Peak of incidence earlier in men than women [3, 4]
Second peak of incidence in women at menopause [19]
Clinical studies
Hormonal status and psychopathological symptoms
Low levels of oestrogens associated with more severe psychotic symptoms [5, 19, 20]
Hormonal status and cognitive symptoms
Menstrual cycle irregularity associated with cognitive impairment [24]
Clinical trials
Administration of exogenous oestrogens
Positive effects of oestrogens on clinical symptoms [5]
Declarations
Author contributions
AGR and JC: Conceptualization, Data curation, Writing—original draft, Writing—review & editing. MVS: Conceptualization, Data curation, Writing—original draft, Writing—review & editing, Supervision.
Conflicts of interest
AGR has received registrations for congresses or travel funds from Janssen Global Services, Lundbeck, Otsuka Pharmaceutical, and Angelini Pharma, and honoraria for lectures from Lundbeck and Otsuka.
Seeman MV. Men and women respond differently to antipsychotic drugs.Neuropharmacology. 2020;163:107631. [DOI] [PubMed]
Seeman MV. Sex differences in schizophrenia relevant to clinical care.Expert Rev Neurother. 2021;21:443–53. [DOI] [PubMed]
Li X, Zhou W, Yi Z. A glimpse of gender differences in schizophrenia.Gen Psychiatr. 2022;35:e100823. [DOI] [PubMed] [PMC]
Kulkarni J. Estrogen – a key neurosteroid in the understanding and treatment of mental illness in women.Psychiatry Res. 2023;319:114991. [DOI] [PubMed]
Ochoa S, Usall J, Cobo J, Labad X, Kulkarni J. Gender differences in schizophrenia and first-episode psychosis: a comprehensive literature review.Schizophr Res Treatment. 2012;2012:916198. [DOI] [PubMed] [PMC]
Bucci P, Giordano GM, Mucci A, Rocca P, Rossi A, Bertolino A, et al.; Italian Network for Research on Psychoses. Sex and gender differences in clinical and functional indices in subjects with schizophrenia and healthy controls: data from the baseline and 4-year follow-up studies of the Italian Network for Research on Psychoses.Schizophr Res. 2023;251:94–107. [DOI] [PubMed]
González-Rodríguez A, Guàrdia A, Álvarez Pedrero A, Betriu M, Cobo J, Acebillo S, et al. Women with schizophrenia over the life span: health promotion, treatment and outcomes.Int J Environ Res Public Health. 2020;17:5594. [DOI] [PubMed] [PMC]
Dion-Albert L, Bandeira Binder L, Daigle B, Hong-Minh A, Lebel M, Menard C. Sex differences in the blood-brain barrier: implications for mental health.Front Neuroendocrinol. 2022;65:100989. [DOI] [PubMed]
Capuzzi E, Caldiroli A, Quitadamo C, Butturini F, Surace T, Clerici M, et al. Novel pharmacotherapy targeting the positive symptoms of schizophrenia.Expert Opin Pharmacother. 2023;24:1623–48. [DOI] [PubMed]
Jönsson AK, Schill J, Olsson H, Spigset O, Hägg S. Venous thromboembolism during treatment with antipsychotics: a review of current evidence.CNS Drugs. 2018;32:47–64. [DOI] [PubMed] [PMC]
Kraepelin E. Dementia praecox and paraphrenia. Robertson GM, editor. Huntington (NY): Robert E. Krieger Publishing Co. Inc.; 1971.
Braatöy T. Männer zwischen 15 und 25 Jahren. Oslo: Fabritius & Sonner; 1934. German.
Noreik K, Ödegård Ö. Age at onset of schizophrenia in relation to socio-economic factors.Br J Soc Psychiat. 1967;1:243–9.
Forrest AD, Hay AJ. The influence of sex on schizophrenia.Acta Psychiatr Scand. 1972;48:49–58. [DOI] [PubMed]
Lewine RR. Sex differences in schizophrenia: timing or subtypes?Psychol Bull. 1981;90:432–44. [DOI] [PubMed]
Seeman MV. Gender and the onset of schizophrenia: neurohumoral influences.Psychiatr J Univ Ottawa. 1981;6:136–8.
