Gender Dysphoria in Disorders of Sexual Development: Approach and Prevalence in a Single Center

ABSTRACT

Context:

Gender dysphoria (GD) is an entity, in which the patient’s gender identity does not correspond with the biological sex.

Aim:

The aim of the study was to analyze the prevalence of GD in adolescent and adult patients with GD as well as to describe the approach used in those patients presenting with GD.

Materials and Methods:

This is a retrospective study, in which patients in the adolescent (between 10–19 years of age) and adult age groups (20 years and above) with disorders of sexual development (DSD) who underwent surgery during the period of 2017–2024 were included in the study. A retrospective analysis was done to assess the prevalence as well as the approach used to treat GD in such patients. All patients underwent surgery after a detailed psychological analysis before surgery.

Results:

Thirty-six patients were included in the study, ages ranging from 11 to 47 years. The mean age of presentation was 18.9 years. GD was found to be most common in patients with 5 alpha-reductase deficiency and least in patients with congenital adrenal hyperplasia and complete androgen insensitivity syndrome as per our analysis.

Conclusion:

Surgical intervention in youth with DSD is a controversial topic. Psychosocial support is extremely important in such patients to help the decision-making process. The main goal of surgical intervention is to normalize appearance and function and forestalling physical and psychosocial morbidity. A multidisciplinary approach is always important in the treatment of DSD to ensure physical as well as psychological welfare of patients.

INTRODUCTION

Disorders of sexual development (DSD) occur when an individual’s chromosomal, gonadal, or anatomical sex develops atypically.[1] Patients with DSD affected by these disorders can present in varied forms of presentation and can present at any age.[2] The prevalence of DSD is estimated to be 0.1%–2% worldwide.[3] Patients diagnosed with DSD require a multidisciplinary approach at a center specialized in the management of these patients.[2]

Psychosexual development determines gender identity (whether an individual sees themselves as male or female), gender role (interest in gender-typical possessions and display of gender-typical temperaments or behaviors), and sexual orientation.[4] It is extremely difficult to predict the psychosexual characteristics that each individual will develop in adult life.[5]

Many tertiary centers advocate early surgical management in patients with DSD.[6] Biological reasons include the maternal estrogenic effect on infant tissues, satisfactory results, and reduced incidence of urinary tract infection.[6] Early surgery is psychologically beneficial because normally appearing genitalia allow for proper gender development and less stigma associated with DSD while also minimizing parental anxiety, allowing for better bonding.[6]

However, presently there exists a controversy surrounding the early intervention of DSD. Some patient advocacy groups are calling for this practice to be abandoned.[7] They argue that performing such an operation that is irreversible and has profound life effects without an individual’s informed consent is unethical.[7]

In gender dysphoria (GD), a person feels discomfort or distress that is caused by a discrepancy between the gender identity and that person’s assigned birth sex.[8] The prevalence of GD is considerably higher in individuals with DSD as compared to the general population.[9] The overlap existing between GD and DSD is linked to the possibility in both conditions of discomfort or distress caused by a discrepancy between gender identity and gender assigned at birth.[9]

Ideally, patients with DSD are diagnosed during infancy. However, in India, with the marked limitation of medical resources and the lack of many tertiary centers dedicated to the management of DSD, many patients are not diagnosed with DSD in infancy.[7] As a result, a heterogenous mix of patients of all age groups: infancy, adolescents, and adults present to our institute with DSD. There are many ongoing studies in India to establish guidelines for the management of such patients in India.[7]

Before deciding surgical management of patients with DSD, it is important to identify the various difficulties that are faced during the management of patients with DSD.[10] Patients in the 46 XX group, mainly congenital adrenal hyperplasia (CAH), represent the most common diagnosis. There is usually no gender issue in this group, except in cases of late diagnosis or severely masculinized 46 XX individuals.[10] The 46 XY DSD group is a more heterogenous group, including 5 alpha reductase, testicular biosynthesis defects, and androgen insensitivity syndrome.[10] In such patients, the feminine phenotype with virilization at puberty and the presence of testes in the inguinal region present two situations where controversies exist regarding gender assignment, sex of rearing, and surgery.[10]

Another issue to be tackled in 46 XY group is the fate of the testicles: Should they be kept in place until the hypothetical age of self-gender determination? Or if female sex of rearing is decided on, should they be removed early to avoid pubertal virilization?[10] Temporarily blocking pubertal virilization with a GnRH analog until gender-identity development is settled is an option.[10] The risk of gonadal tumors is small in such patients.

