The effects of clomiphene citrate on the hypothalamic-pituitary-gonadal axis in anorexia nervosa

Serum luteinizing hormone (LH) responses to a course of clomiphene citrate were studied in eleven patients with anorexia nervosa at different stages of the illness. In malnourished patients basal levels of LH were invariably low. With the resumption of a normal weight a small but definite rise in LH levels was observed but this spontaneous response to weight gain was variable in that many patients continued to exhibit abnormally low LH levels. The response to clomiphene in terms of a rise in basal LH levels after administration of the drug, followed by a second peak of LH and subsequent menstrual bleeding, was clearly dependent in part on the patient's nutritional state. In the malnourished state the response to clomiphene was usually either absent or incomplete. After the resumption of a more normal weight, the patients invariably showed an initial rise in LH after the clomiphene, but the second LH peak and subsequent menstruation were frequently not demonstrated. Six patients maintained a normal body weight for at least six months after a course of clomiphene, but only three of them resumed cyclical menstrual bleeding. It was concluded that factors additional to the nutritional state contribute to the prolonged amenorrhoea in anorexia nervosa and that clomiphene appears to have only a limited role in the treatment and management of patients with the disorder. Some aspects of current knowledge of the endocrine mechanisms that regulate normal menstruation and of the mode of action of clomiphene are outlined. The results of the present study are discussed against this background in an attempt to elucidate further the hypothalamic disorder underlying the amenorrhoea in anorexia nervosa.