Early treatment depends on recognition of prodromal signs, which may differ from those of men; lack of recognition delays timely access to intervention services. Women who present with delusional ideas and report hearing voices but are cognitively intact and show appropriate affect and few negative symptoms (apathy, social avoidance), need careful monitoring for schizophrenia. Brand and collaborators [26] recommend physician education on male/female divergence in these respects. A second recommendation is a routine exploration of childhood adverse events in women. A third recommendation is an inquiry into symptom fluctuation over the menstrual month. Premenstrual increase in psychotic symptom severity can be addressed by a slight dose increase of antipsychotic drugs over the three-day period preceding menses [26].

Because most antipsychotics induce hyperprolactinemia, especially in women, sexual function may be negatively impacted, and galactorrhea, as well as amenorrhea, can emerge [27], confusing symptoms for women because they mimic the signs of pregnancy. Women need to be warned of these possibilities before starting treatment and to be reassured about their meaning. All things being equal, women need to be treated with relatively prolactin-sparing antipsychotics.

Nallani and collaborators [27] also investigated the risk of 25-hydroxy vitamin D deficiency and other metabolic abnormalities in women who experience hyperprolactinemia. They found that 37% of women with schizophrenia show low vitamin D levels, a consequence of high prolactin as well as infrequent exposure to sunlight. Hyperprolactinemia also exerts a negative influence on cognition [28]. Gurvich and collaborators [28] investigated the effects of hypothalamic-pituitary-gonadal axis disturbance on cognitive performance in 240 women with schizophrenia. Cognition was assessed by means of the Repeatable Battery for the Assessment of Neuropsychological Status. They found that menstrual cycle irregularity was positively associated with defective cognitive performance in three domains: psychomotor speed, verbal fluency, and verbal memory [28]. Women may be conscious of increased cognitive deficiencies, so, again, need reassurance.

High prolactin levels reduce fertility. Yu and collaborators [29] asked about reproductive concerns in 15 women with schizophrenia (age 26–40). The women’s main concerns were psychological barriers to reproduction such as discouragement by their partners and by medical/psychiatric staff. Based on anxiety about the women’s ability to handle the extra stress of parenting and also about their childcare competence, staff often steer women with schizophrenia away from motherhood. While this is well-intentioned, it is also a form of prejudgement or stigmatization [30]. The issue of parenting needs to be raised with women with schizophrenia, and thoroughly discussed. If children are not wanted or motherhood is unrealistic at the time, it is important to ensure that contraceptive measures are in place [31]. A systematic scoping review by Vickers and collaborators [32] investigated sexual and reproductive health in adolescents and young adults with psychotic disorders. Sexual dysfunction was attributed to psychosis, but, additionally, to the use of antipsychotic medications, especially those that markedly raised prolactin levels. Sexual risk behaviours, with their attendant risk of sexually transmissible infections, were frequently reported in this population. Sexual education is, therefore, required. Women need protective as well as contraceptive advice, access to abortion needs discussion, as do sexual violence and coercion, and sexual preference and gender identity confusion, topics that are often not broached with women with schizophrenia because of fear that they will induce delusional thinking [30].

An attempt was made by Posada Correa and co-workers [33] to address sexual and reproductive health issues and the use of contraception and sexual counselling in patients with schizophrenia and bipolar disorder. Although relatively few patients with schizophrenia reported having an active sexual life, almost all who did report, in this sample, to be using contraception. The majority of patients stated that they had never received information about family planning from their physicians. Nevertheless, 78.8% of those with schizophrenia considered themselves well-informed on the subject. The authors of the study recommended the provision of psychoeducation in areas such as contraception, family planning, and sexually transmitted diseases. This is an important issue for both men and women. Because women with schizophrenia show low rates of sexual satisfaction and high rates of both sexual dysfunction and sexual coercion [34], sexual health interventions are particularly recommended for women. A systematic review and meta-analysis that included 10 observational studies of 3,570 patients, 1,161 of whom suffered from schizophrenia [35], found statistically significant correlations between schizophrenia and sexual dysfunction in both men and women and advocated for psychological as well as pharmacological (prolactin-lowering) interventions. Therapeutic conversations about sex need to be attuned to age, and cultural context, to intimate partner status, and to the different needs and potential risks of sexual activity in men and women.

Attention has been paid in recent years to decision-making capacity with respect to pregnancy and abortion in women suffering from mental disorders [36]. While many women with severe mental illness retain their decision-making capacity despite the presence of psychotic symptoms, the appointment of a guardian or surrogate decision-maker may be necessary, especially when termination decisions need to be made within a short time period. Such decisions benefit from consultation with ethics experts [37].

