Amenorrhea Flashcards
A 16 yo girl is brought to you by her worried parents because she has never had a menstrual period. She denies any vaginal spotting, sexual activity, or cyclical pain. A pregnancy test is negative.
Physical examination of the patient demonstrates Tanner V development of breasts and of pubic and axillary hair. There is no evidence of vaginal agenesis or imperforate hymen. A pelvic ultrasound is unremarkable. Lab data reveal no abnormalities. You diagnose the patient with hypothalamic-pituitary-adrenal-ovarian axis immaturity, and recommend she return in 3-6 months if she has not yet menstruated.
definition and etiologies
-No menses by age 15, OR no secondary sex characteristics by age 13
-Occurs in about 2.5% of all patients
-MC etiology- Hypothalamic-pituitary-adrenal-ovarian axis immaturity
-Local etiologies:
-Imperforate hymen
-Vaginal agenesis
-Androgen insensitivity
-Ovarian etiologies:
-Primary ovarian insufficiency due to:
-Iatrogenesis- Chemotherapy, Radiation therapy
-Illness- Viruses (mumps, varicella), Malaria, Tuberculosis, Autoimmune illness
-Genetic etiologies- Turner syndrome, Fragile X syndrome
-Hypogonadotropic hypogonadism- Kallman’s syndrome
-Sheehan’s syndrome- Pituitary dysfunction from surgery or radiation therapy
-Hypothalamic amenorrhea- Anorexia nervosa, Excessive exercise
imperforate hymen
-Vaginal vault is present, but the vaginal introitus is not patent
-Treat with hymenotomy (an outpatient procedure)
hematocolpos due to imperforate hymen
vaginal agenesis
-there is no vaginal vault present
-due to a mullerian tract anomaly
-may affect formation of the cervix and/or uterus, and kidneys
-failure of vaginal vault to form in embryonic life
-occurs in 1:4000-5000 pts
-often due to mullerian tract anomaly type 1:
-uterus is also absent or is hypoplastic
-transverse vaginal septum
dx and tx of vaginal agenesis
-Dx:
-Absent vaginal introitus and vault on PE
-US is confirmatory- Rudimentary structures may be visible
-May also reveal anomalies of kidneys or ureters
-Treatment:
-Creation of neovagina, if desired- May be accomplished via use of dilators or via neovaginoplasty
-No other treatment is necessary if the patient has functional ovaries
-Otherwise, treat with hormone therapy
androgen insensitivity syndrome
-genotypically 46,XY but is insensitive to endogenous testosterone
-Due to loss-of-function gene in long arm of X chromosome
-Occurs in 1:20,000 liveborn genotypic males worldwide
-In complete androgen insensitivity:
-No male genitals develop
-Gonads remain in abdominal cavity or in inguinal region
-Female genitalia develop instead- Vagina is usually shorter than normal
-No female upper genital tract organs develop
-Increased risk of testicular CA
partial androgen insensitivity syndrome
-genitalia may appear to be those of a virilized female or of an undervirilized male
complete androgen insensitivity syndrome
-Primary amenorrhea
-Possible labial swelling or inguinal mass (descended testicle)
-Scanty axillary and pubic hair
-Tall stature
dx and tx of androgen insensitivity syndrome
-Dx:
-Increased LH
-Increased testosterone
-Increased serum anti-Müllerian hormone
-Ultrasound demonstrates no evidence of uterus, tubes or upper vagina
-46, XY karyotype
-Tx:
-Gonadectomy at age 16-18 due to the risk of gonadal malignancy (5-10%) to permit completion of puberty
-Discussion with parents and/or patient regarding findings and management
-Estrogen replacement
-Referral for counseling
-Vaginal lengthening if and when the patient is interested and is old enough to consider benefits
sequelae of androgen insensitivity syndrome
-osteoporosis
-potential issues regarding gender identity
primary amenorrhea work up
secondary amenorrhea
-amenorrhea occurring at some point after menarche
-MC dx is pregnancy
other common dx of secondary amenorrhea
-Menopause
-Premature ovarian insufficiency
-Prolactinoma
-Hyperthyroidism
-Post-pill amenorrhea
-Anorexia nervosa
-Medication effects
-Outlet obstruction
-Polycystic ovarian syndrome
signs and sx of menopause or premature ovarian insufficiency
-amenorrhea
-vasomotor instability
-vulvovaginal atrophy or dyspareunia
-age >40 - any age with premature ovarian failure
-no reason to obtain FSH if the pt is >45yo
-FSH >30 is indicative of menopause
tx of menopause/premature ovarian insufficiency
-Menopause:
-No treatment needed
-The patient may choose to take HRT if no contraindications exist
-See text and menopause lecture handout for more details
-Premature ovarian insufficiency:
-Must replace estrogens to prevent
-Osteoporosis
-Vulvovaginal atrophy
-See text and menopause lecture handout for more details
prolactinoma
-A benign prolactin-secreting tumor of the anterior pituitary
-May be asymptomatic
-May cause:
-Amenorrhea
-Galactorrhea
-Possible visual field cuts due to compression of the optic chiasm
-Infertility (due to amenorrhea)
-Headaches
-Osteopenia or osteoporosis
-Dx:
-Suspect with evidence of hyperprolactinemia- Avoid breast exam prior to drawing prolactin level to prevent false elevation
-If the patient has hyperprolactinemia, obtain MRI of brain with contrast to rule out a prolactinoma
management of prolactinoma
-Hyperprolactinemia: prolactin >25 ng/ml
-Microadenoma: measures <1 cm on MRI
-May be treated with dopamine agonists
-Bromocriptine
-Cabergoline
-Macroadenoma: measures >1 cm on MRI
-Requires resection
-Refer to Neurosurgery
-Refer to ophthalmology or neuro-ophthalmology for formal visual field studies
-Consider contraception in patients who do not desire fertility
hyperthyroidism
-low TSH: obtain T4
-high T4: hyperthyroidism
-low T4: pituitary (secondary) hypothyroidism
-treat accordingly or refer to endo
post-pill amenorrhea
-May occur while or after a patient stops using hormonal contraception due to an atrophic endometrium
-The patient has a negative pregnancy test
-Diagnosis is made by relevant history and negative UCG
-Treatment: reassure; no other treatment necessary
anorexia nervosa
Amenorrhea is often but not always present due to low body fat and low estrogen stores
medication effect
-Many medications may cause amenorrhea
-Most are hormones
-Estrogens
-Combined estrogens and progestins
-Testosterone
-Other steroid hormones
-Psychiatric medications may also cause amenorrhea
-Changes in secretion of prolactin
outlet obstruction
-Pts who have had cervical surgery may have scarring of endocervical canal or endometrial cavity, impeding flow of menses
-C/O cyclical crampy abdominal pain, breast tenderness, etc. without vaginal bleeding
-Attempt passage of instrument into uterine cavity (endometrial biopsy catheter, etc.)