Patients with gonadal dysgenesis, especially mixed gonadal dysgenesis with a mosaic pattern of karyotyping present with severe hypospadias and/or micropenis with the presence of Mullerian structures and one streak gonad and another normal gonad which present a high chance of tumor formation. These patients also pose a difficulty in deciding the gender assignment and the sex of rearing and invariably the surgical management.[10]

Patients with complete androgen insensitivity have a female phenotype and the diagnosis is often delayed until puberty, where a normal-appearing girl presents with primary amenorrhea. In these patients, gender assignment is usually not an issue.

Patients with partial androgen insensitivity syndrome often present with variable phenotypes but often having severe degree of hypospadias with a smaller phallus size than normal. Most patients are reared as males.

Ovotesticular DSD patients also pose a major dilemma regarding gender assignment and sex of rearing as they have both ovarian and testicular tissues with abnormally differentiated genital structures.

The decision of sex of rearing is made usually at the neonatal period. The indicators for gender assignment in the neonatal period include:[10]

1. The “internal sex” of the child, which includes biological and genetic profiles

2. The appearance of external genitalia (“external sex”), which is based on the size of the phallus, the presence of palpable gonads, and a vaginal opening

3. The expected potential ability of sexual intercourse and reproduction

4. Family education.

In this study, we focus on those patients who had a late diagnosis of DSD, mainly in the adolescent and adult age groups, and we also describe the prevalence of GD in these patients as well as the approach used in those patients with GD.

MATERIALS AND METHODS

Patients

A retrospective study was done of patients presenting with DSD in the adolescent (between 10 and 19 years of age) and adult age groups (20 years and above), from the period of January 2017 to October 2024. All patients included in this study were referred to us by an endocrinologist for surgical reconstruction who is part of our multidisciplinary team.

Preoperatively, all patients underwent detailed clinical examination and evaluation with karyotyping, genetic analysis, and imaging in the form of USG to look for Mullerian structures/gonads. All patients underwent a compulsory psychiatric evaluation to determine gender identity before the procedure. All patients were operated by the same operative team.

Psychiatric evaluation done for all patients was done based on the three main domains of psychosexual development, that is, gender identity (self-identification as either a male or a female, and fundamental sense of belonging), gender role (behaviors, attitudes, and personality traits that a society designates as masculine or feminine, depending on the culture), and sexual orientation (whether heterosexual or homosexual, though homosexuality is not considered as an indication of incorrect sex assignment). Psychiatrists also assessed individual IQ as well as basic level of understanding of gender before determining the presence the GD.

The diagnosis of GD was made based on the criteria as per the Diagnostic and Statistical Manual of Mental Disorders, 5^th Edition and included the following:

Gender dysphoria in children

1. A marked incongruence between one’s experienced/expressed gender and assigned gender, of at least 6 months duration, as manifested but at least six of the following (one of which must be criteria A1)

   1. A strong desire to be of the other gender or an insistence that they are the other gender (or some alternative gender different from one’s assigned gender)

   2. In boys (assigned gender), a strong preference for cross-dressing or simulating female attire or, in girls (assigned gender), a strong preference for wearing only typical masculine clothing and strong resistance to wearing typical feminine clothing

   3. A strong preference for cross-gender roles in make-believe play or fantasy play

   4. A strong preference for the toys, games, or activities stereotypically used or engaged in by the other gender

   5. A strong preference for playmates of the other gender

   6. In boys (assigned gender), a strong rejection of typically masculine toys, games, and activities and a strong avoidance of rough-and-tumble play or, in girls (assigned gender), a strong rejection of typically feminine toys, games, and activities

   7. A strong dislike of one’s sexual anatomy

   8. A strong desire for the primary and/or secondary sex characteristics matching one’s experienced gender.

2. The condition is associated with clinically significant distress or impairment in social, school, or other important areas of functioning.

Gender dysphoria in adolescents and adults

1. A marked incongruence between one’s experienced/expressed gender and assigned gender of at least 6 months duration, as manifested by at least two of the following:

   1. A marked incongruence between one’s experienced/expressed gender and primary and/or secondary sex characteristics (or, in young adolescents, the anticipated secondary sex characteristics)

   2. A strong desire to be rid of one’s primary and/or secondary sex characteristics because of a marked incongruence with one’s experienced/expressed gender (or, in young adolescents, a desire to prevent the development of the anticipated secondary sex characteristics)

   3. A strong desire for the primary and/or secondary sex characteristics of the other gender

   4. A strong desire to be of the other gender (or some alternative gender different from one’s assigned gender)

   5. A strong desire to be treated as the other gender (or some alternative gender different from one’s assigned gender)

   6. A strong conviction that one has the typical feelings and reactions of the other gender (or some alternative gender different from one’s assigned gender)

2. The condition is associated with clinically significant distress or impairment in social, occupational, or other important areas of functioning.

