystic ovary syndrome. Clin Endocrinol (Oxf). 2006 Aug. 65(2):137-45. [Medline].

  14. Toulis KA, Goulis DG, Farmakiotis D, et al. Adiponectin levels in women with polycystic ovary syndrome: a systematic review and a meta-analysis. Hum Reprod Update. 2009 May-Jun. 15(3):297-307. [Medline].

  15. Dunaif A, Wu X, Lee A, Diamanti-Kandarakis E. Defects in insulin receptor signaling in vivo in the polycystic ovary syndrome(PCOS). Am J Physiol Endocrinol Metab. 2001 Aug. 281(2):E392-9. [Medline].

  16. Ehrmann DA, Kasza K, Azziz R, Legro RS, Ghazzi MN. Effects of race and family history of type 2 diabetes on metabolic status of women with polycystic ovary syndrome. J Clin Endocrinol Metab. 2005 Jan. 90(1):66-71. [Medline].

  17. Vink JM, Sadrzadeh S, Lambalk CB, Boomsma DI. Heritability of polycystic ovary syndrome in a Dutch twin-family study. J Clin Endocrinol Metab. 2006 Jun. 91(6):2100-4. [Medline].

  18. Barber TM, Bennett AJ, Groves CJ, et al. Association of variants in the fat mass and obesity associated (FTO) gene with polycystic ovary syndrome. Diabetologia. 2008 Jul. 51(7):1153-8. [Medline].

  19. Wickenheisser JK, Quinn PG, Nelson VL, Legro RS, Strauss JF 3rd, McAllister JM. Differential activity of the cytochrome P450 17alpha-hydroxylase and steroidogenic acute regulatory protein gene promoters in normal and polycystic ovary syndrome theca cells. J Clin Endocrinol Metab. 2000 Jun. 85(6):2304-11. [Medline].

  20. Tucci S, Futterweit W, Concepcion ES, et al. Evidence for association of polycystic ovary syndrome in caucasian women with a marker at the insulin receptor gene locus. J Clin Endocrinol Metab. 2001 Jan. 86(1):446-9. [Medline].

  21. San Millan JL, Corton M, Villuendas G, Sancho J, Peral B, Escobar-Morreale HF. Association of the polycystic ovary syndrome with genomic variants related to insulin resistance, type 2 diabetes mellitus, and obesity. J Clin Endocrinol Metab. 2004 Jun. 89(6):2640-6. [Medline].

  22. Goodarzi MO, Shah NA, Antoine HJ, Pall M, Guo X, Azziz R. Variants in the 5alpha-reductase type 1 and type 2 genes are associated with polycystic ovary syndrome and the severity of hirsutism in affected women. J Clin Endocrinol Metab. 2006 Oct. 91(10):4085-91. [Medline].

  23. Vassiliadi DA, Barber TM, Hughes BA, et al. Increased 5 alpha-reductase activity and adrenocortical drive in women with polycystic ovary syndrome. J Clin Endocrinol Metab. 2009 Sep. 94(9):3558-66. [Medline].

  24. Chen ZJ, Zhao H, He L, et al. Genome-wide association study identifies susceptibility loci for polycystic ovary syndrome on chromosome 2p16.3, 2p21 and 9q33.3. Nat Genet. 2011 Jan. 43(1):55-9. [Medline].

  25. Azziz R, Woods KS, Reyna R, Key TJ, Knochenhauer ES, Yildiz BO. The prevalence and features of the polycystic ovary syndrome in an unselected population. J Clin Endocrinol Metab. 2004 Jun. 89(6):2745-9. [Medline]. [Full Text].

  26. Knochenhauer ES, Key TJ, Kahsar-Miller M, et al. Prevalence of the polycystic ovary syndrome in unselected black and white women of the southeastern United States: a prospective study. J Clin Endocrinol Metab. 1998 Sep. 83(9):3078-82. [Medline].

  27. Cahill D. PCOS. BMJ Clin Evid. 2009 Jan 15. 2009:[Medline]. [Full Text].

  28. Asuncion M, Calvo RM, San Millan JL, et al. A prospective study of the prevalence of the polycystic ovary syndrome in unselected Caucasian women from Spain. J Clin Endocrinol Metab. 2000 Jul. 85(7):2434-8. [Medline].

