A Single-Center, Observational Study of 607 Children and Young People Presenting With Differences of Sex Development (DSD).

Context: Differences of sex development (DSD) represent a wide range of conditions presenting at different ages to various health professionals. Establishing a diagnosis, supporting the family, and developing a management plan are important. Objective: We aimed to better understand the presentation and prevalence of pediatric DSD. Methods: A retrospective, observational cohort study was undertaken in a single tertiary pediatric center of all children and young people (CYP) referred to a DSD multidisciplinary team over 25 years (1995-2019). In total, 607 CYP (520 regional referrals) were included. Data were analyzed for diagnosis, sex-assignment, age and mode of presentation, additional phenotypic features, mortality, and approximate point prevalence. Results: Among the 3 major DSD categories, sex chromosome DSD was diagnosed in 11.2% (68/607) (most commonly 45,X/46,XY mosaicism), 46,XY DSD in 61.1% (371/607) (multiple diagnoses often with associated features), while 46,XX DSD occurred in 27.7% (168/607) (often 21-hydroxylase deficiency). Most children (80.1%) presented as neonates, usually with atypical genitalia, adrenal insufficiency, undescended testes or hernias. Those presenting later had diverse features. Rarely, the diagnosis was made antenatally (3.8%, n = 23) or following incidental karyotyping/family history (n = 14). Mortality was surprisingly high in 46,XY children, usually due to complex associated features (46,XY girls, 8.3%; 46,XY boys, 2.7%). The approximate point prevalence of neonatal referrals for investigation of DSD was 1 in 6347 births, and 1 in 5101 overall throughout childhood. Conclusion: DSD represent a diverse range of conditions that can present at different ages. Pathways for expert diagnosis and management are important to optimize care.

Epidemiological surveillance study of female genital mutilation in the UK.

OBJECTIVES: Describe cases of female genital mutilation (FGM) presenting to consultant paediatricians and sexual assault referral centres (SARCs), including demographics, medical symptoms, examination findings and outcome. DESIGN: The well-established epidemiological surveillance study performed through the British Paediatric Surveillance Unit included FGM on the monthly returns. SETTING: All consultant paediatricians and relevant SARC leads across the UK and Ireland. PATIENTS: Under 16 years old with FGM. INTERVENTIONS: Data on cases from November 2015 to November 2017 and 12 months later meeting the case definition of FGM. MAIN OUTCOME MEASURES: Returns included 146 cases, 103 (71%) had confirmed FGM and 43 (29%) did not meet the case definition. There were none from Northern Ireland. RESULTS: The mean reported age was 3 years. Using the WHO classification of FGM, 58% (n=60) had either type 1 or type 2, 8% (n=8) had type 3 and 21% (n=22) had type 4. 13% (n=13) of the cases were not classified and none had piercings or labiaplasty. The majority, 70% had FGM performed in Africa with others from Europe, Middle East and South-East Asia. There were few physical and mental health symptoms. Only one case resulted in a successful prosecution. CONCLUSIONS: There were low numbers of children presenting with FGM and in the 2 years there was only one prosecution. The findings may be consistent with attitude changes in FGM practising communities and those at risk should be protected and supported by culturally competent national policies.

The Prevalence of Endometriosis in Adolescents with Pelvic Pain: A Systematic Review.

STUDY OBJECTIVE: Endometriosis is a recognized cause of pelvic pain in adolescents with menstrual symptoms that significantly affect education, activity, and social interactions. We aim to provide an updated systematic review of the prevalence of endometriosis in adolescents with pelvic pain presenting for gynecological investigation. DATA SOURCES: We searched Medline, Embase, and Cinahl from 2011 to July 2019. METHODS OF STUDY SELECTION: We included cohort studies of adolescents with pelvic pain undergoing gynecological investigation. Two authors independently selected studies and extracted study characteristics and prevalence data. Methodological quality was assessed using the Critical Appraisal Skills Program for cohort studies. RESULTS: This updated systematic review evaluated a total of 19 studies including 1243 symptomatic adolescents. In all, 648 of 1011 (64%) adolescents undergoing laparoscopy were found to have endometriosis. The prevalence ranged from 25% to 100%, with a mean prevalence of 64%. Thirteen studies including 381 participants categorized disease severity using the revised American Society of Reproductive Medicine classification. Among these, 53% of participants (201/381) had stage I, 28% (105/381) had stage II, 20% (76/381) had stage III, and 13% (49/381) had stage IV disease. CONCLUSIONS: The prevalence of endometriosis among adolescents with pelvic pain symptoms is high. Endometriosis is treatable, and prompt recognition will help to ensure that adolescents are signposted earlier to appropriate specialists. The management of adolescents with suspected endometriosis should be consistent with best practice guidance. Despite recommendations to increase the awareness and knowledge of endometriosis in adolescence, minimal research has followed.

