Basics
Description
- Polycystic ovary syndrome (PCOS) is a heterogeneous familial disorder characterized by hyperandrogenism, chronic anovulation, and infertility. Hirsutism, polycystic ovaries, obesity, insulin resistance, and hyperinsulinemia may be present but are not required for diagnosis.
- The 1990 NIH consensus meeting criteria for the diagnosis of PCOS were chronic anovulation, hyperandrogenism, and exclusion of other disorders. The 2006 Rotterdam criteria expanded the diagnostic features to include polycystic ovary morphology on US. The Androgen Excess-PCOS Society criteria emphasized the importance of hyperandrogenism.
- Using adult criteria to diagnose PCOS may be inappropriate for adolescent girls because irregular menses and multifollicular ovaries are common during adolescence.
Epidemiology
- Very common endocrine disorder affecting approximately 6 " “8% of reproductive-aged women
- Onset often during the peripubertal years
- May be preceded by premature adrenarche
Genetics
- Multifactorial polygenic familial disorder
- More prevalent in 1st-degree relatives of affected women
- A few genes associated with PCOS have been identified and replicated in women of European and Chinese ancestry. These genes include fibrillin-3 (FBN-3), DENN/MADD domain containing 1A (DENND1A), FSH receptor (FSHR), and LH receptor (LHCGR) variants.
Pathophysiology
- PCOS is associated with follicular growth arrest. Most follicles arrest at the small antral stage prior to selection of a dominant follicle, giving rise to the typical pattern of multiple small follicles forming a ring in the ovary. Failure to select a dominant follicle leads to chronic anovulation.
- Characterized by a paradox regarding insulin sensitivity. Muscle, liver, and adipose tissue manifest insulin resistance, whereas the adrenal, ovary, and perhaps, the hypothalamus retain insulin sensitivity. The insulin resistance leads to increased insulin secretion by pancreatic beta cells to maintain euglycemia. The elevated insulin concentrations amplify LH- and IGF-1 " “stimulated theca cell androgen production and decrease SHBG production leading to increased free testosterone concentrations. Obesity exacerbates insulin resistance, intensifies PCOS symptomatology, and increases the risk for development of type 2 diabetes (T2D).
- Prenatal and childhood factors appear to influence the development of insulin resistance consistent with the hypotheses regarding early developmental origins of PCOS. Infants born small for gestational age (SGA) who experience fetal growth restriction followed by significant postnatal catch-up growth show increased insulin resistance prior to the onset of puberty.
- PCOS symptoms tend to improve with age as demonstrated in a 20-year follow-up of young women with PCOS. These women demonstrated decreased androgen concentrations and decreased ovarian volumes without any significant change in BMI or insulin sensitivity.
Etiology
- The precise etiology or initiating events remain to be elucidated. Likely, there are several potential mechanisms that initiate the perpetual cycle involving neuroendocrine abnormalities, excessive ovarian (and adrenal) androgen secretion, and metabolic dysfunction.
- LH hypersecretion is commonly observed in women with PCOS. For some, this might represent an intrinsic neuroendocrine abnormality. However, in most instances hyperandrogenism is responsible for LH hypersecretion. Amelioration of the LH hypersecretion by flutamide, an androgen receptor blocker, supports the relationship of hyperandrogenism and LH hypersecretion. One potential mechanism identified in adolescent girls is decreased hypothalamic sensitivity to progesterone.
- Although the molecular mechanisms responsible for insulin resistance and hyperinsulinemia in PCOS remain to be better characterized, post insulin receptor signal transduction is impaired. The compensatory hyperinsulinemia promotes ovarian (adrenal) androgen secretion. Adipose tissue dysfunction may provoke insulin resistance, but aberrant adipocyte function may also represent a consequence of hyperinsulinemia. Improved insulin sensitivity brought about by weight loss or metformin improves the symptomatology associated with PCOS.
Commonly Associated Conditions
- Obesity
- Insulin resistance
- Impaired glucose tolerance
- T2D
- Endometriosis
- Metabolic syndrome
- Dyslipidemia
- Hypertension
- Increased risk for cardiovascular disease
- Nonalcoholic fatty acid liver disease
- Sleep apnea
- Depression and impaired quality of life
Diagnosis
Signs and Symptoms
- Irregular menses
- Infertility
- Hyperandrogenism
- Hirsutism
- Polycystic ovaries on US
- Exclusion of other disorders such as nonclassical congenital adrenal hyperplasia
- Obesity and insulin resistance may occur but are not required for diagnosis.