  29. Diamanti-Kandarakis E, Kouli CR, Bergiele AT, et al. A survey of the polycystic ovary syndrome in the Greek island of Lesbos: hormonal and metabolic profile. J Clin Endocrinol Metab. 1999 Nov. 84(11):4006-11. [Medline].

  30. Zhao X, Ni R, Li L, et al. Defining hirsutism in Chinese women: a cross-sectional study. Fertil Steril. 2011 Sep. 96(3):792-6. [Medline].

  31. Christian RC, Dumesic DA, Behrenbeck T, Oberg AL, Sheedy PF 2nd, Fitzpatrick LA. Prevalence and predictors of coronary artery calcification in women with polycystic ovary syndrome. J Clin Endocrinol Metab. 2003 Jun. 88 (6):2562-8. [Medline].

  32. Conway GS, Agrawal R, Betteridge DJ, Jacobs HS. Risk factors for coronary artery disease in lean and obese women with the polycystic ovary syndrome. Clin Endocrinol (Oxf). 1992 Aug. 37(2):119-25. [Medline].

  33. Dokras A. Cardiovascular disease risk factors in polycystic ovary syndrome. Semin Reprod Med. 2008 Jan. 26(1):39-44. [Medline].

  34. Vryonidou A, Papatheodorou A, Tavridou A, et al. Association of hyperandrogenemic and metabolic phenotype with carotid intima-media thickness in young women with polycystic ovary syndrome. J Clin Endocrinol Metab. 2005 May. 90(5):2740-6. [Medline].

  35. American Association of Clinical Endocrinologists. American Association of Clinical Endocrinologists position statement on metabolic and cardiovascular consequences of polycystic ovary syndrome. National Guideline Clearinghouse. Available at http://guideline.gov/summary/summary.aspx?doc_id=7108. Accessed: August 28, 2009.

  36. Hardiman P, Pillay OC, Atiomo W. Polycystic ovary syndrome and endometrial carcinoma. Lancet. 2003 May 24. 361(9371):1810-2. [Medline].

  37. Carmina E, Legro RS, Stamets K, et al. Difference in body weight between American and Italian women with polycystic ovary syndrome: influence of the diet. Hum Reprod. 2003 Nov. 18(11):2289-93. [Medline].

  38. Ehrmann DA, Barnes RB, Rosenfield RL, et al. Prevalence of impaired glucose tolerance and diabetes in women with polycystic ovary syndrome. Diabetes Care. 1999 Jan. 22(1):141-6. [Medline].

  39. Legro RS, Kunselman AR, Dodson WC, Dunaif A. Prevalence and predictors of risk for type 2 diabetes mellitus and impaired glucose tolerance in polycystic ovary syndrome: a prospective, controlled study in 254 affected women. J Clin Endocrinol Metab. 1999 Jan. 84(1):165-9. [Medline].

  40. Gopal M, Duntley S, Uhles M, Attarian H. The role of obesity in the increased prevalence of obstructive sleep apnea syndrome in patients with polycystic ovarian syndrome. Sleep Med. 2002 Sep. 3(5):401-4. [Medline].

  41. Vgontzas AN, Legro RS, Bixler EO, et al. Polycystic ovary syndrome is associated with obstructive sleep apnea and daytimesleepiness: role of insulin resistance. J Clin Endocrinol Metab. 2001 Feb. 86(2):517-20. [Medline].

  42. Hecht Baldauff N, Arslanian S. Optimal management of polycystic ovary syndrome in adolescence. Arch Dis Child. 2015 Nov. 100 (11):1076-83. [Medline].

  43. Nieman LK. Diagnostic tests for Cushing's syndrome. Ann N Y Acad Sci. 2002 Sep. 970:112-8. [Medline].

  44. American Diabetes Association. Diagnosis and classification of diabetes mellitus. Diabetes Care. 2009 Jan. 32 Suppl 1:S62-7. [Medline]. [Full Text].

