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PubMed This is a summary of 22 peer-reviewed journal articles Updated
Endocrinology

Understanding 46,XX Testicular DSD

At a Glance

46,XX Testicular DSD is a rare genetic condition where an individual with two X chromosomes develops male physical traits and testicular tissue. Most individuals live a normal lifespan but experience infertility and may require testosterone replacement therapy to maintain hormone balance.

Receiving a diagnosis of 46,XX Testicular Difference of Sex Development (DSD) can feel overwhelming, whether it happens in the delivery room or during an infertility evaluation in adulthood. It is important to know that while this condition is rare, it is well-studied, and there is a clear, supportive path forward for your health and well-being. [1][2]

Understanding the Condition

In most people, a karyotype (the map of a person’s chromosomes) consists of 46 chromosomes. Typically, individuals with an XX pair develop as female, and those with an XY pair develop as male. 46,XX Testicular DSD occurs when an individual has an XX karyotype but develops a male phenotype (physical appearance) and testicular tissue. [3][4]

This usually happens in one of two ways:

  • SRY-Positive: In about 80% of cases, a small piece of the Y chromosome—specifically the SRY gene, which acts as the master switch for male development—has moved (translocated) onto an X chromosome. [5][6]
  • SRY-Negative: In the remaining 20%, the SRY gene is absent, but other genetic signals (such as duplications of the SOX3 or SOX9 genes) trigger the development of testicular tissue. [7][8]

Incidence and Rarity

This condition is rare, occurring in approximately 1 in 20,000 to 1 in 25,000 individuals assigned male at birth. [9][3] Because it is uncommon, it is best managed by a specialized medical team familiar with the nuances of hormone health and genetics. [1]

Navigating the Name Change

You may see older medical records or websites use the term 46,XX male syndrome. In 2006, a global group of experts met at the “Chicago Consensus” and updated the terminology to Disorders of Sex Development (DSD). [10][11] Many patients, families, and clinicians now prefer to use the word Differences instead of “Disorders” to reduce stigma and more accurately describe a natural biological variation. [12][11]

The name change was designed to:

  • Standardize care: Provide a consistent language for doctors worldwide to share research and improve treatments. [13]
  • Move away from labels: Shift the focus from “what” a person is to the specific genetic and medical needs they have. [2]
  • Acknowledge complexity: Recognize that sex development is a multi-step biological process that can follow many different paths. [14]

Stabilizing Facts for the Journey Ahead

It is natural to feel a range of emotions—from confusion to grief or anxiety—when learning about this diagnosis. As you process this information, keep these evidence-based facts in mind:

  1. Life Expectancy is Normal: This condition does not shorten your life. With proper medical monitoring, individuals with 46,XX Testicular DSD live full, typical lifespans. [15]
  2. Gender Identity is Stable: Most individuals with 46,XX Testicular DSD identify strongly as male. The diagnosis does not change who you are or your sense of self. [16][17]
  3. Clear Standards of Care Exist: There is an established medical roadmap for managing this condition. This typically involves a multidisciplinary team including endocrinologists (hormone specialists), urologists, and psychosocial support providers. [1][2]
  4. Physical Health is Manageable: While most men with this condition will face infertility (the inability to conceive a child naturally) due to the absence of certain Y-chromosome regions needed for sperm production, other aspects of health, such as erectile function and the development of secondary sex characteristics, are typically typical or manageable with hormone support. [5][18][6]
  5. Hormone Support is Available: If the body does not produce enough testosterone during puberty or adulthood (a condition called hypogonadism), testosterone replacement therapy is a standard and effective treatment to support bone health, energy levels, and muscle mass. [19][20]
  6. You Are Not Alone: Psychosocial support is now considered an integral part of modern DSD care. Connecting with specialized counselors and support groups can help families and individuals navigate the emotional and social aspects of the diagnosis. [21][22]