As mentioned, antipsychotic treatment, via hyperprolactinemia [38] lowers fertility and needs to be addressed by a judicious choice of drug treatment and also by stress reduction techniques and social support because stress itself raises prolactin levels [30]. Some women with schizophrenia, however, perhaps especially those who are not adherent to their antipsychotic regimen and/or who lack effective contraception, go through repeated pregnancies [39]. In these cases, the postnatal period has been touted as an ideal opportunity to initiate the implementation of contraceptive measures to prevent what often leads to repeated maternal loss of offspring to adoption services or foster care [30]. Such losses intensify psychotic symptoms.

It is important to reiterate that women with schizophrenia require reproductive counselling. Frayne and collaborators [40] carried out a cross-sectional survey of an antenatal clinic in Australia consisting of 38 women participants with severe mental illness. The following variables were noted: unintended pregnancies, initiation of immediate postpartum contraception, use of prenatal and pregnancy vitamins, presence of obesity, use/discontinuation of smoking, alcohol, and street drugs, and presence of comorbid medical conditions. In 56% of women with schizophrenia, the pregnancy was unintended (compared to 26% to 40% of all Australian women) [41, 42]. Contrary to recommendation, 45% of the women had not started contraception prior to postnatal discharge. Twenty-one percent smoked during pregnancy (compared to 8.6% in Australian pregnant women in general) [43] and 35% were obese (compared to 22% of pregnant women in Australia), statistics that indicate inadequate care [40]. The reasons for poor adherence to antenatal health may be partly due to the positive, negative, and cognitive symptoms inherent in psychotic disorder and reduced by effective treatment, but also to the associated social risk factors—poverty, social exclusion, lack of support, lack of education [44, 45], a change of which requires strong advocacy and political will.

A recent systematic review and meta-analysis examined the evidence on pregnancy, delivery, neonatal complications, and infant mortality in schizophrenia women, pregnancy in schizophrenia being considered high risk [46]. The findings were that this population experiences a disproportionally high rate of gestational diabetes, pre-eclampsia and eclampsia, antepartum and postpartum haemorrhage, placental abruption, and premature rupture of membranes. Infants of schizophrenia mothers have been found at risk for neonatal and early death, all of which make effective intervention a public health priority. A minority of women with schizophrenia show a psychotic denial of pregnancy [47], which, for this subgroup, explains the lack of prenatal care.

Simoila and collaborators [48] compared the reproductive health of women with schizophrenia and schizoaffective disorder, focusing on pregnancy, delivery, and postpartum outcomes. Women with schizophrenia were younger at the time of giving birth than those with schizoaffective disorder, but no other differences were found. Compared to the general population, women with schizophrenia have been found to have fewer pregnancies and higher rates of induced abortions, but the pregnancy rate in this population is increasing, perhaps because newer antipsychotics interfere less with fertility than older drugs [49]. It is important in schizophrenia pregnancies to monitor antipsychotic levels and health indices across the three trimesters. Schizophrenia-induced and drug-induced risks both result in obstetric complications that can negatively affect infant development [50].

Harris and collaborators [51] carried out a retrospective study of 98 pregnant women with schizophrenia in order to determine hospitalization risk during the gestational period. Approximately 41% of the women required hospital admission during pregnancy, the first trimester being the period of greatest risk. Inadequate prenatal care, drug and alcohol use disorders, and the intervention of child protection services were the three most common factors responsible for psychiatric admissions. A multidisciplinary approach to these problems was recommended. Active collaboration between psychiatrists and gynaecologists and childcare agencies during pregnancy has been suggested [52].

One of the more controversial aspects of treatment during pregnancy is the use of long-acting injectable antipsychotics (LAI, whether 1st or 2nd generation). Nguyen and collaborators [53] conducted a case-series study in a tertiary maternity hospital with the aim of examining pregnancy, neonatal, and psychosocial outcomes of women receiving LAI, between 1999 and 2017. Measures included: socioeconomic variables, smoking, alcohol and other substance use disorders, pregnancy complications, and child protection involvement. Thirty-eight pregnancies of 36 women treated with LAI were compared to pregnancies of women in the general population. The LAI-treated women were more likely than controls to experience gestational diabetes and preeclampsia. The percentage of congenital malformations did not differ. The authors reported high rates of psychiatric admission in these women, with similar outcomes between those exposed to first- and second-generation antipsychotics. A recent descriptive observational study investigated neonatal outcomes in women suffering from bipolar and other psychotic disorders who received LAI during pregnancy [54]. Assessment at follow-up consisted of an interview with either the patient or the physician-in-charge. Here again, it was found that treatment with LAI was not associated with an increased risk of malformations. Importantly, pregnancy outcomes of LAI have not been compared to those of women with schizophrenia in general, whether untreated or treated solely with oral medications. The assumption that a history of non-compliance to oral antipsychotics necessitates LAI and that this precludes a treatment switch to oral meds during pregnancy is worth noting. It has been found that close monitoring during pregnancy allows switching to oral meds, at least for the critical time period of the third trimester [55], which would avoid high drug levels in neonates.

