Estimates for the incidence of androgen insensitivity syndrome are based on a relatively small population size, thus are known to be imprecise. CAIS is estimated to occur in one of every 20,400 46,XY births. A nationwide survey in the Netherlands based on patients with genetic confirmation of the diagnosis estimates that the minimal incidence of CAIS is one in 99,000. The incidence of PAIS is estimated to be one in 130,000. Due to its subtle presentation, MAIS is not typically investigated except in the case of male infertility, thus its true prevalence is unknown.

Individuals with CAIS are raised as females. They are born phenotypically female and almost always have a heterosexual female gender identity; the incidence of homosexuality in women with CAIS is thought to be less than unaffected women. However, at least two case studies have reported male gender identity in individuals with CAIS.

Challenges presented to people affected by this condition include: psychologically coming to terms with the condition, difficulties with sexual function, infertility. Long-term studies indicate that with appropriate medical and psychological treatment, women with CAIS can be satisfied with their sexual function and psychosexual development. CAIS women can lead active lives and expect a normal lifespan.

There is increasing evidence that the harmful products of tobacco smoking may damage the testicles and kill sperm, but their effect on male fertility is not clear. Some governments require manufacturers to put warnings on packets. Smoking tobacco increases intake of cadmium, because the tobacco plant absorbs the metal. Cadmium, being chemically similar to zinc, may replace zinc in the DNA polymerase, which plays a critical role in sperm production. Zinc replaced by cadmium in DNA polymerase can be particularly damaging to the testes.

Pre-testicular factors refer to conditions that impede adequate support of the testes and include situations of poor hormonal support and poor general health including:

- Hypogonadotropic hypogonadism due to various causes

- Obesity increases the risk of hypogonadotropic hypogonadism. Animal models indicate that obesity causes leptin insensitivity in the hypothalamus, leading to decreased Kiss1 expression, which, in turn, alters the release of gonadotropin-releasing hormone (GnRH).

- Undiagnosed and untreated coeliac disease (CD). Coeliac men may have reversible infertility. Nevertheless, CD can present with several non-gastrointestinal symptoms that can involve nearly any organ system, even in the absence of gastrointestinal symptoms. Thus, the diagnosis may be missed, leading to a risk of long-term complications. In men, CD can reduce semen quality and cause immature secondary sex characteristics, hypogonadism and hyperprolactinaemia, which causes impotence and loss of libido. The giving of gluten free diet and correction of deficient dietary elements can lead to a return of fertility. It is likely that an effective evaluation for infertility would best include assessment for underlying celiac disease, both in men and women.

- Drugs, alcohol

- Strenuous riding (bicycle riding, horseback riding)

- Medications, including those that affect spermatogenesis such as chemotherapy, anabolic steroids, cimetidine, spironolactone; those that decrease FSH levels such as phenytoin; those that decrease sperm motility such as sulfasalazine and nitrofurantoin

- Genetic abnormalities such as a Robertsonian translocation

Depending on the mutation, a person with a 46,XY karyotype and AIS can have either a male (MAIS) or female (CAIS) phenotype, or may have genitalia that are only partially masculinized (PAIS). The gonads are testes regardless of phenotype due to the influence of the Y chromosome. A 46,XY female, thus, does not have ovaries or a uterus, and can neither contribute an egg towards conception nor gestate a child.

Several case studies of fertile 46,XY males with AIS have been published, although this group is thought to be a minority. Additionally, some infertile males with MAIS have been able to conceive children after increasing their sperm count through the use of supplementary testosterone. A genetic male conceived by a man with AIS would not receive his father's X chromosome, thus would neither inherit nor carry the gene for the syndrome. A genetic female conceived in such a way would receive her father's X chromosome, thus would become a carrier.

