Cortisol levels alter the response to metoclopramide in patients with hypothalamic amenorrhea

The reduction in frequency and/or amplitude of gonadotropin-releasing hormone (GnRH) pulses in patients with amenorrhea of hypothalamic origin has been attributed to increased dopamine activity. The objective of the present study was to determine the role of dopamine in the pathogenesis of hypothalamic amenorrhea. Fourteen patients with hypothalamic amenorrhea, nine of whom had psychogenic amenorrhea and five anorexia nervosa, were studied and compared with nine normal women during the early follicular phase. Metoclopramide (10 mg), a dopamine antagonist, was infused intravenously and blood samples were collected at 15-min intervals for 2 h for follicle-stimulating hormone (FSH) and luteinizing hormone (LH) measurement by radioimmunoassay. Both the hypothalamic amenorrhea (psychogenic amenorrhea and anorexia nervosa) and control groups were unresponsive to FSH, suggesting that dopamine may have little or no effect on FSH secretion. Five patients of the psychogenic amenorrhea group responded to LH (responsive psychogenic amenorrhea) and four did not (non-responsive psychogenic amenorrhea). No anorexia nervosa or control patient responded to the stimulus. Responsive psychogenic amenorrhea patients showed decreased basal cortisol levels compared to the non-responsive psychogenic amenorrhea and anorexia nervosa groups. It is possible that patients with exclusive alterations in the dopaminergic system are those who respond to metoclopramide (responsive psychogenic amenorrhea group), whereas patients who also have involvement of the hypothalamic-adrenal axis like the women with anorexia nervosa, are not responsive to metoclopramide and tend to have elevated cortisol levels. The non-responsive psychogenic amenorrhea group, with elevated cortisol levels, probably represents an intermediate step between the responsive psychogenic amenorrhea and anorexia nervosa patients.