Written and signed opinions from all members included in the multidisciplinary committee (pediatric surgeon, endocrinologist, psychiatrist, child psychologist, and pediatrician) were taken before proceeding with surgery.

Each patient presenting with DSD, with or without GD, was discussed extensively as a multidisciplinary committee and each patient’s further surgical management was decided based mainly on the patients’ gender identity as well as the appearance of external genitalia, the reproductive potential, and the risk of gonadal tumors.

46 XX disorders of sexual development (congenital adrenal hyperplasia)

Most of these patients are declared and reared as females. The question of gender assignment arises in the case of severely virilized genitalia.

Those patients that presented to us as 46 XX males did not have GD, hence all these patients underwent masculinizing genitoplasty.

46 XX females did not have GD and underwent feminizing genitoplasty.

46 XY disorders of sexual development

In this group, the most complex and controversial situations are found.

1. DSD with female phenotypes with subsequent pubertal virilization (testicular biosynthesis defect and 5 alpha reductase deficiency):

   • In this group, patients were initially reared as females and then presented at puberty with signs of virilization, and on further evaluation, the majority of these patients were also found to have GD. In all of these patients, masculinizing genitoplasty was done

   • Those females that did not have GD underwent feminizing genitoplasty with hormonal therapy.

2. Partial androgen insensitivity:

   • In our institution, the majority of patients presenting with partial androgen insensitivity were reared as males and hence underwent masculinizing genitoplasty

   • The rare patients, that had presented to us in the adolescent period with partial androgen insensitivity identified as females with a strong desire to continue being females. Also considering the appearance of the external genitalia, mainly with small phallus, these patients underwent feminizing genioplasty.

3. Complete androgen insensitivity:

   • Gender assignment is not an issue in these patients and these patients usually present as normal-appearing girls with primary amenorrhea

   • Feminizing genitoplasty was done in all these patients.

4. Mixed gonadal dysgenesis:

   • This is probably one of the most complex situations as no decision is completely satisfactory. The combination of male and female structures, potential short height at adulthood, and low fertility make the decision process extremely difficult for the parents as well as the multidisciplinary committee

   • Hence, the decision as to the type of surgery done was decided based on the gender identity of the patient as per psychiatric evaluation.

5. Ovotesticular DSD:

   • Again, due to the presence of male and female structures in such patients, the decision of gender assignment becomes complex

   • Hence, these patients underwent surgery depending on their gender identity.

Masculinizing genitoplasty includes excision of the vaginal pouch with laparoscopic excision of Mullerian structures in selected cases, hypospadias repair, and scrotoplasty [Figures 1-4]. An initial cystogenitoscopy is done to determine the presence of a vaginal pouch and the length of the vaginal pouch. This is followed by excision of vaginal pouch by a perineal approach. The vaginal pouch one identified is dissected off the urethra and excised in toto.

Figure 1.

Dissection of vaginal pouch through midline perineal incision. Initial cystogenitoscopy done to determine the length of the vaginal pouch

Figure 4.

Laparoscopic Mullerian structure excision in a 14-year-old patient, reared as a male with 46XX CAH, who underwent masculinizing genitoplasty

Figure 2.

Stage 1 Bracka’s urethroplasty using inner preputial skin after removal of the vaginal pouch

Figure 3.

Final appearance after stage 2 Bracka’s urethroplasty. Note complete masculine appearance of genitalia after surgery

Hypospadias repair in masculinizing genitoplasty was done either as a single stage or two stage repair. Single-stage procedures done included Duckett’s repair and Hodgson’s XX repair. Two-stage repairs included Byar’s repair and Bracka’s repair. Brackas repair in these patients was done using inner preputial skin graft. In patients with undescended testes, orchidopexy was done at a later date or during the same surgery as per surgeon’s decision. Patients that required the removal of gonads were provided with testicular prostheses at a later date.

Patients with Mullerian structures then underwent laparoscopy to confirm the presence of Mullerian structures followed by a excision of Mullerian structures. Patients with streak gonads or ovotestis underwent excision of the same.

