Search tips
Search criteria 


Logo of jpnSubmit a ManuscriptEmail AlertsAbout JPNJournal of Psychiatry and Neuroscience
J Psychiatry Neurosci. 1996 March; 21(2): 123–127.
PMCID: PMC1188751

The role of estrogen in schizophrenia.


This paper reviews 3 recent studies from different clinics correlating psychotic symptoms with phases of the menstrual cycle in women with schizophrenia. The aim of the paper is to focus on the estrogen protection hypothesis which would suggest that low estrogen phases correlate with more severe symptoms, and high estrogen phases correlate with less severe symptoms. Although the methodology of the 3 studies was different, the hypothesis was essentially upheld. High levels of estrogens protect against symptom exacerbations in women with schizophrenia. A corollary to this finding is that, for optimal efficacy and safety, neuroleptic doses could be reduced at certain times of the month and increased at others.

Full text

Full text is available as a scanned copy of the original print version. Get a printable copy (PDF file) of the complete article (1009K), or click on a page image below to browse page by page. Links to PubMed are also available for Selected References.

Selected References

These references are in PubMed. This may not be the complete list of references from this article.
  • Angermeyer MC, Goldstein JM, Kuehn L. Gender differences in schizophrenia: rehospitalization and community survival. Psychol Med. 1989 May;19(2):365–382. [PubMed]
  • AYD FJ., Jr A survey of drug-induced extrapyramidal reactions. JAMA. 1961 Mar 25;175:1054–1060. [PubMed]
  • Bedard P, Langelier P, Villeneuve A. Oestrogens and extrapyramidal system. Lancet. 1977 Dec 24;2(8052-8053):1367–1368. [PubMed]
  • Biehl H, Maurer K, Schubart C, Krumm B, Jung E. Prediction of outcome and utilization of medical services in a prospective study of first onset schizophrenics. Results of a prospective 5-year follow-up study. Eur Arch Psychiatry Neurol Sci. 1986;236(3):139–147. [PubMed]
  • Bromet E, Harrow M, Kasl S. Premorbid functioning and outcome in schizophrenics and nonschizophrenics. Arch Gen Psychiatry. 1974 Feb;30(2):203–207. [PubMed]
  • Castle DJ, Wessely S, Murray RM. Sex and schizophrenia: effects of diagnostic stringency, and associations with and premorbid variables. Br J Psychiatry. 1993 May;162:658–664. [PubMed]
  • Chakos MH, Mayerhoff DI, Loebel AD, Alvir JM, Lieberman JA. Incidence and correlates of acute extrapyramidal symptoms in first episode of schizophrenia. Psychopharmacol Bull. 1992;28(1):81–86. [PubMed]
  • Chang SS, Renshaw DC. Psychosis and pregnancy. Compr Ther. 1986 Oct;12(10):36–41. [PubMed]
  • Di Paolo T. Modulation of brain dopamine transmission by sex steroids. Rev Neurosci. 1994 Jan-Mar;5(1):27–41. [PubMed]
  • Dworkin RH. Patterns of sex differences in negative symptoms and social functioning consistent with separate dimensions of schizophrenic psychopathology. Am J Psychiatry. 1990 Mar;147(3):347–349. [PubMed]
  • Franzek E, Beckmann H. Sex differences and distinct subgroups in schizophrenia. A study of 54 chronic hospitalized schizophrenics. Psychopathology. 1992;25(2):90–99. [PubMed]
  • Galdos PM, van Os JJ, Murray RM. Puberty and the onset of psychosis. Schizophr Res. 1993 Jun;10(1):7–14. [PubMed]
