Until the last revision, one of necessary criteria for the diagnosis of AN was amenorrhoea. The fourth edition of the Diagnostic and Statistical Manual of Mental Disorder (DSM-IV) specifies the diagnostic criterion for amenorrhoea in AN as “the absence of at least three consecutive menstrual cycles (a woman is considered to have amenorrhoea if her periods occur only following hormone)”. In the updated edition fifth edition (DSM-5) as well as in the upcoming International classification of disease (ICD-11), amenorrhoea has been removed from diagnostic criteria for AN. Several arguments have been advanced for this removal. The first is the lack of specificity of amenorrhoea regarding AN. Indeed, in comparison of groups of patients with AN according to DSM IV criteria and of patients who meet all the criteria with the exception of the amenorrhoea, there are no differences in behavioural phenotype or on any aspects of the psychopathological and neuropsychological functioning between [28]. Moreover, in a latent class analysis amenorrhoea is not linked to AN but distributed in all lower weight classes [4]. We currently do not have markers of anorexia specific enough beings used for diagnostic purposes, but some adipocytokines such as leptin or ghrelin seems to have a higher specificity towards anorexia than amenorrhoea [23]. Another argument is the clinical utility of amenorrhoea as a marker of malnutrition. Amenorrhoea is no more predictive of physical complications and somatic consequences (including bone remodelling) of AN than current BMI and lowest BMI lifetime [1]. On a biological level, the most predictive somatic marker of complications related to under nutrition is the prealbumin [8]. Also, the requirement of amenorrhoea is irrelevant in some subgroups of patients with AN such as women under contraceptive medication, men or menopausal women. Finally, a recurrent critical made to DSM-IV diagnosis was the proportion of patients not responding to a specified disorder (AN, bulimia nervosa). Without amenorrhoea but with all the others features of the disease, AN patients were switched to a category called Eating Disorders Not Otherwise Specified (EDNOS). Up to 60 % of eating disorders were classified in this category [7]. This heterogeneous category initially designed to include residual disorders, was actually a wastebasket class of no interest to identify a clinical description and guide treatment. By relaxing the criteria of AN and bulimia nervosa, and including a new category the binge eating disorders as a separate diagnosis, as well as a number of smaller sub-diagnoses, the DSM-5 aims to reduce numbers of EDNOS. All these arguments therefore logically led to moving amenorrhoea from a mandatory diagnosis criterion to an associated features supporting diagnosis.

The weight restoration with a return of menstruation is considered the prerequisite to an improvement of the disease. The global aim of care is to restore normal weight, a suitable and relaxed behaviour with food, improve social and interpersonal relationships, as well as self-perception of patients. Given alterations in gonadal function usually observed in patients suffering from AN, it has been proposed to compensate low oestrogens levels by introduction of substitution therapy. Several studies hypothesised that replacement might be effective in increasing BMD. However, randomized clinical trials using different molecules (Premarin, Provera, ethinyl estradiol, norethindrone) [10, 12, 16] showed no significant benefits on BMD. However, the response to the treatment may depend on various factors. Klibanski et al. [16] reported that patients with the lowest percent ideal body weight had the most significant improvement in spinal BMD during oestrogen administration, suggesting that oestrogen replacement therapy may be beneficial in preventing bone loss in young women with extremely low body weight. It was also probable that the lack of significant BMD gain may be attributed to the dose which is usually too low to have a favourable impact on BMD [17]. A too short duration of prescription as well as a poor compliance might also be in play [14]. Klibanski et al. [16] reported a marked improvement in spinal BMD in patients who spontaneously resumed menses during the study, suggesting that resumption of normal menstrual function has a different effect on bone mass than oestrogen replacement. It was probable that oestrogen treatment alone cannot correct the multiple factors (nutritional or other hormonal variable) contributing to bone loss [16]. From these results, hypoestrogenia may be considered only as a contributing factor to the bone alteration in AN patients, and it may be implicated principally in the reduction of the volumetric BMD, while malnutrition may account for reduced bone size [14]. For a better efficacy, hormonal replacement therapy should be considered soon after diagnosis.