Feminising genitoplasty includes reduction clitoroplasty (excision of erectile tissue in a subtunical plane), vaginoplasty, and labioplasty [Figure 5]. All patients underwent an initial cystogenitoscopy to determine the length of the vagina as well as the distance between bladder neck and confluence. If there is a low confluence, perineal U flap vaginoplasty is done. But if a hugh confluence is seen, or difficulty is expected with pull through vaginoplasty, sigmoid vaginoplasty can be done. Reducton clitoroplasty includes subtunical excision of bilateral erectile tissue with special care taken to preserve the neurovascular supply to the glans [Figures 6 and 7]. A U flap vaginoplasty is done which includes a posterior U shaped perineal skin flap being raised and an approximation of flap to the posterior wall of the vagina after division in the midline until adequate lumen of the vagina is achieved [Figure 8]. Sigmoid vaginoplasty includes the isolation of an adequate segment of the sigmoid colon preserving its mesenteric pedicle which will reach the perineum without tension. Labia majora and minora are fashioned using phallic skin [Figure 9]. Any testicular tissue is excised.

Figure 5.

Incision marking for feminising genitoplasty

Figure 6.

Dissection of erectile tissue in a subtunical plane to preserve neurovascular supply to the glans

Figure 7.

Bilateral erectile tissue after complete dissection and preservation of the glans. This is then ligated proximally and excised

Figure 8.

Dissection of the common urogenital channel to delineate the urethra and vagina separately followed by U flap vaginoplasty (black arrow: urethra., yellow arrow: vagina., blue arrow: perineal U shaped skin flap)

Figure 9.

Final appearance after completion of feminising genitoplasty (catheter in urethra and tube in vagina)

Once the plan of management has been decided by the multidisciplinary team, the patient and parents are counselled. Only after written and informed consents from the patient and parents did we proceed with the decided plan of management. Written and verbal consents were taken from the patient as well as both parents after detailed discussion regarding overall management. Data were collected as per previous records and the prevalence of GD was analyzed and tabulated.

RESULTS

Overall, 105 patients presented to our institute with disorders of sexual differentiation. Ages ranged from 1 to 47 years. The mean age of presentation was 8.4 years. The different types of DSD presenting to us included 5 alpha reductase deficiency (35.2%), CAH (31.4%), mixed gonadal dysgenesis (6.6%), complete androgen insensitivity (6.6%), partial androgen insensitivity (2.8%), ovotesticular DSD (9.5%), testicular biosynthesis defect (6.6%), and pure gonadal dysgenesis (0.9%) [Table 1].

Table 1.

Disorders of sexual differentiation and its types

	CAH	PAIS	CAIS	5 alpha reductase deficiency	Ovotesticular DSD	MGD	Others
Number of patients	33	7	3	37	10	7
Others
Testicular biosynthesis defect							7
Pure gonadal dysgenesis							1

CAH: Congenital adrenal hyperplasia, PAIS: Partial androgen insensitivity syndrome, CAIS: Complete androgen insensitivity syndrome, MGD: Mixed gonadal dysgenesis, DSD: Disorders of sexual differentiation

Of these, 36 patients presented to us in the adolescent and adult age groups, with mean age of presentation of 18.9 years, with 38.8% of patients diagnosed with 5 alpha reductase deficiency, 22.2% having CAH, 8.3% having complete/partial androgen insensitivity, 11.1% having ovotesticular DSD, 11.1% having mixed/pure gonadal dysgenesis, and 8.3% having testicular biosynthetic defect (17 beta hsd 3 deficiency and 17 alpha hydroxylase deficiency) [Table 2].

Table 2.

Adolescent and adult patients presenting with disorders of sexual differentiation

	CAIS/PAIS	5 alpha reductase deficiency	CAH	Ovotesticular DSD	MGD/PGD	Testicular biosynthesis defect
Number of patients	3	14	8	4	4	3

CAIS: Complete androgen insensitivity syndrome, CAH: Congenital adrenal hyperplasia, DSD: Disorders of sexual differentiation, MGD: Mixed gonadal dysgenesis, PGD: Pure gonadal dysgenesis, PAIS: Partial androgen insensitivity syndrome

Table 3 describes each patient who presented to us with DSD that is included in the study.

Table 3.

