Individuals with mild (or minimal) androgen insensitivity syndrome (grade 1 on the Quigley scale) are born phenotypically male, with fully masculinized genitalia; this category of androgen insensitivity is diagnosed when the degree of androgen insensitivity in an individual with a 46,XY karyotype is great enough to impair virilization or spermatogenesis, but is not great enough to impair normal male genital development. MAIS is the mildest and least known form of androgen insensitivity syndrome.

The existence of a variant of androgen insensitivity that solely affected spermatogenesis was theoretical at first. Cases of phenotypically normal males with isolated spermatogenic defect due to AR mutation were first detected as the result of male infertility evaluations. Until then, early evidence in support of the existence of MAIS was limited to cases involving a mild defect in virilization, although some of these early cases made allowances for some degree of impairment of genital masculinization, such as hypospadias or micropenis. It is estimated that 2-3% of infertile men have AR gene mutations.

Examples of MAIS phenotypes include isolated infertility (oligospermia or azoospermia), mild gynecomastia in young adulthood, decreased secondary terminal hair, high pitched voice, or minor hypospadias repair in childhood. The external male genitalia (penis, scrotum, and urethra) are otherwise normal in individuals with MAIS. Internal genitalia, including Wolffian structures (the epididymides, vasa deferentia, and seminal vesicles) and the prostate, is also normal, although the bitesticular volume of infertile men (both with and without MAIS) is diminished; male infertility is associated with reduced bitesticular volume, varicocele, retractile testes, low ejaculate volume, male accessory gland infections (MAGI), and mumps orchitis. The incidence of these features in infertile men with MAIS is similar to that of infertile men without MAIS. MAIS is not associated with Müllerian remnants.

Spinal and bulbar muscular atrophy (SBMA), also known as Kennedy's disease, is a severe neurodegenerative syndrome that is associated with a particular mutation of the androgen receptor's polyglutamine tract called a trinucleotide repeat expansion. SBMA results when the length of the polyglutamine tract exceeds 40 repetitions.

Although technically a variant of MAIS, SBMA's presentation is not typical of androgen insensitivity; symptoms do not occur until adulthood and include neuromuscular defects as well as signs of androgen inaction. Neuromuscular symptoms include progressive proximal muscle weakness, atrophy, and fasciculations. Symptoms of androgen insensitivity experienced by men with SBMA are also progressive and include testicular atrophy, severe oligospermia or azoospermia, gynecomastia, and feminized skin changes despite elevated androgen levels. Disease onset, which usually affects the proximal musculature first, occurs in the third to fifth decades of life, and is often preceded by muscular cramps on exertion, tremor of the hands, and elevated muscle creatine kinase. SBMA is often misdiagnosed as amyotrophic lateral sclerosis (ALS) (also known as Lou Gehrig's disease).

The symptoms of SBMA are thought to be brought about by two simultaneous pathways involving the toxic misfolding of proteins and loss of AR functionality. The polyglutamine tract in affected pedigrees tends to increase in length over generations, a phenomenon known as "anticipation", leading to an increase in the severity of the disease as well as a decrease in the age of onset for each subsequent generation of a family affected by SBMA.

The symptoms of isolated 17,20-lyase deficiency, in males, include pseudohermaphroditism (i.e., feminized, ambiguous, or mildly underdeveloped (e.g., micropenis, perineal hypospadias, and/or cryptorchidism (undescended testes)) external genitalia), female gender identity, and, in non-complete cases of deficiency where partial virilization occurs, gynecomastia up to Tanner stage V (due to low androgen levels, which results in a lack of suppression of estrogen); in females, amenorrhoea or, in cases of only partial deficiency, merely irregular menses, and enlarged cystic ovaries (due to excessive stimulation by high levels of gonadotropins); and in both sexes, hypergonadotropic hypogonadism (hypogonadism despite high levels of gonadotropins), delayed, impaired, or fully absent adrenarche and puberty with an associated reduction in or complete lack of development of secondary sexual characteristics (sexual infantilism), impaired fertility or complete sterility, tall stature (due to delayed epiphyseal closure), eunuchoid skeletal proportions, delayed or absent bone maturation, and osteoporosis.

