PCOS - Orvieto

Question 1

What is Stein and Leventhal syndrome?

Answer 1

Extreme presentation of polycystic ovary syndrome

Obese patients with hirsuitism, acne and amenorrhea

Question 2

What is the definition of PCOS under the Rotterdam Criteria?

Answer 2

Must have 2 of the 3:

1. Oligo- or anovulation
2. Clinical and/or biochemical signs of hyperandrogenism
3. Polycystic ovaries
   - exclusion of other etiologies (CAH (adrenal hyperplasia), androgen-secreting tumors, Cushing’s syndrome)

Possible combinations (spectrum of hyperandrogenism):

-Hyperandrogenism and chronic anovulation
-Hyperandrog nism and PCO but ovulatory
cycles
-Chronic anovulation and PCO but no clinical
or biochemical hyperandrogenism
- Hyperandrogenism, chronic anovulation and PCO (Stein- Leventhal)

Question 3

What is the ultrasound definition of polycystic ovaries?

Who is this seen in?

Answer 3

Presence of 12 or more follicles in each ovary
measuring 2–9 mm in diameter, and/or increased
ovarian volume (10 mL)
“Necklace sign”
The subjective appearance of PCO- not valid
The follicle distribution/ increase in stromal echogenicity and volume- omitted
Only one ovary fitting this definition is sufficient (other one can be normal)

US evidence of PCO in:
30-37% of women with amenorrhea
75-90% of women with oligomenorrhea
87% of hirsute women with regular menses
22% of “normal population”

Question 4

What is the biochemical characterization in PCOS?

Answer 4

The most consistent biochemical abnormality is hyperandrogenism

• High ovarian androgen levels (testosterone, androstenedione)- 50 to 150% higher than in controls
• Elevated adrenal androgens (DHEAS) (50%, treated with steroids)
• Augmented LH and LH:FSH ratio, elevated or normal free E2 and E1 (If >2 or 3 is pathognomonic)
• Hyperprolactinemia (5-30%)
• Impaired GH secretion
• Insulin resistance (elevated serum insulin & glucose, leads to hyperandrogenism)
• Reduced concentration of SHBG
• Elevated LDL cholesterol
• Elevated TG
• Impairment of fibrinolysis (elevated PAI-1)

Question 5

What are the management options for PCOS?

Answer 5

A. General measures

1. Weight modification
2. Exercise modification
   - Need to consider CV risk factors

B. Prophylactic measures

• treats oligomenorrhea and unopposed estrogen but not infertility
  1. Progestin cycling
  2. Oral contraceptive pill cycling

C. Abnormal uterine bleeding:
Medical Rx:
1. Progestin cycling
2. OC’s
3. MIRENA

Surgical Rx:

1. D&C
2. Endometrial ablation
3. TAH + BSO

Management
D. Hirsutism:
medical Rx:
1. OC’s
2. CPA
3. Spironolactone (competitive androgen inhibitor)
4. GnRH-a +/- OC’s
5. Flutamide
6. Finasteride
7. Ketoconazole
8. Metformin (for insulin resistence and reduces androgen production)
-Diane: estrogen and progesterone, antiandrogenic. If doesn’t work alone, combine with Androcur

E. Ovulation induction (for pregnancy)
Weight Reduction
Clomiphene Citrate (stimulates GnRH)
Insulin sensitizing agents
Aromatase inhibitors
Gonadotropin (low dose, used in those that don’t respond to CC)
Chronic Low Dose
Ovarian cautery (holes punching ovaries)
IVF (28% of patients need this)

Question 6

What is the mode of action of metformin?

What problems in PCOS does it improve?

Answer 6

1. Blunting of hepatic gluconeogenesis
2. Diminished intestinal absorption of glucose
3. Increased peripheral glucose uptake and
   utilization
4. Does not modify pancreatic insulin secretion
   Side- effects:
5. Nausea and diarrhea, bloating, flatulence or
   vomiting (20%)
6. Lactic acidosis

Decreased BMI/ p ratio (WHR)
Decreased Systolic blood pressure
Decreased LH and LH/FSH ratio
Decreased total and free testosterone
Decreased fasting insulin in hyperinsulinemic PCOS
patients
Reversed hyperinsulinemia-driven endocrinopathy
Decreased PAI-1 1
Decreased Lp(a)

(i) Metformin alone is less effective than CC in
inducing ovulation in women with PCOS.
(ii) There seems to be no advantage to adding
metformin to CC in women with PCOS.
(iii) At present, use of metformin in PCOS should be
restricted to those patients with glucose intolerance.
(iv) Decisions about continuing insulin sensitizers during pregnancy in women with glucose
intolerance should be left to obstetricians providing care and based on a careful evaluation of risks and
benefits.