  • Gattaz WF, Vogel P, Riecher-Rössler A, Soddu G. Influence of the menstrual cycle phase on the therapeutic response in schizophrenia. Biol Psychiatry. 1994 Jul 15;36(2):137–139. [PubMed]
  • Goldstein JM. Gender differences in the course of schizophrenia. Am J Psychiatry. 1988 Jun;145(6):684–689. [PubMed]
  • Goldstein JM, Faraone SV, Chen WJ, Tolomiczencko GS, Tsuang MT. Sex differences in the familial transmission of schizophrenia. Br J Psychiatry. 1990 Jun;156:819–826. [PubMed]
  • Goldstein JM, Faraone SV, Chen WJ, Tsuang MT. Gender and the familial risk for schizophrenia. Disentangling confounding factors. Schizophr Res. 1992 Jul;7(2):135–140. [PubMed]
  • Goldstein JM, Link BG. Gender and the expression of schizophrenia. J Psychiatr Res. 1988;22(2):141–155. [PubMed]
  • Häfner H, Behrens S, De Vry J, Gattaz WF. An animal model for the effects of estradiol on dopamine-mediated behavior: implications for sex differences in schizophrenia. Psychiatry Res. 1991 Aug;38(2):125–134. [PubMed]
  • Häfner H, Maurer K, Löffler W, Riecher-Rössler A. The influence of age and sex on the onset and early course of schizophrenia. Br J Psychiatry. 1993 Jan;162:80–86. [PubMed]
  • Häfner H, Riecher A, Maurer K, Löffler W, Munk-Jørgensen P, Strömgren E. How does gender influence age at first hospitalization for schizophrenia? A transnational case register study. Psychol Med. 1989 Nov;19(4):903–918. [PubMed]
  • Hallonquist JD, Seeman MV, Lang M, Rector NA. Variation in symptom severity over the menstrual cycle of schizophrenics. Biol Psychiatry. 1993 Feb 1;33(3):207–209. [PubMed]
  • Hambrecht M, Maurer K, Häfner H. Evidence for a gender bias in epidemiological studies of schizophrenia. Schizophr Res. 1993 Jan;8(3):223–231. [PubMed]
  • Jonsson H, Nyman AK. Predicting long-term outcome in schizophrenia. Acta Psychiatr Scand. 1991 May;83(5):342–346. [PubMed]
  • Kendell RE, Chalmers JC, Platz C. Epidemiology of puerperal psychoses. Br J Psychiatry. 1987 May;150:662–673. [PubMed]
  • Leff J, Sartorius N, Jablensky A, Korten A, Ernberg G. The International Pilot Study of Schizophrenia: five-year follow-up findings. Psychol Med. 1992 Feb;22(1):131–145. [PubMed]
  • Lieberman J, Bogerts B, Degreef G, Ashtari M, Lantos G, Alvir J. Qualitative assessment of brain morphology in acute and chronic schizophrenia. Am J Psychiatry. 1992 Jun;149(6):784–794. [PubMed]
  • Lewis S. Sex and schizophrenia: vive la différence. Br J Psychiatry. 1992 Oct;161:445–450. [PubMed]
  • Loyd D, Simpson JC, Tsuang MT. Are there sex differences in the long-term outcome of schizophrenia? Comparisons with mania, depression, and surgical controls. J Nerv Ment Dis. 1985 Nov;173(11):643–649. [PubMed]
  • Luggin R, Bernsted L, Petersson B, Jacobsen AT. Acute psychiatric admission related to the menstrual cycle. Acta Psychiatr Scand. 1984 Jun;69(6):461–465. [PubMed]
  • Maier W, Lichtermann D, Minges J, Heun R, Hallmayer J. The impact of gender and age at onset on the familial aggregation of schizophrenia. Eur Arch Psychiatry Clin Neurosci. 1993;242(5):279–285. [PubMed]
  • McCreadie RG, Robertson LJ, Wiles DH. The Nithsdale schizophrenia surveys. IX: Akathisia, parkinsonism, tardive dyskinesia and plasma neuroleptic levels. Br J Psychiatry. 1992 Jun;160:793–799. [PubMed]
