Issues of gender identity disorders (GIDs) have recently become more and more relevant, which is reflected in the increase in the number of patients in medical clinics around the world with requests for gender reassignment [1-6]. It remains unclear whether the increase in the attendance rate of patients with gender dysphoria reflects a real increase in the prevalence of this pathology or whether the rejection of one's gender is an option for solving certain social problems or, perhaps, is a consequence of other mental disorders or represents a new social trend. It should be noted that some people who identify themselves as "transgender" do not seek medical help [3][7]. The results of a survey conducted in the United States in 2016 showed that 0.6% of American adults considered themselves "transgender", which was twice the figures obtained over the previous decade [8]. In a survey conducted in the Netherlands, 1.1% of men and 0.8% of women identified themselves with the opposite sex [9]. In several foreign studies, it was demonstrated that 1.2–1.3% of school students considered themselves "transgender", and 2.5% doubted their gender identity [10][11]. According to other data, about 11% of adolescents identified themselves within the framework of "nonbinary genders", more often classifying themselves as "gender-fluid" or "gender-neutral" [12]. However, there are more and more foreign studies devoted to "detransition", i.e., "reverse" sex change, which may indicate existing problems in the diagnosis of these conditions and methods of providing medical care to patients with GIDs. The most challenging problems when treating patients experiencing gender dysphoria, in addition to identifying the true causes of GIDs, are the preservation of fertility after gender-affirmative interventions, possible regrets after surgeries, and provision of medical care to minors. Treatment should not harm the person emotionally, mentally, socially, or physically; however, in the case of irreversible gender-affirmative interventions, the risk of adverse outcomes is high. In this regard, it is important to carefully approach the diagnosis of GIDs, to identify their true cause, and to provide therapeutic measures considering a number of medical and social factors.

GIDs, which included transsexualism, as a nosological category first appeared in the American classification of mental illnesses DSM-III (Diagnostic and Statistical Manual of Mental Disorders) in the "Sexual deviations" section [13]. In DSM-III-R [14], GIDs were classified as the "Disorders usually first diagnosed in infancy, childhood or adolescence" category. The DSM-IV [15] included GIDs under the category "Sexual and gender identity disorders". In DSM-V, the term "transsexualism" was no longer used. A new concept of "gender dysphoria" was introduced which meant not the presence of transsexualism itself, but the distress associated with it. The diagnosis of "gender dysphoria" did not require the exclusion of other mental disorders, including psychotic ones. The rubric itself was moved to a separate category called "Gender dysphoria".

In ICD-9 [16], transsexualism was included under the rubric "Sexual perversions and violations." At present, ICD-10 includes transsexualism in the section "Disorders of adult personality and behavior", the diagnostic group "Gender identity disorders" [17].

In ICD-11, the term "transsexualism" was replaced by "gender incongruence" and moved from the class "Mental and behavioral disorders" to a new class called "Conditions related to sexual health". This implied that transsexualism was no longer considered a mental pathology [18, 19]. These changes in the classification were due to an attempt to reduce the stigmatization of people with GIDs [18], who were equated with people with mental illness. Nevertheless, the exclusion of transsexualism from the field of mental pathology by some domestic authors seems to be a controversial issue due to the possible underestimation of the psychopathological component of these disorders [20][21].

It should be noted that recently, the concept of "gender" identity has increasingly been used instead of "sexual" identity, which is also reflected in the new version of the ICD, where the term "gender incongruence" is used. This highlights the differences between sex as a biological characteristic and gender as a psychological one. Sex is binary, that is, a person can be either a man or a woman (with the exception of intersex conditions) [22]. Gender is defined as a "psychological" or "social" sex, which is determined by biological, psychological, and socio-cultural factors [23]. It is believed that gender can be nonbinary and include a whole range of possible identifications. An individual can be, for example, a "transgender" or "agender" person, or have an unstable gender identity. The issue of such gender diversity is ambiguous. Nonbinary identification can be viewed as the individual's right to freedom of choice in terms of self-expression; however, in terms of psychiatry, the diversity of gender options has no medical basis.

According to ICD-10, transsexualism is defined as "the desire to live and be accepted as a person of the opposite sex", which is usually combined with "a feeling of discomfort from one's anatomical sex, a desire to receive hormonal and surgical treatment in order to make one's body more appropriate to the chosen sex" [17]. It is noted that this diagnosis requires "the existence of a stable transsexual identification for at least two years", while the symptoms should not be a manifestation of other mental, genetic, or chromosomal diseases [18]. These criteria are not clear enough; there are no specific indications for differential diagnosis with other mental illnesses, within which similar symptoms can be observed.