The postpartum period of a woman’s life is a period of high vulnerability to the occurrence of psychiatric symptoms and exacerbation of mental disorders, which may be partly explained by the decline of circulating oestrogens [56]. In fact, the rapid drop of oestradiol at the end of pregnancy has been implicated in the aetiology of postpartum disorders, and oestrogens combined with progesterone have been tested as potential treatments for these conditions [57].

With regard to breastfeeding in women suffering from schizophrenia, recent work highlights the relative lack of evidence in this field. A cross-sectional descriptive study [58], using self-report questionnaires, investigated attitudes towards breastfeeding among women with schizophrenia among health professionals (nurses, midwives, health visitors) from health care settings in Athens. In general, healthcare professionals showed favourable attitudes towards breastfeeding and recommended a rating scale to evaluate the effect of breastfeeding on outcomes in both mothers and children. Despite acknowledged benefits to the infant (and to the mother) of breastfeeding, there are concerns, on one hand about antipsychotic drugs being transmitted to the infant, and, on the other, about women stopping their much-needed medications to avoid child exposure. There are dose and feeding schedules that will minimize the dangers of exposure, and many experts are now leaning toward encouraging breastfeeding in all women, including those being treated for schizophrenia [59].

Rarely, psychosis, especially postpartum psychosis, can lead to pathological filicide—a mentally ill mother killing her child. A recent study investigated the characteristics of 17 mentally ill filicidal mothers by retrospective chart review conducted in a secure unit in France [60]. Forty-one percent of the sample suffered from schizophrenia, 41.2% from bipolar disorder or depressive disorders, and 17.6% from personality disorders. Two different profile groups were identified. In the first group, filicide was attributed to a defensive response to a perceived threat to the child induced by delusional beliefs or auditory hallucinations. In the second group, the act was precipitated by the mother’s belief, real or imagined, that the child was about to be taken away from her. In 39% of filicide cases, women are reported to also attempt suicide [61]. In general, filicide is considered multifactorial in aetiology, with aggressive/violent relationships and social isolation playing an important part in the behaviour. Study authors underline the importance of maintaining contact with new mothers with mental illness whenever they fail to attend scheduled visits.

One relatively unusual syndrome in high income countries, but frequent elsewhere, especially in women with schizophrenia, is delusional pregnancy, an insistence by the woman that she is pregnant, frequently accompanied by signs of pregnancy (amenorrhea, nausea, breast swelling, and galactorrhea, abdominal swelling, urinary frequency) without evidence of a fetus [62]. This is a delusion that may be difficult to manage because the woman, considering herself pregnant, will not agree to take antipsychotic medications.

The complexity of management of women with schizophrenia during the perinatal period has led to very much needed recommendations for decision-making models and international guidelines with respect to optimal care during this vulnerable time period [63].

Women with schizophrenia are at considerable risk for interpersonal violence, a risk that increases during pregnancy. A recent population-based cohort study in Canada compared rates of interpersonal violence in women with and without schizophrenia who attended an emergency department (ED) while pregnant or within one year postpartum [64]. Measures taken were sociodemographic characteristics, history of substance use disorders, and interpersonal violence. From a total sample of 1,802,645 pregnant women, 4,470 had a diagnosis of schizophrenia, of whom 137 (3.1%) visited an ED prenatally due to interpersonal violence. Pregnant women suffering from schizophrenia were more likely to report interpersonal violence compared to women without schizophrenia, confirming that pregnancy is a period of special risk in this population, perhaps attributable to risky marital choices [65]. All women with schizophrenia need to be tactfully questioned about their intimate relationships with the possibility of domestic abuse in mind, especially during pregnancy.

Zerihun and collaborators [66] carried out a cross-sectional study of reproductive-age women suffering from chronic mental illnesses and intimate partner violence (IPV). One hundred seventy study participants were diagnosed with schizophrenia, and 116 with bipolar disorder. A structured questionnaire was used to assess IPV, as well as sexual, physical, and emotional abuse. Lifetime IPV was present in 62% of the women, emotional abuse being the most common form (60%). Marital status, occupation, duration of illness, and degree of control exerted by the male partner were all significantly associated with IPV. This is a significant safety issue that needs to be sensitively probed during psychiatric visits and any visible sign of abuse investigated; patients often do not reveal abuse voluntarily [67].

