The oestrogen dysfunction hypothesis in schizophrenia: The need for an integrative approach to treat postmenopausal women

To the Editor

The oestrogen dysfunction hypothesis has provided important insights into the relationship between hormonal changes and schizophrenia; however, this question remains still unclear (Kulkarni et al., 2015).

Menopause is a universal process for women that determines a decline in oestrogen levels (Riecher-Rössler and Kulkarni, 2011). It has been associated with later onset of schizophrenia, occurrence of psychotic exacerbations, poorer outcomes and lower antipsychotic responses. Furthermore, adjunctive oestrogen therapy has been recently found to have a positive effect on central nervous system through genomic and non-genomic mechanisms (Kulkarni et al., 2015), irrespective of oestrogen levels.

One of the most important predictors of the age at natural menopause is the follicular reserve, mainly affected by endogenous or exogenous/surgical factors. For instance, smoking, psychosocial and genetic factors and oophorectomy are associated with earlier age at menopause (Riecher-Rössler and Kulkarni, 2011). Several studies have also found a weight gain at the time of menopause (Seeman, 2012), higher rates of nicotine dependence and life-shortening in schizophrenia women (Riecher-Rössler and Kulkarni, 2011). Furthermore, long-term antipsychotic-induced hyperprolactinaemia may increase risk of bone mineral density (BMD) loss (Seeman, 2012).

From our point of view, although menopause is a universal process for women, the impact that menopause has on mental well-being varies between women. For this reason, developing specific prevention programmes to address the influence of menopause on medical and psychiatric difficulties in women with schizophrenia would be an interesting topic for future studies, with particular consideration for the genomic and non-genomic effects of oestrogens (Kulkarni et al., 2015). These programmes should be integrated by mental health professionals, physicians, gynaecologists and nurses, with the main aim of promoting higher attendance rates at gynaecological appointments, preventing and treating antipsychotic-induced hyperprolactinaemia (e.g. antipsychotic switching), combining lifestyle intervention (Seeman, 2012) and considering new oestrogen therapies in this population (Kulkarni et al., 2015). A brief description of the following clinical case might illustrate this point. Mrs R. is a 59-year-old postmenopausal smoker women diagnosed with schizophrenia. In 2001, she had presented to our outpatient service stabilised with venlafaxine 225 mg/day and risperidone 3 mg/day. At the age of menopause, the patient developed a worsening of positive and negative symptoms, presented episodes of severe aggressive behaviour and needed higher doses of antipsychotics leading to increasing levels of prolactin. Specific intervention for smoking cessation was recommended and dual-energy X-ray absorptiometry (i.e. lumbar and hip bones) suggested the need to treat BMD loss.