Overview of adolescent and adult patients presenting to our institute with disorders of sexual differentiation

Age (years)	Diagnosis	Gender	Surgery
20	46XX DSD with ovotesticular DSD	Reared as male and identifies as male	Masculinizing genitoplasty
15	46XY DSD with 5 alpha-reductase deficiency	Reared as female and identifies as female	Feminizing genitoplasty
18	46XX DSD with CAH	Reared as female and identifies as female	Feminizing genitoplasty
18	46XY DSD with 5 alpha-reductase deficiency	Reared as female and identifies as female	Feminizing genitoplasty
25	46XY DSD with MGD	Reared as male and identifies as male	Masculinising genitoplasty
18	46XY DSD with 5 alpha-reductase	Initially reared as female and but identifies as male (gender dysphoria+)	Masculinising genitoplasty
22	46XY DSD with 5 alpha-reductase deficiency	Reared as female and identifies as female	Feminizing genitoplasty
16	46XY DSD with CAH	Reared as female and identifies as female	Feminizing genitoplasty
12	46XY DSD with 5 alpha-reductase deficiency	Reared as male and identifies as male	Masculinizing genitoplasty
15	46XY DSD with 5 alpha-reductase deficiency	Reared as female but identified as male. Dressed up as a male and had a general dissatisfaction with being female (gender dysphoria +)	Masculinizing genitoplasty
19	46XY DSD with pure gonadal dysgenesis	Identifies as female	Feminizing genitoplasty
28	46XY DSD with ovotesticular DSD	Reared as male, identifies as male	Masculinising genitoplasty
19	46XY DSD with MGD	Reared as female, identifies as female	Masculinizing genitoplasty
23	46XY DSD with 5 alpha-reductase deficiency	Reared as male, identifies as male	Masculinizing genitoplasty
15	46XX DSD with CAH	Reared as male and identifies as male	Masculinizing genitoplasty
35	46XX DSD with CAH	Reared as male, identifies as male	Masculinizing genitoplasty
19	46XY DSD with 5 alpha-reductase deficiency	Reared as male, identifies as male	Masculinising genitoplasty
18	46XX DSD with CAH	Reared as male, identifies as male	Masculinising genitoplasty
12	46XY DSD with 5 alpha-reductase deficiency	Reared as female but identifies as male (gender dysphoria +)	Masculinising genitoplasty
19	46XY DSD with 5 alpha-reductase deficiency	Initially reared as female but identified as male (gender dysphoria +)	Masculinizing genitoplasty
22	46XY DSD with 17 alpha-hydroxylase deficiency	Reared as male, identifies as male	Masculinizing genitoplasty
15	46XY DSD with 5 alpha-reductase deficiency	Initially reared as male, but identifies as female (gender dysphoria +)	Feminizing genitoplasty
24	46XY DSD with testicular biosynthesis defect	Initially reared as female, but identifies as male (gender dysphoria+)	Masculinising genitoplasty
12	46XY DSD with testicular biosynthesis defect	Initially reared as female but identifies as male (gender dysphoria +)	Masculinising genitoplasty
16	46XX DSD with CAH	Reared as female and identifies as female	Feminizing genitoplasty
17	46XX DSD with CAH	Reared as female, identifies as female	Feminizing genitoplasty
48	46XY DSD with PAIS	Reared as female, identifies as female	Feminizing genitoplasty
18	46XY DSD with ovotesticular DSD	Initially reared as female, but identifies as male (gender dysphoria+)	Masculinising genitoplasty
18	46XX DSD with CAH	Reared as female, identifies as female	Feminizing genitoplasty
17	46XY DSD with PAIS	Reared as female, identifies as female	Feminizing genitoplasty
11	46XY DSD with 5 alpha reductase deficiency	Reared as female, identifies as female	Feminizing genitoplasty
11	46XY DSD with PAIS	Reared as female and identifies as female	Feminizing genitoplasty
21	46XY DSD with 5 alpha reductase deficiency	Reared as female, identifies as female	Feminizing genitoplasty
18	46XX DSD with ovotesticular dsd	Reared as male, identifies as male	Masculinising genitoplasty
14	60% XX/40% XY DSD with MGD	Reared as female, identifies as female	Feminizing genitoplasty
14	46 XY DSD with 5 alpha-reductase deficiency	Initially reared as male but identified as female (gender dysphoria+)	Feminizing genitoplasty

CAH: Congenital adrenal hyperplasia, PAIS: Partial androgen insensitivity syndrome, CAIS: Complete androgen insensitivity syndrome, MGD: Mixed gonadal dysgenesis, DSD: Disorders of sexual differentiation

Of the patients that underwent masculinising genitoplasty, eight patients underwent single stage urethroplasty (Hodgson’s/Duckett’s) and 11 patients underwent 2 stage urethroplasty (Byar’s/Bracka’s) based on phallic size and size of the glans.

