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  • Section Writer: Dr. Om J Lakhani
  • Section Editor: Dr. Om J Lakhani

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• Diagnosis of polycystic ovary syndrome in adults

• Q. Give the diagnostic criteria for PCOS?

  • Rotterdam Criteria (two out of three required)
    • Oligo or anovulation
    • Clinical and/or biochemical signs of hyperandrogenism
    • Polycystic ovaries (by ultrasound)
  • AES definition 2008 (all required)
    • Clinical and/or biochemical signs of hyperandrogenism
    • Ovarian dysfunction
      • oligo-anovulation
      • and/or polycystic ovaries on ultrasound
    • Exclusion of others:
      • androgen excess or
      • ovulatory disorders

• Q. What is the significant difference between NIH and AES criteria?

  • NIH – does not ask for USG for the establishment of anovulation
  • AES – asks for clinical / USG criteria for anovulation

• Q. When to measure DHEAS in a case which looks like PCOS clinically?

  • Only when signs of virilization are present

• Q. Rotterderm USG criteria, requires one ovary or both ovaries to show typical morphology?

  • One ovary showing characteristic morphology is enough

• Q. When to use a cut-off of 12 follicles and when to use 25 follicles cut-off in Rotterdam criteria?

  • If TVS done with probe < 8 Hz – use 12 follicles
  • If TVS done with probe > 8 Hz- use 25 follicle criteria

• #Clinicalpearl

  • Remember Rotterdam criteria is based on TVS and not TAS

• Q. Which tests are done to rule out other causes of oligomenorrhea?

  • Prolactin – hyperprolactinemia
  • TSH – hypothyroidism
  • FSH- high FSH suggest POI
  • 17 OHP- Non-classical CAH
  • Measurement of LH is not required

• **Additional tests once the diagnosis is established **

• Q. What additional test must be done once the diagnosis of PCOS is established?

  • OGTT (oral glucose tolerance test)
  • Lipid profile
  • BP measurement

• Q. Are tests for diagnosis of insulin resistance (HOMA-IR etc.) indicated?

  • No

• Q. Should women with PCOS be screened for anxiety and depression?

  • Yes

• Q. How to screen for depression?

  • PHQ9 is ideal
  • PHQ2 – can be used for quick assessment

• Q. What are the questions asked in PHQ2?

  • During the last month, have you often been bothered by feeling down, depressed, or hopeless?
  • During the last month, have you often been bothered by having little interest or pleasure in doing things?
  • You can either score from 0 to 3 or ask yes or no
    • If single Yes- suggest depression
    • Or score >/= 3 / 6 suggest depression

• Q. How is screening for anxiety disorder done?

  • GAD-7 questionnaire

• Q. Should you screen these women for OSA?

  • Questions about symptoms of OSA
  • If present – refer to sleep medicine

• Q. Summarize the additional tests done once the diagnosis is established?

  • 1. Cardiometabolic screen
    • OTT
    • BP measurement
    • Lipid profile
  • 2. Question about depression and anxiety/eating disorder
    • PHQ9/PHQ2 for depression
  • 3. Question about symptoms of OSA
  • 4. Fertility evaluation if pregnancy is planned

• USE OF AMH FOR PCOS DIAGNOSIS and FOLLOW-UP

• Q. What is the basis of using AMH for the diagnosis of PCOS?

  • AMH is produced by the small antral follicles
  • They are the same ones that are seen on ultrasound in PCOS
  • Hence AMH can be used as a surrogate biochemical marker of PCOS

• Q. What is the biggest challenge in the use of AMH for PCOS diagnosis?

  • The AMH assay is not standardized

• Q. Which cells in the ovary produce AMH?

  • They are produced by granulosa cells of ovaries

• Q. Which follicles produce AMH?

  • There expression starts right from the primordial follicle
  • Highest levels are seen in the preantral follicle and small-antral follicles
  • The Primordial, primary, secondary and small tertiary (grafiaan follicles) produce AMH

• Q. What is the role of AMH in these follicles?