It should be noted that the clinical manifestations of transsexualism appear from childhood, namely from 3–7 years of age, when the formation of sexual self-awareness takes place [24], and are expressed in the inversion of gender-role behavior (in the preference for clothes and games characteristic of the opposite sex, as well as communication with children of the opposite sex) [25]. However, modern studies evidence that the GID signs observed in childhood do not always persist at a later age. One of the studies [26] has shown that among 77 patients who experienced gender dysphoria at the age of 5–12 years, only in 27% of them, these symptoms persisted during adolescence and adulthood. Another study [27] has demonstrated that in girls, the symptoms of gender dysphoria observed in childhood also persisted in adulthood, in contrast to boys, who showed a reduction of symptoms with age. However, in children who had GID signs, predominantly homosexual or bisexual orientation of sexual desire had developed.

Among patients who have recently applied for a gender reassignment, more and more people claim the onset of gender dysphoria from adolescence and that they experience no corresponding signs in childhood, or the information they provide about the existence of symptoms of gender dysphoria in childhood is not confirmed by their relatives. On the one hand, this makes one think about the "truth" of gender disorders that first appeared in adolescence; on the other hand, it allows establishing the probable pathomorphosis of the clinical picture.

Gender dysphoria can occur not only in transsexualism but also in other mental disorders. Gender reassignment mindsets can be observed in schizophrenic spectrum disorders, affective pathology, personality disorders, organic brain disorders [18], dual role transvestism, egodystic homosexual orientation, and be accompanied by a variety of psychopathological symptoms [3][28][29]. In particular, in schizophrenia spectrum disorders, phenomena of depersonalization and dysmorphophobia, psychopathy- or neurosis-like symptoms, affective disorders are often revealed, and the mindsets themselves to reassign sex are overvalued or delusional in nature [30].

At the same time, GID can be combined with another mental pathology and manifested independently of it [3]; however, a concomitant mental disorder can affect the clinical picture of GID and vice versa. A systematic review by Dias de Freitas et al. [31] has shown that concomitant mental pathology in persons with GID was observed in 53.2% of persons with these disorders. Especially often in patients with gender incongruence, anxiety and affective disorders, addictions to psychoactive substances, and increased suicidal risk have been detected [3][32][33]. The high level of mental disorders among this contingent can be explained by a high level of stress against the background of gender dysphoria, as well as social problems, discrimination, and stigmatization [31]. At the same time, GIDs can develop against the background of pre-existing mental illnesses. There is evidence that in men, the emergence of female identification or the actualization of mindsets toward sex reassignment is characteristic of the manic phases of bipolar or schizoaffective disorder, in the depressive phase these mindsets weaken; while in women, male identification appears or increases in the depressive phase [34][35].

In scientific literature [36][37], there are indications of a high incidence rate of gender dysphoria among people with schizophrenia, as well as with schizoid and schizotypal personality accentuations. Among individuals with gender incongruence, there is a high prevalence of autism spectrum disorders (ASDs) [38][39][40]. At the same time, in patients with ASD and gender dysphoria, higher levels of gender variability, i.e., non-binary genders are revealed [41]. It is assumed that the frequent combination of GID and ASD may be due to the fact that individuals with ASD have only a cognitive rather than a sensory idea of their gender due to the distortion of the image of the "I" and the difficulty of social interaction [39].

Many factors influence gender identity development: the features of upbringing in the family, the social circle, the media, as well as the perception of psychosexual social standards by the personality itself [42]. Nevertheless, the basis for establishing gender-role socialization is laid by the family, namely its composition, the professional roles of parents, and the nature of marital and parent-child relationships [43-45]. Much depends on the identity and role models of parents and their ideas about what a child should be. In the process of gender identification, each child tries to match the behavior of the parent of his/her own gender: girls, for example, show tenderness and care, while boys show resilience and masculinity [45][46]. In addition to parent-child relations, child-child relationships can arise in the family, which also affect the gender characteristics of the child: the presence of an older brother, for example, affects the masculine identification of a boy; the presence of an older sister affects the feminine identification of a girl [45][47].