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;19:903–18. [DOI] [PubMed]
McEwen BS, Davis PG, Parsons B, Pfaff DW. The brain as a target for steroid hormone action.Annu Rev Neurosci. 1979;2:65–112. [DOI] [PubMed]
González-Rodríguez A, Seeman MV. Pharmacotherapy for schizophrenia in postmenopausal women.Expert Opin Pharmacother. 2018;19:809–21. [DOI] [PubMed]
Brzezinski-Sinai NA, Brzezinski A. Schizophrenia and sex hormones: What is the link?Front Psychiatry. 2020;11:693. [DOI] [PubMed] [PMC]
Riecher-Rössler A. Oestrogens, prolactin, hypothalamic-pituitary-gonadal axis, and schizophrenic psychoses.Lancet Psychiatry. 2017;4:63–72. [DOI] [PubMed]
Thomas N, Gurvich C, Hudaib AR, Gavrilidis E, Kulkarni J. Dissecting the syndrome of schizophrenia: associations between symptomatology and hormone levels in women with schizophrenia.Psychiatry Res. 2019;280:112510. [DOI] [PubMed]
Herceg M, Puljić K, Sisek-Šprem M, Herceg D. Influence of hormonal status and menstrual cycle phase on psychopathology in acute admitted patients with schizophrenia.Psychiatr Danub. 2018;30:175–9. [PubMed]
Searles S, Makarewicz JA, Dumas JA. The role of estradiol in schizophrenia diagnosis and symptoms in postmenopausal women.Schizophr Res. 2018;196:35–8. [DOI] [PubMed]
Culbert KM, Thakkar KN, Klump KL. Risk for midlife psychosis in women: critical gaps and opportunities in exploring perimenopause and ovarian hormones as mechanisms of risk.Psychol Med. 2022;52:1612–20. [DOI] [PubMed] [PMC]
Brand BA, de Boer JN, Dazzan P, Sommer IE. Towards better care for women with schizophrenia-spectrum disorders.Lancet Psychiatry. 2022;9:330–6. [DOI] [PubMed]
Nallani MC, Powell MM, Pugh S, Kearns AM, Adams HA, Weiner E, et al. 25-hydroxyvitamin D and metabolic-related laboratory values in women with schizophrenia and hyperprolactinemia.J Psychiatr Res. 2022;151:25–9. [DOI] [PubMed]
Gurvich C, Gavrilidis E, Worsley R, Hudaib A, Thomas N, Kulkarni J. Menstrual cycle irregularity and menopause status influence cognition in women with schizophrenia.Psychoneuroendocrinology. 2018;96:173–8. [DOI] [PubMed]
Yu K, Wang Y, Wang XQ, Ma R, Li YL, Zhou YQ. Experience of reproductive concerns in women with schizophrenia: a descriptive phenomenological study.Int J Nurs Stud. 2022;135:104343. [DOI] [PubMed]
Seeman MV. Women who suffer from schizophrenia: critical issues.World J Psychiatry. 2018;8:125–36. [DOI] [PubMed] [PMC]
Sethuraman B, Rachana A, Kurian S. Knowledge, attitude, and practice regarding contraception among women with schizophrenia: an observational study from south India.Indian J Psychol Med. 2019;41:323–30. [DOI] [PubMed] [PMC]
Vickers ML, Choi YK, Eriksson L, Polyakova-Nelson Y, Jokovic Z, Parker SD, et al. Sexual and reproductive health in adolescents and young adults with psychotic disorders: a scoping review.Schizophr Bull. 2023;49:108–35. [DOI] [PubMed] [PMC]
Posada Correa AM, Andrade Carrillo RA, Suarez Vega DC, Gómez Cano S, Agudelo Arango LG, Tabares Builes LF, et al. Sexual and reproductive health in patients with schizophrenia and bipolar disorder.Rev Colomb Psiquiatr (Engl Ed). 2020;49:15–22. [DOI] [PubMed]
Barker LC, Vigod SN. Sexual health of women with schizophrenia: a review.Front Neuroendocrinol. 2020;57:100840. [DOI] [PubMed]
Zhao S, Wang X, Qiang X, Wang H, He J, Shen M, et al. Is there an association between schizophrenia and sexual dysfunction in both sexes? A systematic review and meta-analysis.J Sex Med. 2020;17:1476–88. [DOI] [PubMed]
Ross NE, Webster TG, Tastenhoye CA, Hauspurg AK, Foust JE, Gopalan PR, et al. Reproductive decision-making capacity in women with psychiatric illness: a systematic review.J Acad Consult Liaison Psychiatry. 2022;63:61–70. [DOI] [PubMed] [PMC]
