Amenorrhea & Abnormal Uterine Bleeding
A boards-focused walkthrough of amenorrhea and abnormal uterine bleeding — from HPO-axis and outflow-tract pathophysiology through the reflex next-best-steps: β-hCG first, FSH-based localization, the breast × uterus grid, PALM-COEIN, and \"postmenopausal bleeding = endometrial cancer until proven otherwise.\"
Framework: two axes, one reflex
Amenorrhea and abnormal uterine bleeding (AUB) both trace to the hypothalamic–pituitary–ovarian (HPO) axis plus a patent outflow tract (uterus → cervix → vagina). Boards test them as reflexes: in any reproductive-age patient, the first step is always β-hCG — pregnancy is the most common cause of secondary amenorrhea.
Primary amenorrhea = no menses by age 15 with normal secondary sexual characteristics, or by age 13 with none. Work it up along two axes: breast development (a marker of estrogen exposure) and presence of a uterus (exam/ultrasound).
Secondary amenorrhea = absent menses for ≥3 months (previously regular) or ≥6 months (previously oligomenorrheic). After excluding pregnancy, check prolactin, TSH, and FSH to localize the lesion to hypothalamus/pituitary vs ovary.
AUB is bleeding abnormal in frequency, regularity, duration, or volume, classified by FIGO's PALM-COEIN system. The single highest-yield rule: postmenopausal bleeding is endometrial cancer until proven otherwise.
- β-hCG first in every case — always.
- Progesterone challenge test: withdrawal bleeding ⇒ adequate estrogen and patent outflow tract (points to anovulation, e.g., PCOS). No bleed ⇒ low estrogen or outflow obstruction/endometrial scarring.
- High FSH/LH (hypergonadotropic): ovarian failure — Turner (45,X), premature ovarian insufficiency (POI, <40 y).
- Low FSH/LH (hypogonadotropic): hypothalamic/pituitary — functional hypothalamic amenorrhea (stress, low weight, elite exercise → the female athlete triad), Kallmann (anosmia), hyperprolactinemia.
- ↑Prolactin inhibits GnRH → amenorrhea + galactorrhea → MRI pituitary for prolactinoma; also check TSH (hypothyroidism raises prolactin).
- PCOS = Rotterdam ≥2 of 3: oligo/anovulation, hyperandrogenism, polycystic ovaries; ↑LH:FSH ratio and insulin resistance are supportive (not diagnostic).
- Asherman syndrome: secondary amenorrhea after uterine instrumentation/D&C (intrauterine adhesions); negative progesterone challenge despite normal hormones.
Primary amenorrhea: localize by breasts (estrogen) × uterus
| Breasts | Uterus | Diagnosis | Key clue / next step |
|---|---|---|---|
| Present | Absent | Müllerian agenesis (MRKH) | 46,XX; normal (female-range) testosterone; normal pubic hair; normal ovaries → check renal US |
| Present | Absent | Androgen insensitivity (AIS) | 46,XY; testes; ↑ (male-range) testosterone; scant pubic/axillary hair |
| Absent | Present | Turner (45,X) / POI | ↑↑FSH; short stature, webbed neck, coarctation → karyotype |
| Absent | Present | Kallmann / hypothalamic | ↓FSH/LH; anosmia (Kallmann); low-weight/stress |
| Present | Present | Outflow obstruction | Cyclic pelvic pain + bulging blue membrane = imperforate hymen |
Vignette: A 16-year-old presents with primary amenorrhea. She has normal breast development (Tanner V) but a blind-ending vaginal pouch and no uterus on ultrasound.
The split: absent uterus + normal breasts = MRKH or androgen insensitivity syndrome (AIS).
Next best step: karyotype + serum testosterone.
- 46,XX, female-range testosterone, normal pubic/axillary hair → MRKH (Müllerian agenesis). Ovaries — and thus estrogen — are normal; order a renal ultrasound (associated renal/skeletal anomalies).