History
- Age at onset and sequence of pubertal development
- Menstrual history
- Infertility and reproductive history
- Signs and symptoms of androgen excess, for example, hirsutism, acne, male pattern baldness
- Family history of PCOS, hyperandrogenism, and fertility
Physical Exam
- Increased terminal hair growth in androgen-dependent areas (hirsutism)
- Acne
- Obesity
- Acanthosis nigricans
Diagnostic Tests & Interpretation
- Hormone determinations:
- Testosterone and free testosterone
- Sex hormone " “binding globulin
- 17-hydroxyprogesterone
- Androstenedione
- DHEAS
- LH and FSH
- Prolactin
- Thyroid function studies (T4, TSH)
- HgbA1c
- Antim ƒ ¼llerian hormone (AMH)
- Stimulation and tolerance tests:
- Oral glucose tolerance test to assess for impaired glucose tolerance, impaired fasting glucose tolerance, or diabetes
- Consider referral to endocrinologist for ACTH stimulation test to exclude the diagnosis of 21-hydroxylase deficiency and other disorders of steroidogenesis.
- Euglycemic and hyperinsulinemic clamp studies can be performed to assess insulin sensitivity. These tests are generally reserved for research purposes.
- Imaging studies:
- Ovarian US to assess ovarian volume and follicle number. For the postpubertal girl, revised criteria suggest that a total ovary threshold count of 26 follicles provided the optimal compromise between sensitivity and specificity to distinguish polycystic from normal ovaries.
- Pelvic MRI: ovarian volume and the number of ovarian follicles
Differential Diagnosis
- Nonclassic congenital adrenal hyperplasia
- Cushing syndrome
- Androgen-secreting tumors
- Hyperprolactinemia
- Thyroid dysfunction
- Exogenous androgen use
Treatment
General Measures
- Treatment should to be individualized to best address the needs of each patient. Common goals include reduced symptoms of hyperandrogenism, regular menses and ovulation, fertility, and decreased risk for comorbidities.
- Lifestyle. Lifestyle intervention to promote weight loss and regular exercise is extremely beneficial.
- Pharmacologic
- Oral contraceptives
- Metformin
- Spironolactone
- Antiandrogens
- Statins
- Monthly progestins
Surgery/Other Procedures
Ovarian wedge resection was used in the past. This treatment is no longer advocated. ‚
Ongoing Care
Complications
- One systemic review of 35 studies concluded that women with PCOS have a 2.5-fold increased prevalence of impaired glucose tolerance, 2.5-fold increased prevalence of metabolic syndrome, and 4-fold increased prevalence of T2D.
- Women with the most extreme degrees of androgen excess and insulin resistance demonstrate increased risks for impaired oocyte development and may experience high rate of miscarriages.
- During pregnancy, risk of developing gestational diabetes, pregnancy-induced hypertension, and pre-eclampsia are increased.
- Possible cancer risk
- Quality of life concerns and issues
Additional Reading
- Abbott ‚ DH, Bacha ‚ F. Ontogeny of polycystic ovary syndrome and insulin resistance in utero and early childhood. Fertil Steril. 2013;100(1):2 " “11. ‚ [View Abstract]
- Bates ‚ GW, Legro ‚ RS. Long term management of polycystic ovarian syndrome (PCOS). Mol Cell Endocrinol. 2013;373(1 " “2):91 " “97. ‚ [View Abstract]
- Blank ‚ SK, McCartney ‚ CR, Chhabra ‚ S, et al. Modulation of gonadotropin-releasing hormone pulse generator sensitivity to progesterone inhibition in hyperandrogenic adolescent girls " ”implications for regulation of pubertal maturation. J Clin Endocrinol Metab. 2009;94(7):2360 " “2366. ‚ [View Abstract]
- Carmina ‚ E, Campagna ‚ AM, Lobo ‚ RA. A 20-year follow-up of young women with polycystic ovary syndrome. Obstet Gynecol. 2012;119(2, Pt 1):263 " “269. ‚ [View Abstract]
