4.23 - PCOS Flashcards
Describe symptoms associated with PCOS (hyperandrogenism, chronic anovulation,
polycystic ovaries, insulin resistance and sometimes obesity).
2003 rotterdam criteria - 2 of the following 3:
-hyperandrogenism
-chronic anovulation
-polycystic ovaries (enlarged ovaries containing at least 12 follicles each; updated to 20 follicles each in 2018)
Describe the prevalence of PCOS and the diseases for which it is a risk factor
prevalence 5-10%
-often presents with insulin resistance, sometimes associated with obesity, major risk factor for type 2 diabetes, gestational diabetes and cardiovascular disease
Explain the basis for ovarian hyperandrogenism associated with PCOS. Include mention
of the GnRH pulsatility, LH:FSH ratio, androgen production by theca cells, and
aromatization by granulosa cells
-pulsatile GnRH release is essential for maintenance of gonadotropin secretion
-frequency of GnRH pulses determines which gonadotropin hormone is preferentially synthesized
–rapid GnRH pulses favor LH (normally occurs prior to the LH surge)
–slower GnRH pulses favor FSH
–
PCOS pts have increased (faster)
If you increase both LH and FSH, then the main steroid product of the follicle will be:
estradiol
If you increase LH, but not FSH, the main steroid product of the follicle will be:
androstenedione/testosterone
Describe the symptoms resulting from ovarian hyperandrogenism (hirsutism, acne and
androgenic alopecia) and explain why mild hyperandrogenism may confer a small
advantage for female athletes with PCOS.
hirsutism - dark, coarse, thick hair on face, chest, abdomen and back
acne - stimulated by androgens
androgenic alopecia - male-pattern hair loss
–
slight increased athletic performance, increased testosterone
Explain the basis for anovulation in women with PCOS. Include mention of follicular
cysts, their developmental state and the roles of LH, FSH, androgen and progesterone
how anovulation happens
Explain why PCOS is associated with infertility
-starts with abnormal secretion of gonadotropins (LH > FSH), androgen excess, genetic factors
-androgens promote early (small antral) follicle growth
-elevated androgen:estrogen ratio decreases quality of developing oocyte in follicle
-low FSH is not sufficient to stimulate follicle development
-corpus luteum doesn’t form so progesterone remains low
Explain why women with PCOS have elevated AMH levels
All of their follicles get stuck at small antrals and they continue to make AMH
Explain why insulin resistance in PCOS patients results in hyperglycemia and
hyperinsulemia.
-PCOS patients are insulin resistant resulting in elevated blood glucose
-elevated blood glucose stimulates more insulin secretion from pancreatic beta cells in effort to stimulate glucose uptake
-higher glucose infusion rate indicates higher rate of peripheral GU
-PCOS: high insulin -> low PI3K -> low GU
Explain why PCOS and obesity decrease the glucose infusion rate observed during a
hyperinsulinemic-euglycemic clamp.
Explain why insulin-dependent GLUT-4 mediated glucose uptake is lower in PCOS
patients (i.e., PCOS patients are insulin-resistant). Include mention of IR, IRS-1/2, PI3K
and glucose uptake.
Describe the consequences of PCOS-associated hyperinsulinemia for liver SHBG
production, circulating free androgen levels, liver free fatty acid release, storage of extra
glucose as fat in adipose and GnRH pulsatility
Describe the effect of insulin on theca cell androgen production. Include mention of the
effect of insulin on serine phosphorylation of 17a-hydroxylase (P450c17). Indicate how
this demonstrates selective insulin resistance
Discuss the treatments for PCOS. Include mention of oral contraceptives, progestins
with minimal androgenic (norgestimate, desogestral) or anti-androgenic properties
(drospirenone), spironolactone, endometrial hyperplasia, diet and exercise, clomid, FSH,
and metformin.
