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Pseudohermaphroditism | |
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Other names | Pseudo-hermaphroditism |
Specialty | Gynecology, endocrinology |
Pseudohermaphroditism is an outdated [1] term for when an individual's gonads were mismatched with their internal reproductive system and/or external genitalia. The term was contrasted with "true hermaphroditism" (now known as ovotesticular syndrome), a condition describing an individual with both female and male reproductive gonadal tissues. Associated conditions includes Persistent Müllerian duct syndrome and forms of androgen insensitivity syndrome.
Sexual development is determined by chromosomes during fertilization. In the early stages of human development, a human embryo has the precursors of female (paramesonephric or Müllerian ducts) and male (mesonephric ducts or Wolffian) gonads. [2] If a Y chromosome is lacking, or defective as seen in Swyer syndrome, the embryo will reabsorb the mesonephric ducts and proceed with paramesonephric ducts, which give rise to ovaries. The Y chromosome contains a sex-determining region called the SRY gene. Thus, the developmental plan of the embryo is altered only if this gene is present and functional. [3]
Mutations affecting the androgen receptor (AR) gene may cause either complete or partial androgen insensitivity syndrome. Androgens are a group of hormones which regulate the development and maintenance of male characteristics. Between 8 and 12 weeks, human male fetuses become externally distinct as androgens enlarge the phallus and produce a penis with a urethra and scrotum. [4]
Female pseudohermaphroditism refers to an individual with ovaries and external genitalia resembling those of a male. Male pseudohermaphroditism refers to an individual with testicles and external genitalia resembling those of a female. [5] [6] In some cases, external sex organs associated with pseudohermaphroditism appear intermediate between a typical clitoris and penis. Thus, pseudohermaphroditism is sometimes not identified until puberty or adulthood.
Persistent Müllerian duct syndrome was considered a form of pseudohermaphroditism, developed through Müllerian-inhibiting factor defects. In such instances, duct derivatives are present in males, including the uterus, fallopian tubes, and upper vagina. [7]
Surgery is sometimes performed to alter the appearance of the genitals. Sex-specific cancers present on the gonads may require surgical removal. [8] [9] [10] [11]
John Money is perhaps the best-known early researcher in this area. His doctoral thesis was titled Hermaphroditism: An Inquiry into the Nature of a Human Paradox, and awarded by Harvard University in 1952. [12]
Narave pigs, which are native to Malo Island, Vanuatu, are pseudohermaphrodite male domestic pigs that are kept for ceremonial purposes. [13] [14] [15]
The term "Pseudohermaphroditimus" (pseudohermaphroditism) was coined in German by Edwin Klebs in 1876. [16] [17] Klebs had included the term as a synonym for the earlier coined, "spurious hermaphroditism" (which he referred to as Schein-Zwitter in German). [17] "Spurious hermaphroditism" was coined in 1836 by J. Y. Simpson. [18]
Although "pseudohermaphroditism" persisted in the International Classification of Diseases, Versions 9 (ICD-9) and 10 (ICD-10) as 752.7 (Indeterminate sex and pseudohermaphroditism) [19] and Q56 (Interdeterminate sex and pseudohermaphroditism), [20] it has since been removed in the eleventh version (ICD-11), in favor of LD2A.Y (Other specified malformative disorders of sex development). [21]
Some experts have indicated that both pseudohermaphroditism (also called false hermaphroditism) and true hermaphroditism are outdated, [22] [23] [24] [25] [26] [27] confusing, [24] [28] and potentially pejorative terms, [24] [27] [28] [29] [30] indicating replacement with "disorders of sex development", "disorders of sexual development", "differences of sex development" (all abbreviated as DSD) [22] [24] [27] or "intersex". [23] [30]
Additionally, intersex activists have noted that: "The qualifiers 'pseudo' and 'true' are even more harmful [than hermaphrodite on its own], because they imply a sort of authenticity, or lack of same, that carry powerful emotional baggage". [31] Dreger et al had also noted that "division of many intersex types into true hermaphroditism, male pseudohermaphroditism, and female pseudohermaphroditism is scientifically specious and clinically problematic". [32]
5α-Reductase 2 deficiency (5αR2D) is an autosomal recessive condition caused by a mutation in SRD5A2, a gene encoding the enzyme 5α-reductase type 2 (5αR2). The condition is rare, affects only genetic males, and has a broad spectrum.
