Site of Action of Clomiphene Citrate in Men: A Study of the Pituitary-Leydig Cell Axis1

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Abstract
Clomiphene citrate, 100–200 mg/day for 6–9 days, stimulated the pituitary-Leydig cell axis in 14 normal men as evidenced by an increase in plasma LH and testosterone levels after 2 and 6 days, respectively. After 6 days of clomiphene, LH levels increased by 160% and testosterone levels 80 %. The elevation of plasma testosterone concentration was due to increased testosterone secretion rather than decreased clearance of this steroid from blood. Clomiphene had no effect upon the LH and testosterone levels of men in whom these hormones were suppressed with the synthetic androgen, fluoxymesterone. In men with hypopituitarism clomiphene did not increase plasma LH or stimulate testosterone secretion. Clomiphene stimulates the pituitary-Leydig cell axis in men by inducing LH release. Clomiphene may be useful clinically in the evaluation of the capacity of the anterior pituitary to secrete LH.