What are the three diagnostic criteria that diagnose PCOS?
hyperandrogegism
ovulatory dysfunction
polycystic ovaries
A disease that is only done when when other conditions are ruled out
What are characteristics of hyper-androgenism?
hirsutism or alopecia (too much or loss of hair)
acne
adipose deposition
metabolic dysfunction
What are characteristics of ovarian dysfunction?
oligo-or amenorrhea
follicular cyst development
impaired ovulation
Infertility
What are other conditions that can be mistaken for PCOS?
adrenal hyperplasia
cushing’s syndrome
hyperprolactinemia
primary hypothyroidism
acromegaly
hypothyroidism
pregnancy
premature ovarian failure
obesity
drug-related condition or effect
What could be three possible pathways to treat hyperandrogenism?
oral contraceptives → not seeking pregnancy
anti-androgen therapy → aldosterone antagonist
normalize hair growth → hirsutism or alopecia
What are the risks and benefits of oral contraceptives pills (OCPs) for PCOS?
benefits
stabilize menstrual cycle
decreased risk of endometrial cancer (less endometrial hyperplasia)
decreased risk of ovarian cyst development
risks
thrombosis (DVT and PE)
what OCs have the highest androgenic (progestin) activity?
norgestrel
levonorgestrel
What OCs have moderate androgenic activity?
norethindrone
norethindrone acetate
What OCs have the least androgenic activity?
ethynodiol
norgestimate
gestodene
desogestrel
How can you induce a period? and why would you do it?
induce a LH surge
reduces risk of endometrial cancer
What MOA do contraceptive have that threat PCOS?
alters GnRH pulsating frequency
decreases anterior pituitary’s responsiveness to GnRH
secondary mechanisms
alteration of cervical mucus
endometrial receptivity
tubal peristalsis
What medication is used to treat hirsutism and acne with PCOS?
Spironolactone
What is the MOA of Spironolactone?
Aldosterone receptor antagonist (K sparing effect)
decreases androgen effects on skin, hair growth (acne/ excessive hair growth)
What is an important clinical pearl for patients taking spironolactone?
may cause birth defects
avoid pregnancy or patients planning to be pregnant
What are some topical medications for management of hirsutism ?
Eflornithine (Vaniqa)
What is the MOA of Eflornithine and an important clinical pearl?
inhibits ornithine decarboxylase (ODC) reduces the rate of hair growth
Warning: Pregnancy category C - used with caution
What medication is used to treat hyperandrogenic alopecia and its MOA?
Finasteride - Propecia
MOA: 5-alpha-reductase inhibitor
What is the 1st line intervention for overweight or obese women with PCOS?
Metformin - Biguanide
What is the MOA of Metformin?
Biguanide
decreases hepatic glucose & fatty acid & cholesterol
increases glucose uptake in skeletal muscles
exhibits both AMPK dependent and independent mechanisms
What are options for PCOS patients who desire pregnancy?
cyst removal to promote healthy ovaries
Ovulation stimulation
SERM
Aromatase inhibition
Gonadotropin
What is the brand/generic of a SERM therapy?
Clomiphene - Clomid
What is the MOA of Clomiphene?
Induces ovulation by interfering with estrogen feedback → increased FSH release
-anti-estrogen effects can thin endometrium
What are 2 clinical pearls for Clomiphene therapy?
Most patients ovulate but 50% conceive
Increased risk of multi-gestational pregnancy bc increased antral follicles w/ PCOS (more resting follicles)
What is the name of the aromatase inhibitor used for PCOS?
Letrozole
What is the MOA of Letrozole?
decreases estrogen synthesis, less negative feedback on pituitary
aromatase inhibitor - (no negative feedback from estrogen → FSH release)
promotes natural ovulation
When are Gonadotropins used to stimulate ovulation in women with PCOS?
When clomiphene or letrozole fail
almost all pts ovulate when using
What gonadotropin is used to promote ovulation?
FSH- follicle stimulating hormone
What are patients with PCOS at a higher risk for?
Infertility
endometrial hyperplasia & cancer
Insulin resistance → metabolic syndromes T2DM
CV disease, anxiety, depression, HTN, HDL
What is acanthosis nigrican?
discolored velvety skin in the folds of skin by the neck, knuckles, or elbow
What is Oligoovulation compared to anovulation?
< 9 periods per year
No periods
What days of a women’s cycle would she take Letrozole to promote ovulation?
cycle days 3-7
What days of a women’s cycle would she take clomiphene to promote ovulation?
cycle days 5-10
What are CI and AE of Letrozole?
CI: pregnancy
AE: hot flashes, night sweats, insomnia, increased likelihood of multiple births (menopause like symptoms)
What are CI and AE of Clomiphene?
AE: hot flashes, breast discomfort, ovarian hyperstimulation syndrome , abdominal distention/ bloating, increased likelihood of multiple births
CI: pregnancy and liver disease
What are some non-pharmacological options for hyperandrogegism or hirsutism?
shaving
waxing
depilatories
laser and electrolysis
What 2 treatments affect all objectives of PCOS?
Metformin & Pioglitazone
(hirsutism & oligomenorrhea & ovulation induction & insulin lowering)
What MOA does Piolglitazone have that positively affects ovulation?
insulin sensitizer → reduction of androgen production → greater likelihood of ovulation
AE: edema & weight gain @ higher doses & not used in pregnancy
Which therapies for insulin resistance can cause weight loss?
GLP-1
SGLT-2
What is the MOA of spironolactone?
decreases adrenal androgen production & blocks receptor
use w/ OC bc risks with pregnancy and break through bleeding - synergistic effect
monitor for hyperkalemia
What is the MOA of Eflornithine (Vaniqa)?
Inhibits ornithine decarboxylase → decreased hair growth
still need other hair removal techniques
What is an important counseling point for Eflornithine?
Do not wash skin for 8 hours after application
applied twice daily - 8 hours apart
What are AE of Eflornithine?
pruritus
burning/tingling skin
dry skin
rash
What kind of OC is preferred for pts with PCOS?
low androgenic progestins w/ combo