Androgen insensitivity syndrome (AIS) is a condition involving the inability to respond to androgens, typically due to androgen receptor dysfunction.
XY complete gonadal dysgenesis, also known as Swyer syndrome, is a type of defect hypogonadism in a person whose karyotype is 46,XY. Though they typically have normal vulvas, the person has underdeveloped gonads, fibrous tissue termed "streak gonads", and if left untreated, will not experience puberty. The cause is a lack or inactivation of an SRY gene which is responsible for sexual differentiation. Pregnancy is sometimes possible in Swyer syndrome with assisted reproductive technology. The phenotype is usually similar to Turner syndrome (45,X0) due to a lack of X inactivation. The typical medical treatment is hormone replacement therapy. The syndrome was named after Gerald Swyer, an endocrinologist based in London.
The paramesonephric ducts are paired ducts of the embryo in the reproductive system of humans and other mammals that run down the lateral sides of the genital ridge and terminate at the sinus tubercle in the primitive urogenital sinus. In the female, they will develop to form the fallopian tubes/oviducts, uterus, cervix, and the upper one-third of the vagina.
Intersex medical interventions (IMI), sometimes known as intersex genital mutilations (IGM), are surgical, hormonal and other medical interventions performed to modify atypical or ambiguous genitalia and other sex characteristics, primarily for the purposes of making a person's appearance more typical and to reduce the likelihood of future problems. The history of intersex surgery has been characterized by controversy due to reports that surgery can compromise sexual function and sensation, and create lifelong health issues. The medical interventions can be for a variety of reasons, due to the enormous variety of the disorders of sex development. Some disorders, such as salt-wasting disorder, can be life-threatening if left untreated.
Persistent Müllerian duct syndrome (PMDS) is the presence of Müllerian duct derivatives in what would be considered a genetically and otherwise physically normal male animal by typical human based standards. In humans, PMDS typically is due to an autosomal recessive congenital disorder and is considered by some to be a form of pseudohermaphroditism due to the presence of Müllerian derivatives. PMDS can also present in non-human animals.
The male reproductive system consists of a number of sex organs that play a role in the process of human reproduction. These organs are located on the outside of the body, and within the pelvis.
Ovotesticular syndrome is a rare congenital condition where an individual is born with both ovarian and testicular tissue. It is one of the rarest DSDs, with only 500 reported cases. Commonly, one or both gonads is an ovotestis containing both types of tissue. Although it is similar in some ways to mixed gonadal dysgenesis, the conditions can be distinguished histologically.
Gonadal dysgenesis is classified as any congenital developmental disorder of the reproductive system characterized by a progressive loss of primordial germ cells on the developing gonads of an embryo. One type of gonadal dysgenesis is the development of functionless, fibrous tissue, termed streak gonads, instead of reproductive tissue. Streak gonads are a form of aplasia, resulting in hormonal failure that manifests as sexual infantism and infertility, with no initiation of puberty and secondary sex characteristics.
Partial androgen insensitivity syndrome (PAIS) is a condition that results in the partial inability of the cell to respond to androgens. It is an X linked recessive condition. The partial unresponsiveness of the cell to the presence of androgenic hormones impairs the masculinization of male genitalia in the developing fetus, as well as the development of male secondary sexual characteristics at puberty, but does not significantly impair female genital or sexual development. As such, the insensitivity to androgens is clinically significant only when it occurs in individuals with a Y chromosome. Clinical features include ambiguous genitalia at birth and primary amenhorrhoea with clitoromegaly with inguinal masses. Müllerian structures are not present in the individual.
Sexual differentiation in humans is the process of development of sex differences in humans. It is defined as the development of phenotypic structures consequent to the action of hormones produced following gonadal determination. Sexual differentiation includes development of different genitalia and the internal genital tracts and body hair plays a role in sex identification.
Disorders of sex development (DSDs), also known as differences in sex development or variations in sex characteristics (VSC), are congenital conditions affecting the reproductive system, in which development of chromosomal, gonadal, or anatomical sex is atypical. DSDs is a clinical term used in some medical settings for what are otherwise referred to as intersex traits. The term was first introduced in 2006 and has not been without controversy.
