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Differences of Sex Development

Differences (formerly "disorders") of sex development (DSD) are congenital conditions in which chromosomal sex, gonadal differentiation, or genital anatomy develops atypically.[2] Many patients are identified in infancy, but a substantial proportion first present in adolescence — with delayed puberty, primary amenorrhea, virilization, or questions about gender identity and fertility — precisely as care must move from pediatric to adult services.[4] DSD transitional care is now counted among urology's highest-priority research topics, even as its evidence base remains thin.[1]

This page covers the DSD-specific adult and transitional urological problems. For the general transition framework (readiness tools, hand-off, barriers) see Transitional Urology; for reoperative hypospadias technique see Hypospadias & Epispadias; for the lower-urinary-tract management ladder see Neurogenic Bladder. DSD is distinct from gender-affirming care, though there is conceptual overlap with GAS.

Classification (Orientation)​

The 2006 Chicago Consensus introduced the "DSD" umbrella term, replacing "intersex" and "hermaphroditism," and organized the field by karyotype:[2][3]

  • 46,XX DSD — e.g., congenital adrenal hyperplasia (CAH), ovotesticular DSD
  • 46,XY DSD — e.g., androgen insensitivity syndrome (AIS), 5α-reductase deficiency, gonadal dysgenesis
  • Sex-chromosome DSD — e.g., Turner (45,X), Klinefelter (47,XXY), mixed gonadal dysgenesis (45,X/46,XY)

Pediatric DSD care is well-organized around multidisciplinary teams (endocrinology, urology/surgery, genetics, psychology); adult services are far less developed, so DSD patients are at high risk of loss to follow-up — compromising gonadal surveillance, hormonal management, and psychosocial well-being.[4][5][6][7] The urologist's adult role concentrates in a few DSD-specific domains below.

Gonadal Tumor Surveillance and Gonadectomy Timing​

This is the urologist's most distinctive DSD responsibility. Several conditions — particularly those with Y-chromosome material and dysgenetic gonads — carry an elevated risk of gonadal germ-cell tumors (gonadoblastoma, dysgerminoma/seminoma), while risk is low in others (e.g., complete AIS in situ before adulthood).[8][9][10]

  • The choice between prophylactic gonadectomy and gonadal retention with surveillance is risk-stratified by diagnosis, gonadal location, and histology, and — where risk permits — is increasingly deferred so the patient can participate in shared decision-making.[8][9]
  • Retained gonads require structured monitoring: self-examination, periodic imaging (testicular/inguinal ultrasound for accessible gonads), and tumor markers; intra-abdominal dysgenetic gonads with Y material carry the highest risk and are the usual indication for removal.[8][9][10]
  • Mixed gonadal dysgenesis (45,X/46,XY) is the prototype of the surveillance-vs-removal dilemma and benefits from explicit, individualized counseling.[10]

Timing of Genital Surgery​

The timing of DSD genital surgery is among the most debated questions in the field. Current consensus emphasizes shared decision-making and, where feasible, deferring irreversible procedures until the individual can participate — directly relevant at transition, when adolescents may be making autonomous decisions about genitoplasty, gonadectomy, or fertility preservation for the first time.[2][4]

Revision After Feminizing Genitoplasty​

Vaginal stenosis is the most common indication for revision in adults who underwent childhood feminizing genitoplasty (most often for CAH with a urogenital sinus). In a single-center series, all patients presenting for revision (median age 19) had undergone infant vaginoplasty and presented with inability to have intercourse from stenotic tissue.[11] Approach by severity:[11][12]

  • Distal stenosis — partial urogenital mobilization with perineal or lateral flaps achieves physiological vaginal length/width in nearly all.
  • Complete cicatrization / high stenosis — bowel vaginoplasty is reserved for these severe cases.
  • Primary vaginoplasty deferred to adulthood — total urogenital mobilization with perineal flap or modified McIndoe gives good outcomes.

