Amenorrhea: Symptom Checklist, Etiologies, and Diagnostic Approach

Definitions

• Primary: No menarche by age 15 (or 13 without secondary sexual characteristics).
• Secondary: Absence of menses ≥3 months (previously regular) or ≥6 months (irregular).

Symptom Clusters

Presentation	Associated Features
Hypoestrogenic	Hot flashes, night sweats, vaginal dryness, low libido, bone loss
Hyperandrogenic	Hirsutism, acne, male-pattern hair loss, obesity
Galactorrhea	Prolactinoma, medications, hypothyroidism
Mass effect	Headache, visual field defects (pituitary adenoma)

Etiologic Framework (Secondary)

1. Pregnancy (most common)
2. Hypothalamic/pituitary: Functional hypothalamic amenorrhea (stress, weight loss, exercise), hyperprolactinemia, Sheehan syndrome, tumors.
3. Ovarian: PCOS (most common), POI, resistant ovary syndrome.
4. Uterine: Asherman syndrome (intrauterine adhesions).
5. Endocrine: Thyroid, adrenal (Cushing's, CAH).
6. Medications: OCP, depot progestin, antipsychotics, chemotherapy, TKIs.
7. Chronic disease: CKD, liver failure, malnutrition.

Initial Workup

β-hCG → TSH, prolactin, FSH, LH, estradiol → if FSH high: ovarian failure; if low/normal: hypothalamic/pituitary → MRI if indicated. Androgens if hirsute.

When to Refer

• Primary amenorrhea
• Secondary amenorrhea >6 months
• Suspected neoplasm, eating disorder, complex endocrine
• Fertility desired