Hostname: page-component-78c5997874-t5tsf Total loading time: 0 Render date: 2024-11-10T11:26:39.119Z Has data issue: false hasContentIssue false
  • English
  • Français

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

Published online by Cambridge University Press:  09 July 2009

A. Wakeling ,
J. C. Marshall ,
C. J. Beardwood ,
V. F. A. de Souza  and
G. F. M. Russell
A. Wakeling*
Affiliation:
Academic Department of Psychiatry, Royal Free Hospital School of Medicine, London
J. C. Marshall
Affiliation:
Academic Department of Psychiatry, Royal Free Hospital School of Medicine, London
C. J. Beardwood
Affiliation:
Academic Department of Psychiatry, Royal Free Hospital School of Medicine, London
V. F. A. de Souza
Affiliation:
Academic Department of Psychiatry, Royal Free Hospital School of Medicine, London
G. F. M. Russell
Affiliation:
Academic Department of Psychiatry, Royal Free Hospital School of Medicine, London
*
1Address for correspondence: Dr A. Wakeling, Academic Department of Psychiatry, Royal Free Hospital School of Medicine, Pond Street, London NW3 2QG.
Get access Rights & Permissions [Opens in a new window]

Synopsis

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.

Type
Research Article
Information
Psychological Medicine , Volume 6 , Issue 3 , August 1976 , pp. 371 - 380
Copyright
Copyright © Cambridge University Press 1976

Access options

Get access to the full version of this content by using one of the access options below. (Log in options will check for institutional or personal access. Content may require purchase if you do not have access.)

References

REFERENCES

Bardin, C. W., Ross, G. T. & Lipsett, M. B. (1967). Site of action of clomiphene citrate in men: a study of the pituitary–leydig cell axis. Journal of Clinical Endocrinology and Metabolism 27, 1558–1564.CrossRefGoogle Scholar
Beumont, P. J. V., Carr, P.J. & Gelder, M. G. (1973). Plasma levels of luteinizing hormone and of immuno-reactive oestrogens (oestradiol) in anorexia nervosa: response to clomiphene citrate. Psychological Medicine 3, 495–501.CrossRefGoogle Scholar
Cargille, C. M., Ross, S. T. & Bardin, C. W. (1968). Clomiphene and gonadotrophin in men. Lancet ii, 1298.CrossRefGoogle Scholar
Crisp, A. H. (1967). Anorexia nervosa. Hospital Medicine 1, 713–718.Google Scholar
Crisp, A. H., Chen, C., Mackinnon, P. C. B. & Corker, C. (1973). Observations of gonadotrophic and ovarian hormone activity during recovery from anorexia nervosa. Postgraduate Medical Journal 49, 584–590.CrossRefGoogle ScholarPubMed
Dally, P. (1969). Anorexia Nervosa. Heinemann: London.Google Scholar
Donovan, B. T. & Van der Werff Ten Bosch, J.J. (1965). Physiology of Puberty. Monographs of the Physiology Society. Edward Arnold: London.Google Scholar
Franchimont, P. (1971). The regulation of follicle stimulating hormone and luteinizing hormone secretion in humans. Frontiers in Neuroendocrinology 1971 (ed. Martini, L. & Ganong, W. F.), pp. 331–358. Oxford University Press: London.Google Scholar
Jacobson, A., Marshall, J. R., Ross, S. T. & Cargille, C. M. (1968). Plasma gonadotrophins during clomiphene-induced ovulatory cycles. American Journal of Obstetrics and Gynaecology 102, 284–290.CrossRefGoogle ScholarPubMed
Kay, D. W. K. & Leigh, D. (1954). The natural history, treatment and prognosis of anorexia nervosa, based on a study of 38 patients. Journal of Mental Science 100, 411–431.CrossRefGoogle ScholarPubMed
Kelch, R. P., Grumbach, M. M. & Kaplan, S. L. (1972). Studies in the mechanism of puberty in men. In Gonadotrophins (ed. Saxena, B. B.), pp. 524–534. John Wiley & Sons: New York.Google Scholar
Knobil, E., Dietschke, D. J., Yanaji, T., Hotchkiss, J. & Weick, R. F. (1972). Role of oestrogen in the positive and negative feedback control of LH secretion during the menstrual cycles of the rhesus monkey. In Gonadotrophins (ed. Saxena, B. B.), pp. 72–86. John Wiley & Sons: New York.Google Scholar
McCann, S. M., Kalra, S. P., Kalra, P. S., Donoso, A. O., Bishop, W., Schneider, M. P. G., Fawcett, C. P. & Krolich, L. (1972). The role of monoamines in the control of gonadotrophins and prolactin secretion. In Gonadotrophins (ed. Saxena, B. B.), pp. 49–60. John Wiley & Sons: New York.Google Scholar
Marshall, J. C. & Russell Fraser, T. (1971). Amenorrhoea in anorexia nervosa: assessment and treatment with clomiphene citrate. British Medical Journal 4, 590–592.CrossRefGoogle ScholarPubMed
Marshall, J. C., Anderson, D. C., Burke, C. W., Calvao-Teles, A. & Fraser, T. R. (1972). Clomiphene citrate in men: increase in Cortisol, luteinizing hormone, testosterone and steroid binding globulins. Journal of Endocrinology 53, 261–276.CrossRefGoogle ScholarPubMed
Marshall, J. C., Morris, R., Court, J. & Butt, W. R. (1973). Absent positive feedback of oestrogens: a cause of amenorrhoea in hypothalmic–pituitary disease. Journal of Endocrinology 59, xxiv.Google Scholar
Ross, G. T., Cargille, C. M., Lipsett, M. B., Rayford, P. L., Marshall, J. R., Strott, C. A. & Rodbold, D. (1970). Pituitary and gonadal hormones in women during spontaneous and induced ovulatory cycles. Recent Progress in Hormone Research 26, 1–62.Google ScholarPubMed
Roy, S., Greenblatt, R. B., Mahesh, V. B. & Jungck, E. C. (1963). Clomiphene citrate: further observations on its use in induction of ovulation in the human and its mode of action. Fertility and Sterility 14, 575–595.CrossRefGoogle ScholarPubMed
Russell, G. F. M. (1969). Metabolic endocrine and psychiatric aspects of anorexia nervosa. In The Scientific Basis of Medicine Annual Reviews, chap. 14, pp. 236–255. Athlone Press: London.Google Scholar
Russell, G. F. M. (1970). Anorexia nervosa: its identity as an illness and its treatment. In Modern Trends in Psychological Medicine, vol. 2 (ed. Price, J. H.), pp. 131–164. Butter-worths: London.Google Scholar
Russell, G. F. M. (1973). The management of anorexia nervosa. In Symposium: Anorexia Nervosa and Obesity (ed. Robertson, R. F.), pp. 44–62. Royal College of Physicians at Edinburgh, Publication 42.Google Scholar
Russell, G. F. M. & Beardwood, C.J. (1968). The feeding disorders, with particular reference to anorexia nervosa and its associated gonadotropin changes. In Endocrinology and Human Behaviour (ed. Michael, R. P.), pp. 310–329. Oxford University Press: London.Google Scholar