What is polycystic ovary syndrome (PCOS)?
~ multiple causes, essentially ovulatory dysfunction and hyperandrogenism (male sex hormones) ~ implication on fertility, cycle, risk of metabolic syndrome (increased likelihood of dyslipidemia, DMIII (insulin insensitivity,), CV illnesses and endometrial carcinoma ~ one of the most common endocrine disorders
Diagnostic criteria for PCOS?
think hirsutism, anovulation and polycystic ovaries 2 out of 3 of: * hyperandrogenism - "clinical or biochemical signs of hyperandrogenism"= either confirmed by test or through visual characteristics (excess hair with male distribution pattern = hirsutism, treatment refractory acne, etc) * menstrual irregularity - oligomenorrhea (< 9 periods /year or > 35 day cycle); amenorrhea (no periods for >=3 months) * polycystic ovary on imaging (transvaginal ultrasound or physical) (medium estrogen, low FSH and LH (reminder that low and medium esteren strongcks into pituitary so LFH and LH low, only in high estrogen do they become high) but NOT SPECIFIC TO PCOS!
How do you evaluate for possible PCOS?
History ~ irregular menstruations ~ signs of hyperandrogenism Physical ~ see above Tests ~ total testosterone, can measure DHEA-S if want to r/o androgen-secreting tumour ~ ALWAYS hCG - r/o pregnancy ~ prolactin (r/o prolactinemia, prolactin down regulates FSH/LH), TSH (r/o thyroid disease, down regulates FSH/LH), FSH (ovarian insufficiency - b/c reacts to FSH first in follicular phase, and LH in luteal phase and just pre-ovulation) ~ transvaginal ultrasound also, patients with PCOS at risk of various metabolic things, so measure: ~ blood pressure ~ glucose = OGTT ideal, fasting can do too ~ lipid profile
Tx for PCOS if pregnancy desired?
depends if pregnancy desired or not: #1 if pregnancy desired: clomiphene (claw + me + fan) citrate - estrogen receptor blocker at the level of hypothalamus and pituitary - even though medium levels of estrogen in PCOS (because each follicle produces some and multiple follicles present), LH and FSH not released for follicles to mature, so clomiphene citrate encourages brain to release FSH/LH to aid in ovulation idea: estrogen downregulates LH/FSH at pituitary (unless levels really high), block estrogen receptors -> LH and FSH released -> follicular cycle starts (LH already high, but byproduct here, need FSH at all cost) #2 letrozole "let-Roz(y)- O(vu)l(at)e" - off label, aromatase inhibitor, blocks conversion of testosterone into estrogen -> low estrogen -> FSH/LH release as above #3 FSH shots/IVF - expensive #4 ovarian drilling - essentially burning holes in ovaries if clomiphene fails and no money for IVF - shocks ovaries into decreased androgen production and gives about 6 months of ovulation, but risk of scarring ALSO: ~ weight loss really helps if overweight ~ metformin (due to insulin insensitivity frequent in PCOS) - not shown to be effective
Tx for PCOS if pregnancy not desired?
#1. exercise and weight loss if appropriate #2. oral birth control - especially important because unopposed estrogen (estrogen, but no ovulation, so no progesterone -> endometrium growing too much -> hyperplasia -> risk of CA -> need progesterone to shed uterine lining) also helps with acne and regulates periods do combined OC for that reason, if not wanting, do at least progesterone every few months to get menses to shed lining - progestin in divided doses alone will not reduce acne/or do contraception, unless taking continuous progesterone OC - "mini-pill" = MICROnor, IM Depo-Provera or Mirena IUD. also good for breastfeeding don't forget to treat insulin resistance, dyslipidemia (statins), high bp and other conditions (usually metabolic) often present with PCOS
Pathogenesis of PCOS?