It is normally difficult to distinguish a case of KS / HH from a straightforward constitutional delay of puberty. However, if puberty has not started by either age 14 (girls) or 15 (boys) and one or more of the non-reproductie features mentioned belowe is present then a referral to reproductive endocrinologist might be advisable.

The features of Kallmann syndrome (KS) and other forms of hypogonadotropic hypogonadism (HH) can be split into two different categories; "reproductive" and "non reproductive".

The exact genetic nature of each particular case of KS / HH will determine which, if any, of the non-reproductive features will occur. The severity of the symptoms will also vary from case to case. Even family members will not show the same range or severity of symptoms.

KS / HH is most often present from birth but adult onset versions are found in both males and females. The hypothalamic-pituitary-gonadal axis (HPG axis) functions normally at birth and well into adult life giving normal puberty and normal reproductive function. The HPG axis then either fails totally or is reduced to a very low level of GnRH release, in adult life with no obvious cause such as a pituitary tumour. This will lead to a fall in testosterone or oestrogen levels and infertility.

Functional hypothalamic amenorrhoea is seen in females where the HPG axis is suppressed in response to physical or psychological stress or malnutrition. It is reversible with the removal of the stressor.

Some cases of KS / HH appear to reverse during adult life where the HPG axis resumes its normal function and GnRH, LH, and FSH levels return to normal levels. This occurs in an estimated 10 to 20% of cases, primarily normosmic CHH cases rather than KS cases and only found in patients who have undergone some form of testosterone replacement therapy.

It is only normally discovered when testicular volume increases while on testosterone treatment alone and testosterone levels return to normal when treatment is stopped. This type of KS / HH rarely occurs in cases where males have had a history of un-descended testes.

Affected individuals with KS and other forms of HH are almost invariably born with normal sexual differentiation; i.e., they are physically male or female. This is due to the human chorionic gonadotrophin (hCG) produced by placenta at approximately 12 to 20 weeks gestation (pregnancy) which is normally unaffected by having KS or CHH.

People with KS / HH lack the surge of GnRH, LH, and FSH that normally occurs between birth and six months of age. This surge is particularly important in infant boys as it helps with testicular descent into the scrotum. The surge of GnRH/LH/FSH in non KS/HH children gives detectable levels of testosterone in boys and oestrogen & progesterone in girls. The lack of this surge can sometimes be used as a diagnostic tool if KS / HH is suspected in a newborn boy, but is not normally distinct enough for diagnosis in girls.

A supplemental system of phenotypic grading that uses seven classes instead of the traditional three was proposed by pediatric endocrinologist Charmian A. Quigley et al. in 1995. The first six grades of the scale, grades 1 through 6, are differentiated by the degree of genital masculinization; grade 1 is indicated when the external genitalia is fully masculinized, grade 6 is indicated when the external genitalia is fully feminized, and grades 2 through 5 quantify four degrees of increasingly feminized genitalia that lie in the interim. Grade 7 is indistinguishable from grade 6 until puberty, and is thereafter differentiated by the presence of secondary terminal hair; grade 6 is indicated when secondary terminal hair is present, whereas grade 7 is indicated when it is absent. The Quigley scale can be used in conjunction with the traditional three classes of AIS to provide additional information regarding the degree of genital masculinization, and is particularly useful when the diagnosis is PAIS.

Partial androgen insensitivity syndrome is diagnosed when the degree of androgen insensitivity in an individual with a 46,XY karyotype is great enough to partially prevent the masculinization of the genitalia, but is not great enough to completely prevent genital masculinization. This includes any phenotype resulting from androgen insensitivity where the genitalia is partially, but not completely masculinized. Genital ambiguities are frequently detected during clinical examination at birth, and consequently, a PAIS diagnosis can be made during infancy as part of a differential diagnostic workup.

Pubertal undervirilization is common, including gynecomastia, decreased secondary terminal hair, and / or a high pitched voice. The phallic structure ranges from a penis with varying degrees of diminished size and hypospadias to a slightly enlarged clitoris. Wolffian structures (the epididymides, vasa deferentia, and seminal vesicles) are typically partially or fully developed. The prostate is typically small or impalpable. Müllerian remnants are rare, but have been reported.