Of the patients that underwent feminizing genitoplasty, only one patient required a sigmoid segment for vaginal reconstruction. The rest of the patients underwent perineal U flap vaginoplasty followed by vaginal dilatation to lengthen the vaginal pouch in XY DSD patients and to prevent vaginal stenosis in xx DSD patients.

Of these patients, 9 (25%) patients were found to have GD. 6 patients who were diagnosed with 5 alpha reductase were found to have GD, one patient with ovotesticular DSD was found to have GD, and two patients with testicular biosynthesis defect presented with GD. No patient diagnosed with CAH, complete/partial androgen insensitivity syndrome, or gonadal dysgenesis was found to have GD [Table 4].

Table 4.

Patients having gender dysphoria

	CAIS	PAIS	CAH	5 alpha reductase deficiency	Testicular biosynthesis defect	Ovotesticular DSD	MGD/PGD
Number of patients	-	-	-	6	2	1	-

CAIS: Complete androgen insensitivity Syndrome, CAH: Congenital adrenal hyperplasia, DSD: Disorders of sexual differentiation, MGD: Mixed gonadal dysgenesis, PGD: Pure gonadal dysgenesis, PAIS: Partial androgen insensitivity syndrome

As per the approach used by our multidisciplinary team described above, the type of surgery decided upon on each patient can be broadly explained as follows.

46XX disorders of sexual development

1. All 46 XX females underwent feminizing genitoplasty and none of them presented with GD

2. None of the 46 XX males presented with GD, hence all underwent masculinizing genitoplasty.

46 XY disorders of sexual development

This group was more complex and posed the most controversial situations in regards to the type of surgery required.

1. Patients with 5 alpha-reductase deficiency and testicular biosynthetic defects reared as females with pubertal virilization:

   • A total of eight patients presented to us with 5 alpha-reductase deficiency and testicular biosynthesis defect, of which six patients had the abovementioned presentation with GD (these patients identified as males). All of these patients underwent masculinizing genitoplasty

   • The other two patients expressed strong desires to continue as females, and hence, it was decided to proceed with feminizing genitoplasty in these patients after detailed counseling with the patients and their families.

2. Partial androgen insensitivity

   • The two patients included in our study having partial androgen insensitivity were reared as females and did not have GD. Also considering the feminine appearance of their external genitalia and small phallus, it was decided to proceed with feminizing genitoplasty in these patients.

3. Complete androgen insensitivity:

   • In our study, only one patient was found to have complete androgen insensitivity, with an appearance of a normal girl with primary amenorrhea. This patient did not have GD and hence the patient underwent feminizing genitoplasty.

4. Mixed gonadal dysgenesis:

   • Four patients of mixed gonadal dysgenesis were identified, of which 3 were reared as males and identified as males and 1 was reared as a female and identified as female. None of these patients had GD

   • All these patients underwent surgery based on their gender identity.

5. Ovotesticular DSD:

   • These patients were managed in a similar fashion to the patients with mixed gonadal dysgenesis. Of the four patients with this diagnosis in our study, one patient had GD (reared as female but identified as male). All of these patients were managed based on their gender identity.

None of the patients included in the study had undergone prior genital reconstruction at an earlier age. All patients were operated by the same surgical team after a detailed discussion with the multidisciplinary committee. Postoperatively, all patients were satisfied with cosmetic appearance. Patients were referred back to the endocrinologist for hormonal replacement as required.

On follow-up, all patients were satisfied with gender identity as well. None of the patients included in the study expressed any dissatisfaction regarding their choice postsurgery or on long-term follow-up.

DISCUSSION

GD is defined as the distress that may accompany the incongruence between one’s expressed gender and the assigned gender. The intense emotional pain may cause impairment in their functional lives. There are many psychiatric comorbidities that may occur as a result of GD, which include, depression, anxiety, personality disorders, substance abuse, and suicide.[5] Hence, it is extremely important to approach patients with DSD who have GD with care. It is very important that such patients are satisfied with the external appearance of their genitalia following surgery as it contributes to psychosexual treatment as well and prevents the development of psychiatric comorbidities.[9] In fact, the primary goal in DSD is to have a gender assignment consistent with the underlying gender identity to prevent the distress related to a forthcoming GD.[8]

Historically, gender assignment was based essentially on surgical outcomes, assuming the neutrality of gender identity at birth. This policy has been challenged in the past decade refocusing on the importance of prenatal and postnatal hormonal and genetic influences on psychosexual development.[8] Many studies have advocated the treatment of patients with DSD at in early ages to prevent GD and that is also followed in our institute.[6] However, in resource-poor countries like India, where not all births are supervised by healthcare workers, some of these children remain undiagnosed until puberty or even later.[7] Hence, a significant number of patients have presented to us during the adolescent and middle age period. The ongoing debate of early or late surgery can be better understood depending on the type of DSD the patient presents with.