Gonadectomy at time of diagnosis is the current recommendation for PAIS if presenting with cryptorchidism, due to the high (50%) risk of germ cell malignancy. The risk of malignancy when testes are located intrascrotally is unknown; the current recommendation is to biopsy the testes at puberty, allowing investigation of at least 30 seminiferous tubules, with diagnosis preferably based on OCT3/4 immunohistochemistry, followed by regular examinations. Hormone replacement therapy is required after gonadectomy, and should be modulated over time to replicate the hormone levels naturally present in the body during the various stages of puberty. Artificially induced puberty results in the same, normal development of secondary sexual characteristics, growth spurt, and bone mineral accumulation. Women with PAIS may have a tendency towards bone mineralization deficiency, although this increase is thought to be less than is typically seen in CAIS, and is similarly managed.

Management of AIS is currently limited to symptomatic management; methods to correct a malfunctioning androgen receptor protein that result from an AR gene mutation are not currently available. Areas of management include sex assignment, genitoplasty, gonadectomy in relation to tumor risk, hormone replacement therapy, and genetic and psychological counseling.

There are several forms of gonadal dysgenesis. The term “pure gonadal dysgenesis” (PGD) has been used to describe conditions with normal sets of sex chromosomes (e.g., 46,XX or 46,XY), as opposed to those whose gonadal dysgenesis results from missing all or part of the second sex chromosome. The latter group includes those with Turner syndrome (i.e., 45,X) and its variants, as well as those with mixed gonadal dysgenesis and a mixture of cell lines, some containing a Y chromosome (e.g., 46,XY/45,X).

Thus Swyer syndrome is referred to as PGD, 46,XY, and XX gonadal dysgenesis as PGD, 46,XX. Patients with PGD have a normal karyotype but may have defects of a specific gene on a chromosome.

All forms of androgen insensitivity are associated with infertility, though exceptions have been reported for both the mild and partial forms. Lifespan is not thought to be affected by AIS.

Sex determination and differentiation is generalized with chromosomal sex during fertilization. At early stages, phenotypic sex does not match chromosomal sex—until later during intrauterine development, sexual maturation is reached. During intrauterine development, females change to male with the testes moving down from a blind vaginal pouch with a developing scrotum, as well as a penis which initially resembled a clitoris. What seems like a female phenotype is altered by increased testosterone levels secretion.

Mutations affecting the androgen receptor (AR) gene may cause either complete or partial androgen insensitivity syndrome. Androgen, a hormone used to describe a group of sex steroid hormones, is responsible for affecting male pseudohermaphroditism. The differentiation of the fetus as male takes place during the sixth or seventh week of gestation. The development is directed by the testicular determining factor: the gene SRY (sex determining region on Y chromosome). Throughout 9th to 13th week, the development of a male genitalia is dependent upon the conversion of testosterone to the more potent androgen by the action of 5α-reductase within the target tissues of the genitalia. A type of internal male pseudohermaphroditism is Persistent Müllerian duct syndrome, which is developed through synthesis of Müllerian-inhibiting factor defects. In such instances, duct derivatives are now in 46XY males—this includes the uterus, fallopian tubes, and upper vagina. These individuals with a hernia sac and bowel loops were found with duct derivatives as well as testes.

A study on a male pseudohermaphrodite kitten showed there was a combination of gastrointestinal and urogenital congenital abnormalities. It was confirmed to have type II atresia ani and rectovaginal fistula that is associated with male pseudohermaphroditism.

Infertility observed in adult males with congenital adrenal hyperplasia (CAH) has been associated with testicular adrenal rest tumors (TART) that may originate during childhood. TART in prepubertal males with classic CAH could be found during childhood (20%). Martinez-Aguayo et al. reported differences in markers of gonadal function in a subgroup of patients, especially in those with inadequate control.

Nearly all mammals display sex-dimorphic reproductive and sexual behavior (e.g., lordosis and mounting in rodents). Much research has made it clear that prenatal and early postnatal androgens play a role in the differentiation of most mammalian brains. Experimental manipulation of androgen levels in utero or shortly after birth can alter adult reproductive behavior.

Girls and women with CAH constitute the majority of genetic females with normal internal reproductive hormones who have been exposed to male levels of testosterone throughout their prenatal lives. Milder degrees of continuing androgen exposure continue throughout childhood and adolescence as a consequence of the imperfections of current glucocorticoid treatment for CAH. The psychosexual development of these girls and women has been analyzed as evidence of the role of androgens in human sex-dimorphic behaviors.