  • AMH in these early follicles discourages its further development and prevent it from developing into a dominant follicle in future

#Clinicalpearl
- AMH has an inhibitory role on primordial follicle recruitment and its development

• Q. How does the AMH induce this inhibitory effect?

  • It reduces the sensitivity of the ovarian follicles to FSH

• Q. What is the AMH assay method?

  • It is assayed with ELISA

• Q. What is the problem with the assay?

  • There is a lack of standardization, and hence no value is agreed upon
  • Hence value will differ from lab to lab
  • Recently, there has been automatization of the process, and hence there is hope that there will be uniformity

• **AMH as an indicator of ovarian reserve **

• Q. What is ovarian reserve?

  • It is defined as the number of remaining primordial follicles

• Q. How many primordial follicles are present at the time of puberty?

  • About 400,000

• Q. Is AMH a good marker of ovarian reserve?

  • Yes
  • Because it is produced by the follicles which are kept in reserve – the primordial follicle and the pre-antral follicles
  • Hence it is an excellent biochemical marker of ovarian reserve
  • It correlates well with antral follicular count on TVS

• Q. What size follicles are counted in AFC?

  • Follicles of size 2-9 mm are counted
  • They are precisely the ones that produce AMH
  • AMH may be better than AFC because it also includes the primordial follicles and pre-antral follicles, which are not counted in AFC

• Q. What are the controversies regarding AMH use as a marker of ovarian reserve?

  • Some say obesity can reduce AMH value physiologically
  • The effect of OC pills on AMH is not known
  • PCOS and AMH

• Pathophysiology of PCOS from AMH perspective

• Q. Which follicular cells are increased in PCOS?

  • Pre-antral and small antral cells
  • These cells are 2-4 times higher than in normal women
  • These cells specifically produce AMH

• Q. Is there a relation between androgens and AMH?

  • Yes
  • Increase androgens are associated with an increase of AMH values

• Q. What is the impact of FSH on AMH?

  • It has a dual-action
  • FSH increase AMH per se in pre-antral follicles which do not produce Estradiol
  • The follicles which have aromatase produce estradiol in the presence of FSH
  • Estradiol, on the other hand, suppresses AMH
  • So basically, FSH may increases AMH in pre-antral follicles, which suppresses AMH in later follicles

• Q. Is AMH part of the pathogenesis in PCOS?

  • It could very well be
  • AMH prevents the action of FSH on ovarian follicles
  • Hence if AMH is in excess,  it will block the development of ovarian follicles
  • This would lead to follicular arrest, which is classically seen in PCOS

• Q. What is the effect of LH on AMH?

  • LH enhances AMH production

• Q. But granulosa cells do not have LH receptors, so how does the LH enhance AMH?

  • In PCOS, the granulosa cell acquire LH receptor early

• **AMH in the diagnosis of PCOS **

• Q. Do all growing follicles contribute to the Serum AMH pool?

  • Tough earlier follicles produce AMH; they are not reflected in the serum because they are not vascularized
  • It is the secondary follicle onwards that are vascularized, which contribute to the serum AMH value

• Q. What cut-off of AMH value helps in the diagnosis of PCOS?

  • It is impossible to have one cut off because of AMH assay related issues
  • However, AMH cut-off of >4.9 ng/ml is an excellent diagnostic cut-off for PCOS with good sensitivity and specificity.
  • This cut-off is proposed by EIA kit for AMH by Beckman colter

• Q. Does the value of AMH correlate with the severity of PCOS symptoms?

  • Yes

• Q. Can AMH be used in adolescent PCOS diagnosis?

  • Yes
  • It may be a good test since the USG is not reliable in adolescents
  • However, cut off in adolescents are different – AMH is higher in adolescents

• **Use of AMH in the follow-up of the treatment of PCOS **

• Q. What is the potential use of AMH in PCOS and infertility?

  • Though cut-offs are not established, AMH can help decide the ovulation induction protocol for infertile PCOS while avoiding ovarian hyperstimulation

• Q. Does AMH help in predicting the efficacy of OC pill treatment in PCOS?