Reardon DC. The abortion and mental health controversy: a comprehensive literature review of common ground agreements, disagreements, actionable recommendations, and research opportunities.SAGE Open Med. 2018;6:2050312118807624. [DOI] [PubMed] [PMC]
Edinoff AN, Silverblatt NS, Vervaeke HE, Horton CC, Girma E, Kaye AD, et al. Hyperprolactinemia, clinical considerations, and infertility in women on antipsychotic medications.Psychopharmacol Bull. 2021;51:131–48. [PubMed] [PMC]
Gupta R, Brown HK, Barker LC, Dennis CL, Vigod SN. Rapid repeat pregnancy in women with schizophrenia.Schizophr Res. 2019;212:86–91. [DOI] [PubMed]
Frayne J, Hauck Y, Nguyen T, Liira H, Morgan VA. Reproductive planning, vitamin knowledge and use, and lifestyle risks of women attending pregnancy care with a severe mental illness.Scand J Prim Health Care. 2021;39:60–6. [DOI] [PubMed] [PMC]
Taft AJ, Shankar M, Black KI, Mazza D, Hussainy S, Lucke JC. Unintended and unwanted pregnancy in Australia: a cross-sectional, national random telephone survey of prevalence and outcomes.Med J Aust. 2018;209:407–8. [DOI] [PubMed]
Crear-Perry J, Correa-de-Araujo R, Lewis Johnson T, McLemore MR, Neilson E, Wallace M. Social and structural determinants of health inequities in maternal health.J Womens Health (Larchmt). 2021;30:230–5. [DOI] [PubMed] [PMC]
Etchecopar-Etchart D, Mignon R, Boyer L, Fond G. Schizophrenia pregnancies should be given greater health priority in the global health agenda: results from a large-scale meta-analysis of 43,611 deliveries of women with schizophrenia and 40,948,272 controls.Mol Psychiatry. 2022;27:3294–305. [DOI] [PubMed] [PMC]
Dua D, Grover S. Delusion of denial of pregnancy: a case report.Asian J Psychiatr. 2019;45:72–3. [DOI] [PubMed]
Simoila L, Isometsä E, Gissler M, Suvisaari J, Sailas E, Halmesmäki E, et al. Pregnancy, delivery and postpartum in women with schizophrenia or schizoaffective disorder in Finland: a national register-based comparative study.Psychiatry Res. 2020;294:113504. [DOI] [PubMed]
Dazzan P. Schizophrenia during pregnancy.Curr Opin Psychiatry. 2021;34:238–44. [DOI] [PubMed]
Heinonen E, Forsberg L, Nörby U, Wike K, Källén K. Antipsychotic use during pregnancy and risk for gestational diabetes: a national register-based cohort study in Sweden.CNS Drugs. 2022;36:529–39. [DOI] [PubMed] [PMC]
Harris EL, Frayne J, Allen S, Renganathan K, Nguyen TN. Psychiatric admission during pregnancy in women with schizophrenia who attended a specialist antenatal clinic.J Psychosom Obstet Gynaecol. 2019;40:211–6. [DOI] [PubMed]
Skórska M, Makara-Studzińska M. A pregnant patient with schizophrenia – dilemmas of treatment and care. A problem still not only for psychiatrists.Psychiatr Pol. 2020;54:715–25. [DOI] [PubMed]
Nguyen T, Frayne J, Watson S, Lebedevs T, Teoh S, Galbally M. Long-acting injectable antipsychotic treatment during pregnancy: outcomes for women at a tertiary maternity hospital.Psychiatry Res. 2022;313:114614. [DOI] [PubMed]
Eleftheriou G, Butera R, Sangiovanni A, Palumbo C, Bondi E. Long-acting injectable antipsychotic treatment during pregnancy: a case series.Int J Environ Res Public Health. 2023;20:3080. [DOI] [PubMed] [PMC]
Iwata Y, Aruga Y, Ohtsuki M, Inoue M, Yasuda K, Hirata T, et al. Successful introduction of paliperidone palmitate for pregnant woman with schizophrenia: case presentation and literature review.J Clin Psychopharmacol. 2021;41:210–2. [DOI] [PubMed]
