2/17 Amenorrhea - Jasani Flashcards
compartments and hormones for menses
definitions:
primary amenorrhea
secondary amenorrhea
oligomenorrhea
primary amenorrhea
-
never had a period
- age 16 w secondary sex chars
- age 14 w/out secondary sex chars
- > 3y between onset of sex chars and no menses
- thelarche (breast) → adrenarche (pubic hair) → menarche (menses)
secondary amenorrhea
- have had prev period BUT 6mo+ with no menses
oligomenorrhea
- 35d < menstrual interval < 6mo
classification of amenorrhea
1. hypothalamic/pituitary dysfx
- hypogonadotropic hypogonadism
- low/nl FSH
2. ovarian dysfx
- normal FSH (PCOS)
- hypergonadotropic hypogonadism
- high FSH (ovarian failure, primary ovarian failure)
3. outflow tract abnormality
- nl FSH
amenorrhea workup
- history
- menstrual hx
- symptomatology - menopausal, pain
- inciting events - surgery, stress, wt change
- physical exam
- body habitus, BMI, gen health
- sexual chars
- gynecologic exam
- laboratory evaluation
secondary amenorhhea
algorithm
ddx
- pregnancy
- menopause
- PCOS
- hypothalamic amenorrhea
- ovarian failure
- hyperPRLemia
hypothyroidism
(secondary amenorrhea)
-
incr TRH
- disrupts GnRH pulses
- can case elev PRL level
-
Hashimoto’s thyroiditis
- primary: incr TSH, low T4, low T3
- secondary: (hypothal/pituitary): decr TSH
tx: thyroid replacement tx, levothyroxine, recheck 6wk
hyperprolactinemia
(secondary amenorrhea)
causes
-
physiologic
- preg, breastfeeding, sleep, hypoglycemia, stress, exercise, orgasm, nipple stim
-
pharmacologic
- DA antagonists (haloperidol, risperidone, metoclopramide, methyldopa)
-
pathologic
- PRLoma, meningioma, glioma, TB, craniopharyngioma, GH secreting tumor
- renal failure: disruption of PRL elim
prolactinoma
1 pituitary tumor
prolactin secreting pituitary adenoma
amenorrhea due to inhibition of GnRH
- galactorrhea, headache, visual disturbances
dx: check PRL in AM fasting, follicular phase
abnl? repeat. confirmed? brain MRI
tx microadenomas
DOPAMINE AGONIST
1. bromocriptine
- n/v, headache, faintness
- contraindicated: hypertrophic valvular heart disease
2. cabergoline (D2 DA receptor agonist)
- minimal side effects
if preg undesired…estrogen! (combo hormonal contraceptives)
tx macroadenoma
- serial PRL
- imaging: brain MRI, head CT
- DA agonist
- surgical management
- radiation tx
most common overall cause of (secondary) amenorrhea
test to check?
SECONDARY TO ABNORMAL OVARIAN FX
test: protestin challenge!
-
bleed?
- normal physio levels of estrogen bc progestin makes lining secretory → sloughs off
- suggests: anovulation, PCOS
-
no bleed?
-
give both estrogen and progestin
-
bleed?
- think about FSH issues to distinguish between ovarian failure (see high FSH) or hypothal/pit dysfx (see low/nl FSH)
-
no bleed?
- suggests: utero-vag obstruction
-
bleed?
-
give both estrogen and progestin
hypothalamic/pituitary dysfx
exercise amenorrhea
training before menarche can delay menses up to 3yr
mech: exercise, stress, anorexia → incr CRH and ACTH →→ direct/indirect decr of gonadotropin by inhibition of GnRH
Sheehan’s Syndrome
postpartum hypopituitarism or postpartum pituitary necrosis
- acute infarction, ischemic necrosis from postpartum hemorrhage/hypovol shock
- hormone loss (FLAT PEG)
most common sx: failure of lactation
PCOS
polycystic ovary syndrome
- 80-90% of women with excess androgens have PCOS!!!
- unknown cause
- strong correlation with metabolic syndrome (insulin resistance, diabetes, obesity)
sx:
- oligomenorrhea, amenorrhea
- infertility
- hirsutism
dx: anolulation/oligoovulation, androgen excess, polycystic ovaries on pelvic ultrasound
hyperinsulinemia →
- incr GnRH pulse
- LH > FSH
- incr androgen
- decr follicle maturation
- decr SHBG
tx:
- reduce production/circ level of androgens
- assess/treat metabolic syndrome
- protect endometrium from unopposed estrogen (→ cancer/hyperplasia)
- induce ovulation if trying to get preg
components of sexual development
genetic vs gonadal vs phenotypic
genetic sex
- determined at fertilization: XX vs XY
gonadal sex
- influenced by genetic sex to act on undifferentiated gonads → ovaries and testes
- bipotential gonad devpt is balanced by opposing forces; SRR is the key factor
- SRY region of Y chromosome (testicular determining factor) upregs high mobility group (HMG), SOX9 → testicular devpt
- WNT4, RSPO1 represses SOX9 → ovarian devpt
- deterines hormonal environment
- Sertoli cells: SOX9 induces AMG → Mullerian regression
- Leydig cells: produce testosterone → stimulates Woffian dept, stim testicular descent, converted to DHT → external male genitalia devpt
phenotypic sex
- external genitalia and secondary sexual characteristics
rules to remember:
no breasts
no uterus
PRIMARY AMENORRHEA
breast present, uterus absent
breasts: high estrogen, but…
no uterus: AMH present or congenital agenesis
ddx
-
MRKH (Mullerian agenesis)
- 46XX, normal female testosterone
- congenital malformation → failure of Mullerian duct devpt
- normal ovaries, repro hormones → normal secondary sex chars in puberty with amenorhea
- assoc with renal anomalies, skeletal anomalies
-
AIS (androgen insensitivity syndrome)
- 46XY
- X linked recessive androgen receptor defect
- testes without spermatogenesis, lack of Mullerian, might lack of Wollfian
- complete AIS: normal ext female genitalia with short, blind end vagina. presents at puberty
- gonadectomy after puberty (to avoid gernm cell tumor)
- incomplete AIS: ambiguous genitalia
PRIMARY AMENORRHEA
breasts absent, uterus absent
extremely rare, but think about…
no breasts: low estrogen
no uterus: AMH present
ddx
- 17 OHase deficiency
- testicular regression syndrome
amenorrhea
inherited or acquired
amenorrhea
hyper/hypo/eugonadotropic