The gonads in individuals with PAIS are testes, regardless of phenotype; during the embryonic stage of development, testes form in an androgen-independent process that occurs due to the influence of the SRY gene on the Y chromosome. Cryptorchidism is common, and carries with it a 50% risk of germ cell malignancy. If the testes are located intrascrotally, there may still be significant risk of germ cell malignancy; studies have not yet been published to assess this risk.

Predominantly male phenotypes vary in the degree of genital undermasculinization to include micropenis, chordee, scrotum, and / or pseudovaginal perineoscrotal hypospadias. Impotence may be fairly common, depending on phenotypic features; in one study of 15 males with PAIS, 80% of those interviewed indicated that they had some degree of impotence. Anejaculation appears to occur somewhat independently of impotence; some men are still able to ejaculate despite impotence, and others without erectile difficulties cannot. Predominantly female phenotypes include a variable degree of labial fusion and clitoromegaly. Ambiguous phenotypic states include a phallic structure that is intermediate between a clitoris and a penis, and a single perineal orifice that connects to both the urethra and the vagina (i.e. urogenital sinus). At birth, it may not be possible to immediately differentiate the external genitalia of individuals with PAIS as being either male or female, although the majority of individuals with PAIS are raised male.

Given the wide diversity of phenotypes associated with PAIS, the diagnosis is often further specified by assessing genital masculinization. Grades 2 through 5 of the Quigley scale quantify four degrees of increasingly feminized genitalia that correspond to PAIS.

Grade 2, the mildest form of PAIS, presents with a predominantly male phenotype that presents with minor signs of undermasculinized genitalia, such as isolated hypospadias, which can be severe. Hypospadias may manifest with a partially formed channel from the urethral opening to the glans. Until recently, it was thought that isolated micropenis was not a manifestation of PAIS. However, in 2010, two cases of PAIS manifesting with isolated micropenis were documented.

Grade 3, the most common phenotypic form of PAIS, features a predominantly male phenotype that is more severely undermasculinized, and typically presents with micropenis and pseudovaginal perineoscrotal hypospadias with scrotum.

Grade 4 presents with a gender ambiguous phenotype, including a phallic structure that is intermediate between a clitoris and a penis. The urethra typically opens into a common channel with the vagina (i.e. urogenital sinus).

Grade 5, the form of PAIS with the greatest degree of androgen insensitivity, presents with a mostly female phenotype, including separate urethral and vaginal orifices, but also shows signs of slight masculinization including mild clitoromegaly and / or partial labial fusion.

Previously, it was erroneously thought that individuals with PAIS were always infertile; at least one case report has been published that describes fertile men that fit the criteria for grade 2 PAIS (micropenis, penile hypospadias, and gynecomastia).

Isolated 17,20-lyase deficiency (ILD), also called isolated 17,20-desmolase deficiency, is a rare endocrine and autosomal recessive genetic disorder which is characterized by a complete or partial loss of 17,20-lyase activity and, in turn, impaired production of the androgen and estrogen sex steroids. The condition manifests itself as pseudohermaphroditism (partially or fully underdeveloped genitalia) in males, in whom it is considered to be a form of intersex, and, in both sexes, as a reduced or absent puberty/lack of development of secondary sexual characteristics, resulting in a somewhat childlike appearance in adulthood (if left untreated).

Unlike the case of combined 17α-hydroxylase/17,20-lyase deficiency, isolated 17,20-lyase deficiency does not affect glucocorticoid production (or mineralocorticoid levels), and for that reason, does not result in adrenal hyperplasia or hypertension.

Individuals with 5-ARD are born with male gonads, including testicles and Wolffian structures. They can have normal male external genitalia, ambiguous genitalia, or normal female genitalia, but usually tend towards a female appearance. As a consequence, they are often raised as girls, but usually have a male gender identity.

The development of the genital tubercle tissue (which by week 9 of a fetus' gestation becomes either a clitoris or a penis) tends towards a size qualifying it as an ambiguous macroclitoris/micropenis (large clitoris/small penis), and the urethra may attach to the phallus.

