## Mechanism of Clomiphene Citrate **Key Point:** Clomiphene citrate is a non-steroidal selective oestrogen receptor modulator (SERM) that works centrally, NOT peripherally on the ovary. ### How Clomiphene Works 1. **Central action (hypothalamic–pituitary):** - Blocks oestrogen negative feedback at the hypothalamus and anterior pituitary - Results in increased GnRH pulsatility and elevated FSH/LH secretion - Leads to follicular recruitment and growth 2. **Peripheral action (ovarian):** - Does NOT directly stimulate granulosa cells - The ovary responds to the elevated FSH/LH, not to clomiphene itself - Clomiphene has minimal direct ovarian effects ### Pharmacokinetics | Property | Value | | --- | --- | | Half-life | 30–40 hours | | Accumulation | Yes, with repeated dosing | | Metabolism | Hepatic (enterohepatic circulation) | | Dosing | 50–100 mg daily for 5 days | **High-Yield:** Clomiphene is a **central** agent (hypothalamic–pituitary), not a direct ovarian stimulant. This distinguishes it from gonadotropins (FSH/hCG), which act directly on the ovary. **Clinical Pearl:** The long half-life and accumulation explain why clomiphene is dosed for only 5 consecutive days — continued dosing would lead to excessive oestrogen receptor blockade and paradoxical suppression of FSH/LH. ### Why Option 3 Is Wrong Clomiphene does NOT directly stimulate ovarian granulosa cells. It works entirely through central disinhibition of FSH/LH. The ovary responds to the elevated gonadotropins, not to clomiphene itself.
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