A 28-year-old woman with a 3-year history of regular menstruation presents with secondary amenorrhea for the past 6 months. She denies pregnancy, weight loss, or stress. On examination, she appears well-nourished with normal secondary sexual characteristics. Serum β-hCG is negative. FSH and LH are normal. Prolactin is 45 ng/mL (normal <25). What is the most common cause of secondary amenorrhea in this clinical presentation?

## Clinical Clue Recognition This patient has: - Secondary amenorrhea (previously regular cycles) - Elevated prolactin (45 ng/mL; normal <25) - Normal FSH/LH (excludes ovarian failure) - Negative β-hCG (excludes pregnancy) - No obvious systemic illness ## Most Common Cause: Hyperprolactinemia **Key Point:** Elevated serum prolactin is the **most common endocrine cause** of secondary amenorrhea, accounting for 40–50% of cases with hormonal abnormalities. **High-Yield:** Prolactin inhibits GnRH secretion and directly suppresses FSH/LH release. Even modest elevations (>25 ng/mL) can cause amenorrhea. The most common pathological cause is a **prolactin-secreting pituitary adenoma (prolactinoma)**, which accounts for ~40% of all secondary amenorrhea cases. **Clinical Pearl:** Patients with hyperprolactinemia often present with: - Amenorrhea or oligomenorrhea - Galactorrhea (present in only ~30% of cases) - Decreased libido - Headache or visual disturbance (if macroadenoma) ## Differential Diagnosis of Secondary Amenorrhea by Frequency | Cause | Frequency | Key Distinguishing Feature | |-------|-----------|---------------------------| | Hyperprolactinemia | 40–50% (hormonal) | Elevated prolactin level | | PCOS | 20–30% | Elevated androgens, polycystic ovaries, hirsutism | | Hypothyroidism | 10–15% | Elevated TSH, low T4 | | Premature ovarian failure | 5–10% | Elevated FSH (>40 IU/L) | | Asherman syndrome | 5–10% | History of curettage/infection, normal hormones | **Mnemonic:** **HAPS** for common hormonal causes of secondary amenorrhea: - **H**yperprolactinemia (most common) - **A**ndrogen excess (PCOS) - **P**remature ovarian failure - **S**heehan syndrome / hypothyroidism ## Workup Algorithm for Secondary Amenorrhea ```mermaid flowchart TD A[Secondary Amenorrhea]:::outcome --> B{β-hCG positive?}:::decision B -->|Yes| C[Pregnancy]:::outcome B -->|No| D[Check Prolactin]:::action D --> E{Prolactin elevated?}:::decision E -->|Yes| F[Hyperprolactinemia]:::outcome E -->|No| G[Check FSH]:::action G --> H{FSH > 40 IU/L?}:::decision H -->|Yes| I[Premature Ovarian Failure]:::outcome H -->|No| J[Check Androgens & TSH]:::action J --> K{Elevated androgens?}:::decision K -->|Yes| L[PCOS]:::outcome K -->|No| M[Check TSH]:::action M --> N{TSH elevated?}:::decision N -->|Yes| O[Hypothyroidism]:::outcome N -->|No| P[Anatomical obstruction or other]:::outcome ``` [cite:Harrison 21e Ch 346]