If the condition has not already been diagnosed, it usually becomes apparent at puberty around age twelve with primary amenorrhoea and virilization. This may include descending of the testes, hirsutism (facial/body hair considered normal in males - not to be confused with hypertrichosis), deepening of the voice, and enlargement of the clitoris into what would then be classed as a penis.

In adulthood, individuals do not experience male-pattern baldness. As DHT is a far more potent androgen than testosterone alone, virilization in those lacking DHT may be absent or reduced compared to males with functional 5-AR. It is hypothesized that rising testosterone levels at the start of puberty are able to generate sufficient levels of DHT either by the action of 5α-reductase type I (active in the adult liver, non-genital skin and some brain areas) or through the expression of low levels of 5α-reductase type II in the testes.

5-ARD is associated with an increased risk of cryptorchidism and testicular cancer.

The symptoms of Leydig cell hypoplasia include pseudohermaphroditism (i.e., feminized, ambiguous, or relatively mildly underdeveloped (e.g., micropenis, severe hypospadias, and/or cryptorchidism (undescended testes)) external genitalia), a female gender identity or gender variance, hypergonadotropic hypogonadism (hypogonadism despite high levels of gonadotropins), delayed, impaired, or fully absent puberty with an associated reduction in or complete lack of development of secondary sexual characteristics (sexual infantilism), impaired fertility or complete sterility, tall stature (due to delayed epiphyseal closure), eunuchoid skeletal proportions, delayed or absent bone maturation, and osteoporosis.

Women with hypogonadism do not begin menstruating and it may affect their height and breast development. Onset in women after puberty causes cessation of menstruation, lowered libido, loss of body hair and hot flashes. In boys it causes impaired muscle and beard development and reduced height. In men it can cause reduced body hair and beard, enlarged breasts, loss of muscle, and sexual difficulties. A brain tumor (central hypogonadism) may involve headaches, impaired vision, milky discharge from the breast and symptoms caused by other hormone problems.

The symptoms of hypogonadotrophic hypogonadism, a subtype of hypogonadism, include late, incomplete or lack of development at puberty, and sometimes short stature or the inability to smell; in females, a lack of breasts and menstrual periods, and in males a lack of sexual development, e.g., facial hair, penis and testes enlargement, deepening voice.

AIS is broken down into three classes based on phenotype: complete androgen insensitivity syndrome (CAIS), partial androgen insensitivity syndrome (PAIS), and mild androgen insensitivity syndrome (MAIS). A supplemental system of phenotypic grading that uses seven classes instead of the traditional three was proposed by pediatric endocrinologist Charmian A. Quigley et al. in 1995. The first six grades of the scale, grades 1 through 6, are differentiated by the degree of genital masculinization; grade 1 is indicated when the external genitalia is fully masculinized, grade 6 is indicated when the external genitalia is fully feminized, and grades 2 through 5 quantify four degrees of decreasingly masculinized genitalia that lie in the interim. Grade 7 is indistinguishable from grade 6 until puberty, and is thereafter differentiated by the presence of secondary terminal hair; grade 6 is indicated when secondary terminal hair is present, whereas grade 7 is indicated when it is absent. The Quigley scale can be used in conjunction with the traditional three classes of AIS to provide additional information regarding the degree of genital masculinization, and is particularly useful when the diagnosis is PAIS.

Observed physiological abnormalities of the condition include a dramatic overexpression of aromatase and, accordingly, excessive levels of estrogens including estrone and estradiol and a very high rate of peripheral conversion of androgens to estrogens. In one study, cellular aromatase mRNA expression was found to be at least 10 times higher in a female patient compared to the control, and the estradiol/testosterone ratio after an injection of testosterone in a male patient was found to be 100 times greater than the control. Additionally, in another study, androstenedione, testosterone, and dihydrotestosterone (DHT) were found to be either low or normal in males, and follicle-stimulating hormone (FSH) levels were very low (likely due to suppression by estrogen, which has antigonadotropic effects as a form of negative feedback inhibition on sex steroid production in sufficiently high amounts), whereas luteinizing hormone (LH) levels were normal.