Common questions in this guide

What causes 46,XX Testicular DSD?
In about 80% of cases, it is caused by the SRY gene—the master switch for male development—moving from the Y chromosome to an X chromosome. In the remaining cases, other genetic signals trigger testicular development even without the SRY gene.
Is 46,XX Testicular DSD the same as 46,XX male syndrome?
Yes, '46,XX male syndrome' is an older term for the exact same condition. Today, experts and patients prefer the term 'Differences of Sex Development' (DSD) to reduce stigma and describe it as a natural biological variation.
Does 46,XX Testicular DSD affect life expectancy?
Yes, this condition does not shorten your life expectancy. With proper medical monitoring and multidisciplinary care, individuals with 46,XX Testicular DSD live full, typical lifespans.
Can men with 46,XX Testicular DSD have children?
Most men with this condition experience infertility because they lack the specific regions of the Y chromosome needed for natural sperm production. However, a fertility specialist can help you explore alternative options for family planning.
Will I need testosterone replacement therapy?
You may need hormone treatment if your body does not produce enough testosterone on its own, a condition known as hypogonadism. Testosterone replacement therapy is a safe and standard treatment used to maintain energy, bone health, and muscle mass.

Questions to Ask Your Doctor

Curated prompts to bring to your next appointment.

  1. 1.What is my (or my child's) SRY status, and how does this influence our expected health journey?
  2. 2.Who should be on our multidisciplinary care team (e.g., endocrinologist, urologist, psychologist)?
  3. 3.At what age should we begin monitoring hormone levels, such as testosterone?
  4. 4.What are the current options for addressing fertility or future family planning?
  5. 5.How do you recommend we talk to our child about this diagnosis as they grow?

Questions For You

Tap a prompt to share your answer — we'll use it plus this page's context to start a tailored conversation.

References

References (22)
  1. 1

    Society for Endocrinology UK Guidance on the initial evaluation of a suspected difference or disorder of sex development (Revised 2021).

    Ahmed SF, Achermann J, Alderson J, et al.

    Clinical endocrinology 2021; (95(6)):818-840 doi:10.1111/cen.14528.

    PMID: 34031907
  2. 2

    Differences of Sex Development: Current Issues and Controversies.

    Johnson EK, Whitehead J, Cheng EY

    The Urologic clinics of North America 2023; (50(3)):433-446 doi:10.1016/j.ucl.2023.04.010.

    PMID: 37385705
  3. 3

    SRY-negative 46,XX testicular/ovotesticular DSD: Long-term outcomes and early blockade of gonadotropic axis.

    Lambert S, Peycelon M, Samara-Boustani D, et al.

    Clinical endocrinology 2021; (94(4)):667-676 doi:10.1111/cen.14389.

    PMID: 33296530
  4. 4

    [Genetic and clinical characteristics of 46,XX testicular disorders of sex development].

    Ye QL, Fang JZ, Yang XY

    Zhonghua nan ke xue = National journal of andrology 2024; (30(2)):118-122.

    PMID: 39177343
  5. 5

    Sex-determining Region of Y-gene Translocation and 46,XX Testicular Disorders of Sex Development: Cytogenetic and Molecular Insights into Male Infertility.

    Priya PK, Patel H, Dalal D, Shah A

    Journal of human reproductive sciences 2025; (18(4)):254-258 doi:10.4103/jhrs.jhrs_167_25.

    PMID: 41560884
  6. 6

    The importance of genetic research in cases of severe male factor infertility: A case of 46,XX testicular disorder of sex development.

    Faleiro D, Iser B, Silva AAD, Höher MA

    JBRA assisted reproduction 2022; (26(3)):559-562 doi:10.5935/1518-0557.20210092.

    PMID: 34978171
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    Testicular differentiation in 46,XX DSD: an overview of genetic causes.

    Ferrari MTM, Silva ESDN, Nishi MY, et al.

    Frontiers in endocrinology 2024; (15()):1385901 doi:10.3389/fendo.2024.1385901.

    PMID: 38721146
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    A 46,XX testicular disorder of sex development caused by a Wilms' tumour Factor-1 (WT1) pathogenic variant.

    Gomes NL, de Paula LCP, Silva JM, et al.

