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Clomiphene citrate + dopamine agonist is a combination therapy used to manage complex cases of hyperprolactinemia associated with secondary hypogonadism and metabolic complications, such as morbid obesity. Clomiphene citrate is a selective estrogen receptor modulator (SERM) that acts as an antagonist at estrogen receptors in the hypothalamus and pituitary gland. This action blocks the negative feedback of estrogen, leading to an increase in the secretion of gonadotropin-releasing hormone (GnRH), luteinizing hormone (LH), and follicle-stimulating hormone (FSH), which subsequently stimulates endogenous testosterone production in males. Dopamine agonists (such as cabergoline or bromocriptine) target D2 receptors on pituitary lactotroph cells to inhibit prolactin secretion and reduce the size of prolactin-secreting adenomas. The combination is employed when dopamine agonist monotherapy is insufficient to restore the hypothalamic-pituitary-gonadal axis or when adjunctive treatment is needed to address severe obesity and insulin resistance linked to prolactinomas.
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