The Endocrine Society CAH guideline notes that urinary incontinence is rare long-term, a minority need additional vaginal surgery after puberty, and premenarchal dilation should be avoided; persistent complications include introital scarring, urethrovaginal fistula, and clitoral pain or loss of sensation.[13] Dissatisfaction with surgical function and clitoral arousal is high (≈ 47% each) in partially androgenized 46,XY women after feminizing surgery.[14]

Masculinizing Genitoplasty and Hypospadias Sequelae​

Adults raised male after masculinizing DSD surgery (or PAIS, proximal hypospadias) present with the familiar reconstructive sequelae — urethral stricture, fistula, hair-bearing or persistent hypospadias, and chordee. The reoperative technique (staged buccal-mucosa urethroplasty, outcomes, predictors) is covered on the Hypospadias & Epispadias page and the urethroplasty atlas — it is not reproduced here. The DSD-specific point is the patient-reported burden: physician-rated anatomical appearance is poor in ~11%, and ~38% report dissatisfaction with anatomical appearance after masculinizing/hypospadias surgery — appearance and function should be reassessed at transition.[15]

Testicular Adrenal Rest Tumors (TART) in CAH​

TART is the defining benign testicular pathology in adult males with classic CAH — prevalence 30–50% — and, although always benign, it compresses seminiferous tubules and causes pain, hypogonadism, and infertility.[16][18]

  • Screening — periodic testicular ultrasound from adolescence, repeated every 1–2 years; high-frequency ultrasound is as sensitive as MRI.[13][17]
  • Medical management — intensifying/optimizing glucocorticoid therapy to suppress ACTH may shrink TART and improve spermatogenesis; long-standing fibrotic lesions become unresponsive.[16][18]
  • Surgery is generally avoided — testis-sparing surgery has not improved gonadal function and is reserved for size-related pain.[16]
  • Crinecerfont (CRF1 antagonist, FDA-approved 2025) permits glucocorticoid dose reduction without losing androgen control, though it did not shrink TART in its phase-3 trial.[19]
  • Fertility — offer semen analysis and cryopreservation early, before TART-related tubular damage becomes irreversible.[18]

Androgen Insensitivity Syndrome — Adult Benign Issues​

For adults with complete AIS (CAIS):[20][21]

  • Vaginal hypoplasia — vaginal dilation is first-line to achieve functional depth and avoid dyspareunia; surgical vaginoplasty is reserved for dilation failure.
  • Bone health — bone mineral density is reduced (androgens contribute directly, independent of estrogen); DXA at presentation and every 2 years, with weight-bearing exercise, calcium/vitamin D, and bisphosphonates as indicated.
  • Hormone replacement after gonadectomy — continuous unopposed estrogen (no uterus); some women add testosterone for wellbeing/libido.

In partial AIS raised male, ongoing issues include hypospadias-complication management (cross-linked above), gynecomastia, and hypogonadism monitoring.[20][22]

Lower Urinary Tract, Sexual, and Fertility Health​

  • Lower urinary tract — after urogenital reconstruction, post-void dribbling and stricture-related symptoms are common (e.g., 39% dribbling, 28% needing dilation in one long-term series); bladder behavior can change at puberty. Management follows standard NLUTD principles with awareness of altered anatomy — see Neurogenic Bladder.[23][24][25]
  • Sexual health — dysfunction is pervasive across subtypes; in the European DSD-LIFE study (n = 1,040) many reported reduced sexual activity and dissatisfaction, with high dyspareunia rates (≈ 56% in partially androgenized 46,XY women, ≈ 70% in CAIS). Sexuality should be explicitly addressed, with referral to pelvic-floor physiotherapy, sexual-health counseling, and psychology.[14][26]
  • Fertility — address in adolescence with reproductive-medicine collaboration; potential varies widely by diagnosis (often preserved in CAH and 46,XX, limited in gonadal dysgenesis).[4][18]

Transition and Models of Care​

The general transition machinery — readiness assessment, joint pediatric-adult clinics, transition coordinators, and the barriers (scarce adult DSD expertise, geographic and financial disparity) — is shared across congenital urology and is detailed on the Transitional Urology hub.[27][28] DSD adds two emphases: psychology as a continuous cornerstone (disclosure, body image, gender identity, relationships) and the value of standardized longitudinal DSD registries for an evidence base that remains thin.[6][29]