According to a recent review, estrone levels have been elevated in 17 of 18 patients (94%), while estradiol levels have been elevated only in 13 of 27 patients (48%). As such, estrone is the main estrogen elevated in the condition. In more than half of patients, circulating androstenedione and testosterone levels are low to subnormal. The ratio of circulating estradiol to testosterone is >10 in 75% of cases. FSH levels are said to be consistently low in the condition, while LH levels are in the low to normal range.

It is notable that gynecomastia has been observed in patients in whom estradiol levels are within the normal range. This has been suggested to be due to "in situ" conversion of adrenal androgens into estrone and then estradiol (via local 17β-HSD) in breast tissue (where aromatase activity may be particularly high).

The symptoms of AES, in males, include heterosexual precocity (precocious puberty with phenotypically-inappropriate secondary sexual characteristics; i.e., a fully or mostly feminized appearance), severe prepubertal or peripubertal gynecomastia (development of breasts in males before or around puberty), high-pitched voice, sparse facial hair, hypogonadism (dysfunctional gonads), oligozoospermia (low sperm count), small testes, micropenis (an ususually small penis), advanced bone maturation, an earlier peak height velocity (an accelerated rate of growth in regards to height), and short final stature due to early epiphyseal closure. The incidence of gynecomastia appears to be 100%, with 20 of 30 male cases opting for mastectomy according to a review.

In females, symptoms of AES include isosexual precocity (precocious puberty with phenotypically-appropriate secondary sexual characteristics), macromastia (excessively large breasts), an enlarged uterus, menstrual irregularities, and, similarly to males, accelerated bone maturation and short final height. Of seven females described in one report, three had macromastia (rate of ~43%). A 10-year-old girl with gigantomastia has subsequently also been described.

Fertility, though usually affected to one degree or another—especially in males—is not always impaired significantly enough to prevent sexual reproduction, as evidenced by vertical transmission of the condition by both sexes.

All forms of androgen insensitivity are associated with infertility, though exceptions have been reported for both the mild and partial forms.

PAIS is associated with a 50% risk of germ cell malignancy when the testes are undescended. If the testes are located intrascrotally, there may still be significant risk of germ cell malignancy; studies have not yet been published to assess this risk. Some men with PAIS may experience sexual dysfunction including impotence and anejaculation. A few AR mutations that cause PAIS are also associated with prostate and breast cancers.

Vaginal hypoplasia, a relatively frequent finding in CAIS and some forms of PAIS, is associated with sexual difficulties including vaginal penetration difficulties and dyspareunia.

At least one study indicates that individuals with an intersex condition may be more prone to psychological difficulties, due at least in part to parental attitudes and behaviors, and concludes that preventative long-term psychological counseling for parents as well as for affected individuals should be initiated at the time of diagnosis.

Lifespan is not thought to be affected by AIS.

Individuals with complete androgen insensitivity syndrome (grades 6 and 7 on the Quigley scale) are born phenotypically female, without any signs of genital masculinization, despite having a 46,XY karyotype. Symptoms of CAIS do not appear until puberty, which may be slightly delayed, but is otherwise normal except for absent menses and diminished or absent secondary terminal hair. Axillary hair (i.e. armpit hair) fails to develop in one third of all cases. External genitalia is normal, although the labia and clitoris are sometimes underdeveloped. The vaginal depth varies widely, but is typically shorter than unaffected women; one study of eight women with CAIS measured the average vaginal depth to be 5.9 cm (vs. 11.1 ± 1.0 cm for unaffected women ). In some extreme cases, the vagina has been reported to be aplastic (resembling a "dimple"), though the exact incidence of this is unknown.

The gonads in these women are not ovaries, but instead, are testes; during the embryonic stage of development, testes form in an androgen-independent process that occurs due to the influence of the SRY gene on the Y chromosome. They may be located intra-abdominally, at the internal inguinal ring, or may herniate into the labia majora, often leading to the discovery of the condition. Testes in affected women have been found to be atrophic upon gonadectomy. Testosterone produced by the testes cannot be directly used due to the mutant androgen receptor that characterizes CAIS; instead, it is aromatized into estrogen, which effectively feminizes the body and accounts for the normal female phenotype observed in CAIS.