Practices that have been recommended by the World Health Organization for all neonates, such as breastfeeding and skin-to-skin contact, have not, until recently, been investigated in new mothers with schizophrenia. Taylor and collaborators [59] carried out a population-based cohort study based on medical records of new mothers with (n = 471) and without (n = 218) schizophrenia to determine whether skin-to-skin contact and breastfeeding were started within the first 2 h after birth. The findings were that maternal schizophrenia was associated with lower skin-to-skin contact and lower rates of breastfeeding immediately postpartum when compared to the rate of these behaviours in new mothers in the general population. These are behaviours that exert a theoretical impact on mother-child bonding and the finding suggests that new mothers with schizophrenia require individualized support that actively promotes best practices. As mentioned earlier, best practice has now swung toward recommending breastfeeding for mothers with schizophrenia taking antipsychotics.

The need for specialized care for mothers with schizophrenia is underscored by the finding that maternal schizophrenia is positively associated with perinatal complications [68]. Vigod and colleagues [68] conducted a population-based cohort study of 5,066 children of mothers with schizophrenia and 25,324 children of mothers without schizophrenia. Maternal age, parity, immigrant status, income, region of residence, other maternal medical and psychiatric conditions, and childhood chronic health conditions (Childhood-CC) were all noted. A significantly larger percentage of children of mothers with schizophrenia developed Childhood-CC when compared to children of schizophrenia-free mothers. This is consistent with another recent study investigating the prevalence of complex chronic conditions in children born to women with schizophrenia. In this population-based study of 5,066 children of women with schizophrenia and 2,939,320 control children [69], complex chronic conditions were again more frequently reported in the index children. These conditions tended to be neuromuscular, cardiovascular, respiratory, and immunodeficiency disorders. Preconception psychoeducation for mothers and counselling that targets strict adherence to prenatal instructions is strongly recommended.

Maternal schizophrenia has been also associated with an elevated risk of child injury. Taylor and collaborators [70] stratified children according to sex and age: infancy (0–1 years), pre-school (2–5 years), primary school (6–9 years), and early adolescence (10–15 years). All forms of child injury were noted—e.g., accidental injury, self-injury, assault. Accidental injury and self-injury were most commonly associated with maternal schizophrenia in the 10–15-year-old group, whereas assault was associated with exposure to maternal schizophrenia in infancy and pre-school. It has been emphasized that mothers with schizophrenia need support, aid, and monitoring to prevent accidental child injuries and injuries that result from neglect or abuse [71]. Referrals to childcare agencies may be required.

The Taylor and colleagues’ group [72] also investigated adherence to infant check-up schedules and vaccination schedules (up to age two) in mothers with or without schizophrenia, using provincial medical records. The recommended rate of well-baby visits was achieved in 50.3% of children exposed to maternal schizophrenia compared to 58.6% of control children. Full vaccine schedule adherence occurred in 40% of children of mothers with schizophrenia versus 46% of children of controls. Close liaison with paediatrics is recommended for mental health practitioners when treating mothers with schizophrenia. Mental health staff are also encouraged to make home visits for mothers with schizophrenia whenever there are children who live at home.

The diminishing levels of oestrogen that begin at pre-menopause are thought to be responsible for the 2nd incidence peak of schizophrenia in women [25]. For women whose symptoms began earlier in life, menopause is associated with an increase in symptom severity and, frequently, the advent of antipsychotic resistance [73]. Oestrogen loss may also decrease the efficacy of specific CYP enzymes that metabolize individual antipsychotic drugs [74].

Sommer and collaborators [75] carried out a nationwide cohort study of 61,889 individuals investigating clinical outcomes in schizophrenia/schizoaffective disorders. The sample was divided into two groups according to: age < 45 years, and > 45 years. The investigators hypothesized an increase in relapse risk and a reduction of antipsychotic effectiveness leading to hospitalization in women over age 45 when compared to both male age peers and women under age 45. They saw a decrease in antipsychotic efficacy for four drugs—clozapine, olanzapine, quetiapine, and risperidone.

