Lecture 6 Exam 5 Flashcards
What is PCOS
leading cause of anovulatory infertility
What percebnt of women have PCIS
6-10%
What can be caused by PCOS
miscarriage and endometrial cancer
What are the 3 hallmarks for PCOS
Hyperandrogenism
menstrual disturbances
overweight or obese
What are symptoms of hyperandrogenism
Hirsutism
Acne
Alopecia
Symptoms of menstrual disturbances
Amenorrhea
Oligomenorrhea
Anovulation
What are the 3 proposed mechanisms that are thought to cause PCOS
- Inappropriate gonadotropin secretion
- Insulin resistance with hyperinsulinemia
- Excessive androgen production
Mechanism of inappropriate GnRH secretion in causing PCOS
Increase in GNRH
Causes a surge in LH too soon
No rise in FSH
No dominant follicle
No ovulation
unopposed estrogen
luteal phase never enetered
elevated androgen levels
Compare regular menstrual cycle and PCOS menstrual cycle
Normal- Normal GnRH level
LH and FSH levels spike during cycle
One dominant follicle forms
PCOS cycle
An increase in GNRH causes high LH level
FSH levels stay normal/low
no dominant follicle forms
Why does PCOS cause insulin resistance
PCOS causes body to think that it does not have enough insulin. This causes the body to be in a state of compensatory hyperinsulinemia where it makes more insulin.
Hyperinsulinemia is a major contributor of ________ in PCOS
hyperandrogenism
Where is SHBG produced? What binds to SHBG?
LIver
Testosterone binds to SHBG
What happens to SHBG synthesis in the liver in patients with insulin resistance
In patients with insulin resistance, Liver stops SHBG synthesis, this causes us to have free testosterone in blood stream, increasing free testosterone.
What are the 3 criteria that diagnose PCOS (two have to be met to diagnose PCOS)
hyperandrogenism
PCOS
chronic anovulation
What are some complications that could be caused by PCOS
Infertility
CVS thromboembolism
Type 2 diabetes
HTN
Depression and anxiety
What is a non-pharmacologic and 1st line of treatment for PCOS
exercise and weightloss
leads to improved pregnancy rates, reduced miscarriages, reduced testosterone and hyperinsulinemia
What is the 1st line of pharmacologic treatment for PCOS hyperandrogenism and menstrual irregularity
Combined oral contraceptives
What is the concentration of estrogen that should be given to a PCOS patient
If patient is over 39 yo or obese, give lowest effective dose (20 mcg of EE)
If not then give 30
What kind of progestins do we use for PCOS patients
low androgenic effect progestin
What are some low androgenic effect porgestins that can be used for PCOS patients
Norgestimate (lower VTE risk), norethindrone
What are some progestins to avoid when giving to PCOS patients
Avoid- Desogestrel, Cyproterone, drosperinone
Name two anti-androgen therapies
Spironolactone
5-a-reductase inhibitors
How does spironolactone help as an anti androgen therapy
side effects?
Blocks androgen effect at hair follicle
hyperkalcemia, teratgenic (fetal abnormality)
How does 5-a-reductase help as an antiandrogen therapy?
Most common drug?
Side effects?
Prevents testosterone to DHT conversion
FInasteride
teratogenic
FIrst line of treatment for patients with PCOS and type 2 diabetes after failed lifestyle modifications
Metformin
Can we take metformin if pregnant?
no
Can metformin help with menstrual irregularity and endometrium protection
Metformin can help with menstrual irregularity, but endometrial protection is not established until regular menses and ovulation
What does metformin do in the ovary
reduces insulin rate and androgen production
Dose of metformin?
how long to see results
500 mg—>1000 mg
takes up to 6 months to see results (GI side effects decrease after 2-3 weeks)
Treatment of insulin resistance in PCOS order (1st and 3nd line)
1st- life style modification
2nd- metformin
Treatment of menstrual irregularity 1st line of treatment
COC
treatment of menstrual irregularity 2nd line of treatment
Cyclic progestin (medroxyprogesterone, micronized progeserone)
levonorgestrel IUD
Metformin
What percent of women regain ovulation on metformin
30-40%
What are the treatments of hyperandrogenism in order of preference
1) COC
2) Antiandrogen (spironolactone, finasteride)
3) topical vaniqua (eflorinthine (for facial hair only)))
4) cosmetic procedures
Treatment for PCOS if pregnancy is desired?
Aromatase inhibitors like Letrozole (femara)
name an aromatase inhibitor drug
Femara (letrozole)
Mechanism of femara as an aromatase inhibitor
Non steroidal competitive inhibitor of aromatase enzyme, inhibition stops the conversion of androgen to estrogen)
effect of aromatase inhibitors or estrogen levels
Significant reduction
How do aromatase inhibitors induce ovulation
lower estrogen levels increase LH and FSH secretion, this induces ovulation
side effects of aromatas einhibitors
low estrogen side effects like hot flashes
How do aromatase inhibitors work in relation to BC pills
They work opposite to each other
BC pills trick pituitary gland into thinking that it is giving estrogen and progesterone, so there is no surge in LH
Aromatase inhibitors tell brain there is low estrogen, increasing LH and FSH
Letrozole (femara) dosing
what if ovulation does not occur?
Max number of cycles
2.5-7.5 mg X 5 days
If ovulation does not occur increase by 2.5 mg increments
upto 5 cycles total
Treatment of anovulation in PCOS order of therapy
Letrozole
Low dose gonadotropin or Ovarian drilling
last is invitro fertilization
spironolactone dose
50-100 mg BID