Immature sperm cells in the testes do not mature past an early stage, as sensitivity to androgens is required in order for spermatogenesis to complete. Germ cell malignancy risk, once thought to be relatively high, is now thought to be approximately 2%. Wolffian structures (the epididymides, vasa deferentia, and seminal vesicles) are typically absent, but will develop at least partially in approximately 30% of cases, depending on which mutation is causing the CAIS. The prostate, like the external male genitalia, cannot masculinize in the absence of androgen receptor function, and thus remains in the female form.

The Müllerian system (the fallopian tubes, uterus, and upper portion of the vagina) typically regresses due to the presence of anti-Müllerian hormone originating from the Sertoli cells of the testes. These women are thus born without fallopian tubes, a cervix, or a uterus, and the vagina ends "blindly" in a pouch. Müllerian regression does not fully complete in approximately one third of all cases, resulting in Müllerian "remnants". Although rare, a few cases of women with CAIS and fully developed Müllerian structures have been reported. In one exceptional case, a 22-year-old with CAIS was found to have a normal cervix, uterus, and fallopian tubes. In an unrelated case, a fully developed uterus was found in a 22-year-old adult with CAIS.

Other subtle differences that have been reported include slightly longer limbs and larger hands and feet due to a proportionally greater stature than unaffected women, larger teeth, minimal or no acne, well developed breasts, and a greater incidence of meibomian gland dysfunction (i.e. dry eye syndromes and light sensitivity).

17-β-Hydroxysteroid dehydrogenase III deficiency is clinically characterized by either ambiguous external genitalia or complete female external genitalia at birth; as a consequence of impaired male sexual differentiation in 46,XY individuals, as well as:

- Hypothyroidism

- Cryptorchidism

- Infertility

- Abnormality of metabolism

Aromatase excess syndrome (AES or AEXS), also sometimes referred to as familial hyperestrogenism or familial gynecomastia, is a rare genetic and endocrine syndrome which is characterized by an overexpression of aromatase, the enzyme responsible for the biosynthesis of the estrogen sex hormones from the androgens, in turn resulting in excessive levels of circulating estrogens and, accordingly, symptoms of hyperestrogenism. It affects both sexes, manifesting itself in males as marked or complete phenotypical feminization (with the exception of the genitalia; i.e., no pseudohermaphroditism) and in females as hyperfeminization.

To date, 30 males and 8 females with AES among 15 and 7 families, respectively, have been described in the medical literature.

The phenotypes that result from the insensitivity to androgens are not unique to AIS, thus the diagnosis of AIS requires thorough exclusion of other causes. Clinical findings indicative of AIS include the presence of a short vagina or undermasculinized genitalia, partial or complete regression of Müllerian structures, bilateral nondysplastic testes, and impaired spermatogenesis and/or virilization. Laboratory findings include a 46,XY karyotype and normal or elevated postpubertal testosterone, luteinizing hormone, and estradiol levels. The androgen binding activity of genital skin fibroblasts is typically diminished, although exceptions have been reported. Conversion of testosterone to dihydrotestosterone may be impaired. The diagnosis of AIS is confirmed if androgen receptor gene sequencing reveals a mutation, although not all individuals with AIS (particularly PAIS) will have an "AR" mutation (see Other Causes).

Each of the three types of AIS (complete, partial, and mild) has a different list of differential diagnoses to consider. Depending on the form of AIS suspected, the list of differentials can include:

Although the external genitalia can sometimes be completely female, the vagina consists of only the lower two-thirds of a normal vagina, creating a blind-ending vaginal pouch.

Since the gonad tissue develops into testes rather than ovaries, they are thus unable to create ova but may be able to create sperm. Because of normal action of Müllerian inhibiting factor produced by the testes in utero, individuals with 5-ARD lack a uterus and Fallopian tubes. Thus, they would not physically be able to carry a pregnancy in any event. Even with treatments such as surrogate motherhood, female infertility is caused by the lack of any ova to implant in a surrogate. Male fertility, however, can still be possible if viable sperm is present in the testes and is able to be extracted. In general, individuals with 5-ARD are capable of producing viable sperm.