In patients with CAH, GD is unlikely. Hence, the debate of early or late surgery in these patients is mainly focused on the onset of menstruation and a future sexual life. This implies a vaginal connection to the perineum before puberty starts. In a French study, when several cohorts of adult women who underwent feminizing genitoplasty at various ages were interviewed, all claimed that early surgery is highly preferable to late surgery.[10] However, it has been argued that late surgery has a better accompanying process, with more patient involvement in the decision-making process.[10] It may also reduce the risk of stenosis of the vaginal opening, requiring subsequent vaginal dilatation, as the patient is more cooperative to postoperative vaginal dilatations when necessary. Girls with CAH who underwent early genital surgery have a good and satisfying cosmetic outcome as assessed by healthcare providers, better quality of life.[9,10] The psychological impact of late genital surgery is likely to be more significant than in early life. Our institution is of the belief that early genital surgery is always better in girls with CAH as tissues are more pliable with less bleeding during dissection and lower postoperative complications. From a psychological standpoint, early surgery provides greater satisfaction to the patient as well as the parents and promotes family binding and overall satisfaction. From a psychological standpoint, early surgery provides greater satisfaction to the patient as well as the patients and promotes family bonding and overall satisfaction. In such instances, in our institution, the parents are counseled to rear as a female in view of reproductive potential, and none of these patients are operated on till gender identity has been confirmed.

In patients with 5 alpha-reductase deficiency and testicular biosynthetic defects, due to the high prevalence of GD in those patients that have been reared as girls, it is recommended to delay surgery with pubertal blockade and estrogen therapy until gender identity has been confirmed.[2,10] It is unclear at what age gender identity can be confirmed established.[10] In our institution, patients diagnosed with 5 alpha-reductase deficiency and testicular biosynthetic defects at infancy are assigned a male gender in view of the possibility of reproduction and high incidence of GD. There have been situations where the parents insist on raising the patient as female. In such cases, these patients are reared as girls with preservation of gonads in the inguinal region and pubertal blockade until a gender identity has been confirmed. Once confirmed, the appropriate surgery is planned.

Patients diagnosed with partial androgen insensitivity syndrome present with severe hypospadias and/or micropenis. It is recommended to rear such patients as males as it has been reported that GD is more common in patients reared in females rather than males.[10] In our institution, all young patients with partial androgen insensitivity syndrome are reared as males. In those rare circumstances where these patients are reared as females, surgery is done only once gender identity has been confirmed.

Complete androgen insensitivity syndrome does not pose as much of a surgical dilemma as much as other types of DSD, as these patients have the appearance of a normal girl with no GD. Hence, our general practice is to continue all these patients as females.

Patients with mixed gonadal dysgenesis and ovotesticular DSD pose the most complex situations where no decision can be considered completely satisfactory.[10] The current trend is to keep those patients with a Y chromosomal component as males despite the low fertility potential.[10] If a feminine gender is being considered, surgery is delayed till gender identity is confirmed. Family dynamics and sensitivity are very important in these cases for a decision-making process.[10] Family counseling is extremely important in coming to a decision regarding irreversible genital surgery. The main obstacle faced by the multidisciplinary committee is giving this information to the parents.[10] Accompanying the patient and their family throughout childhood until adulthood is a delicate task for the multidisciplinary team. Hence, the aim is to make the patient and parents accept and cope with the situation.[10] As per our institution protocol, young patients with mixed gonadal dysgenesis and ovotesticular DSD having a Y component in their karyotyping are reared as male. These patients undergo Mullerian structure removal and streak gonad removal at a young age. Those patients that have been reared as female, wait till their gender identity is confirmed before proceeding with surgery. So far, we have encountered very few patients with mixed gonadal dysgenesis and ovotesticular DSD reared as females and all have been operated on only once gender identity is confirmed.

Patients having ovotesticular DSD with 46XX karyotyping, which is more common, when presenting to us in infancy, are advised to be reared as female, since the ovarian tissue in such patients is functional, and pregnancy, though rare, has been reported in such patients.

