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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 -
American Journal of Men's Health 2020During adolescence, androgens are responsible for the development of secondary sexual characteristics, pubertal growth, and the anabolic effects on bone and muscle mass.... (Review)
Review
During adolescence, androgens are responsible for the development of secondary sexual characteristics, pubertal growth, and the anabolic effects on bone and muscle mass. Testosterone is the most abundant testicular androgen, but some effects are mediated by its conversion to the more potent androgen dihydrotestosterone (DHT) or to estradiol. Androgen deficiency, requiring replacement therapy, may occur due to a primary testicular failure or secondary to a hypothalamic-pituitary disorder. A very frequent condition characterized by a late activation of the gonadal axis that may also need androgen treatment is constitutional delay of puberty. Of the several testosterone or DHT formulations commercially available, very few are employed, and none is marketed for its use in adolescents. The most frequently used androgen therapy is based on the intramuscular administration of testosterone enanthate or cypionate every 3 to 4 weeks, with initially low doses. These are progressively increased during several months or years, in order to mimic the physiology of puberty, until adult doses are attained. Scarce experience exists with oral or transdermal formulations. Preparations containing DHT, which are not widely available, are preferred in specific conditions. Oxandrolone, a non-aromatizable drug with higher anabolic than androgenic effects, has been used in adolescents with preserved testosterone production, like Klinefelter syndrome, with positive effects on cardiometabolic health and visual, motor, and psychosocial functions. The usual protocols applied for androgen therapy in boys and adolescents are discussed.
Topics: Adolescent; Androgens; Child; Clinical Protocols; Disorders of Sex Development; Hormone Replacement Therapy; Humans; Klinefelter Syndrome; Male; Outcome Assessment, Health Care; Puberty
PubMed: 32448030
DOI: 10.1177/1557988320922443 -
Nature Reviews. Endocrinology Oct 2014Mammalian sex determination is the unique process whereby a single organ, the bipotential gonad, undergoes a developmental switch that promotes its differentiation into... (Review)
Review
Mammalian sex determination is the unique process whereby a single organ, the bipotential gonad, undergoes a developmental switch that promotes its differentiation into either a testis or an ovary. Disruptions of this complex genetic process during human development can manifest as disorders of sex development (DSDs). Sex development can be divided into two distinct processes: sex determination, in which the bipotential gonads form either testes or ovaries, and sex differentiation, in which the fully formed testes or ovaries secrete local and hormonal factors to drive differentiation of internal and external genitals, as well as extragonadal tissues such as the brain. DSDs can arise from a number of genetic lesions, which manifest as a spectrum of gonadal (gonadal dysgenesis to ovotestis) and genital (mild hypospadias or clitoromegaly to ambiguous genitalia) phenotypes. The physical attributes and medical implications associated with DSDs confront families of affected newborns with decisions, such as gender of rearing or genital surgery, and additional concerns, such as uncertainty over the child's psychosexual development and personal wishes later in life. In this Review, we discuss the underlying genetics of human sex determination and focus on emerging data, genetic classification of DSDs and other considerations that surround gender development and identity in individuals with DSDs.
