PCOS

• Polycystic Ovary Syndrome (PCOS)


  The most common endocrine disorder in reproductive-age women
• PCOS diagnosis


  • Requires finding any two of the following: menstrual irregularity, hyperandrogenism (clinical or biochemical), or polycystic ovaries on ultrasound
• PCOS is heterogeneous and is not a single-gene disorder, although several susceptibility genes have been identified; environmental influences are most likely involved as well
• Treatment of women with PCOS

  1. Directed at the specific complaint: menstrual function, skin disorders of androgen excess, or subfertility

  2. More than one complaint usually exists, and they can be dealt with concomitantly unless the woman is trying to conceive
• Weight gain and metabolic concerns in PCOS

  • Extremely common and should be treated aggressively (usually with lifestyle management), particularly before pregnancy
  • Evidence suggests that cardiovascular morbidity and mortality are not increased in PCOS unless the woman has obesity and/or diabetes
• Long-term consequences of PCOS may include cardiovascular and metabolic concerns and the increased risks of endometrial and ovarian cancer, unless oral contraceptives have been used
• • With ovarian aging, cycles may become more regular, and some but not all the symptoms of PCOS may disappear as women approach menopause
  • The age of menopause may be later
• Polycystic ovary syndrome (PCOS)


  First described in 1935 by Stein and Leventhal as a syndrome consisting of amenorrhea, hirsutism, and obesity in association with enlarged polycystic ovaries
• Classic features of PCOS

  • Signs of elevated androgens, such as hirsutism
  • Oligomenorrhea or amenorrhea
• PCOS is present in as many as 15% to 20% of reproductive-age women, but many may go undiagnosed due to lack of awareness or mild symptoms
• The diagnosis of PCOS is usually made after the exclusion of other causes of irregular cycles and elevated androgens, such as enzymatic disorders, Cushing syndrome, or tumors
• NIH consensus definition of PCOS

  Does not require findings on ultrasound of characteristic polycystic ovaries
• Rotterdam criteria for PCOS

  Requires two of the following: menstrual irregularity, symptoms or findings of hyperandrogenism, and polycystic ovaries on ultrasound
• Phenotypes of PCOS


  • Phenotype A: Classic phenotype with all three criteria (menstrual irregularity, hyperandrogenism, and polycystic ovaries)
  • Phenotype B: NIH definition without ultrasound findings
  • Phenotype C: Hyperandrogenism and polycystic ovaries in ovulatory women
  • Phenotype D: Irregular cycles and polycystic ovaries in the absence of documented hyperandrogenism
• AEPCOS Society definition of PCOS

  Stresses hyperandrogenism as a key feature and recognizes that women with PCOS can have polycystic ovaries on ultrasound or menstrual irregularity (anovulation)
• The Rotterdam criteria have now been universally accepted for the diagnosis of PCOS
• Elevated luteinizing hormone (LH) levels are not a requirement for the diagnosis of PCOS, nor are elevated levels of testosterone or dehydroepiandrosterone sulfate (DHEAS), as long as there are clinical signs of hyperandrogenism such as hirsutism
• • Acne is much more variable as a complaint, and half the cases of acne are not caused by elevated androgens
  • Alopecia also is not a reliable manifestation of hyperandrogenism and could have a purely dermatologic cause
• A class of 11-oxygenated androgens, largely of adrenal origin, are extremely potent and make up more than 50% of circulating androgens but have not been measured until recently by more sophisticated analyses
• Ultrasound features of polycystic ovaries

  • Classic definition required 12 or more peripherally oriented cystic structures (2 to 9 mm) in one sonographic plane
  • Total follicle count in each ovary is most diagnostic, with a range of 19 to 28 follicles per ovary being diagnostic
  • Ovarian volume of 10 mL or more is also diagnostic
• 10% to 25% of the normal reproductive-age population (no symptoms or signs of PCOS) may have polycystic ovaries found on ultrasound, which should not be confused with the diagnosis of PCOS
• Diagnosis of PCOS in adolescence

  • Rotterdam criteria should not be used
  • PCOS should not be diagnosed unless all three criteria (menstrual irregularity, hyperandrogenism, and polycystic ovaries) are firmly in place and at a minimum of 3 years postmenarche
  • For the ovarian ultrasound criterion, ovarian volumes of 10 mL or greater should be the criterion used
• Menstrual irregularity in PCOS

  • Includes oligomenorrhea (cycles longer than 35 days) and a menstrual frequency of every few months and frank amenorrhea (longer than 6 months missed)
  • Some women with the ovulatory phenotype of PCOS may have regular cycles
• Menstrual irregularity is the best correlate of insulin resistance in women with PCOS
• Many women with PCOS with ovulatory function will present with subfertility
• Androgen excess or hyperandrogenism

  • Often considered the cardinal feature of women with PCOS, but may be difficult to diagnose
  • Symptoms of androgen excess, particularly of hirsutism, are sufficient for the inclusion of this criterion for the diagnosis of PCOS
• Ovulatory phenotype


  Reporting regular cycles occurs with variable frequencies in different populations, from 3% in Korea to 30% in Italy among women diagnosed with PCOS
• Ovulatory phenotype


  May have fewer metabolic and cardiovascular risks
• Menstrual irregularity


  The best correlate of insulin resistance in women with PCOS
• Many women with PCOS with ovulatory function will present with subfertility as well
• Androgen excess


  Often considered the cardinal feature of women with PCOS, may be difficult to diagnose
• Androgen excess has been implicated in contributing to abnormalities in LH secretion, weight gain and adipose deposition, and the metabolic derangements of PCOS
• 11-oxygenated androgens


  Derived principally from the adrenal, are quantitatively the most abundant androgens in women with PCOS and may explain many of the symptoms and derangements in metabolism
• Adipose tissues


  Also secrete androgen, and this intraadipose androgen source seems to contribute to lipid abnormalities and insulin resistance in women with PCOS
• Characteristic endocrine findings in PCOS

  • Abnormal gonadotropin secretion caused by increased GnRH pulse amplitude or increased pituitary sensitivity to GnRH
  • Tonically elevated LH levels in approximately two-thirds of women with PCOS
  • Exaggerated response of LH but not of FSH after a bolus of GnRH
  • Obese women with PCOS often have normal LH levels, while thin women with PCOS often have elevated levels
• An elevated LH level or an elevated LH/FSH ratio is neither specific for nor required for the diagnosis of PCOS
• Women with PCOS


  Have increased levels of biologically active (non-SHBG-bound) estradiol, although total circulating levels of estradiol are not increased
• Lowered SHBG level


  Increases the biologically active fractions of androgens in the circulation
• The risk of hyperplasia or endometrial cancer is enhanced further in some women with PCOS who seem to have progesterone resistance
• Androgens elevated in women with PCOS

  • Serum testosterone (0.55 to 1.2 ng/mL)
  • Androstenedione (3 to 5 ng/mL)
  • DHEAS (elevated in approximately 50% of women with PCOS)