PCOS -- Dr. Taylor

What are some risk factors for developing PCOS?

-Genetics

-Obesity

-Sedentary lifestyle

-Intrauterine androgen exposure (possibly?)

What are common comorbidities associated with PCOS?

-T2DM

-Dyslipidemia

-Heart disease

What are the 2 main upstream pathophysiological mechanisms in PCOS?

Increased GnRH pulsatile release and insulin resistance

What does increased GnRH pulsatile release lead to?

Increased LH:FSH ratio

What does an increased LH:FSH ratio cause?

Increased LH stimulation of theca cells, leading to androgen excess

How does insulin resistance contribute to PCOS?

It causes hyperinsulinemia, which increases androgenic enzyme activity and decreases SHBG (sex hormone binding globulin), leading to androgen excess.

What skin finding is associated with insulin resistance in PCOS?

Acanthosis nigricans

What are the clinical manifestations of androgen excess in PCOS?

Hirsutism, ance, alopecia, and comorbid depression

What effect does androgen excess have on follicle development?

Arrest in antral follicle development.

The ovarian follicles stop growing once they reach the antral stage instead of progressing further toward maturity and ovulation.

What ultrasound finding is typical of PCOS?

Polycystic ovaries with a "string of pearls" appearance

What reproductive issues results from arrested follicle development in PCOS?

Anovulation

What happens when there is no corpus luteum due to anovulation?

Decreased progesterone release

What hormonal imbalance results from decreased progesterone release?

Unopposed increased estrogen

What are risks of unopposed estrogen in PCOS?

endometrial hyperplasia and increased risk of endometrial cancer

What menstrual irregularities are common in PCOS?

Anovulatory bleeding, breakthrough bleeding, and irregular cycles

How does PCOS contribute to subfertility?

Impaired oocyte development, increased miscarriage rates, and various obstetrical complications.

What are the reproductive, cutaneous, and metabolic clinical manifestations of PCOS?

Reproductive:

Cutaneous:

Metabolic:

-Reproductive: Irregular menses, infertility

-Cutaneous: Hirsutism, acne, androgenic alopecia

-Metabolic: Type 2 diabetes, metabolic syndrome, hyperlipidemia, obstructive sleep apnea

How is PCOS diagnosed?

At least 2 of the following 3:

-Clinical signs of hyperandrogenism (hirsutism) and/or hyperandrogenemia (elevated testosterone)

-Oligo-ovulation (infrequent/irregular ovulation): less than 9 menses/year

-Polycystic ovaries (by US)

*other known disorders must be excluded i.e hyperprolactinemia, thyroid abnormalities

What are some complications of PCOS?

-Reduced fertility, complications in pregnancy

-Endometrial hyperplasia/cancer

-T2DM, obesity, HTN, dyslipidemia, MASLD, OSA

-Depression, anxiety

Goals of treatment for PCOS:

•Maintain normal endometrium

•Block androgen activity

•Reduce insulin resistance/improve sensitivity

•Reduce weight

•Improve fertility

What does "MY PCOS" stand for in the management of PCOS?

M - metabolic

Metabolic disease management

Lifestyle changes (5-10% weight loss)

Metformin, TZDs, GLP1ra

Y - cYcle control

Hormonal contraception (combined or progestin-only)

P - psychosocial

Mental health management

Medications, CBT

C - cosmetic

Anti-androgens

Spironolactone, finasteride

Vaniqua® cream

Nonpharm (bleaching, waxing)

O - ovulation/fertility

Clomiphene

Metformin

Letrozole

S - sleep apnea

Screening for OSA

CPAP

What is the first-line pharmacologic treatment for metabolic disease in PCOS?

Metformin, promotes insulin sensitivity

What other medications can be used for the management of PCOS metabolic management?

•TZD

•GLP1ra --contraindicated in pregnancy; can use until there is a balance and then take away when actively trying.

What is the first-line treatment for cycle control in PCOS?

Hormonal contraceptives

What medications are used in PCOS to treat cosmetic symptoms like hirsutism and acne?

•Anti-androgens: Spironolactone & Finasteride (cannot be used in pregnancy; if a woman is taking, must be on an OC)

What is What is Vaniqa®, how does it work, and how is it used in PCOS?

•Eflornithine HCl cream

•Inhibits hair growth

•Apply to face twice daily

What is first line for ovulation induction in POS?

Clomiphene

What class is clomiphene and how does it work?

•Selective estrogen receptor modulator (SERM)

•MOA: Binds to estrogen receptors in hypothalamus, inhibits negative feedback loop, LH and FSH increased --> ovulation induction

*in the speaker notes for this slide: With estrogen receptors blocked, the hypothalamus increases the release of GnRH. This, in turn, stimulates the pituitary gland to produce and release more follicle-stimulating hormone (FSH) and luteinizing hormone (LH).*

What are some ADRs of clomiphene?

Hot flashes, breast tenderness, N/V

What is an alternative to clomiphene that can be given to patients for ovulation induction?

Letrozole -- an aromatase inhibitor

How does letrozole induce ovulation?

•Aromatase inhibitors block conversion of testosterone to estrogen

•Low estrogen levels cause the hypothalamic-pituitary axis to release gonadotropin-releasing hormone (GnRH), which stimulates follicle-stimulating hormone (FSH) production.

•Rising FSH stimulate folliculogenesis and improve follicle maturation

PCOS follow-up and monitoring:

•Symptoms: hirsutism, acne, alopecia, weight changes, infertility, mood changes

•Menstrual cycle: cycle regularity, duration, frequency, and presence of ovulation.

•Vitals: blood pressure, heart rate, weight, BMI, waist circumference.

•Labs: Fasting glucose or HbA1c, lipid panel, liver function tests (if on meds), and androgens (testosterone, DHEAS).