Female genital mutilation (FGM) in UK children: a review of a dedicated paediatric service for FGM.

OBJECTIVE: To describe the presentation and management of children with suspected or confirmed female genital mutilation (FGM) referred to a specialist paediatric clinic. METHODS: Data collected included referral source, age, ethnicity, circumstances of FGM and clinical findings in accordance with the WHO FGM classification. RESULTS: Between September 2014 and January 2019, 148 children attended the clinic of whom 55 (37.2%) had confirmed FGM. Police or social care referred 112 (76%) children. The proportion of looked-after children (LAC) was significantly higher in the group with confirmed FGM (17/55, 31%) compared with children where FGM was not confirmed (5/93, 5%). In almost all children where FGM was confirmed, FGM was initially disclosed by the child or family (53/55, 96%) and of these 48/55 (87%) underwent FGM prior to UK entry. The remaining seven cases were British children, potentially meeting legal criteria under the FGM Act, and one resulted in a successful prosecution. CONCLUSIONS: The number of children with FGM was significantly lower than expected based on UK prevalence estimates. Most children had undergone FGM prior to UK entry, and the majority of cases were initially disclosed by the child or family themselves. These results reflect the lack of large-scale proof of the practice of FGM in the UK and are consistent with growing evidence of the abandonment of FGM among communities after migration.

'Botched labiaplasty': a content analysis of online advertising for revision labiaplasty.

A new development in female genital cosmetic surgery (FGCS) is the promotion of revision surgery for 'botched labiaplasty'. This content analysis study reviews the quality of information offered on websites specifically advertising revision labiaplasty. Twelve websites were identified through online searches and were examined for the quality of their clinical information. All sites defined botched labiaplasty as unsatisfactory appearance after labiaplasty. Four gave no further details and five listed asymmetry, irregular labial edges or removal of too much or too little tissue. Four websites described primary botched labiaplasty as 'mutilation'. Inadequacy of the primary surgeon was cited as the cause of botched labiaplasty in 11/12. Only two websites mentioned risks of surgery. Good outcomes were not defined and no website provided outcome data although guaranteed satisfaction was implied in two websites. This study highlights the existence and promotion of services for botched labiaplasty using non-specific and emotive descriptions. These findings suggest that unsatisfactory results from consumers' perspectives are far from uncommon. The same women whose expectations have not been met by primary surgery are now being targeted for repeat surgery with online advertising capitalising on their unchanged motivations.Impact StatementWhat is already known on this subject? Female genital cosmetic surgery (FGCS) is mainly advertised online with labiaplasty as the most commonly performed procedure. A market for labiaplasty revision to correct 'botched' primary procedures is developing. Academic literature and advertising materials are inconsistent when defining indications and determinants of success for labiaplasty or revision.What the results of this study add? A content analysis of websites specifically advertising revision labiaplasty describes the emotive and nonspecific terms used online to promote revision labiaplasty.What the implications are of these findings for clinical practice and/or further research? The existence of services for botched labiaplasty suggests dissatisfaction is common. Women whose expectations have not been met by primary surgery are targeted for repeat surgery through online advertising capitalising on their potentially unchanged motivations. This study demonstrates the need for clearer outcome data for labiaplasty and highlights the need for better advertising standards for FGCS promotion.

Establishing reproductive potential and advances in fertility preservation techniques for XY individuals with differences in sex development.

