Which H2 receptor antagonist is most likely to cause gynecomastia and sexual dysfunction due to its antiandrogenic properties?

Explanation

## H2 Receptor Antagonists: Endocrine Side Effects ### Cimetidine and Antiandrogenic Effects **Key Point:** Cimetidine is unique among H2 blockers because it inhibits cytochrome P450 enzymes (particularly CYP1A2, CYP2C9, CYP2D6, and CYP3A4) AND has direct antiandrogenic properties by inhibiting androgen receptor binding and testosterone synthesis. **High-Yield:** Cimetidine-induced gynecomastia and sexual dysfunction are dose-dependent and reversible upon drug discontinuation. This occurs in approximately 0.3–4% of patients taking cimetidine. ### Mechanism of Antiandrogenic Action 1. **Androgen receptor antagonism** — Cimetidine competitively blocks androgen receptor binding 2. **Reduced testosterone synthesis** — Inhibition of testicular 17α-hydroxylase and 17,20-lyase 3. **Increased estrogen levels** — Enhanced aromatization of androgens to estrogens 4. **Increased prolactin** — H2 blockade increases prolactin secretion, contributing to gynecomastia ### Comparison of H2 Blockers: Endocrine Side Effects | H2 Blocker | Antiandrogenic | Gynecomastia Risk | Sexual Dysfunction | CYP450 Inhibition | | --- | --- | --- | --- | --- | | Cimetidine | Yes (direct) | High (0.3–4%) | Common | Extensive | | Ranitidine | No | Rare | Rare | Minimal | | Famotidine | No | Rare | Rare | Minimal | | Nizatidine | No | Rare | Rare | Minimal | **Clinical Pearl:** Cimetidine should be avoided in patients with erectile dysfunction, infertility concerns, or those already at risk for gynecomastia (cirrhosis, hyperthyroidism). Ranitidine, famotidine, or nizatidine are preferred alternatives. **Mnemonic:** **CIMETIDINE = CYP inhibitor + Endocrine effects** — Remember that cimetidine is the "problem child" of H2 blockers for both drug interactions AND hormonal side effects.