González-Rodríguez and colleagues [76] reviewed the impact of menopause on psychopathological symptoms and comorbidity in women with delusional disorder (DD), a schizophrenia-related disorder. They found an increase in depressive symptoms and also an increase in all psychiatric co-morbidity. Both physical symptoms (vasomotor, physical, sexual) and psychiatric symptoms (depression, insomnia, cognitive, and psychosocial difficulties), in addition to oestrogen decline, appear to trigger the emergence of psychotic symptoms at the time of menopause. Chronic medical problems such as obesity, type 2 diabetes, osteoporosis, and osteoarthritis also emerge at this time, often aggravated by antipsychotic medication [76].

The selective oestrogen receptor modulator (SERM) raloxifene has been described as a promising treatment option for women with schizophrenia for whom replacement oestradiol is contraindicated [77]. It has been shown that raloxifene improves cognitive symptoms in postmenopausal women with schizophrenia, but the results may be inconclusive [78]. The meta-analysis of randomized controlled trials of raloxifene by Wang and collaborators [79] and the meta-analysis of randomized, double-blind, placebo-controlled trials with oestradiol and raloxifene as adjunctive treatment for women with schizophrenia by Li and collaborators [80] demonstrated a significant improvement of symptoms [79, 80]. Adjunctive oestradiol improved total PANSS scores, in addition to improving positive, negative, and general psychopathology scores. Adjunctive raloxifene improved the PANSS total scores, and general psychopathology scores [80]. Both adjunctive treatments were shown to be safe, but, at the moment, aspects such as timing and dosage remain unclear [80].

The effect of add-on raloxifene has been studied in schizophrenia even prior to menopause. Brand and collaborators [81] recently used raloxifene versus placebo adjuncts to antipsychotics in a sample of relatively young men and women with schizophrenia-spectrum disorders (placebo age 39.3 years ± 11.2 years, and raloxifene age 42.0 years ± 11.9 years). The study consisted of 72 men and 28 women in a parallel, randomized, double-blind, placebo-controlled trial across the Netherlands and Belgium. Participants were stratified by age, sex, and global functioning and randomly assigned to 12-week adjunctive raloxifene 120 mg/d or placebo. Intention-to-treat analyses were performed using linear mixed-effect models [81]. Results showed no main effect of raloxifene in the sample as a whole, but, in secondary sex-specific analysis, women on raloxifene showed significant beneficial effects on negative symptoms and working memory, while the working memory of men on raloxifene deteriorated. This potential sex-disparate effect needs to be further studied. There may be women with schizophrenia who respond better to raloxifene than others but it is presently unknown whether that is the case.

An important health concern for individuals with schizophrenia as they age is cancer screening, with relatively low rates of breast and cervical screening being characteristic for this population [82]. Delays in screening postpone effective treatment and decrease survival time. Breast cancer is the main concern in women. In women suffering from schizophrenia, breast cancer has been attributed to genetics, lifestyle (smoking, alcohol use, sedentariness, and unhealthy eating leading to obesity), and other factors associated with schizophrenia such as relatively low parity. Antipsychotics are a concern because these drugs raise prolactin levels. A recent Finnish nationwide register study investigated the potential contribution of prolactin-raising antipsychotics to the breast cancer risk [83]. While exposure to prolactin-sparing antipsychotics was not associated with increased risk, five or more years’ exposure to prolactin-raising antipsychotics was positively associated with the development of breast lobular adenocarcinoma [83]. These results underscore the need to use prolactin-sparing antipsychotic drugs for schizophrenia in women whenever possible [84].

Using data from the New York State Cancer Registry of 10,444 women with breast cancer, Lawrence and collaborators [85] found that the mortality rate from breast cancer of women with pre-existing severe mental illness was significantly higher than that seen in the general population of women. This can be attributed to a combination of patient factors (low screening rates and mistrust of doctors leading to late diagnosis, cognitive problems preventing treatment adherence), physician factors (failure to follow up on missed appointments, failure to recruit women with severe psychiatric illness into chemotherapy trials, diagnostic overshadowing—a form of stigma that attributes all complaints in schizophrenia patients to delusional thinking) and system failures (communication silos between psychiatry and primary care/oncology/surgery). All these factors need reform. Achieving optimal physical healthcare has been considered a major challenge in the management of individuals with severe mental illness; this is being increasingly recognized and addressed. A recent example is the introduction of exercise programs into standard care for schizophrenia patients, an intervention that benefits cognition by reversing hippocampal volume loss and improving memory scores [86]. Exercise-induced weight loss also protects against antipsychotic-induced metabolic complications. Exercise is, of course, important to both men and women but the tendency to drug-induced weight gain and metabolic disturbance is more pronounced in women [87]. Moreover, it has been hypothesized that men and women respond somewhat differently to different kinds of exercise programs [88]. This may, in the future, be important in the optimization of women-specific treatment for schizophrenia.