BACKGROUND: Discordance between gonadal type and gender identity has often led to an assumption of infertility in patients with differences in sex development (DSD). However, there is now greater recognition of fertility being an important issue for this group of patients. Currently, gonadal tissue that may have fertility potential is not being stored for individuals with DSD and, where gonadectomy forms part of management, is often discarded. The area of fertility preservation has been predominantly driven by oncofertility which is a field dedicated to preserving the fertility of patients undergoing gonadotoxic cancer treatment. The use of fertility preservation techniques could be expanded to include individuals with DSD where functioning gonads are present. METHODS: This is a systematic literature review evaluating original research articles and relevant reviews between 1974 and 2018 addressing DSD and fertility, in vitro maturation of sperm, and histological/ultrastructural assessment of gonadal tissue in complete and partial androgen insensitivity syndrome, 17ß-hydroxysteroid dehydrogenase type 3 and 5α-reductase deficiency. CONCLUSION: Successful clinical outcomes of ovarian tissue cryopreservation are paving the way for similar research being conducted using testicular tissue and sperm. There have been promising results from both animal and human studies leading to cryopreservation of testicular tissue now being offered to boys prior to cancer treatment. Although data are limited, there is evidence to suggest the presence of reproductive potential in the gonads of some individuals with DSD. Larger, more detailed studies are required, but if these continue to be encouraging, individuals with DSD should be given the same information, opportunities and access to fertility preservation as other patient groups.

Sexual Experience before Treatment for Vaginal Agenesis: A Retrospective Review of 137 Women.

STUDY OBJECTIVE: To summarize the self-reported sexual experiences of women with vaginal agenesis before treatment and discuss the clinical implications. DESIGN: A retrospective review of pretreatment baseline sexuality data and medical records of women with vaginal agenesis seeking vaginal construction. SETTING: A specialist multidisciplinary center for women with genital differences associated with diverse sex development. PARTICIPANTS: One hundred thirty-seven women with untreated vaginal agenesis associated with Mayer-Rokitansky-Küster-Hauser Syndrome and complete androgen insensitivity syndrome aged 15 to 41 years (mean age, 20 years). INTERVENTIONS: Gynecological examination and completion of questionnaires. MAIN OUTCOME MEASURES: (1) Sexual Experiences Questionnaire; (2) Multidimensional Sexuality Questionnaire; (3) Vaginal Self-Perceptions; and (4) vaginal length. RESULTS: A sizable proportion of women reported having had sexually intimate experiences before any medical intervention on the vagina. Vaginal length, which ranged from dimple to 7 cm and averaged 2.7 cm for the cohort, was unrelated to the range of sexual experiences. Most women perceived their vagina as being too small, but less than half believed that a sexual partner would notice this. Two-thirds of the cohort subsequently completed the dilation program, which was not predicted by pretreatment vaginal length or sexual experience. CONCLUSION: Contrary to the assumption that a vagina of certain dimensions is a prerequisite for women to "have sex," many women with Mayer-Rokitansky-Küster-Hauser syndrome and complete androgen insensitivity syndrome reported having experienced genital and nongenital sexual activities with no medical interventions. It is recommended that treatment providers affirm women's capacity for sexual intimacy, relationships, and enjoyment before they introduce the topic of vaginal construction as a non-urgent choice.

An exploration of attitudes towards female genital mutilation (FGM) in men and women accessing FGM clinical services in London: a pilot study.

This pilot study researched the attitudes towards and the knowledge of female genital mutilation (FGM) in adult women with FGM and their partners. The participant population consisted of English-speaking women and men over 18 years old attending specialist FGM clinics in two London hospitals. The participants completed a questionnaire on the attitudes and the knowledge of FGM, which were adapted with permission from the United Nations Children's Fund and the United States Agency for International Development household surveys. 54 participants (51 women, 3 men) took part in the surveys. 89% of participants thought that FGM should be stopped (95%CI: 0.81-0.97) and 72% said they knew FGM is illegal in the United Kingdom (UK). 15% reported that FGM caused no danger, or were unaware of any danger to women's health. This study demonstrates the opposition to FGM by participants, but some lack of knowledge regarding the legal and health implications. The exploration of attitudes in diaspora community groups is often cited as key to safeguarding girls from FGM. This is one of the first UK studies of individuals from FGM-practising communities, and we recommend use of the study questionnaires for a multicentre, cross-community study. Impact statement What is already known about this subject? Women and children are affected by female genital mutilation (FGM) globally and in the United Kingdom (UK). The majority of knowledge on practices and the attitudes towards FGM comes from UNICEF and USAID research in Africa and there is scant data on FGM practices in diaspora communities in the UK. What do the results of this study add? This study provides an appropriate questionnaire and protocol for use in community-based national research to improve healthcare for women by collecting up-to-date data on the attitudes towards FGM among the members of FGM-practising communities in the UK. What are the implications of these findings for clinical practice and further research? The implications of the results of this study are that health professionals need to understand that patients do not always know the law on FGM, even after a consultation. Health and social care professionals are placed in a unique position to work with community members to educate men and women to end FGM.