Topics: Animals; Disorders of Sex Development; Female; Genetic Variation; Humans; Male; Mutation; Sex Differentiation; Sexual Development; Sexual Dysfunctions, Psychological
PubMed: 25091731
DOI: 10.1038/nrendo.2014.130 -
British Medical Journal Feb 1955
Topics: Disorders of Sex Development; Humans; Male; Ovotesticular Disorders of Sex Development
PubMed: 13230506
DOI: 10.1136/bmj.1.4910.395 -
British Medical Journal Mar 1972
Topics: Adolescent; Age Factors; Androgen-Insensitivity Syndrome; Child; Disorders of Sex Development; Female; Humans; Klinefelter Syndrome; Male; Mouth Mucosa; Pituitary Diseases; Puberty; Turner Syndrome
PubMed: 5014255
DOI: 10.1136/bmj.1.5803.790 -
Proceedings of the Royal Society of... Sep 1958
Topics: 46, XX Disorders of Sex Development; Disorders of Sex Development; Female; Humans
PubMed: 13591289
DOI: No ID Found -
British Medical Journal Jul 1953
Topics: Disorder of Sex Development, 46,XY; Disorders of Sex Development; Humans; Male
PubMed: 13051595
DOI: 10.1136/bmj.2.4827.94 -
Annals of Surgery Nov 1952
Topics: Disorders of Sex Development; Humans; Male; Ovotesticular Disorders of Sex Development
PubMed: 12986666
DOI: 10.1097/00000658-195211000-00010 -
Seminars in Reproductive Medicine Oct 2012Steroidogenic factor-1 (SF-1) (Ad4BP, NR5A1) is a nuclear receptor that plays a key role in adrenal and reproductive development and function. Deletion of the gene... (Review)
Review
Steroidogenic factor-1 (SF-1) (Ad4BP, NR5A1) is a nuclear receptor that plays a key role in adrenal and reproductive development and function. Deletion of the gene encoding Sf-1 (Nr5a1) in mice results in severe developmental defects of the adrenal gland and gonad. Consequently, initial work on the potential effects of SF-1 disruption in humans focused on individuals with primary adrenal failure, a 46,XY karyotype, complete gonadal dysgenesis, and Müllerian structures. This is a rare phenotype, but has been reported on two occasions, because of alterations that affect key DNA-binding domains of SF-1. Attention then turned to a potential wider role of SF-1 in human adrenal and reproductive disorders. Although changes in SF-1 only very rarely cause isolated adrenal failure, it is emerging that variations in SF-1 are a surprisingly frequent cause of reproductive dysfunction in humans. In 46,XY disorders of sex development, a spectrum of phenotypes has been reported including severe and partial forms of gonadal (testicular) dysgenesis, hypospadias, anorchia with microphallus, and even male factor infertility. In 46,XX females, alterations in SF-1 are associated with primary ovarian insufficiency. Thus, SF-1 seems be a more significant factor in human reproductive health than was first envisioned, with implications for adults as well as children.
Topics: 46, XX Disorders of Sex Development; Adrenal Insufficiency; Animals; Disorder of Sex Development, 46,XY; Disorders of Sex Development; Female; Humans; Male; Mutation; Steroidogenic Factor 1
PubMed: 23044873
DOI: 10.1055/s-0032-1324720 -
Nihon Hinyokika Gakkai Zasshi. the... Aug 1994Male pseudohermaphroditism (MPH) is a complex variety of sexual differentiation disorders characterized by deficiency of masculinization of the internal and/or external... (Review)
Review
Male pseudohermaphroditism (MPH) is a complex variety of sexual differentiation disorders characterized by deficiency of masculinization of the internal and/or external genital organs in the presence of testicular development as the male gonad. This condition is caused by embryonic failure in the processes of male sexual development, which is a sequence of mechanisms originating from the genetic sex determination triggered by the SRY gene on the Y chromosome, followed by genital sex differentiation influenced by the fetal testis. Resulting phenotypical features of MPH vary from complete female to mostly normal but with some ambiguity in the maleness. Pubertal changes are also important factors related to etiology. Recent elucidation of detailed mechanisms of male differentiation and its derangements has been achieved in the era of molecular genetics. Classical classification of MPH, mainly based on anatomical and endocrinological findings obviously needs to subject to a complete revision. The newest version of MPH classification is reviewed and discussed in relation to etiological backgrounds of each type of the disorder. Main etiological factors are: failure of the SRY and its related genes involved in the testis determination; failure of anti-mülerian hormone (AMH) for normal involution of the female duct system; disordered production or function of androgen receptors essential for the fetal differentiation of the male genital organs; 5 alpha-reductase deficiency syndrome; defective responsiveness of the testis to gonadotropin due to Leydig cell agenesis; various types of enzyme defects involved in testicular androgen biosynthesis; fetal testicular dysgenesis syndromes occurring at various stages of embryogenesis; and other less clearly defined entities of MPH. Implications are that other types of sexual differentiation disorders than MPH, such as true hermaphroditism, gonadal dysgenesis and some other disorders that have been considered to be distinct entities, may have close linkage to MPH through dysgenetic process of gonadal development with subsequent degeneration and/or tumorigenesis. Molecular basis of these probably related disorders should be elucidated in the near future and some clues to preventive measures for these genetically determined malformations are awaited.
Topics: 3-Oxo-5-alpha-Steroid 4-Dehydrogenase; Androgens; Animals; Disorders of Sex Development; Gonadal Dysgenesis; Humans; Male; Receptors, Androgen; Sex Differentiation
PubMed: 7933752
DOI: 10.5980/jpnjurol1989.85.1189