Not known, but what we do know: EXCESS LH EXCESS ANDROGENS EXCESS INSULIN PREFERENTIAL RELEASE OF LH over FSH theca cells contain LH receptors -> LH -> androgen production (like testosterone) -> blood -> acne/hirsutism etc controlled by pulsatile GnRH release in the hypothalamus - this pattern seems to change in PCOS patients -> encourages preferential release of LH over FSH -> lack of ovulation (need FSH to stimulate follicular maturation) insulin -> somehow helps theca to increase androgen production insulin -> decreases sex hormone binding globulins (transport proteins for sex hormones in the blood, when attached to hormones, not bioavailable) -> increase free testosterone -> bioavailable
MOA of clomiphene citrate?
clomiphene citrate = "Clomide" estrogen receptor blocker at the level of the brain (hypothalamus/pituitary) = FSH increased b/c negative relationship = GOOD unfortunately also blocks estrogen at uterine lining (not helpful b/c need healthy lining, not thin) = BAD cervix: makes cervical mucous thicker = BAD do you need more LH? nope, got tons, but do want FSH to kick start ovulation
What is definition of menopause?
lack of menses for 1 yr - impossible to predict onset, diagnosis only post
Types of menopause (physiological vs premature ovarian failure)?
physiological: average age 51 yrs in Canada (follicular atresia) premature ovarian failure: before age 40 (autoimnune, Turners, iatrogenic (surgical, radiation, chemo)
Clinical features of menopause?
DUE to ESTROGEN DEFICIENCY: vasomotor instability: hot flushes, night sweats, sleep disturbances, nausea, palpitations (estrogen thought to influence heat sensors in hypothalamus and narrow range of temperature variations to which body doesn't react) urogenital atrophy: vagina (prolapse), urethra, bladder dyspareunia (painful sex, often due to lubrication problems), pruritus, vaginal dryness, bleeding, urinary frequency, urgency, incontinence skeletal: osteoporosis, joint and muscle pain skin and soft tissue: thinning of skin and loss of elasticity, decreased breast size psych: mood disturbances, irritability, fatigue, decreased libido, cognitive (memory loss, etc) - treat with SSRI b/c estrogen decreases serotonin
Investigations in menopause?
serum FSH/LH (how hard does brain have to work to produce follicles) = do day 3 if still cycling, FSH> LH, but may not be predictive b/c FSH variates a lot during the month, and esp. during menopause decreased levels of estradiol (later) diagnose by lack of periods for 1 year
Treatment of menopause?
#1 hormone therapy is first line, especially for estrogen withdrawal, like vasomotor instability can give SSRI for psychological symptoms vaginal atrophy: local estrogen cream, like Premarin, vaginal suppository (VagiFem), lubricants urogenital: lifestyle changes (bladder training, weight loss, surgery, estrogen) osteoporosis: 1000-1500 mg Ca, 1000 IU D, weight bearing exercise, no smoking, can give bisphosphonates like alendronate (Bone undergoes constant turnover and is kept in balance (homeostasis) by osteoblasts creating bone and osteoclasts destroying bone. Bisphosphonates inhibit the digestion of bone by encouraging osteoclasts to undergo apoptosis, or cell death, thereby slowing bone loss.) mood/memory: antidepressants CV: manage symptoms
degenerating granulosa and theca fail to react to FSH/LH from ant. pituitary -> less estrogen produced -> decreased negative feedback on hypothalamic-pituitary-adrenal axis (low estrogen -> increased FSH/LH ) -> increased FSH/LH but nothing to ovulate
difference between perimenopausal, menopausal, premenopausal, postmenopausal
menopausal: permanent loss of ovarian follicular activity, 12 consecutive months of amenorrhea, avg. age 51 perimenopause: period of time prior to menopause, menopause and first year after menopause premenopause: the whole reproductive period prior to menopause postmenopause: from final menstrual period onward
outline hormonal changes in menopause?
increased FSH and LH decreased estrogen decreased progesterone slightly decreased androgens (least affected since ovary does not produce a lot)
what are menstrual changes during menopause?
cycles first get shorter than longer abnormal uterine bleeding depletion of primordial follicles amenorrhea eventually
what is a LOOP cycle and a Lag cycle?