  • McEwen BS. Non-genomic and genomic effects of steroids on neural activity. Trends Pharmacol Sci. 1991 Apr;12(4):141–147. [PubMed]
  • McNiel DE, Greenfield TK, Attkisson CC, Binder RL. Factor structure of a brief symptom checklist for acute psychiatric inpatients. J Clin Psychol. 1989 Jan;45(1):66–72. [PubMed]
  • Nedopil N, Pflieger R, Rüther E. The prediction of acute response, remission and general outcome of neuroleptic treatment in acute schizophrenic patients. Pharmacopsychiatria. 1983 Nov;16(6):201–205. [PubMed]
  • Opjordsmoen S. Long-term clinical outcome of schizophrenia with special reference to gender differences. Acta Psychiatr Scand. 1991 Apr;83(4):307–313. [PubMed]
  • Prudo R, Blum HM. Five-year outcome and prognosis in schizophrenia: a report from the London Field Research Centre of the International Pilot Study of Schizophrenia. Br J Psychiatry. 1987 Mar;150:345–354. [PubMed]
  • Rector NA, Seeman MV. Auditory hallucinations in women and men. Schizophr Res. 1992 Sep;7(3):233–236. [PubMed]
  • Riecher-Rössler A, Häfner H. Schizophrenia and oestrogens--is there an association? Eur Arch Psychiatry Clin Neurosci. 1993;242(6):323–328. [PubMed]
  • Riecher-Rössler A, Häfner H, Stumbaum M, Maurer K, Schmidt R. Can estradiol modulate schizophrenic symptomatology? Schizophr Bull. 1994;20(1):203–214. [PubMed]
  • Rubinow DR, Roy-Byrne P. Premenstrual syndromes: overview from a methodologic perspective. Am J Psychiatry. 1984 Feb;141(2):163–172. [PubMed]
  • Salokangas RK, Stengård E. Gender and short-term outcome in schizophrenia. Schizophr Res. 1990 Oct-Dec;3(5-6):333–345. [PubMed]
  • Seeman MV. Interaction of sex, age, and neuroleptic dose. Compr Psychiatry. 1983 Mar-Apr;24(2):125–128. [PubMed]
  • Seeman MV, Lang M. The role of estrogens in schizophrenia gender differences. Schizophr Bull. 1990;16(2):185–194. [PubMed]
  • Shtasel DL, Gur RE, Gallacher F, Heimberg C, Gur RC. Gender differences in the clinical expression of schizophrenia. Schizophr Res. 1992 Sep;7(3):225–231. [PubMed]
  • Swett C., Jr Drug-induced dystonia. Am J Psychiatry. 1975 May;132(5):532–534. [PubMed]
  • Takei N, O'Callaghan E, Sham PC, Glover G, Murray RM. Does prenatal influenza divert susceptible females from later affective psychosis to schizophrenia? Acta Psychiatr Scand. 1993 Nov;88(5):328–336. [PubMed]
  • Takei N, Sham P, O'Callaghan E, Murray GK, Glover G, Murray RM. Prenatal exposure to influenza and the development of schizophrenia: is the effect confined to females? Am J Psychiatry. 1994 Jan;151(1):117–119. [PubMed]
  • Thara R, Rajkumar S. Gender differences in schizophrenia. Results of a follow-up study from India. Schizophr Res. 1992 Apr;7(1):65–70. [PubMed]
  • Villeneuve A, Cazejust T, Côté M. Estrogens in tardive dyskinesia in male psychiatric patients. Neuropsychobiology. 1980;6(3):145–151. [PubMed]
  • Wolyniec PS, Pulver AE, McGrath JA, Tam D. Schizophrenia: gender and familial risk. J Psychiatr Res. 1992 Jan;26(1):17–27. [PubMed]
  • Yassa R, Jeste DV. Gender differences in tardive dyskinesia: a critical review of the literature. Schizophr Bull. 1992;18(4):701–715. [PubMed]

Articles from Journal of Psychiatry & Neuroscience : JPN are provided here courtesy of Canadian Medical Association