Polycystic Overy Syndrome (PCOS) & Endometriosis

What is the most common cause of anovulatory infertility?

PCOS

How many people PCOS affect?

~6-8% of women of reproductive age

When is the typical onset of PCOS?

adolescence

How do you diagnose PCOS?

Rotterdam Criteria

• at least 2 of the following

  • chronic anovulation

  • clinical or biochemical signs of androgen excess

  • polycystic ovaries in the absence of other metabolic disturbances

What is the pathophysiology of PCOS?

• inappropriate GnRH stimulation

• metabolic dysfunction

• decreased sex hormone binding globulin

• increased androgen production

How does PCOS cause inappropriate GnRH stimulation?

• excessive LH and normal FSH secretion

• follicles do not mature and ovulation does not occur

• excessive androgen production

What is the risk of inappropriate GnRH stimulation in PCOS?

endometrial hyperplasia and cancer

What does metabolic dysfunction look like in PCOS?

insulin resistance and hyperinsulinemia

What does decreased sex hormone binding globulin cause in PCOS?

increase in free testosterone

What are the risk factors for PCOS?

family history of PCOS, DM, insulin resistance, irregular menses or anovulation, or CV disease

What are the signs/symptoms of androgen excess in PCOS?

• irregular menses, amenorrhea, or oligomenorrhea

• hirsutism

• acne

• alopecia

What are the signs/symptoms of the metabolic effects of PCOS?

obesity, insulin resistance, dyslipidemia, metabolic syndrome

What are the signs/symptoms of polycystic ovaries?

12 or more follicles measuring 2-9 cm in diameter or increased ovarian volume (>10mL) during ovarian phase

What are the increased risks caused by PCOS?

risk of CV disease, type II DM, dyslipidemia, HTN, and endometrial, breast, and ovarian cancers

What are the non-pharmacologic treatment options for PCOS?

exercise, diet, hirsutism: bleaching, plucking, shaving, Vaniqua cream; acne: topical agents

What is the indication for CHC in PCOS?

menstrual cycle irregularity, hirsutism, acne

What is the MOA of CHCs?

estrogenic component suppresses pituitary LH secretion, suppresses ovarian androgen secretion and increases circulating sex hormone binding globulin

What are the clinical pearls of CHCs in PCOS?

first line, if does not desire fertility; nonandrogenic progestin is preferred

What are examples of nonandrogenic progestins?

norgestimate, desogestrel, drospirenone

What is the indication for antiandrogens in PCOS?

hirsutism, acne

What is the MOA of antiandrogens?

inhibits ovarian and adrenal steroidogenesis and competes for androgen receptors in hair follicles

What are the clinical pearls of antiandrogens?

in patients not desiring fertility; combine with CHC for synergistic effect

What is the most widely used antiandrogen?

spironolactone

What is the indication for insulin sensitizers in PCOS?

hirsutism, acne, menstrual irregularity, anovulation, insulin resistance, infertility

What is the MOA of insulin sensitizers?

increases insulin sensitivity reducing androgen synthesis

What is the most widely used insulin sensitizer for PCOS?

metformin

What are the clinical pearls of insulin sensitizers in PCOS?

recommended as an addition to clomiphene to regulate menstrual cycles and ovulation to improve fertility, particularly in patients who are obese

What is the indication for oral ovulation induction agents in PCOS?

infertility

What is the MOA of oral ovulation induction agents?

stimulates the release of LH and FSH through different mechanisms

What are the clinical pearls of oral ovulation induction agents for PCOS?

letrozole is first line in patients desiring improvements in fertility

What are examples of oral ovulation induction agents used in PCOS?

clomiphene, letrozole

What is the indication for injectable ovulation induction agents in PCOS?

infertility

What is the MOA of injectable ovulation induction agents?

ovulation induction

What are the clinical pearls of oral ovulation induction agents in PCOS?

used in patients who have failed oral therapies for infertility

What is the treatment pathway for PCOS related infertility if the patient is obese?

lifestyle modification x 3-6 months → ovulation induction → add metformin (6 months of trying) → refer to specialist for injectable gonadotropins

What is the treatment pathway for PCOS related infertility if the patient is not obese?

ovulation induction → add metformin (6 months of trying) → refer to specialist for injectable gonadotropins

What is endometriosis?

endometrial tissue outside of the uterus

How many women of reproductive age are affected by endometriosis?

10%

How is endometriosis diagnosed?

based on history and pelvic exam findings but laparoscopy to identify is the gold standard

What is the pathophysiology of endometriosis?

peritoneal disease which is dependent on estrogen for growth, results from retrograde menstruation or lymphatic spread of steroid hormone-sensitive endometrial cells and tissues

• tissues implant on peritoneal surfaces and elicit an inflammatory response

• response is accompanied by angiogenesis, adhesions

What are the risk factors for developing endometriosis?

• obstruction of menstrual outflow (Mullerian anomalies)

• exposure to diethylstilbestrol in utero

• prolonged exposure to endogenous estrogen due to early menarche, late menopause, or obesity

• short menstrual cycles

• low birth weight

• exposure to endocrine-disrupting chemicals

What are the signs/symptoms associated with endometriosis?

• pelvic pain is common

• dysmenorrhea

• dyspareunia

• infertility

• GI symptoms if endometriotic lesion is located in the GI tract

• urinary symptoms if endometriotic lesion is located in the urinary tract

What is the indication of CHCs in endometriosis?

dysmenorrhea (pain)

What is the indication of progestin based contraceptives in endometriosis?

dysmenorrhea (pain)

What is the indication for injectable GnRH agonists in endometriosis?

dysmenorrhea (pain)

What medications are examples of injectable GnRH agonists?

leuprolide, goserelin, nafarelin, buserelin, triptoreline

What are the clinical pearls of injectable GnRH agonists for endometriosis?

add back therapy to mitigate hypoestrogenic effects (e.g., hot flashes, BMD loss). estrogen doses must stay low (<50 pg/mL) to avoid stimulating endometriotic tissue; typical CHCs are not suitable for add-back due to higher estrogen levels; add non-hormonal contraception

• Medication and dosing for add-back therapy

  • oral MPA 20–100 mg daily

  • oral norethindrone acetate 1–5 mg daily

  • oral conjugated equine estrogens 0.625 mg daily plus oral norethindrone acetate 5 mg daily

  • transdermal estradiol 25 μg twice weekly plus oral MPA 5 mg daily

  • oral estradiol 2 mg daily plus oral norethindrone acetate 1 mg daily

What is the indication for oral GnRH antagonists in endometriosis?

dysmenorrhea (pain)

What are examples of oral GnRH antagonsits?

elagolix or relugolix/estradiol/norethindrone + add on non-hormonal contraception

What are examples of last line medications for endometriosis associated pain?

aromatase inhibitors, danazol

What can be add on treatment for endometriosis symptom pain?

NSAIDs

What should be done for infertility caused by endometriosis?

referral to infertility specialist for MAR (IVF, IUI, etc.)