- Carmina ‚ E, Oberfield ‚ SE, Lobo ‚ RA. The diagnosis of polycystic ovary syndrome in adolescents. Am J Obstet Gynecol. 2010;203(3):201.e1 " “201.e5. ‚ [View Abstract]
- Chang ‚ RJ, Cook-Andersen ‚ H. Disordered follicle development. Mol Cell Endocrinol. 2013;373(1 " “2):51 " “60. ‚ [View Abstract]
- Dumesic ‚ DA, Richards ‚ JS. Ontogeny of the ovary in polycystic ovary syndrome. Fertil Steril. 2013;100(1):23 " “38. ‚ [View Abstract]
- Eagleson ‚ CA, Gingrich ‚ MB, Pastor ‚ CL, et al. Polycystic ovarian syndrome: evidence that flutamide restores sensitivity of the gonadotropin-releasing hormone pulse generator to inhibition by estradiol and progesterone. J Clin Endocrinol Metab. 2000;85(11):4047 " “4052. ‚ [View Abstract]
- Goodarzi ‚ MO, Dumesic ‚ DA, Chazenbalk ‚ G, et al. Polycystic ovary syndrome: etiology, pathogenesis and diagnosis. Nat Rev Endocrinol. 2011:7(4):219 " “231. ‚ [View Abstract]
- Lujan ‚ ME, Jarrett ‚ BY, Brooks ‚ ED, et al. Updated ultrasound criteria for polycystic ovary syndrome: reliable thresholds for elevated follicle population and ovarian volume. Hum Reprod. 2013;28(5):1361 " “1368. ‚ [View Abstract]
- McGee ‚ WK, Bishop ‚ CV, Bahar ‚ A, et al. Elevated androgens during puberty in female rhesus monkeys lead to increased neuronal drive to the reproductive axis: a possible component of polycystic ovary syndrome. Hum Reprod. 2012;27(2):531 " “540. ‚ [View Abstract]
- Moran ‚ LJ, Misso ‚ ML, Wild ‚ RA, et al. Impaired glucose tolerance, type 2 diabetes and metabolic syndrome in polycystic ovary syndrome: a systematic review and meta-analysis. Hum Reprod Update. 2010;16(4):347 " “363. ‚ [View Abstract]
- Moran ‚ LJ, Pasquali ‚ R, Teede ‚ HJ, et al. Treatment of obesity in polycystic ovary syndrome: a position statement of the Androgen Excess and Polycystic Ovary Syndrome Society. Fertil Steril. 2009;92(6):1966 " “1982. ‚ [View Abstract]
- Mutharasan ‚ P, Galdones ‚ E, Pe ƒ ±alver ‚ B, et al. Evidence for chromosome 2p16.3 polycystic ovary syndrome susceptibility locus in affected women of European ancestry. J Clin Endocrinol Metab. 2013;98(1):E185 " “E190. ‚ [View Abstract]
- Stepto ‚ NK, Cassar ‚ S, Joham ‚ AE, et al. Women with polycystic ovary syndrome have intrinsic insulin resistance on euglycaemic-hyperinsulaemic clamp. Hum Reprod. 2013;28(3):777 " “784. ‚ [View Abstract]
- Welt ‚ CK, Styrkarsdottir ‚ U, Ehrmann ‚ DA, et al. Variants in DENND1A are associated with polycystic ovary syndrome in women of European ancestry. J Clin Endocrinol Metab. 2012;97(7):E1342 " “E1347. ‚ [View Abstract]
- Xie ‚ GB, Xu ‚ P, Che ‚ YN, et al. Microsatellite polymorphism in the fibrillin 3 gene and susceptibility to PCOS: a case-control study and meta-analysis. Reprod Biomed Online. 2013;26(2):168 " “174. ‚ [View Abstract]
Codes
ICD09
- 256.4 Polycystic ovaries
- 704.1 Hirsutism
ICD10
- E28.2 Polycystic ovarian syndrome
- L68.0 Hirsutism
SNOMED
- 69878008 Polycystic ovaries (disorder)
- 399939002 Hirsutism (disorder)
FAQ
- Q: Can I still get pregnant if I have this syndrome?
- A: Those patients who desire to become pregnant can be treated with ovulation-inducing agents and benefit from treatment by reproductive endocrine specialists.
- Q: I 've noticed increased facial hair recently. Is there anything I can do about this?
- A: Yes. Oral contraceptives and spironolactone may be helpful. Cosmetic methods may be necessary to remove coarse hair growth.
- Q: Will my daughter inherit this disorder?
- A: Daughters and sisters of affected women have a higher chance of developing PCOS than daughters and sisters of unaffected women.