Plasma Levels of Neuroactive Steroids Are Increased in Untreated Women With Anorexia Nervosa or Bulimia Nervosa

Objective Animal data suggest that neuroactive steroids, such as 3&agr;,5&agr;-tetrahydroprogesterone (3&agr;,5&agr;-THP), dehydroepiandrosterone (DHEA), and its sulfated metabolite (DHEA-S), are involved in the modulation of eating behavior, aggressiveness, mood, and anxiety. Anorexia nervosa (AN) and bulimia nervosa (BN) are eating disorders characterized by abnormal eating patterns, depressive and anxious symptoms, enhanced aggressiveness, and endocrine alterations. Previous studies reported decreased blood levels of DHEA and DHEA-S in small samples of anorexic patients, whereas no study has been performed to evaluate the secretion of these neuroactive steroids in BN as well as the production of 3&agr;,5&agr;-THP in both AN and BN. Therefore, we measured plasma levels of DHEA, DHEA-S, 3&agr;,5&agr;-THP and other hormones in patients with AN or BN and explored possible relationships between neuroactive steroids and psychopathology. Method Ninety-two women participated in the study. There were 30 drug-free AN patients, 32 drug-free BN patients, and 30 age-matched, healthy control subjects. Blood samples were collected in the morning for determination of hormone levels. Eating-related psychopathology, depressive symptoms, and aggressiveness were rated by using specific psychopathological scales. Results Compared with healthy women, both AN and BN patients exhibited increased plasma levels of 3&agr;,5&agr;-THP, DHEA, DHEA-S, and cortisol but reduced concentrations of 17&bgr;-estradiol. Plasma testosterone levels were decreased in anorexic women but not in bulimic women. Plasma levels of neuroactive steroids were not correlated with any clinical or demographic variable. Conclusions These findings demonstrate increased morning plasma levels of peripheral neuroactive steroids in anorexic and bulimic patients. The relevance of such hormonal alterations to the pathophysiology of eating disorders remains to be elucidated.

[1]  M. First,et al.  Structured clinical interview for DSM-IV axis I disorders : SCID-I: clinical version : administration booklet , 1996 .

[2]  W. Regelson,et al.  Dehydroepiandrosterone (DHEA)--the multifunctional steroid. II. Effects on the CNS, cell proliferation, metabolic and vascular, clinical and other effects. Mechanism of action? , 1994, Annals of the New York Academy of Sciences.

[3]  J. Blundell,et al.  Pharmacological approaches to appetite suppression. , 1991, Trends in pharmacological sciences.

[4]  L. Parker Control of adrenal androgen secretion. , 1991, Endocrinology and metabolism clinics of North America.

[5]  M. Hamilton A RATING SCALE FOR DEPRESSION , 1960, Journal of neurology, neurosurgery, and psychiatry.

[6]  J. Polivy,et al.  Development and validation of a multidimensional eating disorder inventory for anorexia nervosa and bulimia. , 1983 .

[7]  C. Freeman,et al.  A Self-rating Scale for Bulimia the ‘BITE’ , 1987, British Journal of Psychiatry.

[8]  J Levin,et al.  Subnormal plasma dehydroisoandrosterone to cortisol ratio in anorexia nervosa: a second hormonal parameter of ontogenic regression. , 1983, The Journal of clinical endocrinology and metabolism.

[9]  D. Bitrán,et al.  Anxiolytic effects of 3α-hydroxy-5α[β]-pregnan-20-one: endogenous metabolites of progesterone that are active at the GABAA receptor , 1991, Brain Research.

[10]  R. Rupprecht The neuropsychopharmacological potential of neuroactive steroids. , 1997, Journal of psychiatric research.

[11]  E. Browne,et al.  Dehydroepiandrosterone: Antiglucocorticoid Action in Mice , 1992 .

[12]  W. Regelson,et al.  Dehydroepiandrosterone (DHEA)–the Multifunctional Steroid , 1994 .

[13]  S. Paul,et al.  Steroid hormone metabolites are barbiturate-like modulators of the GABA receptor. , 1986, Science.

[14]  F Brambilla,et al.  Prolactin response to d-fenfluramine is blunted in people with anorexia nervosa , 1998, British Journal of Psychiatry.

[15]  B. Baranowska,et al.  Enhanced testosterone in female patients with anorexia nervosa: its normalization after weight gain. , 1979, Acta Endocrinologica.