Vaginal Construction and Treatment Providers' Experiences: A Qualitative Analysis.

STUDY OBJECTIVE: To investigate specialist clinicians' experiences of treating vaginal agenesis. DESIGN: Semi-structured interviews. SETTING: Twelve hospitals in Britain and Sweden. PARTICIPANTS: Thirty-two health professionals connected to multidisciplinary teams (MDTs) including medical specialists and psychologists. INTERVENTIONS AND MAIN OUTCOME MEASURES: Theoretical thematic analysis of recorded verbatim data. RESULTS: The gynecologist and psychologist interviewees share certain observations including the importance of psychological readiness for and appropriate timing of treatment. Three overlapping themes are identified in our theoretical analysis of the MDT clinicians' talk: (1) the stigma of vaginal agenesis and the pressure to be "normal" can lead patients to minimize the time, effort, physical discomfort, and emotional cost inherent in treatment. (2) Under pressure, treatment might be presented to patients with insufficient attention to the potential psychological effect of the language used. Furthermore, the opportunity to question what is "normal" in sex is generally not taken up. It can be challenging to help the women to transcend their medicalized experiences to come to experiencing their bodies as sexual and enjoyable. (3) The reality of treatment demands, which are not always adequately processed before treatment, can lead to discontinuation and even disengagement with services. CONCLUSION: The MDT clinicians in this study emphasized the importance of psychological input in vaginal construction. However, such input should proactively question social norms about how women's genitalia should appear and function. Furthermore, rather than steering patients (back) to treatment, the entire MDT could more explicitly question social norms and help the women to do the same. By shifting the definition of success from anatomy to personal agency, the clinical focus is transformed from treatment to women.

Hormone replacement treatment choices in complete androgen insensitivity syndrome: an audit of an adult clinic.

OBJECTIVE: To review the treatment choices of women with complete androgen insensitivity syndrome (CAIS) at a single tertiary centre. DESIGN: Retrospective review. PATIENTS: Women with CAIS identified from our database. RESULTS: The study group comprised 141 women with CAIS. Eleven percent (16/141) of women had gonads in situ, 3 of whom were under workup for gonadectomy. The age of gonadectomy in the remainder 125 women was 17 (0.1-53) years. The most common form of HRT was oral oestrogen or transdermal oestrogen in 80% (113/141). 13/141 (9%) women used vaginal oestrogens alone or together with other forms of HRT. Testosterone preparations had been used by 17% (24/141) of women and were currently used in 10% (14/141). Of those who had used testosterone, 42% (10/24) had chosen not to continue after a therapeutic trial. CONCLUSIONS: In a clinic offering individualised multidisciplinary care for women with CAIS, we found that the majority of women chose oestrogen-based treatment while a significant minority used testosterone.

Bone mineral density in complete androgen insensitivity syndrome and the timing of gonadectomy.

OBJECTIVE: Low bone mineral density (BMD) has been reported in complete androgen insensitivity syndrome (CAIS), but the impact of timing of gonadectomy is not known. We aimed to assess the relationship between age of gonadectomy and BMD in women with CAIS. DESIGN: Retrospective analysis of pre- and post-gonadectomy parameters in women with CAIS attending an adult Disorders of Sex Development (DSD) clinic in a tertiary centre. PATIENTS: One hundred and thirteen women with CAIS. MEASUREMENTS: Dual-energy X-ray absorptiometry (DXA) before and after gonadectomy; and pre-gonadectomy hormone profile. RESULTS: Mean BMD was reduced (95% confidence interval); T-score -1.34 (-1.55 to -1.13; P<.001) at the lumbar spine and -0.3 (-0.49 to -0.12; P=.001) at the hip. There was no relationship between age of gonadectomy and BMD. Thirty-two subjects had BMD measured before or within 2 years of gonadectomy, and mean BMD was reduced (95% CI) at the lumbar spine; T-score: -1.05 (-1.54 to -0.57; P<.001), but was normal at the hip; T-score -0.04 (-0.35 to 0.28; P=.8). There was no relationship between BMD and history of hernia, testosterone, oestradiol or follicle stimulating hormone levels. Twelve subjects had DXA both before and after gonadectomy, and after 4.3 (1.7-12.8) years, there was no change in BMD. CONCLUSIONS: We found reduced BMD at the spine and hip in subjects with CAIS. We found no relationship between age of gonadectomy and BMD, and we also found no drop in BMD in subjects followed up after gonadectomy.

