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Fertility and Sterility Feb 2021
Topics: 46, XX Disorders of Sex Development; Congenital Abnormalities; Humans; Mullerian Ducts
PubMed: 33419516
DOI: 10.1016/j.fertnstert.2020.12.007 -
Human Heredity 2014Disorders of sex development (DSD) are defined as 'congenital conditions in which the development of chromosomal, gonadal, or anatomical sex is atypical' [Lee et al.,... (Review)
Review
Disorders of sex development (DSD) are defined as 'congenital conditions in which the development of chromosomal, gonadal, or anatomical sex is atypical' [Lee et al., Pediatrics 2006;118:e488-e500]. Studies conducted in Western countries, with low rates of consanguinity, show that truly ambiguous genitalia have an estimated incidence of 1:5,000 births. There are indications that the prevalence of DSD is higher in endogamous communities. The incidence of ambiguous genitalia in Saudi Arabia has been estimated at 1:2,500 live births; whilst in Egypt, it has been estimated at 1:3,000 live births. This may be due in part to an increase in disorders of androgen synthesis associated with 46,XX DSD. There is clearly a need for further studies to address the frequency of DSD in communities with high levels of consanguinity. This will be challenging, as an accurate diagnosis is difficult and expensive even in specialized centres. In developing countries with high levels of consanguinity, these limitations can be compounded by cultural, social and religious factors. Overall there is an indication that consanguinity may lead to an increase in incidences of both 46,XY and 46,XX DSD, and a co-ordinated study of populations with higher incidences of consanguinity/endogamy is needed to resolve this.
Topics: Adrenal Hyperplasia, Congenital; Androgens; Cholesterol; Consanguinity; Disorder of Sex Development, 46,XY; Disorders of Sex Development; Female; Humans; Male; Testis
PubMed: 25060274
DOI: 10.1159/000360763 -
Current Opinion in Psychology Feb 2023Psychological research on people with variable sex characteristics (VSC)/intersex is broadening from the traditional exploitation of this population to ask... (Review)
Review
Psychological research on people with variable sex characteristics (VSC)/intersex is broadening from the traditional exploitation of this population to ask nature/nurture questions about sexuality and gender. Healthcare for this population has been highly controversial, prompting research on psychological outcomes, the life-span development of adults with VSC, and distress trajectories of parents of children with VSC. Psychological research on clinical psychologists' roles in multidisciplinary care teams, and on decision making about medical pathways informed by those teams, both inform the evaluation of contemporary healthcare. Research is broadening to consider schoolchildren with VSC, elite athletes with VSC, and public understanding of VSC. The growing interdisciplinary field of intersex studies provides critical resources for psychologists.
Topics: Adult; Child; Humans; Sex Characteristics; Gender Identity; Parents; Disorders of Sex Development; Longevity
PubMed: 36610363
DOI: 10.1016/j.copsyc.2022.101539 -
Hormone Research in Paediatrics 2022Testes were associated with maleness from antiquity, and ancient societies had fanciful myths about the origins of the sexes and about fetal sexual development. 17th... (Review)
Review
Testes were associated with maleness from antiquity, and ancient societies had fanciful myths about the origins of the sexes and about fetal sexual development. 17th century anatomists developed the concept that mammals developed from eggs and discovered sperm in semen; in 1878, Hertwig observed sperm entering eggs (of sea urchins), establishing the cellular basis of sex development. Individuals with atypical genitalia were known clinically in the 17th century, with much debate about their origins, but by the late 19th century it was generally accepted that gonads determined sex, and that sex determined gender role. Testosterone was isolated in 1935, and Alfred Jost showed that both circulating testosterone and diffusible anti-Mullerian hormone were needed for male development. Patients with apparent androgen insensitivity were reported in 1937 and shown to be unresponsive to exogenous androgen by Lawson Wilkins in 1957; androgen receptor mutations were reported in 1989. Steroidogenic errors were associated with differences in sex development (DSDs) starting in the 1940s, and finding mutations in the responsible enzymes explained many forms of hyper- and hypo-androgenism in both sexes. Sex chromosomes were identified in the early 20th century; Y was associated with maleness, and the responsible SRY gene was identified in 1991. Early efforts to manage patients with DSDs were confounded by philosophical perspectives on the relative roles of prenatal biology versus postnatal environment. Approaches to natal sex assignment evolved in the later 20th century and now emphasize a team approach based on data, not guessing, parental involvement, cultural considerations, and the acknowledgement of uncertainty.