Some authors believe that the gender-role identification of boys is more difficult than that of girls. This is associated with a greater distance from the child of the father, in contrast to the mother, with whom the boy spends more time [48]. The boy's primary identification is with his mother, which is why he develops "feminine" qualities (dependence, passivity, etc.); the boy will further have to change his primary feminine identity to masculine, but this is not so simple, since most of the people in his environment are women (mother, grandmother, educators, teachers, etc.) [45]. In this regard, the boy develops his gender-role identity not on the basis of knowledge about the male role, but on the basis of "do not act like a girl", "do not look like a girl". Adults often blame the boy for "non-male" behavior (for example, crying, capriciousness), and this affects the sexual development of boys [45].

The influence of the peer group and the educator lies in the fact that there is a social expectation from the child of a reference sex-role (corresponding to his/her gender) behavior. The child begins to receive feedback from peers, reinforcing his/her positive or negative behavior [45], when being in the kindergarten. The development of truly valuable qualities of masculinity (masculine features) and femininity (feminine features) depends on this. Gender identity is indirectly influenced by the media that offer models of "ideal men" and "ideal women"; and the child can develop his/her gender identity relying on the behavior shown on the TV screen, or on the images described in books and magazines. Both boys and girls have their own idols, and they strive to be like their ideal in appearance and behavior [45].

In modern society, there are changes in the system of traditional gender stereotypes regarding the cultural foundations of understanding masculinity and femininity. A tendency to erase the gender framework, popularize "unisexuality" is revealed.

With the increase in the prevalence of "transgenderism", the study of issues of sexual identity is becoming increasingly relevant. Domestic psychological studies of transsexualism have shown that the structure of self-consciousness of transsexuals is conflicting primarily due to the "confrontation" between the image of the physical "I" and the image of the mental "I", the image of "I-today" and "I-tomorrow" (after surgery) [49]. According to Sokolova, the primary link in the violation of gender identity in transsexualism is a cognitive image that reflects the real bodily organization of a transsexual, and a negative emotional and value attitude arises secondarily, as a reaction to the frustration of vital motives and goals [50][51]. One of the studies has also shown that transsexualism, "perhaps more clearly than any other mental disorder, allows observing a deep dissociation of the ‘I-real’ and ‘I-ideal’" [52].

The sexual identity of women with transsexualism is similar to that of cisgender women. In men with transsexualism, despite the predominance of feminine qualities, a complete inversion of sexual self-awareness is not observed [51]. In other mental illnesses, in the clinical picture of which there are mindsets toward gender reassignment, sexual self-consciousness differs from the profile of transsexuals. In particular, in schizophrenia spectrum disorders, nondifferentiation of sexual self-awareness and gender-role behavior, poorly formed ideas about female and male gender roles are often revealed [50][53].

Treatment activities for people with gender incongruence include social and medical aspects aimed at maximum support for people in this category.

In order to avoid diagnostic errors and to ensure the proper quality of medical care, the main principles for managing patients with GIDs should be the following ones [54]:

In most European countries and the United States, medical care for patients with GIDs is regulated [18] by the Standards of Care for the Health of Transsexual, Transgender and Gender Nonconforming People (SOC-7), developed by the World Professional Association for Transgender Health [18][55]. In Russia today, there are no legislatively fixed standards for providing medical care to patients with GIDs, which creates uncertainty in the algorithm of therapeutic measures.

Nevertheless, there are methodological recommendations [54] that allow determining the stages and volume of treatment. According to them, a set of medical and social measures for people with gender incongruence includes three main stages [51].

Stage 1 — Preparatory. It includes ongoing monitoring by a sexologist and a psychiatrist for up to two years, a comprehensive psychiatric, sexological, psychological, and somatic examination, differential diagnosis with similar pathology, the establishment and confirmation of the diagnosis of "transsexualism", the necessary psycho-corrective measures.

Stage 2 — Sexual reorientation. It includes sex reassignment, hormonal correction, and then sex reassignment surgery according to the indications [56].

Stage 3 — Recovery and rehabilitation. This is a follow-up period with an assessment of the condition of patients after the end of therapy. It includes the supervision of a psychiatrist, a sexologist [56], a somatic examination, supportive psychotherapy, and socio-psychological assistance in case of adaptation difficulties.

After the follow-up period, which should last at least one year, a medical commission is formed to establish sexual reorientation, which includes a psychiatrist, a sexologist, and a medical psychologist. Based on the results of the medical commission [57] (in accordance with the order of October 23, 2017 No. 850n "On approval of the form and procedure for issuing a document on gender reassignment by a medical organization") [29], a decision is made to issue or refuse to issue a Certificate on gender reassignment No. 087/u, which allows changing passport sex.