Setting up a clinic to assess children and young people for female genital mutilation.

It is now mandatory for health, social care professionals and teachers to report to the police all under-18s where female genital mutilation (FGM) has been disclosed by the child or where physical signs of FGM are seen. Such referrals are likely to result in a request for medical examination. New multiagency statutory guidance sets out instructions for physical examination but provides no details how services should be set-up. This review gives practical guidance learnt from the first year of the UK's only dedicated children's FGM service.

Long-term health issues related to disorders or differences in sex development/intersex.

DSD (Disorders or Differences in Sex Development) and Intersex are terms used to describe a diverse group of congenital conditions where the development of the reproductive system is different from what is usually expected. These conditions usually present at birth or adolescence and the health implications are wide ranging and often life-long. Given the complexity of many of the conditions, health care input when required should be provided by a multidisciplinary team who have appropriate expertise. Holistic care should include the consideration of the risk of cancer, prevention of osteoporosis, advice on hormones, sexual health and fertility options, and ongoing support in order to optimise quality of life and wellbeing. There is little evidence on the health of this group of individuals beyond middle age. Research in this field is essential to guide clinicians in providing high-quality care but also to allow affected individuals to make informed decisions about their own health care. This review will focus on the gynaecological aspects of multidisciplinary management.

Multidisciplinary approach to the management of children with female genital mutilation (FGM) or suspected FGM: service description and case series.

OBJECTIVE: To describe the first dedicated clinic in the UK for children with suspected or confirmed female genital mutilation (FGM) including referral patterns, clinical findings and subsequent management. DESIGN AND SETTING: A prospective study of all children seen in a dedicated multidisciplinary FGM clinic for children over a 1-year period. POPULATION: Patients aged under 18 years referred for clinical assessment or for a second opinion on Digital Versatile Disc (DVD) images. METHODS AND MAIN OUTCOME MEASURES: Data were collected on reasons for referral, demography, genital examination findings including FGM type, and clinical recommendations. RESULTS: 38 children were referred of whom 18 (47%) had confirmed FGM; most frequently type 4 (61%). Social care and police referred 78% of cases. According to UK law FGM had been performed illegally in three cases. Anonymous information given to the police led to the referral of six children, none of whom had had FGM. CONCLUSIONS: Mandatory reporting and increased media attention may increase the numbers of referrals of children with suspected FGM. This patient group have complex needs and management in a dedicated multidisciplinary service is essential. Paediatricians and gynaecologists should have the skills to carry out the consultation and detect all types of FGM including type 4 which was the most common type seen in this series. This is the first dedicated FGM service for children in the UK and similar clinics in high-prevalence areas should be established.

Female genital mutilation in children presenting to a London safeguarding clinic: a case series.

OBJECTIVE: To describe the presentation and management of children referred with suspected female genital mutilation (FGM) to a UK safeguarding clinic. DESIGN AND SETTING: Case series of all children under 18 years of age referred with suspected FGM between June 2006 and May 2014. MAIN OUTCOME MEASURES: These include indication for referral, demographic data, circumstances of FGM, medical symptoms, type of FGM, investigations and short-term outcome. RESULTS: Of the 47 girls referred, 27 (57%) had confirmed FGM. According to the WHO classification of genital findings, FGM type 1 was found in 2 girls, type 2 in 8 girls and type 4 in 11 girls. No type 3 FGM was seen. The circumstances of FGM were known in 17 cases, of which 12 (71%) were performed by a health professional or in a medical setting (medicalisation). Ten cases were potentially illegal, yet despite police involvement there have been no prosecutions. CONCLUSIONS: This study is an important snapshot of FGM within the UK paediatric population. The most frequent genital finding was type 4 FGM with no tissue damage or minimal scarring. FGM was performed at a young age, with 15% reported under the age of 1 year. The study also demonstrated significant medicalisation of FGM, which matches recent trends in international data. Type 4 FGM performed in infancy is easily missed on examination and so vigilance in assessing children with suspected FGM is essential.

