PCOS

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What are the three diagnostic criteria that diagnose PCOS?

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What are the three diagnostic criteria that diagnose PCOS?

  1. hyperandrogegism

  2. ovulatory dysfunction

  3. polycystic ovaries

A disease that is only done when when other conditions are ruled out

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What are characteristics of hyper-androgenism?

  • hirsutism or alopecia (too much or loss of hair)

  • acne

  • adipose deposition

  • metabolic dysfunction

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What are characteristics of ovarian dysfunction?

  • oligo-or amenorrhea

  • follicular cyst development

  • impaired ovulation

  • Infertility

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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

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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

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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)

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what OCs have the highest androgenic (progestin) activity?

  • norgestrel

  • levonorgestrel

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What OCs have moderate androgenic activity?

  • norethindrone

  • norethindrone acetate

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What OCs have the least androgenic activity?

  • ethynodiol

  • norgestimate

  • gestodene

  • desogestrel

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How can you induce a period? and why would you do it?

induce a LH surge

  • reduces risk of endometrial cancer

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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

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What medication is used to treat hirsutism and acne with PCOS?

Spironolactone

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What is the MOA of Spironolactone?

Aldosterone receptor antagonist (K sparing effect)

  • decreases androgen effects on skin, hair growth (acne/ excessive hair growth)

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What is an important clinical pearl for patients taking spironolactone?

  • may cause birth defects

  • avoid pregnancy or patients planning to be pregnant

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What are some topical medications for management of hirsutism ?

  • Eflornithine (Vaniqa)

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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

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What medication is used to treat hyperandrogenic alopecia and its MOA?

Finasteride - Propecia

MOA: 5-alpha-reductase inhibitor

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What is the 1st line intervention for overweight or obese women with PCOS?

  • Metformin - Biguanide

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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

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What are options for PCOS patients who desire pregnancy?

cyst removal to promote healthy ovaries

Ovulation stimulation

  • SERM

  • Aromatase inhibition

  • Gonadotropin

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What is the brand/generic of a SERM therapy?

Clomiphene - Clomid

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What is the MOA of Clomiphene?

Induces ovulation by interfering with estrogen feedback → increased FSH release

-anti-estrogen effects can thin endometrium

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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)

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What is the name of the aromatase inhibitor used for PCOS?

Letrozole

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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

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When are Gonadotropins used to stimulate ovulation in women with PCOS?

When clomiphene or letrozole fail

  • almost all pts ovulate when using

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What gonadotropin is used to promote ovulation?

FSH- follicle stimulating hormone

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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

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What is acanthosis nigrican?

discolored velvety skin in the folds of skin by the neck, knuckles, or elbow

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What is Oligoovulation compared to anovulation?

  • < 9 periods per year

  • No periods

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What days of a women’s cycle would she take Letrozole to promote ovulation?

cycle days 3-7

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What days of a women’s cycle would she take clomiphene to promote ovulation?

cycle days 5-10

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What are CI and AE of Letrozole?

CI: pregnancy

AE: hot flashes, night sweats, insomnia, increased likelihood of multiple births (menopause like symptoms)

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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

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What are some non-pharmacological options for hyperandrogegism or hirsutism?

  • shaving

  • waxing

  • depilatories

  • laser and electrolysis

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What 2 treatments affect all objectives of PCOS?

Metformin & Pioglitazone

(hirsutism & oligomenorrhea & ovulation induction & insulin lowering)

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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

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Which therapies for insulin resistance can cause weight loss?

GLP-1

SGLT-2

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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

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What is the MOA of Eflornithine (Vaniqa)?

Inhibits ornithine decarboxylase → decreased hair growth

still need other hair removal techniques

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What is an important counseling point for Eflornithine?

Do not wash skin for 8 hours after application

applied twice daily - 8 hours apart

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What are AE of Eflornithine?

pruritus

burning/tingling skin

dry skin

rash

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What kind of OC is preferred for pts with PCOS?

low androgenic progestins w/ combo

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