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

Abstract

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.

PIP: 11 patients with anorexia nervosa (at different stages of the illness) were treated with clomiphene citrate to determine the effect on the hypothalamic-pituitary-gonadal axis in patients with this disease. In 8 patients clomiphene was given during the acute stage of the illness with the intention of repeating the test after their weight had returned to normal. 3 patients were given a clomiphene test at a later stage of recovery (12 weeks after a return to normal weight). 3 of the 1st group of patients responded to the 1st dose of clomiphene. 3 patients resumed normal menstrual cycles. 4 patients relapsed and lost weight. 1 of these had had 1 period during the test and the others failed to menstruate. Of the remaining who maintained their body weight, 1 failed to menstruate and 2 had only a single period. Luteinizing hormone (LH) values were estimated in all patients on the day before and on the 1st day of clomiphene administration, on the last day of the course, and for the next 7-8 consecutive days. LH levels in malnourished women were 1.0 mU/ml or below. 4 patients showed a rise in serum LH during drug administration with the new level ranging from 2.0 to 5.0 mU/ml. A 2nd peak of LH was seen 5-8 days after stopping clomiphene in 3 of these patients. LH levels in patients who had failed to menstruate during the 1st test were measured after weight gain. In all cases basal LH levels had increased (1.78 mU/ml) but 2 patients had levels below the normal follicular range. In 3 patients a 2nd peak was seen. In patients who had maintained normal weight for 12 weeks, LH levels were low in 2 and low normal in 1. All showed a rise of serum LH during drug therapy. Clomiphene has only a limited role in the treatment of patients with this disorder. It is suggested that psychological factors may contribute to the ability of these patients to return to normal menstruation.