- 46,XY, male-range testosterone, sparse pubic/axillary hair, palpable inguinal/labial gonads → AIS. Manage with gonadectomy after puberty — the cryptorchid, intra-abdominal testes carry germ-cell–tumor risk (gonadoblastoma/seminoma) — plus estrogen replacement.
Buzzword trap: normal pubic hair → MRKH; scant/absent pubic hair (± taller stature) → AIS.
Secondary amenorrhea: pattern recognition
| Cause | FSH/LH | Estrogen | Classic clue |
|---|---|---|---|
| Functional hypothalamic | ↓ | ↓ | Low BMI, athlete, stress, eating disorder (female athlete triad) |
| Hyperprolactinemia | ↓ / normal | ↓ | Galactorrhea, headache, bitemporal hemianopia → MRI |
| PCOS | ↑LH, ↑LH:FSH | normal / ↑ | Hirsutism, acne, obesity, insulin resistance |
| Primary ovarian insufficiency | ↑↑ | ↓ | Age <40, hot flashes; check FMR1 (fragile X), autoimmune |
| Asherman | normal | normal | Post-D&C; no withdrawal bleed despite normal labs |
| Thyroid disease | variable | — | Correct TSH first (hypothyroidism also ↑prolactin) |
PALM-COEIN — the FIGO framework for AUB in reproductive-age patients.
PALM = structural (found on imaging/biopsy):
- Polyp
- Adenomyosis
- Leiomyoma (fibroid)
- Malignancy & hyperplasia
COEIN = non-structural (found on labs/history):
- Coagulopathy (e.g., von Willebrand disease)
- Ovulatory dysfunction (PCOS, thyroid, hyperprolactinemia, perimenopause)
- Endometrial (primary endometrial disorder)
- Iatrogenic (anticoagulants, IUDs, exogenous hormones)
- Not otherwise classified
Board reflex: an adolescent with heavy menstrual bleeding since menarche → screen for coagulopathy (von Willebrand). Anovulatory (ovulatory dysfunction) bleeding dominates both the perimenarchal and perimenopausal ends of reproductive life.
- 2018 FIGO terms: heavy menstrual bleeding replaces "menorrhagia"; intermenstrual bleeding replaces "metrorrhagia."
- Endometrial biopsy to exclude hyperplasia/cancer if: age ≥45, or <45 with risk factors — obesity, unopposed estrogen, PCOS, tamoxifen, Lynch syndrome, or failed medical therapy.
- Postmenopausal bleeding: transvaginal ultrasound first — endometrial stripe ≤4 mm is reassuring; >4 mm or persistent bleeding → endometrial biopsy.
- Acute AUB, hemodynamically stable: high-dose estrogen (IV conjugated or oral), combined OCPs, or oral progestin; tranexamic acid cuts volume.
- Acute AUB, unstable: IV fluids/transfusion + IV conjugated estrogen; if refractory → intrauterine balloon tamponade or D&C.
- Chronic HMB, no structural cause, wants contraception: levonorgestrel IUD is first-line.
- Fibroids → heavy bleeding + bulky, firm uterus; adenomyosis → heavy bleeding + boggy, tender uterus; definitive therapy for both is hysterectomy.
Vignette: A 58-year-old, 12 years postmenopausal, obese, nulliparous woman reports new vaginal spotting for 2 weeks. She has hypertension and type 2 diabetes.
Next best step: transvaginal ultrasound to measure the endometrial stripe (many go directly to endometrial biopsy given her risk profile — either is defensible).
- Stripe >4 mm or ongoing bleeding → endometrial biopsy. Her obesity, nulliparity, diabetes, and hypertension all converge on unopposed-estrogen–driven endometrial hyperplasia/adenocarcinoma.
- Do not attribute postmenopausal bleeding to atrophy up front. Atrophic endometrium/vaginitis is actually the single most common cause of PMB — but it remains a diagnosis of exclusion, assigned only after malignancy is ruled out.
Answer: postmenopausal bleeding = endometrial carcinoma until proven otherwise; evaluate every episode.
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