Girls with CAH have repeatedly been reported to spend more time with "sex-atypical" toys and "rough-and-tumble" play than unaffected sisters. These differences continue into adolescent, as expressed in social behaviors, leisure activities, and career interests. Interest in babies and becoming mothers is significantly lower by most measures.

Cognitive effects are less clear, and reports have been contradictory. Two studies reported spatial abilities above the average for sisters and for girls in general. Other evidence in males with and without androgen deficiencies suggests that androgens may play a role in these aptitudes.

However, gender identity of girls and women with CAH is nearly always unequivocally female. Sexual orientation is more mixed, though the majority are heterosexual. In one study, 27% of women with CAH were rated as bisexual in their orientations. Abnormalities of body image due to the effects of the disease likely play a role in the sexual development of these women, and one cannot conclude that the androgens are the major determinant of their sexuality.

Mild androgen insensitivity syndrome (MAIS) is a condition that results in a mild impairment of the cell's ability to respond to androgens. The degree of impairment is sufficient to impair spermatogenesis and / or the development of secondary sexual characteristics at puberty in males, but does not affect genital differentiation or development. Female genital and sexual development is not significantly affected by the insensitivity to androgens; as such, MAIS is only diagnosed in males. The clinical phenotype associated with MAIS is a normal male habitus with mild spermatogenic defect and / or reduced secondary terminal hair.

MAIS is one of three types of androgen insensitivity syndrome, which is divided into three categories that are differentiated by the degree of genital masculinization: complete androgen insensitivity syndrome (CAIS) is indicated when the external genitalia is that of a normal female, mild androgen insensitivity syndrome (MAIS) is indicated when the external genitalia is that of a normal male, and partial androgen insensitivity syndrome (PAIS) is indicated when the external genitalia is partially, but not fully masculinized.

Androgen insensitivity syndrome is the largest single entity that leads to 46,XY undermasculinization.

Swyer syndrome, or XY gonadal dysgenesis, is a type of hypogonadism in a person whose karyotype is 46,XY. The person is externally female with streak gonads, and if left untreated, will not experience puberty. Such gonads are typically surgically removed (as they have a significant risk of developing tumors) and a typical medical treatment would include hormone replacement therapy.

The syndrome was named by Gerald Swyer, an endocrinologist, based in London, United Kingdom.

While hyperandrogenism in women is caused by external factors, it can also appear from natural causes.

Even though hyperandrogenism is not common in men, there has been studies done to look at the effects of high levels of testosterone in male bodies. A study have shown that even though many of the male participates did not have a behavior changes due to the increased levels of testosterone, there were cases where the participants had instances of uncharacteristic aggression. High levels of testosterone in male has not been seen to have a direct impact on their personality, but within those studies, there have been cases of sudden aggression within the male participants.

Treatment includes androgen (testosterone) supplementation to artificially initiate puberty, testicular prosthetic implantation, and psychological support. Gender Dysphoria may result in anorchic individuals who are assigned male at birth and raised as male despite lacking the necessary masculinizing hormones during prenatal, childhood, and adolescent development. Anorchic individuals who have a female identity may be administered estrogen alone in place of testosterone as no androgen blockers are necessary due to the lack of gonads.

Males and females may be treated with hormone replacement therapy (i.e., with androgens and estrogens, respectively), which will result in normal sexual development and resolve most symptoms. In the case of 46,XY (genetically male) individuals who are phenotypically female and/or identify as the female gender, they should be treated with estrogens instead. Removal of the undescended testes should be performed in 46,XY females to prevent their malignant degeneration, whereas in 46,XY males surgical correction of the genitals is generally required, and, if necessary, an orchidopexy (relocation of the undescended testes to the scrotum) may be performed as well. Namely in genetic females presenting with ovarian cysts, GnRH analogues may be used to control high FSH and LH levels if they are unresponsive to estrogens.