González-Rodríguez A, Seeman MV. The association between hormones and antipsychotic use: a focus on postpartum and menopausal women.Ther Adv Psychopharmacol. 2019;9:2045125319859973. [DOI] [PubMed] [PMC]
Reddy DS, Mbilinyi RH, Estes E. Preclinical and clinical pharmacology of brexanolone (allopregnanolone) for postpartum depression: a landmark journey from concept to clinic in neurosteroid replacement therapy.Psychopharmacology (Berl). 2023;240:1841–63. [DOI] [PubMed] [PMC]
Sakellari E, Iliadou M, Pikouli K, Konstantakopoulos G. Health professionals’ attitudes towards breastfeeding among women with schizophrenia: Greek version of a specific rating scale.Psychiatriki. 2020;31:151–61. [DOI] [PubMed]
Taylor CL, Brown HK, Saunders NR, Barker LC, Chen S, Cohen E, et al. Maternal schizophrenia, skin-to-skin contact, and infant feeding initiation.Schizophr Bull. 2022;48:145–53. [DOI] [PubMed] [PMC]
Raymond S, Ducasse MV, Azoulay M, Gasman I. Maternal filicide and mental illness: a descriptive study of 17 women hospitalized in a French secure unit over a 24-year period.J Forensic Sci. 2021;66:1818–28. [DOI] [PubMed]
Giacco S, Tarter I, Lucchini G, Cicolini A. Filicide by mentally ill maternal perpetrators: a longitudinal, retrospective study over 30 years in a single Northern Italy psychiatric-forensic facility.Arch Womens Ment Health. 2023;26:153–65. [DOI] [PubMed]
Gogia S, Grieb A, Jang A, Gordon MR, Coverdale J. Medical considerations in delusion of pregnancy: a systematic review.J Psychosom Obstet Gynaecol. 2022;43:51–7. [DOI] [PubMed]
Lefebvre A, Pouchon A, Bioulac S, Mallet J, Polosan M, Dondé C. Management of schizophrenia in women during the perinatal period: a synthesis of international recommendations.Expert Opin Pharmacother. 2022;23:1337–50. [DOI] [PubMed]
Leslie K, Barker LC, Brown HK, Chen S, Dennis CL, Ray JG, et al. Risk of interpersonal violence during and after pregnancy among people with schizophrenia: a population-based cohort study.CMAJ. 2023;195:E322–9. [DOI] [PubMed] [PMC]
Beard E, Honey A, Hancock N, Awram R, Miceli M, Mayes R. What roles do male partners play in the mothering experiences of women living with mental illness? A qualitative secondary analysis.BMC Psychiatry. 2019;19:229. [DOI] [PubMed] [PMC]
Zerihun T, Tesfaye M, Deyessa N, Bekele D. Intimate partner violence among reproductive-age women with chronic mental illness attending a psychiatry outpatient department: cross-sectional facility-based study, Addis Ababa, Ethiopia.BMJ Open. 2021;11:e045251. [DOI] [PubMed] [PMC]
Chan B, Sachs CJ. Intimate partner violence and sexual violence.Emerg Med Clin. 2023;41:369–80. [DOI] [PubMed]
Vigod SN, Ray JG, Cohen E, Wilton AS, Saunders NR, Barker LC, et al. Maternal schizophrenia and the risk of a childhood chronic condition.Schizophr Bull. 2022;48:1252–62. [DOI] [PubMed] [PMC]
Toufeili A, Cohen E, Ray JG, Wilton AS, Brown HK, Saunders NR, et al. Complex chronic conditions among children born to women with schizophrenia.Schizophr Res. 2022;241:24–35. [DOI] [PubMed]
Taylor CL, Brown HK, Saunders NR, Barker LC, Chen S, Cohen E, et al. Accidental injury, self-injury, and assault among children of women with schizophrenia: a population-based cohort study.Acta Psychiatr Scand. 2021;143:406–17. [DOI] [PubMed]
Kousoulis AA. Injuries in the children of parents living with mental illness.BMJ. 2020;369:m1317. [DOI] [PubMed]
Taylor CL, Brown HK, Saunders NR, Barker LC, Chen S, Cohen E, et al. Preventive health care among children of women with schizophrenia: a population-based cohort study.J Clin Psychiatry. 2023;84:22m14497. [DOI] [PubMed]
González-Rodríguez A, Monreal JA, Seeman MV. The effect of menopause on antipsychotic response.Brain Sci. 2022;12:1342. [DOI] [PubMed] [PMC]