Topics: Female; Child; Animals; Pregnancy; Male; Humans; Androgens; Semen; Sexual Development; Disorders of Sex Development; Testosterone; Mammals
PubMed: 36446331
DOI: 10.1159/000527042 -
International Journal of Molecular... Nov 2020Disorders (or differences) of sex development (DSD) are congenital conditions characterized by atypical development of genetic, gonadal or phenotypic sex [...].
Disorders (or differences) of sex development (DSD) are congenital conditions characterized by atypical development of genetic, gonadal or phenotypic sex [...].
Topics: Animals; Disease Susceptibility; Disorders of Sex Development; Humans; Mammals; Sex Determination Processes; Sexual Development
PubMed: 33266346
DOI: 10.3390/ijms21239146 -
Expert Review of Endocrinology &... May 2022Differences and disorders of sex development (DSD) are a diverse group of conditions, which often present in early childhood and may require input from a group of... (Review)
Review
INTRODUCTION
Differences and disorders of sex development (DSD) are a diverse group of conditions, which often present in early childhood and may require input from a group of experts in a wide range of clinical fields. Clinical guidance in this field recommends that these experts function as a multidisciplinary team (MDT) within which each expert has a defined role, which ensures an integrated and streamlined approach to the care of affected individuals.
AREAS COVERED
This review will focus on the benefits of multidisciplinary care for people with DSD, as well as the challenges that may be faced.
EXPERT OPINION
Core members of the MDT for people with DSD include endocrinologists, surgeons, psychologists, geneticists, specialist nurses, radiologists, and gynecologists, although many other health-care professionals may also be pertinent, at different stages of the patient's life. With greater acceptance of remote and digital health-care technology, there is a need to review the traditional concepts of the clinical MDT so that new care models can be explored for effective and efficient delivery of complex care.
Topics: Child, Preschool; Disorders of Sex Development; Humans
PubMed: 35535380
DOI: 10.1080/17446651.2022.2072829 -
Journal of Feline Medicine and Surgery Mar 2022Any congenital or developmental abnormality of any part of the male or female reproductive tract is a 'disorder of sexual development' (DSD). The tricolored male cat... (Review)
Review
PRACTICAL RELEVANCE
Any congenital or developmental abnormality of any part of the male or female reproductive tract is a 'disorder of sexual development' (DSD). The tricolored male cat phenotype, cryptorchidism, gonadal hypoplasia and incidental abnormalities such as cystic remnants or embryonic ducts are well-known feline DSDs.
CLINICAL CHALLENGES
Full characterization of DSDs requires sex chromosome determination and identification of genes related to development of the gonads, internal tubular genitalia and external genitalia. Fortunately, affected cats are seen sporadically and the clinical effects are usually minimal.
CLASSIFICATION
The classification nomenclature has changed. In place of intersex, hermaphrodite, pseudohermaphrodite and sex reversal, the newer standard classification, based on sex chromosomes, designates sex chromosome DSD when there is an abnormality in the sex chromosomes, and XX (female) and XY (male) DSDs where there is not. Identification of the gonadal type (testes, ovaries, ovotestes or gonadal dysgenesis) and documentation of the internal and external genital components completes the classification.
EVIDENCE BASE
The original basis of the DSD classification was a consensus reached in humans. It was quickly accepted in veterinary pathology, courtesy of its logic and ease of application, and it has subsequently begun to appear in peer-reviewed papers and clinical reviews. This article reviewing the various disorders in cats is based on application of the classification and draws on the feline peer-reviewed literature encompassing chromosome analysis and definition of reproductive abnormalities, syndromes and diseases.
Topics: Animals; Cat Diseases; Cats; Disorders of Sex Development; Female; Male; Ovary; Sexual Development; Testis
PubMed: 35209773
DOI: 10.1177/1098612X221079711 -
Fertility and Sterility Nov 2010To describe genetic evaluation and response to surgery and letrozole therapy of a 46,XX/SRY-negative true hermaphrodite.
OBJECTIVE
To describe genetic evaluation and response to surgery and letrozole therapy of a 46,XX/SRY-negative true hermaphrodite.
DESIGN
Case report.
SETTING
University Medical Center.
PATIENT(S)
Nineteen-year-old male with penile hypospadias, micropenis, and crytorchidism at the time of birth.
