Reproductive · Amenorrhea
The facts most likely to be tested
The initial diagnostic step for any patient with amenorrhea is a urine human chorionic gonadotropin (hCG) test to rule out pregnancy.
Primary amenorrhea is defined as the absence of menses by age 15 in the presence of secondary sexual characteristics, or by age 13 in their absence.
Müllerian agenesis (Mayer-Rokitansky-Küster-Hauser syndrome) presents with primary amenorrhea, a blind vaginal pouch, and absent uterus despite normal 46,XX karyotype and secondary sexual characteristics.
Androgen insensitivity syndrome presents with primary amenorrhea, absent uterus, sparse axillary/pubic hair, and a 46,XY karyotype with intra-abdominal testes.
Asherman syndrome is the most common cause of secondary amenorrhea following uterine instrumentation or dilation and curettage (D&C) due to intrauterine adhesions.
Functional hypothalamic amenorrhea is a diagnosis of exclusion characterized by low GnRH, low FSH/LH, and low estrogen often triggered by excessive exercise, stress, or low caloric intake.
Prolactinoma is the most common pituitary cause of secondary amenorrhea and should be evaluated with a serum prolactin level and TSH to rule out hypothyroidism.
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A 16-year-old female presents for evaluation of primary amenorrhea. She has normal breast development and normal axillary and pubic hair distribution. Physical examination reveals a blind vaginal pouch and an absent uterus on pelvic ultrasound. Her serum FSH is within normal limits and her karyotype is 46,XX.
What is the most likely diagnosis?
Müllerian agenesis (Mayer-Rokitansky-Küster-Hauser syndrome)
The presence of secondary sexual characteristics and a 46,XX karyotype with an absent uterus and blind vaginal pouch is pathognomonic for Müllerian agenesis, distinguishing it from Androgen Insensitivity Syndrome.
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High yield triage
Etiology / Epidemiology
Primary: no menses by age 15 (with secondary sex characteristics) or age 13 (without). Secondary: absence of menses for 3 cycles or 6 months.
Clinical Manifestations
Look for Mayer-Rokitansky-Küster-Hauser syndrome (absent uterus) or Asherman syndrome (intrauterine adhesions). Hirsutism suggests hyperandrogenism.
Diagnosis
Initial workup: hCG, FSH, TSH, and prolactin. Progestin challenge test assesses estrogen status and outflow tract.
Treatment
Treat underlying cause. Cyclic progestin for anovulation; estrogen/progestin for hypoestrogenism. Avoid estrogen in pregnancy.
Prognosis
Long-term estrogen deficiency leads to osteoporosis. Early diagnosis prevents irreversible bone loss.
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Epidemiology & Etiology
Primary amenorrhea is often genetic or anatomical, while secondary is most commonly caused by pregnancy. Other major drivers include hypothalamic dysfunction (stress, weight loss) and PCOS.
Pertinent Anatomy
The HPO axis requires an intact hypothalamus, pituitary, ovaries, and outflow tract (uterus/vagina). Obstruction at the hymen or cervix prevents menses despite normal hormonal cycling.
Pathophysiology
Hypothalamic suppression reduces GnRH pulsatility, leading to low FSH/LH. Ovarian failure results in elevated FSH due to lack of negative feedback. Outflow obstruction presents with cyclic pelvic pain and a hematocolpos.
Clinical Manifestations
Patients with Turner syndrome present with short stature and webbed neck. Red flag: galactorrhea indicates prolactinoma. Virilization (clitoromegaly) suggests an androgen-secreting tumor.
Diagnosis
The progestin challenge test is the gold standard to assess estrogen status; withdrawal bleeding confirms adequate estrogen and patent outflow. MRI of the sella turcica is required if prolactin >100 ng/mL.
Treatment
Combined oral contraceptives are first-line for PCOS-related amenorrhea. Contraindicated in patients with history of DVT or breast cancer. Surgical lysis is required for Asherman syndrome.
Prognosis
Untreated hypoestrogenism causes bone mineral density loss. Patients with Turner syndrome require lifelong estrogen replacement therapy to prevent cardiovascular and skeletal complications.
Differential Diagnosis
Pregnancy: positive hCG
PCOS: elevated LH:FSH ratio
Hypothalamic amenorrhea: low FSH/LH
Premature ovarian insufficiency: FSH >40 mIU/mL
Imperforate hymen: cyclic pain with hematocolpos