Key Principles​

  • Gonadal tumor surveillance vs gonadectomy is the urologist's signature DSD decision — risk-stratified by karyotype, gonadal location, and histology; defer to shared decision-making where risk permits, monitor retained gonads structurally.[8][9]
  • Defer irreversible genital surgery to patient participation wherever feasible — a live issue at transition.[2][4]
  • Vaginal stenosis is the dominant feminizing-genitoplasty revision — urogenital mobilization with flaps for distal disease, bowel vaginoplasty for severe; avoid premenarchal dilation.[11][13]
  • TART affects 30–50% of classic-CAH men — screen with ultrasound, treat medically, bank sperm early, avoid surgery.[16][18]
  • CAIS adults need vaginal dilation, bone-density surveillance, and estrogen replacement after gonadectomy.[20][21]
  • Don't duplicate — cross-link: hypospadias-cripple reconstruction, the NLUTD ladder, and the transition process each live on dedicated pages.[15][25][27]

See Also​

References​

1. Lopez AD, Kalaga I, Copp HL, Shaw NM, Hampson LA. "Transitional Urology: A Comprehensive Review of the Transitional Care Process." Nat Rev Urol. 2026. doi:10.1038/s41585-026-01152-9

2. Johnson EK, Whitehead J, Cheng EY. "Differences of Sex Development: Current Issues and Controversies." Urol Clin North Am. 2023;50(3):433-446. doi:10.1016/j.ucl.2023.04.010

3. Barthold JS. "Disorders of Sex Differentiation: A Pediatric Urologist's Perspective of New Terminology and Recommendations." J Urol. 2011;185(2):393-400. doi:10.1016/j.juro.2010.09.083

4. Claahsen-van der Grinten HL, van Herwaarden A, Kempers M, et al. "Approach to the Patient: Comprehensive Multidisciplinary Care for Adolescents With Difference in Sex Development (DSD)." J Clin Endocrinol Metab. 2026;111(4):e1183-e1194. doi:10.1210/clinem/dgag023

5. Nowotny HF, Reisch N. "Challenges Waiting for an Adult With DSD." Horm Res Paediatr. 2023;96(2):207-221. doi:10.1159/000527433

6. Crouch NS, Creighton SM. "Transition of Care for Adolescents With Disorders of Sex Development." Nat Rev Endocrinol. 2014;10(7):436-442. doi:10.1038/nrendo.2014.62

7. Chulani VL, Gomez-Lobo V, Kielb SJ, Grimsby GM. "Healthcare Transition for Patients With Differences of Sexual Development and Complex Urogenital Conditions." Semin Pediatr Surg. 2019;28(5):150846. doi:10.1016/j.sempedsurg.2019.150846

8. Hannema SE, O'Connell MA. "Gonadectomy in Individuals With a Difference of Sex Development — For Whom, When, Why, and Why Not?" Best Pract Res Clin Endocrinol Metab. 2025:102019. doi:10.1016/j.beem.2025.102019

9. Wisniewski AB, Batista RL, Costa EMF, et al. "Management of 46,XY Differences/Disorders of Sex Development (DSD) Throughout Life." Endocr Rev. 2019;40(6):1547-1572. doi:10.1210/er.2019-00049

10. Giri D, Yewale S, Hickingbotham H, et al. "Mixed Gonadal Dysgenesis: A Comprehensive Review of Clinical Spectrum, Diagnostic Strategies, and Management Approaches." Clin Endocrinol (Oxf). 2026;104(2):92-102. doi:10.1111/cen.70053

11. Ellerkamp V, Rall KK, Schaefer J, et al. "Surgical Therapy After Failed Feminizing Genitoplasty in Young Adults With Disorders of Sex Development: Retrospective Analysis and Review of the Literature." J Sex Med. 2021;18(10):1797-1806. doi:10.1016/j.jsxm.2021.07.008

12. Ellerkamp V, Rall KK, Schaefer J, Brucker S, Fuchs J. "Techniques of Primary Vaginoplasty in Young Adults With Differences of Sex Development and Female Identification." J Clin Med. 2022;11(13):3688. doi:10.3390/jcm11133688

13. Speiser PW, Arlt W, Auchus RJ, et al. "Congenital Adrenal Hyperplasia Due to Steroid 21-Hydroxylase Deficiency: An Endocrine Society Clinical Practice Guideline." J Clin Endocrinol Metab. 2018;103(11):4043-4088. doi:10.1210/jc.2018-01865