Joseph et al., in their paper, Gender Issues and the related social stigma affecting patients with DSD in India have explained in great detail the social and psychological problems faced by patients with DSD.[7] Similar instances have been noted in patients with DSD who have presented to our institute as well. One patient, who is 47 years of age, was diagnosed with PAIS, 2 weeks before being referred to us. The reason for this late presentation was that though the patient was aware of her ambiguous genitalia, her family was too embarrassed to seek help for her and hence her condition was ignored. As a result, the patient was hesitant to form any social relationships and interacted less with males. Only when the patient found a partner, she decide to get treatment for her condition. Postoperatively, the patient is satisfied with the external appearance of her genitalia and is set to be married in a few months. Another patient, who presented to us at the age of 17 with ovotesticular DSD, was reared as a female since birth and wore feminine clothes. However, the patient was dissatisfied with being a female and anxious about the same as the patient felt that he identified as a male. At the age of 14 years, when he started developing facial hair, the patient was forced to leave his school and town and moved to another town as a male. Since then, he has found that he is less anxious with being a male and has found a sort of mental peace after becoming a male. Postoperatively, the patient was very satisfied with the external genital appearance. Similarly, there have been many patients with GD in our study that have an improved mindset following surgery corresponding to their preferred gender.

A major problem in India regarding the topic of GD in patients with disorders of sexual differentiation seems to be the acceptance of the patients’ preferred gender by family members and relatives. This further leads to psychosocial comorbidities, including depression and suicidal tendencies. Hence, such patients require continued psychological support postoperatively in the form of counseling as well as medications as per individual requirements. Furthermore, it is important that the families of the patients also receive the same support by the multidisciplinary team as that given to the patients.

GD generally affects between 8.5% and 20% of individuals with DSDs, depending on the type of DSD.[9] Furtado et al., in their study, GD associated with disorders of sex development, stated that patients with 5α-reductase 2 and 17β-hydroxysteroid dehydrogenase 3 (testicular biosynthesis defect) deficiencies exhibit the highest rates of GD, which is supported by this study. In our study, we found that 25% of adolescent and adult patients who presented to our institute were found to have GD. As per our study, patients with 5 alpha-reductase deficiency were found to have the highest incidence of GD (66.6%), followed by testicular biosynthesis defect (22.2%) and ovotesticular dsd (11.1%). Patients with CAH, PAIS/CAIS, and gonadal dysgenesis were not found to have GD as per our study.

In patients with 5 alpha reductase deficiency, which was found to have the highest incidence of GD, it is worthwhile to mention that out of the six patients having GD, four patients were reared as females initially and then later converted to males as they identified as males. As per the meta-analysis of GD in DSD presented by Babu and Shah in 2021, the high incidence of GD in 5 alpha reductase is attributed to such patients being reared as females. Most newborns with this condition have female external genitalia at birth, although few infants may present with ambiguous genitalia.[2] Most affected infants are assigned a female sex and raised as girls. But they often virilize at puberty with the deepening of the voice, growth of the phallus, rugation/hyperpigmentation of the scrotum, and descent of intra-abdominal testes.[2] On the basis of the reported high percentage of subjects requesting female-to-male gender reassignment after puberty, together with the potential for paternity, a male sex assignment is recommended, despite feminized external appearance in them during infancy.[2]

The limitations of this study are that it is a retrospective study and that the sample size was small.

The Indian Association of Pediatric Surgeons has published guidelines regarding the management of DSD which explains the need for a multidisciplinary committee in the management of DSD which includes a pediatric endocrinologist, pediatric surgeon, and a child psychiatrist who provides adolescent care and in some cases an adult psychiatrist as well.[2,3]

Although this study is focused on GD in DSD patients, our institute is of the opinion that surgery for DSD should be done at a young age which prevents psychological morbidity and improves parental bonding. The authors would also like to mention that normal patients presenting with GD are not part of our practice and have not been encountered so far.

CONCLUSION

It is obvious that given the complexity and variability of the presentation of DSD, there is no consensus regarding the indications, timing, the procedure required, and the evaluation of the outcome of these patients. Hence, it is important for the multidisciplinary team to analyze every case of DSD in great detail and take into consideration the patient and parents’ wishes and circumstances prior to making a decision regarding the management of these patients.

In our study, we found that GD was found to be more common in patients with 5 alpha-reductase deficiency (mainly those reared as females). Patients with ovotesticular DSD and testicular biosynthesis defect were also found to have GD. Patients with CAH and CAIS were not found to have GD.

The main goal of surgical intervention is to normalize appearance and function and forestalling physical and psychosocial morbidity. Each patient with DSD is unique and hence requires a multidisciplinary team for treatment of such patients which provides treatment from a medical, surgical, and psychosexual point of view.

Conflicts of interest

There are no conflicts of interest.

Funding Statement

Nil.