Loop cycle: Luteal Out Of Phase follicular event = premature formation of a follicle due to a major surge in FSH during the luteal phase lag cycle - long follicular phase with aberrant folliculogenesis (high E low P) cycle changes very typical in menopause
Outline classification of abnormal uterine bleeding: PALM COEIN
STRUCTURAL CAUSES (PALM) ~ Polyps (endometrial or cervical) ~ Adenomyosis (endometrial tissue grows into muscular layer of the uterus) ~ Leiomyoma = fibroids (submucosal worst) ~ Malignancy/ hyperplasia NON-STRUCTURAL COEIN ~ coagulopathy ~ ovulatory dysfunction ~ endometrial (disorders of endometrium) ~ iatrogenic ~ not yet classified >=1 may be present, so if polyps and von Willebrand P1A0L0M0-C1O0I0E0I0N0
Approach to ovarian failure (general + tests)?
history physical investigations HCG, PRL, TSH endometrial biopsy (if at high risk of endo hyperplasia or malignancy) imaging: US or SIS: saline infusion sonography (ink injection into uterus) or hysteroscopy
Explain urogenital concerns in menopause?
~ vaginal atrophy ~ UTIs ~ incontinence ~ pelvic prolapse estrogen receptors in vagina, bladder, urethra, pelvic floor muscles -> lack of estrogen -> atrophy of urogenital epithelium and sub epithelial tissues -> degeneration of collagen/elastin/smooth muscle + decreased blood flow to tissues -> atrophy ex. vaginal atrophy: dyspareunia, vaginal dryness, itching and irritation b/c thinning of the epithelium, less blood flow, vaginal length and diameter shrinks, nerve endings exposed, increased trauma (rugae disappears, moisture gone - thin pale dry surface) ex. more UTIs b/c mucosa thinner, decreasing levels of lactobacilli, reduced lactic acid production (ph up) ex. urinary incontinence - b/c thinning of bladder mucosa, increased irritation - > stress urinary incontinence (cough, sneeze - let go) vs urge incontinence (cannot hold), also angle of urethra and vagina changes ex. pelvic prolapse - uterus can literally prolapse (drop), sometimes out of urogenital triangle and outside
hormone therapy for primary prevention of heart disease?
not recommended, b/c increased risk of breast cancer, coronary heart disease, stroke; but less hip fractures
how does one monitor and treat bone disease in menopause (T-scores)
Bone mineral density scan if T score (deviation) > -1 = normal -1 to -2.5 = low bone mass (osteopenia) < -2.5 osteoporosis use FRAX tool to assess fracture probability, if high, treat, if intermediate, assess more and then decide can treat with bisphosphonates (encourage apoptosis of osteoclasts which resorb bone), raloxifine( selective estrogen receptor modulator (SERM) that has estrogenic actions on bone and anti-estrogenic actions on the uterus and breast. It is used in the prevention of osteoporosis), PTH (parathyroid hormone = tripartite injection - activates osteoblasts, which builds bone), calcitonin
Sx of hypothyroidism?
cold intolerance fatigue sleepiness constipation weight gain irregular + heavy cycles
What is Sheehan's syndrome?
postpartum pituitary necrosis due to severe post partum hemorrhage
Sx of Turner's syndrome?
primary amenorrhea short stature other congenital abnormalities
Why worry about uncontrolled diabetes in pregnancy? Tx for diabetes in pregnancy?
uncontrolled diabetes is teratogenic - fetal anomalies, stillbirths, macrosomia, neonatal hypoglycemia. during pregnancy -> diet and exercise, insulin if levels still high. glyburide or metformin controversial.
Tx for abnormal bleeding (ex. 3 weeks) after medroxyprogesterone?
1. r/o pregnancy - #1 cause of AUB 2. oppose progesterone with estrogen.
Parvovirus B19 poses what risks to newborn?
readily crosses placenta: high rate of spontaneous abortion if early in pregnancy, later in pregnancy destroys immature RBCs, causing anemia and lead to hydrops. unpredictable - most women with prenatal infection deliver healthy infants.
acute pyelonephritis vs cystitis in pregnant women?
acute pyelonephritis: fever, nausea, vomiting, chills. flank pain on exam. labs: urinalysis and urine culture. results: pyuria, + leukocyte esterase, microscopic hematuria. if WBCs present in urine - > renal pyuria -> pyelonephritis. uncomplicated cystitis: gross hematuria. shoot preggos with IV antibiotics
Sx of mastitis?
localized inflammation breast pain localized erythema fever, myalgias most common during first 6 weeks postpartum. culture breast milk if possible for right antibiotic cocktail. Staph aureus, especially MRSA is the most common organism for mastitis, or mastitis + abscess. blood cultures useless unless septic.