Female genital mutilation: what every paediatrician should know.

Female genital mutilation (FGM) is almost always performed on children and consequently paediatricians should have a central role in the detection and prevention of FGM. FGM has no health benefits and can cause lifelong damage to physical and psychological health. Extensive migration of FGM practising communities means that FGM is now a global problem. Paediatricians worldwide need to be familiar with the identification and classification of FGM and its impact upon health as well as current trends in practice. However information about FGM is hampered by the secrecy surrounding the procedure and a lack of rigorous evidence based research. This review summarises what is currently known about the health aspects of FGM and how paediatricians should manage children with FGM in their clinical practice.

Adolescent and adult outcomes in women following childhood vaginal reconstruction for cloacal anomaly.

PURPOSE: We examined outcomes in female adolescents and women who underwent vaginoplasty in childhood during genitourinary reconstruction for cloacal anomalies. MATERIALS AND METHODS: We retrospectively reviewed the medical notes on girls and women attending an adult specialist center for genitourinary anomalies. Data were collected on vaginal reconstruction, menstruation, sexual and reproductive function, and urological and gastroenterological outcomes. RESULTS: We identified 19 patients with a mean age of 22 years (range 13 to 35), of whom 16 (84%) underwent vaginoplasty in the first year of life. Nine of these 16 patients (56%) had required 1 (7) or 2 (2) further vaginal reconstructions to facilitate menstruation or sexual activity. The remaining 7 patients (44%) required no further vaginal reconstruction. Nine of the 19 patients (47%) had associated müllerian anomalies, obstructed menstruation developed in 5 (26%) and 1 required hemihysterectomy. Eight patients were sexually active, of whom 1 experienced difficult penetration. Three patients attempted to conceive, including 1 with a complex preterm delivery and 2 undergoing fertility treatment. Of the patients 74% underwent further reconstruction of the renal tract and 36% had an enteric stoma. CONCLUSIONS: This study confirms the complexity of vaginal reconstruction in this group with a notable vaginoplasty revision rate. Müllerian anomalies were identified in almost half of the patients, a higher incidence than previously reported, and in a quarter obstructed menstruation developed in puberty. A specialist team with gynecologic input should treat patients with cloacal anomalies. Outcome data are sparse. There remains a need for well planned, prospective cohort studies that include assessments of psychological, sexual and reproductive outcomes.

Screening for mutations in 17ß-hydroxysteroid dehydrogenase and androgen receptor in women presenting with partially virilised 46,XY disorders of sex development.

CONTEXT AND OBJECTIVE: The precise diagnosis of partially virilised women with 46,XY disorders of sex development (DSD) is often obscure. In practice, this group often comes under the poorly defined, clinically based label of partial androgen insensitivity syndrome (PAIS). In a previous study, we found that 5α-reductase 2 (SRD5A2) mutations occurred in 43% of women in this subgroup. We expand this work to include biochemical and genetic screening for 17ß-hydroxysteroid dehydrogenase (HSD17B3) and androgen receptor (AR) mutations. METHODS: Analysis of serum androgens (androstenedione and testosterone) and genetic analyses for HSD17B3 and AR were performed in 42 women from 36 pedigrees with partially virilised 46,XY DSD in whom SRD5A2 deficiency had been excluded by urine steroid profiling. RESULTS: Out of 36 unrelated women, 14 (38%) were found to have HSD17B3 mutations and one (2.7%) to have an AR defect. Six novel pathogenic HSD17B3 mutations were identified: three splice site mutations and three missense changes. Seven patients with HSD17B3 deficiency tested before gonadectomy had basal testosterone/androstenedione (T/A) ratio <0.8 (sensitivity 100% and specificity 91%). CONCLUSIONS: HSD17B3 deficiency is prevalent in the adolescent and adult 46,XY female DSD population and is often associated with lesser degrees of virilisation compared with those with 5α-reductase deficiency. This diagnosis should be considered for individuals labelled as PAIS, particularly, but not exclusively, those who present with virilisation at puberty or primary amenorrhoea. Before gondadectomy, T/A ratio is useful to aid diagnosis, but after gonadectomy sequencing of HSD17B3 must be performed to confirm the diagnosis.