14. Köhler B, Kleinemeier E, Lux A, et al. "Satisfaction With Genital Surgery and Sexual Life of Adults With XY Disorders of Sex Development: Results From the German Clinical Evaluation Study." J Clin Endocrinol Metab. 2012;97(2):577-588. doi:10.1210/jc.2011-1441

15. van de Grift TC, Rapp M, Holmdahl G, Duranteau L, Nordenskjold A. "Masculinizing Surgery in Disorders/Differences of Sex Development: Clinician- and Participant-Evaluated Appearance and Function." BJU Int. 2022;129(3):394-405. doi:10.1111/bju.15369

16. Auer MK, Nordenström A, Lajic S, Reisch N. "Congenital Adrenal Hyperplasia." Lancet. 2023;401(10372):227-244. doi:10.1016/S0140-6736(22)01330-7

17. Balagamage C, Arshad A, Elhassan YS, et al. "Management Aspects of Congenital Adrenal Hyperplasia During Adolescence and Transition to Adult Care." Clin Endocrinol (Oxf). 2024;101(4):332-345. doi:10.1111/cen.14992

18. Claahsen-van der Grinten HL, Adriaansen BPH, Falhammar H. "Challenges in Adolescent and Adult Males With Classic Congenital Adrenal Hyperplasia Due to 21-Hydroxylase Deficiency." J Clin Endocrinol Metab. 2025;110(Suppl 1):S25-S36. doi:10.1210/clinem/dgae718

19. Auchus RJ, Hamidi O, Pivonello R, et al. "Phase 3 Trial of Crinecerfont in Adult Congenital Adrenal Hyperplasia." N Engl J Med. 2024;391(6):504-514. doi:10.1056/NEJMoa2404656

20. Hughes IA, Davies JD, Bunch TI, et al. "Androgen Insensitivity Syndrome." Lancet. 2012;380(9851):1419-1428. doi:10.1016/S0140-6736(12)60071-3

21. Gottlieb B, Trifiro MA. "Androgen Insensitivity Syndrome." GeneReviews® [Internet]. Updated 2017.

22. Kosti K, Athanasiadis L, Goulis DG. "Long-Term Consequences of Androgen Insensitivity Syndrome." Maturitas. 2019;127:51-54. doi:10.1016/j.maturitas.2019.06.004

23. Zhang H, Pan J, Ji H, et al. "Long-Term Evaluation of Patients Undergoing Genitoplasty Due to Disorders of Sex Development: Results From a 14-Year Follow-Up." ScientificWorldJournal. 2013;2013:298015. doi:10.1155/2013/298015

24. Woodhouse CR, Neild GH, Yu RN, Bauer S. "Adult Care of Children From Pediatric Urology." J Urol. 2012;187(4):1164-1171. doi:10.1016/j.juro.2011.12.011

25. Ginsberg DA, Boone TB, Cameron AP, et al. "The AUA/SUFU Guideline on Adult Neurogenic Lower Urinary Tract Dysfunction: Treatment and Follow-Up." J Urol. 2021;206(5):1106-1113. doi:10.1097/JU.0000000000002239

26. Kreukels BPC, Cohen-Kettenis PT, Roehle R, et al. "Sexuality in Adults With Differences/Disorders of Sex Development (DSD): Findings From the DSD-Life Study." J Sex Marital Ther. 2019;45(8):688-705. doi:10.1080/0092623X.2019.1610123

27. Peycelon M, Misseri R. "The Basics of Transition in Congenital Lifelong Urology." World J Urol. 2021;39(4):993-1001. doi:10.1007/s00345-020-03116-z

28. Akdağcık Z, Soytürk S, Sılay MS, et al. "Transitional Urology in Congenital and Neurological Conditions: A Global Review of Structured Care Models and Clinical Outcomes." World J Urol. 2025;43(1):628. doi:10.1007/s00345-025-06021-5

29. Flück C, Nordenström A, Ahmed SF, et al. "Standardised Data Collection for Clinical Follow-Up and Assessment of Outcomes in Differences of Sex Development (DSD): Recommendations From the COST Action DSDnet." Eur J Endocrinol. 2019;181(5):545-564. doi:10.1530/EJE-19-0363