Endocrine and metabolic disorders in bulimic women and effects of antiandrogenic treatment

Background: Bulimia is a mental disorder frequently associated with menstrual disturbances and low estradiol levels although most bulimic women are of normal weight. Low bone mass has also been reported in these women. Furthermore, increased androgen levels and polycystic ovaries (PCO) have been described in bulimic women. Little is known about the mechanisms of these hormonal disturbances and the role of sex hormones in the etiology of the disease has not been fully explored. Androgens may promote bulimic behavior by influencing food craving or impulse control.

Aims: The specific aims of this work were to compare women with bulimia to healthy controls with respect to: 1) menstrual disturbances and the occurrence of polycystic ovary syndrome (PCOS) 2) endocrine and nutritionrelated factors predicting bone mass 3) estrogen receptor (ER) â polymorphism in view of the potential role of estrogen signalling in bulimic disease 4) effects of an antiandrogenic oral contraceptive (OC) on appetite and eating behaviour.

Methods: Seventy-seven bulimics and 59 controls were investigated with respect to menstrual status, PCO, symptoms of hyperandrogenism, bone mineral density (BMD), sex hormone levels and ERâ polymorphism. Meal-related appetite response and bulimic symptoms were evaluated in 21 women with bulimia nervosa before and after three months of treatment with an antiandrogenic OC.

Results: 1) Bulimics had a higher occurrence of menstrual disturbances, hirsutism and PCOS than controls. Positive correlations between hirsutism and levels of biologically active testosterone were found in bulimics but not in controls. 2) Bulimics had a lower spinal BMD and higher frequency of osteopenia in the total body than controls. Subgroups of bulimics with a history of amenorrhea or previous anorexia nervosa had the lowest BMD values, whereas those without such history did not differ from controls. Multiple regression analysis including significant endocrine and nutrition-related variables, revealed previous anorexia nervosa to be the strongest determinant of spinal BMD in bulimic women. 3) An association was found between two common polymorphisms in the ERâ gene and bulimic disease. A novel variant changing the primary structure of ERâ protein was identified in one bulimic patient, but an initial characterization of this variant did not reveal any differences compared to the wild type protein. 4) Antiandrogenic OC treatment reduced meal-related hunger and gastric distention in women with bulimia nervosa and improved bulimic behavior in relation to reduced testosterone levels.

Conclusions: 1) Our study supports an increased frequency of PCOS in bulimic women. This endocrine disorder may be of importance for the development of bulimia. 2) Low bone mass in bulimics could be explained by previous anorexia nervosa, whereas bulimia per se does not influence bone mass negatively. 3) Genetic variation in ERâ may play a role in the etiology of bulimic disease. 4) An antiandrogenic OC may develop into a new strategy for treatment of women with bulimia nervosa not responding to conventional therapy and particularly in those with hyperandrogenic symptoms.

List of scientific papers

I. Naessen S, Carlstrom K, Garoff L, Glant R, Hirschberg AL (2006). Polycystic ovary syndrome in bulimic women : an evaluation based on the new diagnostic criteria. Gynecol Endocrinol. 22(7): 388-94.
https://doi.org/10.1080/09513590600847421

II. Naessen S, Carlstrom K, Glant R, Jacobsson H, Hirschberg AL (2006). Bone mineral density in bulimic women : influence of endocrine factors and previous anorexia. Eur J Endocrinol. 155(2): 245-51.
https://doi.org/10.1530/eje.1.02202

III. Nilsson M, Naessen S, Dahlman I, Linden Hirschberg A, Gustafsson JA, Dahlman-Wright K (2004). Association of estrogen receptor beta gene polymorphisms with bulimic disease in women. Mol Psychiatry. 9(1): 28-34.
https://doi.org/10.1038/sj.mp.4001402

IV. Naessén S, Carlström K, Byström B, Pierre Y, Hirschberg AL (2006). Effects of an antiandrogenic oral contraceptive on appetite and eating behavior in bulimic women. [Submitted]