CORTISOL-LEVELS ALTER THE RESPONSE TO METOCLOPRAMIDE IN PATIENTS WITHHYPOTHALAMIC AMENORRHEA

The reduction in frequency and/or amplitude of gonadotropin-releasing hormone (GnRH) pulses in patients with amenorrhea of hypothalamic orig in has been attributed to increased dopamine activity. The objective o f the present study was to determine the role of dopamine in the patho genesis of hypothalamic amenorrhea. Fourteen patients with hypothalami c amenorrhea, nine of whom had psychogenic amenorrhea and five anorexi a 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 for follicle-stimulating hormone (FSH) and luteinizin g hormone (LH) measurement by radioimmunoassay. Both the hypothalamic amenorrhea (psychogenic amenorrhea and anorexia nervosa) and control g roups were unresponsive to FSH, suggesting that dopamine may have litt le or no effect on FSH secretion. Five patients of the psychogenic ame norrhea group responded to LH (responsive psychogenic amenorrhea) and four did not (non-responsive psychogenic amenorrhea). No anorexia nerv osa or control patient responded to the stimulus. Responsive psychogen ic amenorrhea patients showed decreased basal cortisol levels compared to the non-responsive psychogenic amenorrhea and anorexia nervosa gro ups. It is possible that patients with exclusive alterations in the do paminergic system are those who respond to metoclopramide (responsive psychogenic amenorrhea group), whereas patients who also have involvem ent of the hypothalamic-adrenal axis like the women with anorexia nerv osa, are not responsive to metoclopramide and tend to have elevated co rtisol levels. The non-responsive psychogenic amenorrhea group, with e levated cortisol levels, probably represents an intermediate step betw een the responsive psychogenic amenorrhea and anorexia nervosa patient s.