  • It may be helpful in this regard, but data is scarce
  • OC pills should reduce AMH values in PCOS

• Q. what about the efficiency of treatment in obese PCOS?

  • With weight loss –the AMH value normalizes in obese PCOS
  • Hence it may be helpful in this regard

• Q. What about metformin use?

  • Studies have shown a reduction of AMH with the use of metformin in PCOS patients

• Q. Summarize the use of AMH in PCOS?

  • Diagnosis of PCOS in adults
  • Diagnosis of PCOS in adolescence
  • Severity of PCOS symptoms
  • Selection of ovulation induction protocol
  • Evaluate the effect of treatment in PCOS

• DIAGNOSIS OF PCOS IN ADOLESCENTS

• Q. By what time after the start of menses do girls have regular menstrual cycles?

  • First 1-2 years cycles can be shorter or longer
  • By gynecological age 4-5 yrs the cycles become regular adult-type cycles between 21-35 days

• Q. What is the difference between early menstrual cycles in girls and adults?

  • Early menstrual cycles in girls are often anovulatory (but asymptomatic anovulatory)
  • They are what is called “Immature ovulatory cycles” with inadequate progesterone release in the later half of the cycle

• Q. When should you evaluate for ovulatory disorder in adolescence?

  • When the immature anovulatory cycle persists after 1-2 years- then they need to be evaluated

• Q. Uptil what young age can Ferriman Gallaway scored applied to?

  • Ideally, FG score is for women >18 years
  • However, we can go down up to 15 years of age
  • Adult degree of hirsutism can be applied within two years of menarche

• Q. What type of acne in adolescents should be considered abnormal?

  • Mild to moderate comedone acne is normal
  • Inflammatory acne should be considered abnormal, and it suggests hyperandrogenism

• Q. What testosterone levels should be considered for the diagnosis of PCOS in adolescents?

  • Adult testosterone levels are achieved in the peri menarche age
  • You can use adult reference ranges for perimenarche girls for testosterone values

• Q. Is ultrasound criteria a good idea for the diagnosis of PCOS in adolescents?

  • No
  • Lot of adolescents have morphology (1/3rd) of PCOS in ultrasound
  • Hence USG may not be a good idea for the diagnosis of PCOS in adolescents

• Q. What clinical evidence of hyperandrogenism should be considered for the diagnosis of PCOS in adolescents?

  • Inflammatory acne
  • Moderate to severe hirsutism

• Q. What are the criteria for biochemical hyperandrogenism in adolescent girls?

  • Persistently elevated androgen level from reliable reference lab is reliable evidence of hyperandrogenism in adolescents with PCOS
  • Single reading of higher testosterone should not be relied upon
  • Adult reference values may be used in the absence of age-specific reference ranges

• Q. What is clinical evidence of anovulation in adolescents with PCOS?

  • The following is abnormal :
    • Menstrual cycle <20 days or >45 days two years after the onset of menses
    • Menstrual cycle >90 days in first two years after menarche
    • No onset of menarche at age 15 years or 2-3 years after the onset of thelarche

• Q. What is the ultrasound criteria for PCOS in adolescents?

  • Ovarian volume >12 ml (in adults is 10ml) is evidence of PCOM (By trans-abdominal ultrasound)
  • Ovarian follicular count and other features are not reliable in adolescents with PCOS

• Q. Give the Summary of diagnostic criteria for PCOS in adolescents?

  • Diagnosis of PCOS in adolescents
    • Anovulation
    • Hyperandrogenism
    • Ovarian morphology on ultrasound
    • Ruling out other causes
  • Anovulation
    • Cycle <20 days of >45 days – 2 years after the onset of menses
    • Cycle >90 days within 1-2 years of onset of menses
    • No menarche by 15 years / 2-3 years after the onset of thelarche
    • Ultrasound
    • Ovarian volume >12 ml by TAS
  • Hyperandrogenism
    • 1. Clinically
      • Moderate to severe hirsutism
      • Inflammatory acne
    • 2. Biochemical – persistently elevated androgen levels