-Tx:
-cervical dilation after administration of vaginal misoprostol at home
-May be accomplished in office but is painful
Asherman’s syndrome
-Synechiae of the uterus form after uterine instrumentation
-Results in diminished menstrual flow or amenorrhea
-MC occurs after uterine instrumentation following pregnancy
-Diagnosis:
-Hysterosalpingography
-Sonohysterography
-Hysteroscopy
-Treatment: hysteroscopic resection
PCOS
-4-12% of all patients of reproductive age
-Patients also have insulin resistance and high circulating insulin levels
-Causes both amenorrhea, hyperandrogenism and may cause menometrorrhagia
-Results in hirsutism and obesity
-No ovulation results in a thickened proliferative EM (exposed to estrogen but not to progesterone)
-Eventually, patients will bleed heavily
-Pathophysiology:
-Patients with PCOS often produce relatively more LH than FSH
-Theca cells of ovary produce more androgens than estrogens
-Relatively lower FSH levels make it difficult for androgens to aromatize to estrogen
-Anovulation results
PCOS sx
-hirsutism (NOT virilization)
-obesity
-acanthosis nigricans
-PE:
-Usually but not always overweight or obese
-Obtain waist circumference (significant if >34”)
-Evaluate on PE for signs of hyperandrogenism
-Acne
-Acanthosis
-Hirsutism
-Dx:
-UCG or bHCG
-Testosterone
-Sex hormone-binding globulin
-TSH
-Prolactin
-FSH/LH
-Random glucose >200 mg/dL, or Hgb A1c
Imaging:
-US of pelvis- At least 12 follicles measuring 2 mm in diameter or increased ovarian volume
-Evaluate endometrial stripe for possible endometrial hyperplasia
-May demonstrate enlarged ovaries with or without the “string of pearls” sign
-≥12 follicles in one or both ovaries
-pic- 13 follicles are seen
-Possible endometrial hyperplasia -EM stripe >1 cm, within normal limits
PCOS diff dx
Androgen secreting tumor of adrenals or ovaries
Exogenous androgens
Cushing’s syndrome or disease
Congenital adrenal hyperplasia
Acromegaly
Hypothalamic amenorrhea
Primary ovarian insufficiency
Thyroid disease
Hyperprolactinemia
PCOS dx criteria
-Rotterdam criteria for diagnosis of PCOS: presence of at least 2 of the following:
-Androgen excess
-Ovulatory dysfunction
-Polycystic ovaries seen on ultrasound
-(dont need to know) NIH criteria: must have both:
-hyperandrogenism
-oligomenorrhea or amenorrhea
long term sequelae of PCOS
-endometrial hyperplasia or CA
-infertility
-DM
-hyperlipidemia
management of PCOS
-Protect endometrium with progesterone via:
-Oral contraceptives
-Levonorgestrel IUD
-Cyclic progesterone
-Depot medroxyprogesterone acetate (Depo-Provera)
-Manage DM or insulin resistance/glucose intolerance
-Diet
-Exercise
-As per primary care clinician or endocrinologist
-Treat infertility, if desired
-Folic acid, 400 mcg PO daily (to reduce NTD incidence)
-Ovulation induction
-Achieve spontaneous ovulation, if feasible
-Metformin or rosiglitazone or pioglitazone
-Consider LGP-1 agents
-Manage hirsutism
-May prevent new hair growth with spironolactone or finasteride
-Electrolysis or laser hair removal for existing hair growth
-Manage hyperlipidemia
-Diet
-Exercise
-Possible statin
approach to pt with secondary amenorrhea
15yo pt presents with worsening, cyclic pelvic pain that occurs about every 4wks. She denies any hx of vaginal bleeding or sexual activity. which of the following is the most likely dx
-hypothalamic pituitary adrenal ovarian axis immaturity
-imperforate hymen!!!!!!
-PCOS
-prolactinoma