A hermaphrodite is a sexually reproducing organism that produces both male and female gametes. Animal species in which individuals are either male or female are gonochoric, which is the opposite of hermaphroditic.
Complete androgen insensitivity syndrome (CAIS) is an AIS condition that results in the complete inability of the cell to respond to androgens. As such, the insensitivity to androgens is only clinically significant when it occurs in individuals who are exposed to significant amounts of testosterone at some point in their lives. The unresponsiveness of the cell to the presence of androgenic hormones prevents the masculinization of male genitalia in the developing fetus, as well as the development of male secondary sexual characteristics at puberty, but does allow, without significant impairment, female genital and sexual development in those with the condition.
Intersex people are individuals born with any of several sex characteristics, including chromosome patterns, gonads, or genitals that, according to the Office of the United Nations High Commissioner for Human Rights, "do not fit typical binary notions of male or female bodies".
Leydig cell hypoplasia (LCH), also known as Leydig cell agenesis, is a rare autosomal recessive genetic and endocrine syndrome affecting an estimated 1 in 1,000,000 individuals with XY chromosomes. It is characterized by an inability of the body to respond to luteinizing hormone (LH), a gonadotropin which is normally responsible for signaling Leydig cells of the testicles to produce testosterone and other androgen sex hormones. The condition manifests itself as pseudohermaphroditism, hypergonadotropic hypogonadism, reduced or absent puberty, and infertility.
45,X/46,XY mosaicism, also known as X0/XY mosaicism and mixed gonadal dysgenesis, is a mutation of sex development in humans associated with sex chromosome aneuploidy and mosaicism of the Y chromosome. It is a fairly rare chromosomal disorder at birth, with an estimated incidence rate of about 1 in 15,000 live births. Mosaic loss of the Y chromosome in previously non-mosaic men grows increasingly common with age.
WNT4 deficiency is a rare genetic disorder that affects females and it results in the underdevelopment and sometimes absence of the uterus and vagina. WNT4 deficiency is caused by mutations of the WNT4 gene. Abnormally high androgen levels are found in the blood and can initiate and promote the development of male sex characteristics. This is seen as male pattern of hair growth on the chest and face. Those with this genetic defect develop breasts but do not have their period. Mayer–Rokitansky–Küster–Hauser syndrome is a related but distinct syndrome. Some women who have an initial diagnosis of MRKH have later been found to have WNT4 deficiency. Most women with MRKH syndrome do not have genetic mutations of the WNT4 gene. The failure to begin the menstrual cycle may be the initial clinical sign of WNT4 deficiency. WNT4 deficiency can cause significant psychological challenges and counseling is recommended.
The (DoDI) 6130.03, 2018, section 5, 13f and 14m is the writing which bars persons with "true hermaphroditism", "pseudohermaphroditism" and "pure gonadal dysgenesis" from serving in the United States Armed Forces. The three are all intersex conditions and are as of now considered to be medically incompatible with military service in the United States. "DoDI" stands for "Department of Defense Instruction," the 6130.03 instruction concerns "Medical Standards for Appointment, Enlistment, or Induction in the Military Services" in the Armed Forces of the United States. Section 5 focuses on disqualifying conditions of the male and female reproductive system, on the female page the subheader 13 and paragraph f name true hermaphroditism, pseudohermaphroditism and pure gonadal dysgenesis specifically, and on the male page the subheader 14 and paragraph m also name exactly true hermaphroditism, pseudohermaphroditism and pure gonadal dysgenesis, respectively. There is no differentiation made between males and females with these conditions. Many doctors, medical professionals and intersex advocates find the terms hermaphroditism to be outdated and stigmatized, therefore it and its derivative words are seldom used in the 2000s, with the word hermaphrodite itself being considered a slur when used against a human.
Sexual anomalies, also known as sexual abnormalities, are a set of clinical conditions due to chromosomal, gonadal and/or genitalia variation. Individuals with congenital (inborn) discrepancy between sex chromosome, gonadal, and their internal and external genitalia are categorised as individuals with a disorder of sex development (DSD). Afterwards, if the family or individual wishes, they can partake in different management and treatment options for their conditions.