PCOS

Both lecs

What are the three diagnostic criteria that diagnose PCOS?

1. hyperandrogegism
2. ovulatory dysfunction
3. polycystic ovaries

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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

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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?

1. Most patients ovulate but 50% conceive
2. 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

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(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