Week 63 1.1- Amenorrhea
What is Rotterdam criteria for PCOS?
2 out of the 3: - androgen excess (biochemical or clinical) - ovulatory dysfunction - polycystic ovaries (>12 antral follicles in 1 ovary)
What is turner syndrome?
- 45XO (or mosaic) - clinical signs: short stature, webbed neck, low set ears/hairline, wide spaced nipples/shield chest, short 4th metacarpal, wide carrying angle, absent sexual development - 15% begin puberty, 5% menstruate
What is androgen synthesis disorder?
- 5alpha reductase deficiency - autosome recessive - have internal male structures, external female - virilize at puberty!
What are possible CNS etiologies for hypogonadotropic hypogonadism?
- adenoma, prolactinoma, craniopharyngioma, other CNS lesions - Sheehan's syndrome - Kallman's syndrome - idopathic hypogonadotropic hypogonadism - FSH B mutation
What is Sheehan's syndrome?
- aka postpartum pituitary gland necrosis - hypopituitarism caused by ischemic necrosis due to postpartum hemorrhage and hypovolemic shock
What are non-CNS causes of hypogonadotropic hypogonadism?
- anorexia, strenuous exercise - stress - primary hypothyroidism - hyperprolactinemia - physiological delay
What investigations should be ordered in the investigation of primary amenorrhea?
- bHCG! (rule out pregnancy) - FSH, LH, E2 (estradiol) - PRL, TSH - consider progesterone challenge test - consider androgens if symptoms- tesosterone, androstenodione, DHEAS, 17 OH progesterone - pelvic U/S - consider karyopte - consider head MRI
What is the treatment for AIS?
- complete: gonadectomy at puberty - incomplete: may be virilized, gonadectomy at dx
What outflow tract abnormalities can cause eugonadotropic eugonadism?
- congenital: imperforate hymen, vaginal septum, cervical agenesis, mullerian agenesis- MRKH, labial fusion - acquired: asherman's (adhesions)
What is mullerian agenesis (MRKH)?
- defect in anti-mullerian hormone (AMH) gene causes failure of mullerian ducts to devleop - have normal breasts, pubic hair and ovaries - NO uterus, cervix, or upper vagina - 10-40% have renal abnormality, 10-15% skeletal abnormality - treatment: psych support, fertility support, sexual activity (dilators or surgical neovagina)
What is an approach to investigating for amenorrhea?
- determine estrogen status - check PRL + TSH, imaging as indicated evaluate outflow tract
What are the causes of eugonadotropic eugonadism?
- endocrine: PCOS, hyperPRL - structural: reproductive tract (imperforate hymen)
What is the progesterone challenge test?
- give medroxyprogesterone or micronized progesterone for 5-10 days - positive response = if bleeding occurs or not (usually 2-7 days after progestin is finished) - tests whether the uterus has been exposed to estrogen - is also preventative for uterine cancer
Based on Gonadotropic Classification of Amenorrhea, what are the 3 etiologies for amenorrhea?
- hypergonadotropic hypogonadism - hypogonadotropic hypogonadism - eugonadotropic eugonadism (e.g. PCOS)
What are the most common etiologies of primary amenorrhea?
- hypergonadotropic: 43% - 26% abN karyotyope (not ovaries), 17% N karyotope (abnormal ovaries) - hypogonadotropic: 31% - eugonadotropic: 26%
What special tests may be done to investigate hypogonadotropic hypogonadism (low FSH)
- hypogonadotropic = often CNS problem: structural or endocrinologic - so can do MRI head - if concerned, esp. if abnormal PRL level
What are the different organs that can cause amenorrhea?
- hypothalamus - pituitary gland - thyroid gland - adrenal glands - ovaries - uterus - cervix - vagina - hymen
What is the treatment of eugonadotropic eugonadism?
- hypothyroidism: synthroid - hyperPRL: correct underlying cause, bromocriptine, cabergoline - PCOS: healthy weight, treat symptoms, regular progestin withdrawal to prevent endometrial hyperplasia - if want to get pregnant, induce ovulation w clomiphene citrate, metformin, laparoscopic ovarian drilling, gondatotropins
What is the treatment for hypogonadotropic hypogonadism?