    Clinical genetics 2019; (95(1)):172-176 doi:10.1111/cge.13459.

    PMID: 30294972
  9. 9

    [Analysis of clinical features and related genes variation in five patients with 46, XX male syndrome].

    Qin XY, Dong WK, Wang W, et al.

    Zhonghua er ke za zhi = Chinese journal of pediatrics 2016; (54(11)):840-843 doi:10.3760/cma.j.issn.0578-1310.2016.11.010.

    PMID: 27806792
  10. 10

    Clinical tools in the diagnosis of disorders of sex development: a switch from the hormonal to the genetics laboratory?

    Rey RA

    Advances in laboratory medicine 2021; (2(4)):463-467 doi:10.1515/almed-2021-0072.

    PMID: 37360891
  11. 11

    Molecular Aspects of Sex Development in Mammals: New Insight for Practice.

    Audí L, Bertelloni S, Flück CE

    International journal of molecular sciences 2020; (21(23)) doi:10.3390/ijms21239146.

    PMID: 33266346
  12. 12

    Disorders or Differences of Sex Development? Views of Affected Individuals on DSD Terminology.

    Bennecke E, Köhler B, Röhle R, et al.

    Journal of sex research 2021; (58(4)):522-531 doi:10.1080/00224499.2019.1703130.

    PMID: 31985272
  13. 13

    Contexts of care for people with differences of sex development: Diversity is still missing in the laboratory routine.

    Kulle AE, Jürgensen M, Döhnert U, et al.

    Medizinische Genetik : Mitteilungsblatt des Berufsverbandes Medizinische Genetik e.V 2023; (35(3)):181-187 doi:10.1515/medgen-2023-2037.

    PMID: 38840817
  14. 14

    DSD/intersex: historical context and current perspectives.

    Lee PA, Mazur T, Houk CP

    Journal of pediatric endocrinology & metabolism : JPEM 2023; (36(3)):234-241 doi:10.1515/jpem-2022-0582.

    PMID: 36630604
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    Incidence, prevalence, diagnostic delay, morbidity, mortality and socioeconomic status in males with 46,XX disorders of sex development: a nationwide study.

    Berglund A, Johannsen TH, Stochholm K, et al.

    Human reproduction (Oxford, England) 2017; (32(8)):1751-1760 doi:10.1093/humrep/dex210.

    PMID: 28854582
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    Gender of rearing and psychosocial aspect in 46 XX congenital adrenal hyperplasia.

    Gangaher A, Jyotsna VP, Chauhan V, et al.

    Indian journal of endocrinology and metabolism 2016; (20(6)):870-877 doi:10.4103/2230-8210.192922.

    PMID: 27867895
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    Gender Dysphoria in a Patient With Ovotesticular Disorder of Sex Development.

    Moreno T, Ribeiro S, Rodrigues P

    JCEM case reports 2024; (2(1)):luad159 doi:10.1210/jcemcr/luad159.

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  18. 18

    Erectile function in SRY positive 46,XX males with normal phenotype.

    Yiğman M, Tangal S, Haliloğlu AH, Çağlar GS

    Central European journal of urology 2021; (74(1)):95-98 doi:10.5173/ceju.2021.0284.R1.

    PMID: 33976923
  19. 19

    Long-term outcomes in non-CAH 46,XX DSD.

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    Frontiers in endocrinology 2024; (15()):1372887 doi:10.3389/fendo.2024.1372887.

    PMID: 38752171
  20. 20

    Ten cases with 46,XX testicular disorder of sex development: single center experience.

    Akinsal EC, Baydilli N, Demirtas A, et al.

    International braz j urol : official journal of the Brazilian Society of Urology 2017; (43(4)):770-775 doi:10.1590/S1677-5538.IBJU.2016.0505.

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  21. 21

    Psychological support for individuals with differences of sex development (DSD).

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  22. 22

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This page provides educational information about 46,XX Testicular DSD. Always consult a specialized multidisciplinary care team for personalized medical advice, genetic counseling, and treatment options.

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