INTERVENTION(S)
Unilateral gonadectomy, and contralateral conservative gonadal surgery, followed by therapy with letrozole.
MAIN OUTCOME MEASURE(S)
Histopathologic, genetic and hormonal studies.
RESULT(S)
Genetic analysis showed that the subject was 46,XX/SRY-negative. Gonadectomy of the left gonad was performed at 16 years. The gonad resected was an ovotestes. The patient's estradiol was high (492±25 pmol/L), whereas the testosterone was low (4.2±0.5 nmol/L). Nineteen months later, conservative gonadal surgery of the contralateral gonad was performed to resect ovarian tissue, and treatment with letrozole was started. During letrozole treatment, testosterone was significantly increased (8±0.7 nmol/L), but estradiol was not changed (323±118 pmol/L). After letrozole withdrawal, testosterone did not decreased significantly (6.9±0.4 nmol/L), estradiol showed an oscillating pattern and a gonadal ultrasound showed an ovoid structure, which appeared to correspond to a follicle. At that time, estradiol was elevated (393 pmol/L).
CONCLUSION(S)
We present the case of a 46,XX/SRY-negative phenotypic male with bilateral ovotestes. Conservative gonadal surgery should be performed only when all ovarian tissue can be resected. Our results suggest that letrozole is not an adequate treatment for 46,XX true hermaphrodite males with ovotestes.
Topics: Aromatase Inhibitors; Castration; Chromosomes, Human; Gene Deletion; Humans; Letrozole; Male; Nitriles; Ovotesticular Disorders of Sex Development; Sex-Determining Region Y Protein; Triazoles; Young Adult
PubMed: 20451191
DOI: 10.1016/j.fertnstert.2010.03.066 -
Journal of Clinical Research in... 2011Disorders of sex development (DSD) with or without ambiguous genitalia require medical attention to reach a definite diagnosis. Advances in identification of molecular... (Review)
Review
Disorders of sex development (DSD) with or without ambiguous genitalia require medical attention to reach a definite diagnosis. Advances in identification of molecular causes of abnormal sex, heightened awareness of ethical issues and this necessitated a re-evaluation of nomenclature. The term DSD was proposed for congenital conditions in which chromosomal, gonadal or anatomical sex is atypical. In general, factors influencing sex determination are transcriptional regulators, whereas factors important for sex differentiation are secreted hormones and their receptors. The current intense debate on the management of patients with intersexuality and related conditions focus on four major issues: 1) aetiological diagnosis, 2) assignment of gender, 3) indication for and timing of genital surgery, 4) the disclosure of medical information to the patient and his/her parents. The psychological and social implications of gender assignment require a multidisciplinary approach and a team which includes ageneticist, neonatologist, endocrinologist, gynaecologist, psychiatrist, surgeon and a social worker. Each patient should be evaluated individually by multidisciplinary approach.
Topics: Animals; Disorders of Sex Development; Female; Genitalia; Humans; Infant, Newborn; Male; Sex Determination Analysis
PubMed: 21911322
DOI: 10.4274/jcrpe.v3i3.22 -
International Journal of Molecular... Sep 2020The gonads are unique among the body's organs in having a developmental choice: testis or ovary formation. Gonadal sex differentiation involves common progenitor cells... (Review)
Review
The gonads are unique among the body's organs in having a developmental choice: testis or ovary formation. Gonadal sex differentiation involves common progenitor cells that form either Sertoli and Leydig cells in the testis or granulosa and thecal cells in the ovary. Single-cell analysis is now shedding new light on how these cell lineages are specified and how they interact with the germline. Such studies are also providing new information on gonadal maturation, ageing and the somatic-germ cell niche. Furthermore, they have the potential to improve our understanding and diagnosis of Disorders/Differences of Sex Development (DSDs). DSDs occur when chromosomal, gonadal or anatomical sex are atypical. Despite major advances in recent years, most cases of DSD still cannot be explained at the molecular level. This presents a major pediatric concern. The emergence of single-cell genomics and transcriptomics now presents a novel avenue for DSD analysis, for both diagnosis and for understanding the molecular genetic etiology. Such -omics datasets have the potential to enhance our understanding of the cellular origins and pathogenesis of DSDs, as well as infertility and gonadal diseases such as cancer.
Topics: Disorders of Sex Development; Genomics; Gonads; Humans; Sequence Analysis, RNA; Sexual Development; Single-Cell Analysis
PubMed: 32927658
DOI: 10.3390/ijms21186614