Brand BA, Haveman YRA, de Beer F, de Boer JN, Dazzan P, Sommer IEC. Antipsychotic medication for women with schizophrenia spectrum disorders.Psychol Med. 2022;52:649–63. [DOI] [PubMed] [PMC]
Sommer IE, Brand BA, Gangadin S, Tanskanen A, Tiihonen J, Taipale H. Women with schizophrenia-spectrum disorders after menopause: a vulnerable group for relapse.Schizophr Bull. 2023;49:136–43. [DOI] [PubMed] [PMC]
González-Rodríguez A, Seeman MV, Díaz-Pons A, Ayesa-Arriola R, Natividad M, Calvo E, et al. Do sex/gender and menopause influence the psychopathology and comorbidity observed in delusional disorders?J Clin Med. 2022;11:4550. [DOI] [PubMed] [PMC]
Szeliga A, Stefanowski B, Meczekalski B, Snopek M, Kostrzak A, Smolarczyk R, et al. Menopause in women with schizophrenia, schizoaffective disorder and bipolar disorder.Maturitas. 2021;152:57–62. [DOI] [PubMed]
Huerta-Ramos E, Labad J, Cobo J, Núñez C, Creus M, García-Parés G, et al.; RALOPSYCAT Group; Usall J. Effects of raloxifene on cognition in postmenopausal women with schizophrenia: a 24-week double-blind, randomized, parallel, placebo-controlled trial.Eur Arch Psychiatry Clin Neurosci. 2020;270:729–37. [DOI] [PubMed]
Wang Q, Dong X, Wang Y, Li X. Raloxifene as an adjunctive treatment for postmenopausal women with schizophrenia: a meta-analysis of randomized controlled trials.Arch Womens Ment Health. 2018;21:31–41. [DOI] [PubMed]
Li Z, Wang Y, Wang Z, Kong L, Liu L, Li L, et al. Estradiol and raloxifene as adjunctive treatment for women with schizophrenia: a meta-analysis of randomized, double-blind, placebo-controlled trials.Acta Psychiatr Scand. 2023;147:360–72. [DOI] [PubMed]
Brand BA, de Boer JN, Marcelis MC, Grootens KP, Luykx JJ, Sommer IE. The direct and long-term effects of raloxifene as adjunctive treatment for schizophrenia-spectrum disorders: a double-blind, randomized clinical trial.Schizophr Bull. 2023;49:1579–90. [DOI] [PubMed] [PMC]
Solmi M, Firth J, Miola A, Fornaro M, Frison E, Fusar-Poli P, et al. Disparities in cancer screening in people with mental illness across the world versus the general population: prevalence and comparative meta-analysis including 4 717 839 people.Lancet Psychiatry. 2020;7:52–63. [DOI] [PubMed]
Taipale H, Solmi M, Lähteenvuo M, Tanskanen A, Correll CU, Tiihonen J. Antipsychotic use and risk of breast cancer in women with schizophrenia: a nationwide nested case-control study in Finland.Lancet Psychiatry. 2021;8:883–91. [DOI] [PubMed]
González-Rodríguez A, Labad J, Seeman MV. Antipsychotic-induced hyperprolactinemia in aging populations: prevalence, implications, prevention and management.Prog Neuropsychopharmacol Biol Psychiatry. 2020;101:109941. [DOI] [PubMed]
Lawrence WR, Kuliszewski MG, Hosler AS, Leinung MC, Zhang X, Zhang W, et al. Association between preexisting mental illnesses and mortality among medicaid-insured women diagnosed with breast cancer.Soc Sci Med. 2021;270:113643. [DOI] [PubMed] [PMC]
Maurus I, Roell L, Keeser D, Papazov B, Papazova I, Lembeck M, et al. Fitness is positively associated with hippocampal formation subfield volumes in schizophrenia: a multiparametric magnetic resonance imaging study.Transl Psychiatry. 2022;12:388. [DOI] [PubMed] [PMC]
González-Rodríguez A, Seeman MV, Guàrdia A, Natividad M, Román E, Izquierdo E, et al. A review of cardiovascular risk factors in women with psychosis.Women. 2023;3:200–13. [DOI]
Ansdell P, Thomas K, Hicks KM, Hunter SK, Howatson G, Goodall S. Physiological sex differences affect the integrative response to exercise: acute and chronic implications.Exp Physiol. 2020;105:2007–21. [DOI] [PubMed]
