Metabolic Syndrome

Question 1

What is the most common endocrine abnormality of women of reproductive age?

Answer 1

Polycystic Ovary Syndrome (PCOS)

Question 2

• What are the clinical manifestations of PCOS?
• What is PCOS associated with?

Answer 2

• Clinical manifestations include:
  
  • chronic anovulation
    
    • oligo/amenorrhea, infertility
  • hyperandrogenism
    
    • hirsutism, acne, alopecia
• PCOS is associated with an increased risk of diabetes and other metabolic abnormalities which may potentially increase the risk of coronary artery disease

Question 3

Clinical Manifestations of PCOS:

Hyperandrogenism

Answer 3

• **Hirsutism **
• Acne
• Alopecia
  
  • generalized, temporal, frontal
• Deepening of the voice, increased muscle mass, and clitoromegaly may occur
  
  • more suggestive of a virilizing (androgen secreting) tumor
• Chronic presentation, often with peripubertal onset

Question 4

What is the pathophysiology of PCOS?

Answer 4

Complex disorder

• Gonadotropin secretion disturbance
• Steroidogenesis disorder
• Insulin resistance

Question 5

Describe how the endocrine system is affected in PCOS:

Answer 5

1. ∆GnRH ⇒ ↑ LH:FSH
   
   • relative increase in LH with normal or low FSH levels
2. Ovarian theca cells stimulated ⇒ ↑ androgens
   
   • Adrenal androgen secretion may also be increased
3. Normal follicle development is disrupted and many small ovarian follicles may develop
4. A mid-cycle LH surge does not consistently occur, ⇒ progesterone levels are usually low
   
   • Menstrual irregularity
   • Heavy menses
   • Risk for endometrial hyperplasia.

Question 6

How is steroidogenesis affected in PCOS?

Answer 6

• PCOS is associated with underlying insulin resistance
  
  • even when the woman is lean
  • worsened by obesity
  • more than 50% of women with PCOS are obese
• Insulin resistance ⇒ ↑ hyperinsulinemia ⇒ ↑ ovarian androgen production
• Hyperinsulinemia ⇒ decreases SHBG ⇒ ↑ free testosterone

Question 7

What are the features of metabolic syndrome?

Answer 7

• central obesity
• abnormal lipids (elevated TG, low HDL)
• skin tags, acanthosis nigricans
• higher prevalence of IGT and diabetes
• sleep apnea and nonalcoholic steatohepatitis

Question 8

Diagnostic Criteria for PCOS:

Answer 8

at least 2 of the 3:

1. Oligo-or anovulation
2. Clinical and/or biochemical signs of hyperandrogenism
3. Polycystic ovaries on imaging

And

• Absence of secondary causes (CAH, androgen-secreting tumors, Cushing’s syndrome)

Question 9

What are the similarities of PCOS and metabolic syndrome related to insulin resistance?

(redundant but it proves a point)

Answer 9

• Central obesity
• Hyperinsulinemia
• Low SHBG
• Abnormal lipids (elevated TG, low HDL)
• Higher prevalence of IGT and diabetes.
• Increased risk of non alcoholic steatohepatitis (fatty liver).

Question 10

1. How is PCOS diagnosed?
2. What is biochemical evaluation used for in diagnosing PCOS?
3. Are tests for insulin resistance necessary?

Answer 10

1. Diagnosis of PCOS made based on history, clinical suspicion
2. Biochemical evaluation is for excluding less common causes of hirsutism and menstrual irregularities (androgen secreting tumors, CAH, thyroid disease)
   
   • Biochemical testing will often result in “normal” results
3. Tests for insulin resistance are not required to make a diagnosis of PCOS

Question 11

How is treatment for PCOS individualized?

(how do you treat based on the presenting complaint?)

Answer 11

1. Treatment of symptoms of anovulation
   
   • regulate menses
   • induce ovulation
   • endometrial cancer risk reduction
2. Treatment of symptoms of hyperandrogenism
3. Treatment of obesity and metabolic disorders
   
   • Obesity management
   • Sleep apnea screening
   • Diabetes prevention
   • Lipid management and cardiovascular disease risk reduction
4. Screening and treatment for anxiety/depression

Question 12

What can be used as medical therapy for PCOS?

Answer 12

• OCPs
• Spironoloactone

Question 13

What are the therapeutic effects of OCPs for PCOS treatment?

Answer 13

• Suppress ovarian androgen secretion by suppression of gonadotropins
• Increases SHBG
• Decreases free testosterone and free androgen index
• Improves hirsutism
• Regulates menses and provides adequate progestin to protect endometrial lining (lowers risk for endometrial hyperplasia)

Question 14

What are the therapeutic effects of spironolactone?

Answer 14

Competitive inhibitor of androgen receptor

• Improves hirsutism, acne and alopecia
• Does not inhibit androgen secretion
• Requires reliable contraception