  45. Nur MM, Newman IM, Siqueira LM. Glucose metabolism in overweight Hispanic adolescents with and without polycystic ovary syndrome. Pediatrics. 2009 Sep. 124(3):e496-502. [Medline].

  46. Alemzadeh R, Kichler J, Calhoun M. Spectrum of metabolic dysfunction in relationship with hyperandrogenemia in obese adolescent girls with polycystic ovary syndrome. Eur J Endocrinol. 2010 Jun. 162(6):1093-9. [Medline].

  47. Barber TM, Wass JA, McCarthy MI, Franks S. Metabolic characteristics of women with polycystic ovaries and oligo-amenorrhoea but normal androgen levels: implications for the management of polycystic ovary syndrome. Clin Endocrinol (Oxf). 2007 Apr. 66(4):513-7. [Medline].

  48. Kabil Kucur S, Gozukara I, Aksoy A, et al. How medical treatment affects mean platelet volume as a cardiovascular risk marker in polycystic ovary syndrome?. Blood Coagul Fibrinolysis. 2015 Dec. 26 (8):862-5. [Medline].

  49. Trent ME, Rich M, Austin SB, Gordon CM. Fertility concerns and sexual behavior in adolescent girls with polycystic ovary syndrome: implications for quality of life. J Pediatr Adolesc Gynecol. 2003 Feb. 16(1):33-7. [Medline].

  50. [Guideline] Legro RS, Arslanian SA, Ehrmann DA, et al. Diagnosis and treatment of polycystic ovary syndrome: an Endocrine Society clinical practice guideline. J Clin Endocrinol Metab. 2013 Oct 22. [Medline].

  51. [Guideline] Martin KA, Chang RJ, Ehrmann DA, et al. Evaluation and treatment of hirsutism in premenopausal women: an endocrine society clinical practice guideline. J Clin Endocrinol Metab. 2008 Apr. 93(4):1105-20. [Medline].

  52. Abd Elgafor I. Efficacy of combined metformin-letrozole in comparison with bilateral ovarian drilling in clomiphene-resistant infertile women with polycystic ovarian syndrome. Arch Gynecol Obstet. 2013 Jul. 288(1):119-23. [Medline].

  53. Emery G. Letrozole produces more babies in women with polycystic ovary syndrome: study. Medscape from WebMD. 2014 Jul 10. Available at http://www.medscape.com/viewarticle/828062. Accessed: July 14, 2014.

  54. Legro RS, Brzyski RG, Diamond MP, et al. Letrozole versus clomiphene for infertility in the polycystic ovary syndrome. N Engl J Med. 2014 Jul 10. 371(2):119-29. [Medline].

  55. Otta CF, Wior M, Iraci GS, et al. Clinical, metabolic, and endocrine parameters in response to metformin and lifestyle intervention in women with polycystic ovary syndrome: a randomized, double-blind, and placebo control trial. Gynecol Endocrinol. 2010 Mar. 26(3):173-8. [Medline].

  56. Allen HF, Mazzoni C, Heptulla RA, et al. Randomized controlled trial evaluating response to metformin versus standard therapy in the treatment of adolescents with polycystic ovary syndrome. J Pediatr Endocrinol Metab. 2005 Aug. 18(8):761-8. [Medline].

  57. Moghetti P, Castello R, Negri C, et al. Metformin effects on clinical features, endocrine and metabolic profiles, and insulin sensitivity in polycystic ovary syndrome: a randomized, double-blind, placebo-controlled 6-month trial, followed by open, long-term clinical evaluation. J Clin Endocrinol Metab. 2000 Jan. 85(1):139-46. [Medline]. [Full Text].

  58. Hoeger KM, Kochman L, Wixom N, Craig K, Miller RK, Guzick DS. A randomized, 48-week, placebo-controlled trial of intensive lifestyle modification and/or metformin therapy in overweight women with polycystic ovary syndrome: a pilot study. Fertil Steril. 2004 Aug. 82(2):421-9. [Medline].