Pseudohermaphroditism, or pseudo-hermaphroditism, is an old clinical term for an organism is born with primary sex characteristics of one sex but develops the secondary sex characteristics that are different from what would be expected on the basis of the gonadal tissue (ovary or testis). It can be contrasted with the term true hermaphroditism, which described a condition where testicular and ovarian tissue were present in the same individual. This language has fallen out of favor due to misconceptions and pejorative connotations associated with the terms, and also a shift to nomenclature based on genetics.

The term "male pseudohermaphrodite" was used when a testis is present, and the term "female pseudohermaphrodite" was used when an ovary is present.

In some cases, external sex organs associated with pseudohermaphroditism look intermediate between a typical clitoris and penis. In other cases, the external sex organs have an appearance that would be expected to be seen with the "opposite" gonadal tissue. Because of this, pseudohermaphroditism is sometimes not identified until puberty or adulthood.

Associated conditions include 5-α-reductase deficiency and androgen insensitivity syndrome.

Leydig cell hypoplasia (or aplasia) (LCH), also known as Leydig cell agenesis, is a rare autosomal recessive genetic and endocrine syndrome affecting an estimated 1 in 1,000,000 genetic males. 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 (partially or fully underdeveloped genitalia), hypergonadotropic hypogonadism (decreased or lack of production of sex steroids by the gonads despite high circulating levels of gonadotropins), reduced or absent puberty (lack of development of secondary sexual characteristics, resulting in sexual infantilism if left untreated), and infertility.

Leydig cell hypoplasia does not occur in biological females as they do not have either Leydig cells or testicles. However, the cause of the condition in males, luteinizing hormone insensitivity, does affect females, and because LH plays a role in the female reproductive system, it can result in primary amenorrhea or oligomenorrhea (absent or reduced menstruation), infertility due to anovulation, and ovarian cysts.

A related condition is follicle-stimulating hormone (FSH) insensitivity, which presents with similar symptoms to those of Leydig cell hypoplasia but with the symptoms in the respective sexes reversed (i.e., hypogonadism and sexual infantilism in females and merely problems with fertility in males). Despite their similar causes, FSH insensitivity is considerably less common in comparison to LH insensitivity.

Patients with Leydig cell hypoplasia may be treated with hormone replacement therapy (i.e., with androgens), which will result in normal sexual development and the resolution of most symptoms. In the case of 46,XY (genetically "male") individuals who are phenotypically female and/or identify as the female gender, estrogens should be given instead. Surgical correction of the genitals in 46,XY males may be required, and, if necessary, an orchidopexy (relocation of the undescended testes to the scrotum) may be performed as well.

In 2013, an 18-year-old woman with EIS was reported. DNA sequencing revealed a homozygous mutation in ESR1, the gene that encodes the ERα. Within the ligand-binding domain, the neutral polar glutamine 375 was changed to a basic, polar histidine. An "in vitro" assay of ERα-dependent gene transcription found that the EC for transactivation had been reduced by 240-fold relative to normal, non-mutated ERα, indicating an extreme reduction in the activity of the receptor. Clinical signs suggested a profile of complete estrogen insensitivity syndrome with a resemblance to ERα knockout mice. The patient presented with delayed puberty, including an absence of breast development (Tanner stage I) and primary amenorrhea, as well as intermittent pelvic pain. Examination revealed markedly enlarged ovaries with multiple hemorrhagic cysts as the cause of the lower abdominal pain.

Estrogen levels were dramatically and persistently elevated (estradiol levels were 2340 pg/mL, regarded as being about 10 times the normal level, and ranged from 750–3500 pg/mL), gonadotropin levels were mildly elevated (follicle-stimulating hormone and luteinizing hormone levels were 6.7–19.1 mIU/mL and 5.8–13.2 mIU/mL, respectively), and testosterone levels were slightly elevated (33–88 ng/dL). Inhibin A levels were also markedly elevated. Sex hormone-binding globulin, corticosteroid-binding globulin, thyroxine-binding globulin, prolactin, and triglycerides, which are known to be elevated by estrogen, were all within normal ranges in spite of the extremely high levels of estrogen, and inhibin B levels were also normal. Her relatively mildly elevated levels of gonadotropins were attributed to retained negative feedback by progesterone as well as by her elevated levels of testosterone and inhibin A, although it was acknowledged that possible effects of estrogen mediated by other receptors such as ERβ could not be excluded.

