Oestrogen-A Protective Factor in Schizophrenia?

Abstract

Gender differences in schizophrenia, in the age of onset, course, lifetime risk, age distribution of onsets over the life cycle and clinical symptoms will be reviewed from the literature and our own studies. Also, the pre-and postmenopausal course of illness in women will be explored. Explanations for the gender differences using "normal" behavioural sex differences and the protective oestrogen hypothesis will be discussed. The hypothesis of the "protective" effect of oestrogen is based on findings from animal experiments, epidemiological and clinical studies. Oestrogen acts similarly on D 2 , 5-HT A2 and NMDA receptors in both the neurochemical and genomic domains. The neuroprotective effects of oestrogen on a genomic and cellular level might also favourably affect degenerative processes in schizophrenia. The lack of a gender difference in age of onset in familial schizophrenia due to a lower age of onset in pre-menopausal, genetically predisposed women strongly suggests an antagonistic balance between predisposition to the illness and the oestrogen effect.Oestrogen treatment plus antipsychotic therapy, compared with antipsychotic therapy alone, accelerates symptom remission in both women and men, thus corroborating the antipsychotic properties of oestrogen. Oestrogen is the only known substance with preventive potential in schizophrenia. However, health risks associated with long-term oestrogen treatment require careful weighing up of risks and benefits for patients. Future efforts to develop oestrogen-like compounds which do not affect breast and uterine tissue must be strongly encouraged.

From Onset and Prodromal Stage to a Life-Long Course of Schizophrenia and Its Symptom Dimensions: How Sex, Age, and Other Risk Factors Influence Incidence and Course of Illness

“…Psychotic symptoms showing significant age trends; based on data from CIMH (N=1,109) (CIMH: Central Institute of Mental Health) . Source: [33]. …”

“…Previously reported data from the ABC Schizophrenia Study and related studies were used to support this study and are available in articles published by Heinz Häfner, as first or coauthor in various psychiatric journals. These prior studies and datasets are cited at relevant places within the text as [5–12, 18, 22–25, 33, 41, 42, 50, 51, 54, 55, 60, 61].…”

From the catastrophe to a humane mental‐health care and successful research in German psychiatry (1951–2012) – as I remember it

“… on data from the Danish case register and with A. Jablensky and N. Sartorius on data from the WHO ten‐country study . We showed that a social explanation was unlikely and finally discovered, together with W. Gattaz, that biology provided an explanation: there was a protective effect of oestrogen, mediated by a sensitivity reducing effect on D2 receptors . When we compared the prodromal stages of schizophrenia with those of unipolar depression, we found a high degree of similarity .…”

Gender, age at onset, and duration of being ill as predictors for the long-term course and outcome of schizophrenia: an international multicenter study

“…The literature supports such a gender effect [11][12][13][14][15][16][17] which was observed already since the beginning of the 20 th century on the age at onset 18 . There are some data suggesting that age at menarche could be negatively associated with age at onset 19 and more specifically a specific protective effect of estrogens through down regulation of D2 receptors could be in place [20][21][22][23] . In support to this theory there are some data on the beneficial effect of adjunctive oestrogen therapy in refractory female cases [24][25][26][27][28] .…”

“…Patients were grouped according to gender (males vs females) and also according to duration in seven groups (<5, 5-10, 11-15, 16-20, 21-25, 26-30, and >31) and according to age at onset in four groups: very early onset (at age <15), early onset (at age [15][16][17][18][19][20][21][22][23][24], late onset (at age [25][26][27][28][29][30][31][32][33][34], and very late onset (at age >34).…”