- if anorexia or strenuous exercise: weight at which pt had last regular menstrual cycle is the weight they need to get back to - reduce stress - if want to get pregnant, induce ovulation w gonadotropins
What are fragile X (FMR1) premutations?
- increased CGG repeats in FMR1 gene - is most common inherited cause of mental retardation + autism - clinical picture: fam hx of autism, mental retardation, developmental delay, POI - 14% in familial POI, 1-7% in sporadic
What is Kallman's syndrome?
- isolated GnRH deficiency caused by disrupted GnRH neuron migration - anosmia, +/- midline facial defects
What special tests can be done for workup of primary ovarian insufficiency (POI)
- karyotype - autoimmune work up (thyroid, pancreas, adrenals, ovaries)
In hypergonadotropic hypogonadism (high FSH), what additional test can be done to further investigate the etiology?
- karyotype! determines ovaries vs. not ovaries
What is primary ovarian insufficiency (aka premature ovarian failure)
- loss of ovarian function before age of 40 - normal or abnormal karyotype (AIS)
Mullerian Development
- mullerian structures = uterus, cervix and vagina - forms from urogenital sinus and paramesonephric ducts, uterine tubes - have 2 uterine tubes - initially have '2 uteruses' - can cause septation issues in uterus or vagina - hymen is NOT part of this development
What is the definition of primary amenorrhea?
- no menses by 14 yrs AND absence of secondary sex characteristics OR - no menses by 16 yrs WITH presence of secondary sex characteristics
What should be on the ROS for amenorrhea?
- outlet: cyclic abdominal pain, unsuccessful tampon/sexual intercourse - uterus/Cx: pregnancy, STI, previous D&C - ovary: moliminal, menopausal, androgen, mass - pituitary: thyroid, PRL, adrenal - hypothalamus: chronic illness, previous radiation, trauma, diet, exercise, stress, eating disorders - mass symptoms: headache, vision changes - Kallman's syndrome: anosmia
How can estrogen status be determined?
- physical exam (estrogen = light pink vagina, some discharge. no estrogen = bright red, friable) - serum estradiol - progesterone challenge - U/S- endometrial thickness (EMT), size/"activities" of ovaries + uterus, other imaging as needed
What special tests can be performed for workup of euogonadtropic eugonadism?
- physical exam! - TSH, PRL - androgens (testosterone) IF symptomatic- acne, mustache, etc. - progestin challenge test - U/S
What is the definition of secondary amenorrhea?
- previous hx of mesturation, and no menses for 3 cycles or 6 months
What are causes of hypergonadotropic hypogonadism (POI) with NORMAL karyotype?
- previous ovarian sx - chemotherapy, radiation - gonadal dysgenesis - autoimmune (addison's, thyroid, T1DM, MG, SLE) - receptor mutations (rare) - fragile X premutation - idiopathic
What are the causes of hyperprolactinemia?
- prolactin-inducing medications - hypothyroidism - pituitary tumor (prolactinoma)
What is the treatment for hypergonadotropic hypogonadism?
- psychological support - hormone replacement until age of menopause (estrogen + cyclic progestin, combined OCP) - 15% can resume ovulation, 5-10% may become pregnant (counsel on contraception!!) - fertility: oocyte donation, adoption
What is the treatment of Turner syndrome?
- pubertal induction - hormone replacement (bone + cardiac health) - fertility, contraception - gonadectomy if Y present (risk for tumors)
What should be included in a physical exam for amenorrhea workup?
- record of growth, ht/wt % - vitals- BP (important for adrenals) - head to toe: neuro, thyroid, tanner staging, abdomen, genital, skin (acne, hirsutism)
What are causes of hypergonadotropic hypogonadism with ABNORMAL karyotype?
- turner syndrome (or mosaic turner) - 46XY: AIS, swyer syndrome, non-functioning SRY mutation
What is androgen insensitivity syndrome?
- x-linked recessive mutation in gene coding for androgen receptor, resulting in insensitivity to androgens - will have inguinal testes (no spermatogenesis), breast development, no pubic hair, blind vagina, no uterus - breast development b/c of peripheral conversion of testosterone to estrogen