The indications for changing the passport sex are as follows [56]:

The contraindications for changing the passport sex are as follows [56]:

Concomitant mental disorders are not considered to be a contraindication for gender reassignment in most countries, if it is proved that gender dysphoria is not induced by another mental illness, and the patient's mental state is compensated [3][56][58].

After changing the passport sex and before making a decision on hormonal and surgical treatment options, the patient is recommended to undergo a period of adaptation in the chosen social gender role [51][55]. Adaptation means the patient's ability to implement the acquired knowledge (consequences of changing the social role in the family, professional, interpersonal, educational, economic, and legal spheres of life) in real life [51].

It should be noted that not all patients who apply for gender reassignment are willing to go through all the stages of gender-affirmative interventions. Some patients consider surgical sex reassignment surgery the only acceptable option for their further existence, while others do not consider hormonal and surgical treatment necessary and find it sufficient to change only their social gender role, limiting themselves to changing documents [59]. In some cases, hormonal and surgical treatment is impossible for somatic or other reasons.

After gender-affirmative treatment, the symptoms of gender dysphoria usually decrease or disappear, and the symptoms of concomitant anxiety-affective disorders, emotional and behavioral disorders are also reduced [18][60-62]. However, when comparing distress indicators at different stages of gender-affirmative interventions in transgender people, it has been revealed that the decrease in these indicators was most noticeable after the start of hormone therapy, while after surgical interventions, there was no significant change in the results [63].

Psychotherapeutic support for patients with GIDs should be provided at all stages of medical care. During psychotherapy, it is necessary to take into account the fact that patients with gender dysphoria may have difficulties for which their gender identity is not of decisive importance. Specialists should avoid excessive emphasis on gender identity and gender expression when it is not directly related to the needs and problems of patients with gender dysphoria [64]. The planning of the psychotherapeutic process should be performed in cooperation with the patient, which allows patients determining for themselves how important their gender identity is for the purposes of treatment.

In many ways, the methods of psychotherapy for patients with gender dysphoria are no different from the treatment used for cisgender patients. Individuals identifying themselves as transgender, like other patients, most often come to a psychotherapist for discussion and help in understanding interpersonal relationships, as well as coping with the stresses associated with work, family, and social circumstances.

However, even if the patient's gender identity is not the main focus of treatment, its impact on the course of therapy should not be underestimated or overlooked.

The most common unsatisfactory needs in gender-role conflict are the following ones [51]:

The goals of psychotherapy for gender incongruence may differ depending on the stage of sexual reorientation at which the patient is.

So, at the preparatory stage (stage of examination), the main goals of psychotherapy are the following ones:

At the subsequent stages of sexual reorientation, it is important to provide the patient with supportive psychotherapeutic assistance in case of any adaptation difficulties.

The World Standards of Care for Patients with Gender Identity Disorders state that "psychotherapy should not be aimed at changing the gender identity of individuals, but, on the contrary, should help them solve problems related to gender and alleviate gender dysphoria" [55], and that "the long-term goal of psychotherapy is to help transgender, transsexual and gender nonconforming individuals achieve a comfortable expression of their gender identity with a real chance of success in relationships, education and work over the long term" [65].

In 2015, the American Psychological Association published "Guidelines for Psychological Practice with Transgender and Gender Nonconforming People", in which they endorsed trans-affirmative therapy (TA-CBT) (modified cognitive behavioral therapy/gender affirmative). It emphasized that trans-affirmative practice should be "respectful, conscious and supportive of the identity and life experience of transgender people" [63]. TA-CBT is a version of CBT adapted to promote a positive stance on gender diversity, recognize transgender-specific stressors, deliver CBT in a supportive manner, and provide trauma-informed supervision. CBT adapted to the experience of transgender people can help improve mood and increase coping ability by teaching how to identify, challenge, and change inappropriate thoughts, beliefs, and behaviors [66].

Specialists treating patients with GIDs face a number of bioethical dilemmas, diagnostic difficulties, and methodological problems. There are still many unresolved problems related to the phenomenology of these conditions, the assessment of the role of psychopathological, psychological, and social factors in the development of GIDs. Successful assistance to people with these problems requires a multidisciplinary approach, raising the awareness of specialists and patients themselves of this problem, developing clearer diagnostic criteria and creating unified therapeutic algorithms considering the presence of comorbid mental pathology.