PCOS/Hirsutism/Obesity Flashcards
Contributors to obesity
- Down-regulation of adiponectin (which increases insulin sensitivity)
- Defect in leptin receptor
4 Adipokines that change after meal
Somatostatin, ghrelin, leptin, NPY
Somatostatin change after meal
Increases after meal
Somatostatin source cells
Release from gastric D-cells
Somatostatin regulation
Regulated by ANS with catecholamines inhibiting and cholinergic mediators stimulating peptide release
Somatostatin function and MOA
Inhibitory function; decreases blood flow, GI motility, gallbladder contraction and inhibition of GI hormones
Ghrelin change after meal
Decreases after meal
Ghrelin production location
Upper stomach
Ghrelin action
Stimulates secretion of GH, increases food intake and produces weight gain
Ghrelin relation to fasting, eating, and hyperglycemia
- Secreted under fasting conditions
- Low levels after eating and with hyperglycemia
Leptin after meal
Increases after meal
Leptin function
- Decreases appetite and food consumption
- Increases heat production and activity
- Stimulates CRH expression
NPY after meal
Decreases after meal
Adipokine levels after gastric bypass surgery
Ghrelin – decreases
Leptin – decreases (less body fat?)
NPY – increases
Mechanism of hyperandrogenemia in PCOS
o Insulin stimulation of theca via insulin receptor (inositolphosphoglycan mediates androgen production)
o Decreased hepatic SHBG production (+androgens, which also decrease hepatic SHBG production)
o Insulin potentiated action of LH – increase LH pulse frequency (~1 pulse/hour) and (lesser extent) amplitude
When is development of hair follicles complete
22 weeks gestation (no new follicles develop afterwards)
Concentration of hair follicles where does not vary between sexes
Facial skin
Major factor determining hair follicle concentration
Race/ethnicity
MOA insulin and androgen synthesis
Insulin acts directly on the theca cells via insulin (tyrosine kinase) receptors - to stimulate androgen synthesis
Other places insulin acts besides theca cells
- Insulin also acts on the IGF-1 receptor at high concentrations
- Insulin acts via inositolphosphoglycan (PI-3K) mediators – different than that of LH
Metformin drug class
Biguanide oral insulin-sensitizing agent
Metformin MOA
- Decreases hepatic glucose production
- Decreases intestinal glucose uptake
- Increases peripheral insulin sensitivity (up to 20%)
- Inhibits lipolysis (decreases circulating free fatty acids, reduces hepatic gluconeogenesis)
Metformin clinical benefits
- Decreases weight and BMI (3-5%)
* Decreases BP and LDL
Metformin guidelines for stopping pre-procedure
- Canadian guidelines: eGFR < 60, stop taking metformin at the time of contrast administration
- European guidelines: eGFR < 45, stop metformin 48 hours before CT
Metformin guidelines for stopping pre-procedure
- Canadian guidelines: eGFR < 60, stop taking metformin at the time of contrast administration
- European guidelines: eGFR < 45, stop metformin 48 hours before CT
Ovarian drilling subsequent physiologic changes
- Destroys theca cells -> decreased androgen and LH levels
- Androstenedione, LH, and LH/FSH ratio all decrease; no change in dopaminergic inputs
