Polycystic ovary syndrome

Question 1

Definition of PCOS and its manifestations 1

Answer 1

• PCOS is characterized by chronic anovulation, and clinical/biochemical evidence of hyperandrogenism w/o other causes
• Hyperandrogenism: hirsutism (body hair), acne
• The cysts in PCOS are follicles that are arrested in development
• In PCOS women have elevated T/androgens which suppresses FSH and leads to arrest of follicular development

Question 2

Definition of PCOS and its manifestations 2

Answer 2

• Anovulation means there is constantly low progesterone/E2 (which inhibit LH release), thus there is constitutively high LH
• Manifestations of PCOS: ovulatory dysfxn, androgen excess, polycystic ovaries, obesity
• Things to rule out: pregnancy, congenital adrenal hyperplasia, prolactinoma, thyroid abnormalities, androgen secreting tumor, cushings

Question 3

Pathogenesis of PCOS 1

Answer 3

• Low birth weight (≤2.5kg), early pubarche (before 8yrs), family Hx, and obesity are risk factors
• Underlying problem is in the ovary- it is making too much androgens, also have hypothalamic-pit axis disturbance and insulin resistance (latter two are secondary effects from hyperandrogenism)
• In the ovaries of PCOS women there is an increased theca cell volume (theca cells stick around after all of the follicles undergo atresia)

Question 4

Pathogenesis of PCOS 2

Answer 4

• The theca cells have an increased expression of LH receptors on them, leading to an exaggerated response to the already high LH levels
• Theca cells make androgens which are normally converted into estrogens by granulosa cell
• However since the FSH levels in PCOS women are very low there’s not enough activation of granulosa cells (via FSH receptors) to convert the androgens to estrogens
• Overall there is a high LH:FSH ratio, due to high androgens (inhibits FSH release), low E/P (anovulation from no FSH) which leads to high LH

Question 5

Effects of hyperinsulinemia

Answer 5

• High insulin levels lead to augmented theca androgen response to LH
• It also suppresses hepatic SHBG production (increases free androgens), stimulates LH secretion directly, and sensitizes LH secreting cells to GnRH
• Insulin resistance alone is not enough to cause PCOS
• Insulin resistance is believed to be a secondary effect (comes after hyperandrogenism)

Question 6

PCOS Rx w/ fertility desired

Answer 6

• Ovulation induction includes weight loss, clomiphene citrate (first line)
• Next line: aromatase inhibitors, gonadotropins, ovarian drilling
• Also can add metformin (insulin sensitizers improve menstrual cyclicity, restores spontaneous ovulation)
• Weight loss is key for all Rx: decreases T and insulin, increases SHBG

Question 7

PCOS Rx w/o fertility desired

Answer 7

• Oral contraceptives: low dose estrogen and non-androgenic progestin (COC) are first line Rx
• COCs increase SHBG, decreases hirsutism, acne
• Anti-androgens: reduce biochemical and clinical hyperandrogenism, improves cyclicity (are 2nd line after COCs)
• 2 choices: flutamine (non-steroidal antagonist of androgen nuclear receptor), spironolactone (K-sparing diuretic w/ anti-androgen effect)