The patient had a small uterus, with an endometrial stripe that could not be clearly identified. At the age of 15 years, 5 months, her bone age was 11 or 12 years, and at the age of 17 years, 8 months, her bone age was 13.5 years. Her bone mass was lower than expected for her age, and levels of osteocalcin and C-terminal telopeptide were both elevated, suggesting an increased rate of bone turnover. She was 162.6 cm tall, and her growth velocity indicated a lack of estrogen-induced growth spurt at puberty. The patient had normal pubic hair development (Tanner stage IV) and severe facial acne, which could both be attributed to testosterone. Her ovarian pathology was attributed to the elevated levels of gonadotropins. In addition to her absence of breast development and areolar enlargement, the patient also appeared to show minimal widening of the hips and a lack of subcutaneous fat deposition, which is in accordance with the established role of estrogen and ERα in the development of female secondary sexual characteristics.

Treatment of the patient with conjugated equine estrogens and high doses of estradiol had no effect. Although the authors of the paper considered her ERα to be essentially unresponsive to estrogen, they stated that they "[could not] exclude the possibility that some residual estrogen sensitivity could be present in some tissues", which is in accordance with the fact that the EC of her ERα had been reduced 240-fold but had not been abolished. Treatment with a progestin, norethisterone, reduced her estradiol concentrations to normal levels and decreased the size of her ovaries and the number of ovarian cysts, alleviating her hypothalamic-pituitary-gonadal axis hyperactivity and ovarian pathology.

Follicle-stimulating hormone (FSH) insensitivity, or ovarian insensitivity to FSH in females, also referable to as ovarian follicle hypoplasia or granulosa cell hypoplasia in females, is a rare autosomal recessive genetic and endocrine syndrome affecting both females and males, with the former presenting with much greater severity of symptomatology. It is characterized by a resistance or complete insensitivity to the effects of follicle-stimulating hormone (FSH), a gonadotropin which is normally responsible for the stimulation of estrogen production by the ovaries in females and maintenance of fertility in both sexes. The condition manifests itself as hypergonadotropic hypogonadism (decreased or lack of production of sex steroids by the gonads despite high circulating levels of gonadotropins), reduced or absent puberty (lack of development of secondary sexual characteristics, resulting in sexual infantilism if left untreated), amenorrhea (lack of menstruation), and infertility in females, whereas males present merely with varying degrees of infertility and associated symptoms (e.g., decreased sperm production).

A related condition is luteinizing hormone (LH) insensitivity (termed Leydig cell hypoplasia when it occurs in males), which presents with similar symptoms to those of FSH insensitivity but with the symptoms in the respective sexes reversed (i.e., hypogonadism and sexual infantilism in males and merely problems with fertility in females); however, males also present with feminized or ambiguous genitalia (also known as pseudohermaphroditism), whereas ambiguous genitalia does not occur in females with FSH insensitivity. Despite their similar causes, LH insensitivity is considerably more common in comparison to FSH insensitivity.

Isolated 17,20-lyase deficiency is caused by genetic mutations in the gene "CYP17A1", which encodes for 17,20-lyase, while not affecting 17α-hydroxylase, which is encoded by the same gene.

Observed physiological abnormalities of the condition include markedly elevated serum levels of progestogens such as progesterone and 17α-hydroxyprogesterone (due to upregulation of precursor availability for androgen and estrogen synthesis), very low or fully absent peripheral concentrations of androgens such as dehydroepiandrosterone (DHEA), androstenedione, and testosterone and estrogens such as estradiol (due to the lack of 17,20-lyase activity, which is essential for their production), and high serum concentrations of the gonadotropins, follicle-stimulating hormone (FSH) and luteinizing hormone (LH) (due to a lack of negative feedback on account of the lack of sex hormones).