[16]  F. Holsboer,et al.  The Neurosteroid Tetrahydroprogesterone Attenuates the Endocrine Response to Stress and Exerts Glucocorticoid-like Effects on Vasopressin Gene Transcription in the Rat Hypothalamus , 1996, Neuropsychopharmacology.

[17]  H. Engeland,et al.  Adrenal androgens and aggression in conduct disorder prepubertal boys and normal controls , 1998, Biological Psychiatry.

[18]  Dehydroepiandrosterone (DHEA) treatment of depression , 1997, Biological Psychiatry.

[19]  E. Browne,et al.  Effect of Dehydroepiandrosterone on Neurotransmitter Levels and Appetite Regulation of the Obese Zucker Rat: The Obesity Research Program , 1993, Diabetes.

[20]  S. Yen,et al.  Effects of replacement dose of dehydroepiandrosterone in men and women of advancing age. , 1994, The Journal of clinical endocrinology and metabolism.

[21]  Functional antagonism of gonadal steroids at the 5-hydroxytryptamine type 3 receptor. , 1998, Molecular endocrinology.

[22]  N C Andreasen,et al.  The family history method using diagnostic criteria. Reliability and validity. , 1977, Archives of general psychiatry.

[23]  F. Holsboer,et al.  Neuroactive steroids: mechanisms of action and neuropsychopharmacological perspectives , 1999, Trends in Neurosciences.

[24]  K. Halmi,et al.  The Yale-Brown-Cornell Eating Disorder Scale: a new scale to assess eating disorder symptomatology. , 1995, The International journal of eating disorders.

[25]  A. Buss,et al.  An inventory for assessing different kinds of hostility. , 1957, Journal of consulting psychology.

[26]  F Brambilla,et al.  Plasma prolactin response to d-fenfluramine is blunted in bulimic patients with frequent binge episodes , 1998, Psychological Medicine.

[27]  K. Pirke,et al.  Disturbances in the hypothalamo-pituitary-adrenal and other neuroendocrine axes in bulimia , 1990, Biological Psychiatry.

[28]  W. Dixon,et al.  BMDP statistical software , 1983 .

[29]  F. Petraglia,et al.  Circulating levels of allopregnanolone in humans: gender, age, and endocrine influences. , 1998, The Journal of clinical endocrinology and metabolism.

[30]  L. Parker,et al.  Evidence for adrenocortical adaptation to severe illness. , 1985, The Journal of clinical endocrinology and metabolism.

[31]  G. Spalletta,et al.  Concentrations of 3α-reduced neuroactive steroids and their precursors in plasma of patients with major depression and after clinical recovery , 1999, Biological Psychiatry.

[32]  N. Ling,et al.  The responses of plasma adrenocorticotropin and cortisol to corticotropin-releasing hormone (CRH) and cerebrospinal fluid immunoreactive CRH in anorexia nervosa patients. , 1986, The Journal of clinical endocrinology and metabolism.

[33]  B. McEwen Steroid hormones are multifunctional messengers to the brain , 1991, Trends in Endocrinology & Metabolism.

[34]  H. Koppeschaar,et al.  A comparative and longitudinal study on endocrine changes related to ovarian function in patients with anorexia nervosa. , 1990, The Journal of clinical endocrinology and metabolism.

[35]  D. Farber,et al.  Dissociation of adrenal androgen and cortisol levels in acute stress. , 1985, Hormone and metabolic research = Hormon- und Stoffwechselforschung = Hormones et metabolisme.

[36]  E. Baulieu,et al.  Neurosteroids: Pregnenolone and Dehydroepiandrosterone in the Brain , 1987 .

[37]  E. Baulieu Neurosteroids: a new function in the brain , 1991, Biology of the cell.

[38]  J. Lacey,et al.  Ovarian morphology and insulin sensitivity in women with bulimia nervosa , 1995, Clinical endocrinology.

[39]  W. Kaye,et al.  Adrenocorticotropin-stimulated adrenal androgen secretion in anorexia nervosa: impaired secretion at low weight with normalization after long-term weight recovery. , 1985, The Journal of clinical endocrinology and metabolism.

[40]  O. Wolkowitz,et al.  Double-blind treatment of major depression with dehydroepiandrosterone. , 1999, The American journal of psychiatry.

[41]  F. Holsboer,et al.  The neurosteroid tetrahydroprogesterone counteracts corticotropin-releasing hormone-induced anxiety and alters the release and gene expression of corticotropin-releasing hormone in the rat hypothalamus , 1994, Neuroscience.