  59. Begum MR, Khanam NN, Quadir E, et al. Prevention of gestational diabetes mellitus by continuing metformin therapy throughout pregnancy in women with polycystic ovary syndrome. J Obstet Gynaecol Res. 2009 Apr. 35(2):282-6. [Medline].

  60. Khattab S, Mohsen IA, Aboul Foutouh I, et al. Can metformin reduce the incidence of gestational diabetes mellitus in pregnant women with polycystic ovary syndrome? Prospective cohort study. Gynecol Endocrinol. 2011 Oct. 27(10):789-93. [Medline].

  61. Cheang KI, Huszar JM, Best AM, Sharma S, Essah PA, Nestler JE. Long-term effect of metformin on metabolic parameters in the polycystic ovary syndrome. Diab Vasc Dis Res. 2009 Apr. 6(2):110-9. [Medline]. [Full Text].

  62. US Food and Drug Administration. Safety: statins and HIV or hepatitis C drugs: drug safety communication - interaction increases risk of muscle injury. Posted: March 1, 2012. Available at http://www.fda.gov/Safety/MedWatch/SafetyInformation/SafetyAlertsforHumanMedicalProducts/ucm294294.htm. Accessed: May 22, 2012.

  63. US Food and Drug Administration. Safety: statin drugs - drug safety communication: class labeling change. Posted: February 28, 2012. Available at http://www.fda.gov/Safety/MedWatch/SafetyInformation/SafetyAlertsforHumanMedicalProducts/ucm293670.htm. Accessed: May 22, 2012.

  64. US Food and Drug Administration. Safety: Zocor (simvastatin): label change - new restrictions, contraindications, and dose limitations. Posted: June 8, 2011. Available at http://www.fda.gov/Safety/MedWatch/SafetyInformation/SafetyAlertsforHumanMedicalProducts/ucm258384.htm. Accessed: May 22, 2012.

  65. US Food and Drug Administration. Safety: Meridia (sibutramine): market withdrawal due to risk of serious cardiovascular events. Posted: October 8, 2010. Available at http://www.fda.gov/Safety/MedWatch/SafetyInformation/SafetyAlertsforHumanMedicalProducts/ucm228830.htm. Accessed: May 22, 2012.

  66. Kiddy DS, Hamilton-Fairley D, Bush A, et al. Improvement in endocrine and ovarian function during dietary treatment of obese women with polycystic ovary syndrome. Clin Endocrinol (Oxf). 1992 Jan. 36(1):105-11. [Medline].

  67. Moran LJ, Pasquali R, Teede HJ, Hoeger KM, Norman RJ. Treatment of obesity in polycystic ovary syndrome: a position statement of the Androgen Excess and Polycystic Ovary Syndrome Society. Fertil Steril. 2009 Dec. 92(6):1966-82. [Medline].

  68. Lord JM, Flight IH, Norman RJ. Metformin in polycystic ovary syndrome: systematic review and meta-analysis. BMJ. 2003 Oct 25. 327(7421):951-3. [Medline]. [Full Text].

  69. Rotondi M, Cappelli C, Magri F, et al. Thyroidal effect of metformin treatment in patients with polycystic ovary syndrome. Clin Endocrinol (Oxf). 2011 Sep. 75(3):378-81. [Medline].

  70. Leeman L, Acharya U. The use of metformin in the management of polycystic ovary syndrome and associated anovulatory infertility: the current evidence. J Obstet Gynaecol. 2009 Aug. 29(6):467-72. [Medline].

  71. Nestler JE, Jakubowicz DJ, Evans WS, Pasquali R. Effects of metformin on spontaneous and clomiphene-induced ovulation in the polycystic ovary syndrome. N Engl J Med. 1998 Jun 25. 338(26):1876-80. [Medline].

  72. Sinawat S, Buppasiri P, Lumbiganon P, Pattanittum P. Long versus short course treatment with metformin and clomiphene citrate for ovulation induction in women with PCOS. Cochrane Database Syst Rev. 2008 Jan 23. CD006226. [Medline].

  73. Badawy A, State O, Abdelgawad S. N-Acetyl cysteine and clomiphene citrate for induction of ovulation in polycystic ovary syndrome: a cross-over trial. Acta Obstet Gynecol Scand. 2007. 86(2):218-22. [Medline].