In individuals with an ambiguous genital resulting in a macroclitoris/micropenis, the genital may be capable of ejaculations as well as erections, but may be of insufficient size for penetrative sexual intercourse.

Fertility is further compromised by the underdevelopment of seminal vesicles and prostate.

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.

People with 46,XX testicular DSD have male external genitalia. They generally have small testes and may also have abnormalities such as undescended testes (cryptorchidism) or the urethra opening on the underside of the penis (hypospadias). A small number of affected people have external genitalia that do not look clearly male or clearly female (ambiguous genitalia). Affected children are typically raised as males and are likely to have a male gender identity.

Mutations that result in some residual 21-hydroxylase activity cause milder disease, traditionally termed simple virilizing CAH (SVCAH). In these children the mineralocorticoid deficiency is less significant and salt-wasting does not occur. However, genital ambiguities are possible.

Estrogen insensitivity syndrome (EIS), or estrogen resistance, is a form of congenital estrogen deficiency or hypoestrogenism which is caused by a defective estrogen receptor (ER) – specifically, the estrogen receptor alpha (ERα) – that results in an inability of estrogen to mediate its biological effects in the body. Congenital estrogen deficiency can alternatively be caused by a defect in aromatase, the enzyme responsible for the biosynthesis of estrogens, a condition which is referred to as aromatase deficiency and is similar in symptomatology to EIS.

EIS is an extremely rare occurrence. As of 2016, there have been three published reports of EIS, involving a total of five individuals. The reports include a male case published in 1994, a female case published in 2013, and a familial case involving two sisters and a brother which was published in 2016.

EIS is analogous to androgen insensitivity syndrome (AIS), a condition in which the androgen receptor (AR) is defective and insensitive to androgens, such as testosterone and dihydrotestosterone (DHT). The functional opposite of EIS is hyperestrogenism, for instance that seen in aromatase excess syndrome.

Hyperandrogenism affects 5-10% of females of reproductive age. Hyperandrogenism can affect both males and females, but is more noticeable in females due to the fact that elevated levels of androgens in females often facilitates virilization. Due to the fact that hyperandrogenism is characterized by the elevation of male sex hormone levels, symptoms of hyperandrogenism in men are often negligible. Hyperandrogenism in females is typically diagnosed in late adolescence with a medical evaluation. The medical evaluation tends to consist of a pelvic exam, observation of external symptoms, and a blood test measuring androgen levels.

All forms of androgen insensitivity, including CAIS, are associated with infertility, though exceptions have been reported for both the mild and partial forms.

CAIS is associated with a decreased bone mineral density. Some have hypothesized that the decreased bone mineral density observed in women with CAIS is related to the timing of gonadectomy and inadequate estrogen supplementation. However, recent studies show that bone mineral density is similar whether gonadectomy occurs before or after puberty, and is decreased despite estrogen supplementation, leading some to hypothesize that the deficiency is directly attributable to the role of androgens in bone mineralization.

CAIS is also associated with an increased risk for gonadal tumors (e.g. germ cell malignancy) in adulthood if gonadectomy is not performed. The risk of malignant germ cell tumors in women with CAIS increases with age and has been estimated to be 3.6% at 25 years and 33% at 50 years. The incidence of gonadal tumors in childhood is thought to be relatively low; a recent review of the medical literature found that only three cases of malignant germ cell tumors in prepubescent girls have been reported in association with CAIS in the last 100 years. Some have estimated the incidence of germ cell malignancy to be as low as 0.8% before puberty.

Vaginal hypoplasia, a relatively frequent finding in CAIS and some forms of PAIS, is associated with sexual difficulties including vaginal penetration difficulties and dyspareunia.

At least one study indicates that individuals with an intersex condition may be more prone to psychological difficulties, due at least in part to parental attitudes and behaviors, and concludes that preventative long-term psychological counseling for parents as well as for affected individuals should be initiated at the time of diagnosis.

Lifespan is not thought to be affected by AIS.