Week 3: Polycystic Ovary Syndrome

Question 1

hormones in PCOS

Answer 1

• in PCOS, there is a steady level of hormones. no fluctuations. Constantly elevated LH and low FSH.
• low estradiol levels
• Elevated testosterone suppresses FSH. FSH levels don’t reach level required to induce follicle maturity. (have many follicles arrested in dev.
• absence of progesterone leads to elevated LH (since never have development of corpus luteum)

Question 2

Definition of PCOS

Answer 2

1. NIH
   - major criteria: chronic involution, evidence of hyperandrogenism, exclusion of other cases
   - minor: insulin resistance, perimenarchal onset of hirsutism and obesity, elevated LH/FSH ratio
2. Androgen excess and PCOS society–need all 3 of:
   - hyperandrogenism
   - ovarian dysfunction (oligoanovulation and/or polycystic ovaries)
   - exclusion of related disorders

Question 3

Diagnostic testing of PCOS

Answer 3

1. anovulation -menstrual hx
   - less than 9 menses/year or more than 3 consecutive months without menses
2. Hyperandrogenism
   - PE: hirsutism, acne
   - serum androgen levels: testosterone, free T, DHEA-S
3. Pelvic ultrasound
4. diagnosis of exclusion
   - pregnancy (b-hCG), CAH (17-OH progesterone), hyperprolactinemia (prolactin), thyroid abn. (TSH), Cushings (24 hr cortisol)
   - androgen secretin tumor: suspected if T> 200 ng/dl or DHEAS >700mcg/dl

Question 4

Who gets PCOS?

Answer 4

• 6-8% of reproductive age women
• multifactorial origin, genetic predisposition (acts like autosomal dom.)
• phenotypic expression determined by environmental factors in utero
• risk factors in teens: low birth weight, premature pubarche (before 8 yrs), family hx (1st degree), obesity

Question 5

Underlying problem in PCOS

Answer 5

1. Hyperandrogenism
   - excess androgen from ovary. Increased thecal cell volume
   - increased expression of LH receptors on thecal cells
   - exagerrated androgen production occurs when LH binds to receptors on thecal cells of ovary
2. hypothalamic-pit-ovarian axis disturbance
   - elevated LH pulse freq., amplitude, release: may be due to lack of progesterone
   - decreased FSH: may be due to feedback from androgens
3. insulin resistance and hyperinsulinemia
   - activation of insulin receptor in ovary augments thecal androgen response to LH
   - suppression of hepatic SHBG production (increases free androgen)
   - direct stimulation of LH secretion by insulin
   - sensitization of LH secretin cells to GnRH

Question 6

Treatment of PCOS

Answer 6

• symptom dependent
  1. Infertility
• weight loss
• clomiphene citrate (SERM, induce ovulation)
• aromatase inhibitors, injectable gonadotropins, laparoscopic ovarian drilling, Metformin
  2. Skin, hirsutism
• OCPs: los dose estrogen and non-androgenic progestin. Increases SHBG. restores regular menstrual cycles, decreases hirsutism, acne.
• antiandrogens: spironolactone, flutamide
  3. Dysfunctional uterine bleeding: endometrial biopsy, OCPs or cyclic progestins
  4. Obesity
• lifestyle management, diet, exercise, metformin

Question 7

Periodic screening of PCOS patients

Answer 7

• 2 hr oral glucose tolerance test
• lipid profile
• blood pressure
• may or may not do endometrial biopsy: monitor for endometrial cancer-proliferation of endometrial cells with no sloughing of endometrial cells from unopposed estrogen.