  74. Koulouri O, Conway GS. Management of hirsutism. BMJ. 2009 Mar 27. 338:b847. [Medline].

  75. Rosenfield RL. Clinical practice. Hirsutism. N Engl J Med. 2005 Dec 15. 353(24):2578-88. [Medline].

  76. Paparodis R, Dunaif A. The Hirsute woman: challenges in evaluation and management. Endocr Pract. 2011 Sep-Oct. 17(5):807-18. [Medline].

  77. Cumming DC, Yang JC, Rebar RW, Yen SS. Treatment of hirsutism with spironolactone. JAMA. 1982 Mar 5. 247(9):1295-8. [Medline].

  78. Roth LW, Huang H, Legro RS, et al. Altering hirsutism through ovulation induction in women with polycystic ovary syndrome. Obstet Gynecol. 2012 Jun. 119(6):1151-6. [Medline]. [Full Text].

  79. Liepa GU, Sengupta A, Karsies D. Polycystic ovary syndrome (PCOS) and other androgen excess-related conditions: can changes in dietary intake make a difference?. Nutr Clin Pract. 2008 Feb. 23(1):63-71. [Medline].

  80. Ornstein RM, Copperman NM, Jacobson MS. Effect of weight loss on menstrual function in adolescents with polycystic ovary syndrome. J Pediatr Adolesc Gynecol. 2011 Jun. 24(3):161-5. [Medline].

  81. Cussons AJ, Watts GF, Mori TA, Stuckey BG. Omega-3 fatty acid supplementation decreases liver fat content in polycystic ovary syndrome: a randomized controlled trial employing proton magnetic resonance spectroscopy. J Clin Endocrinol Metab. 2009 Oct. 94(10):3842-8. [Medline].

  82. Wehr E, Pilz S, Schweighofer N, et al. Association of hypovitaminosis D with metabolic disturbances in polycystic ovary syndrome. Eur J Endocrinol. 2009 Oct. 161(4):575-82. [Medline].

  83. Poujade O, Gervaise A, Faivre E, Deffieux X, Fernandez H. Surgical management of infertility due to polycystic ovarian syndrome after failure of medical management. Eur J Obstet Gynecol Reprod Biol. 2011 Oct. 158(2):242-7. [Medline].

  84. Farquhar C, Lilford RJ, Marjoribanks J, Vandekerckhove P. Laparoscopic 'drilling' by diathermy or laser for ovulation induction in anovulatory polycystic ovary syndrome. Cochrane Database Syst Rev. 2007 Jul 18. CD001122. [Medline].

  85. Roos N, Kieler H, Sahlin L, et al. Risk of adverse pregnancy outcomes in women with polycystic ovary syndrome: population based cohort study. BMJ. 2011 Oct 13. 343:d6309. [Medline]. [Full Text].

  86. Percy CA, Gibbs T, Potter L, Boardman S. Nurse-led peer support group: experiences of women with polycystic ovary syndrome. J Adv Nurs. 2009 Oct. 65(10):2046-55. [Medline].

  87. Rotondi M, Cappelli C, Magri F, et al. Thyroidal effect of metformin treatment in patients with polycystic ovary syndrome. Clin Endocrinol (Oxf). 2011 Sep. 75(3):378-81. [Medline].

  88. Palomba S, Pasquali R, Orio F Jr, Nestler JE. Clomiphene citrate, metformin or both as first-step approach in treating anovulatory infertility in patients with polycystic ovary syndrome (PCOS): a systematic review of head-to-head randomized controlled studies and meta-analysis. Clin Endocrinol (Oxf). 2009 Feb. 70(2):311-21. [Medline].

 
Previous
Next
 
Longitudinal transabdominal ultrasonogram of an ovary. This image reveals multiple peripheral follicles.
Low power, H and E of an ovary containing multiple cystic follicles in a patient with PCOS.
 
 
 
All material on this website is protected by copyright, Copyright © 1994-2016 by WebMD LLC. This website also contains material copyrighted by 3rd parties.