A 26 years old female complainaning absence of periods since 3 months , usg done - nad
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"amenorrhea" AND "diagnosis" AND "management"
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Secondary Amenorrhea - 26F, 3 months, USG NAD
USG NAD (No Abnormality Detected) means the uterus, ovaries, and pelvic anatomy are normal. This is the classic starting point for the hormonal workup of secondary amenorrhea with normal pelvic anatomy.
Step 1: Rule Out Pregnancy FIRST
- Urine or serum β-hCG - mandatory before any further workup. Even "unlikely" cases must be excluded.
Causes of Secondary Amenorrhea (USG Normal)
The causes are organized by anatomical level (hypothalamus → pituitary → ovary → uterus/outflow):
| Level | Cause |
|---|---|
| Hypothalamic | Functional Hypothalamic Amenorrhea (FHA) - stress, weight loss, excessive exercise |
| Hypothalamic | PCOS (hypothalamic-pituitary dysregulation) |
| Pituitary | Hyperprolactinemia (prolactinoma, drug-induced) |
| Pituitary | Acquired hypopituitarism (Sheehan syndrome, trauma, tumor) |
| Ovarian | Primary Ovarian Insufficiency (POI) - premature ovarian failure <40 yrs |
| Thyroid | Hypothyroidism / Hyperthyroidism |
| Adrenal | Late-onset congenital adrenal hyperplasia, Cushing syndrome |
| Uterine | Asherman syndrome (intrauterine adhesions - USG may miss early cases) |
| Drugs | Antipsychotics, antidepressants, progestins, OCP withdrawal |
Note: Asherman syndrome causes amenorrhea due to outflow tract obstruction but USG alone can be unreliable - hysteroscopy is the gold standard if suspected.
Step 2: Hormonal Workup (First-Line)
Per Berek & Novak's Gynecology (the standard reference):
- β-hCG (serum/urine) - rule out pregnancy
- Serum Prolactin - rule out hyperprolactinemia
- Serum TSH - rule out thyroid dysfunction
- Serum FSH - classifies amenorrhea into:
- FSH high (>25-40 mIU/mL on 2 samples) = Hypergonadotropic → POI (premature ovarian insufficiency)
- FSH low/normal = Hypogonadotropic → FHA, pituitary pathology
- FSH normal + LH elevated → PCOS pattern
- Serum LH - LH:FSH ratio >2:1 supports PCOS
- Serum Estradiol - E2 >40 pg/mL indicates estrogen sufficiency
Step 3: Second-Line Tests (Based on First-Line Results)
| Finding | Next Step |
|---|---|
| High prolactin | MRI pituitary (to rule out prolactinoma / macroadenoma) |
| High FSH (confirmed x2) | Karyotype (rule out Turner mosaic), FMR1 (fragile X premutation), autoimmune screen |
| Low FSH + low LH | MRI pituitary/hypothalamus, GnRH stimulation test |
| LH:FSH >2, + androgens | Serum testosterone, DHEAS, 17-OHP (PCOS vs. LOCAH) |
| Suspected Cushing's | 24-hr urinary cortisol or overnight dexamethasone suppression test |
Step 4: Progestogen Challenge Test (if cause still unclear)
- Give medroxyprogesterone acetate 10 mg/day for 5-10 days
- Withdrawal bleed occurs → Estrogen is adequate, outflow tract intact; likely anovulation (PCOS, FHA, stress)
- No withdrawal bleed → Either hypoestrogenic state (low estrogen) OR outflow tract problem (Asherman syndrome) → measure FSH + consider hysteroscopy
Clinical Clues to Guide Diagnosis
| Clinical Feature | Think of... |
|---|---|
| Weight loss, exercise, stress, low BMI | Functional Hypothalamic Amenorrhea (FHA) |
| Weight gain, hirsutism, acne, irregular periods since puberty | PCOS |
| Galactorrhea, headache, visual field defects | Hyperprolactinemia / Prolactinoma |
| Hot flashes, night sweats, vaginal dryness | POI (premature ovarian insufficiency) |
| Postpartum hemorrhage history | Sheehan syndrome |
| H/o D&C, uterine surgery | Asherman syndrome |
| Thyroid symptoms (fatigue, cold intolerance, weight gain) | Hypothyroidism |
| Drug history (antipsychotics, OCPs, metoclopramide) | Drug-induced amenorrhea |
Most Common Cause in a 26F with USG NAD
In clinical practice, the most common diagnoses in this scenario (in order of frequency) are:
- PCOS - most common cause of secondary amenorrhea in reproductive-age women
- Functional Hypothalamic Amenorrhea - stress/weight/exercise-related
- Hyperprolactinemia
- Thyroid dysfunction
- Primary Ovarian Insufficiency
Summary Workup Algorithm
β-hCG (rule out pregnancy)
↓ Negative
TSH + Prolactin + FSH + LH + E2 + (Testosterone + DHEAS if hirsutism)
↓
Prolactin high → MRI pituitary
TSH abnormal → Treat thyroid
FSH high (x2) → POI workup (karyotype, FMR1, autoimmune)
FSH low/normal + LH elevated → PCOS (confirm with antral follicle count on repeat TVS, androgens)
FSH low/normal + LH low → FHA (MRI brain if no clear cause)
All normal → Progesterone challenge → if no bleed → hysteroscopy (Asherman?)
Sources: Berek & Novak's Gynecology, Chapter 34 (Amenorrhea); Tietz Textbook of Laboratory Medicine, 7th ed. (Secondary Amenorrhea evaluation); Saadedine M et al., Functional Hypothalamic Amenorrhea - Mayo Clin Proc 2023.
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