PCOS Flashcards
Clinical presentation
Hyperandrogenism: Hirsutism, Acne, Alopecia
Menstrual disturbances: amenorrhea, oligomenorrhea, anovulation
Overweight or obese
Pathophysiology
Primary defect is unknown
- inappropriate gonadotropin secretion
- insulin resistance with hyperinsulinemia
- Excessive androgen production
Inappropriate gonadotropin secretion
- increase in GnRH
- Cause increase in LH surge too soon
- No rise in FSH
- No dominant follicle
- No ovulation
- Unopposed estrogen
- Luteal phase never happens
- Elevated levels of androgen
Regular Menstrual cycle vs. PCOS Cycle
Normal: normal GnRH level
LH and FSH levels spike during the cycle
One dominant follicle form
PCOS: Increase in GnRH
High LH level in baseline
FSH levels stay normal
No dominant follicle form
Insulin resistance
occurs in obese and non-obese women
potential defects in insulin receptor
In ovary: Insulin +/- LH increase androgens
Excess Androgen production
normally produced in ovary to facilitate follicular growth
Hypersecretion of LH and insulin leads to increase androgen production
-abnormal sex steroid synthesis
-hyperandrogenism
-hyperandrogenemia
increase in free testosterone concentrations
PCOS Diagnosis criteria
- Hyperandrogenism
- Chronic anovulation
- Polycystic ovaries
2 of the 3 must be present
Complications from PCOS
Infertility
CV
VTE
Type 2 diabetes
Dyslipidemia
Hypertension
Non-alcoholic fatty liver disease
Endometrial hyperplasia and cancer
Depression and anxiety
Obstructive sleep apnea
Pregnancy complications
Treatment decision considerations
- patient priorities
- efficacy vs. risks of treatment
- desire to become pregnant
NON PHARM TREATMENT
WEIGHT LOSS–> 5-15% (or more)
-improved pregnancy rates/reduce miscarriages
-improve ovarian function
-reduce free testosterone
-reduce hyperinsulinemia
EXERCISE
-30 minutes of moderate-vigorous physical activity daily
-reduce blood pressure and insulin levels
PHARMACOLOGIC TREATMENT
1ST LINE: COC
Estrogen component: lowest effective dose (20 mcg-30 mcg EE)
20 mcg EE for high risk VTE (obese or >39
< 35 mcg EE
LH suppression decrease androgen production
Progestin component: prefer low androgenic effects: norgestimate, norethindrone LOWER VTE RISK
NO COC HAS PROVEN SUPERIORITY FOR CLINICAL HYPERANDROGENISM
MONOPHASIC COC COMMON
Pharmacologic Treatment anti-androgen therapy
Spironolactone
50-100 mg BID
Blocks androgenic effects at follicle
Adverse effects: vaginal bleeding, beast tenderness, headache, dizziness
Takes 6-9 months to work
Used as an add on therapy
5 alpha reductase inhibitor
prevent conversion of testosterone to DHT
when COC and spironolactone are relatively ineffective for severe hirsutism
Finasteride 2.5-5 mg daily
headache, orthostasis
MUST use reliable forms of contraception
Insulin sensitizer
Metformin is 1st line of treatment in PCOS with type 2 diabetes and failed lifestyle modifications
2nd line: reduces insulin concentration and androgen production in ovary
500 mg PO DAILY or 100 mg BID
Up to 6 months to see results
GI side effects decrease after 2-3 weeks, taken with meal
Consider d/c if pregnant
No endometrial protection until regular menses and ovulation is reached
Treatment: insulin resistance
- Lifestyle modifications
- Metformin
Treatment: menstrual irregularity
- COC
- Cyclic progestin therapy
- DEPOT SHOT
- Micronized progestin
- POP
- Levonorgestrel IUD
-Metformin
Treatment: hyperandrogenism
- COC
- Spironolactone, Finasteride
- Topical Vaniqa
- Cosmetic procedures
Pharmacologic treatment if pregnancy is desired
Aromatase inhibitors
Letrozole
MOA: Nonsteroidal competitive inhibitor of the aromatase enzyme
Inhibition stops conversion of androgens to estrogen
Aromatase inhibitors
highly selective, reversible, highly potent
Inhibit aromatase activity
Induce ovulation by trigger hypothalamus to increase LH and FSH
Side effects: hot flashes, edema, dizziness, headache
Letrozole
2.5-7.5 mg po for 5 days, starting day 3 of menses
Treatment: anovulation
- Letrozole
- Low dose gonadotropin therapy, drilling
- IVF
