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).

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).

Swyer syndrome represents one phenotypic result of a failure of the gonads to develop properly, and hence is part of a class of conditions termed gonadal dysgenesis. There are many forms of gonadal dysgenesis.

Swyer syndrome is an example of a condition in which an externally unambiguous female body carries dysgenetic, atypical, or abnormal gonads. Other examples include complete androgen insensitivity syndrome, partial X chromosome deletions, lipoid congenital adrenal hyperplasia, and Turner syndrome.

Gonadal dysgenesis is any congenital developmental disorder of the reproductive system characterized by a progressive loss of germ cells on the developing gonads of an embryo. This loss leads to extremely hypoplastic (underdeveloped) and dysfunctioning gonads mainly composed of fibrous tissue, hence the name streak gonads—i.e., a form of aplasia in which the ovary is replaced by functionless tissue. The accompanying hormonal failure also prevents the development of secondary sex characteristics in either sex, resulting in a sexually infantile female appearance and infertility.

The first type of gonadal dysgenesis discovered was Turner syndrome.

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.

The condition may be due to:

- Turner syndrome, and its variations (i.e. mosaicism)

- XX gonadal dysgenesis, also pure gonadal dysgenesis, 46,XX

- Swyer syndrome, also pure gonadal dysgenesis, 46,XY

- Perrault syndrome, XX gonadal dysgenesis + sensorineural hearing loss

- Mixed gonadal dysgenesis

- Exposure to environmental endocrine disruptors

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.

The diagnosis of infertility begins with a medical history and physical exam by a physician, physician assistant, or nurse practitioner. Typically two separate semen analyses will be required. The provider may order blood tests to look for hormone imbalances, medical conditions, or genetic issues.

The history should include prior testicular or penile insults (torsion, cryptorchidism, trauma), infections (mumps orchitis, epididymitis), environmental factors, excessive heat, radiation, medications, and drug use (anabolic steroids, alcohol, smoking).

Sexual habits, frequency and timing of intercourse, use of lubricants, and each partner's previous fertility experiences are important.

Loss of libido and headaches or visual disturbances may indicate a pituitary tumor.

The past medical or surgical history may reveal thyroid or liver disease (abnormalities of spermatogenesis), diabetic neuropathy (retrograde ejaculation), radical pelvic or retroperitoneal surgery (absent seminal emission secondary to sympathetic nerve injury), or hernia repair (damage to the vas deferens or testicular blood supply).

A family history may reveal genetic problems.

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.

Anorchia (or anorchism) is an XY disorder of sex development in which individuals have both testes absent at birth. Within a few weeks of fertilization, the embryo develops rudimentary gonads (testes), which produce hormones responsible for the development of the reproductive system. If the testes fail to develop within eight weeks, the baby will develop female genitalia (see Swyer syndrome). If the testes begin to develop but are lost or cease to function between eight and 10 weeks, the baby will have ambiguous genitalia when it is born. However, if the testes are lost after 14 weeks, the baby will have partial male genitalia with the notable absence of gonads.

Tests include observable lack of testes, low testosterone levels (typical female levels), elevated follicle stimulating hormone and luteinizing hormone levels, XY karyotype, ultrasound or magnetic resonance imaging showing absent gonadal tissue, low bone density, low anti-Müllerian hormone levels, and surgical exploration for evidence of male gonadal tissue.

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.

Hypospadias presents as an abnormal location for the end of the urethra which is typically found on the distal end of the penis. It is generally diagnosed at birth from visual confirmation of the hallmark features. As well as an unusual location of the urethra, the prepuce (foreskin) is typically incomplete as well. The abnormal ‘hooded’ prepuce is what often draws attention to the condition but can occur separately to hypospadias.

In Cryptorchidism a diagnosis is made from a physical examination which is performed when the baby is lacking one or both testes in the dependant portion of the scrotal sac. 70% of cryptorchid testes can be felt and are unable to be pulled into the scrotum or retreats quickly after being pulled into a higher position. In 30% of cases the testes cannot be felt indicating an intra-abdominal location. The risk factors for Cryptorchidism are:

- A family history of the condition

- Low birth weight

- Prematurity

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.

External genitalia are often ambiguous, the degree depending mainly on the amount of testosterone produced by the testicular tissue between 8 and 16 weeks of gestation.

There is a small body of research on the psychology of cryptorchidism, that attempts to determine whether this condition can cause lasting psychological problems. The psychological research on cryptorchism consists of only a few case reports and small studies. This research also has serious methodological problems: major variables are completely uncontrolled, such as the small physical stature of many cryptorchid boys, and the psychological effects of corrective surgery.

Existing research indicates that boys with undescended testicles do not tend to be gender-disordered, effeminate, or pre-homosexual. A disturbed self-image forms only when the family dynamics are destructive to developing male self-esteem. Such pathogenic attitudes were found in parents who focused on the boy’s genital defect as a sign of his presumed effeminacy. However, when the cryptorchism is surgically corrected a healthy masculinity becomes possible. The basic sexual normality of these boys was confirmed in a small retrospective study that tested adolescent boys several years after their condition was surgically repaired. They had developed into fairly well-adjusted teenagers without special sexual or gender problems, and with no distinctive traits of psychopathological relevance.

Many men who were born with undescended testes have reduced fertility, even after orchiopexy in infancy. The reduction with unilateral cryptorchidism is subtle, with a reported infertility rate of about 10%, compared with about 6% reported by the same study for the general population of adult men.

The fertility reduction after orchiopexy for bilateral cryptorchidism is more marked, about 38%, or 6 times that of the general population. The basis for the universal recommendation for early surgery is research showing degeneration of spermatogenic tissue and reduced spermatogonia counts after the second year of life in undescended testes. The degree to which this is prevented or improved by early orchiopexy is still uncertain.

Although similar in some ways to true hermaphroditism, the conditions can be distinguished histologically and by karyotyping. The observable characteristics (phenotype) of this condition are highly variable, ranging from gonadal dysgenesis in males, to Turner-like females and phenotypically normal males. The phenotypical expression may be ambiguous, intersex, or male or female depending on the extent of the mosaicism. The most common presentation of 45,X/46,XY karyotype is phenotypically normal male, next being genital ambiguity.

There is a range of chromosomal anomalies within 45,X/46,XY where the variations are very complex, and the actual result in living individuals is often not a simple picture. Most patients with this karyotype are known to have abnormal gonadal histology and heights considerably below their genetic potential. High gonadotropin levels have been described in both male and female patients, as well as low levels of testosterone in male patients. Dosage loss of SHOX gene is commonly associated with short stature. Psychomotor development is normal.

As the gonads may not be symmetrical, the development of the Müllerian duct and Wolffian duct may be asymmetrical, too. Because of the presence of dysgenetic gonadal tissue and Y chromosome material, there is a high risk of the development of a gonadoblastoma.

45,X/46,XY mosaicism, also known as X0/XY mosaicism and mixed gonadal dysgenesis, is a rare disorder of sex development in humans associated with sex chromosome aneuploidy and mosaicism of the Y chromosome. This is called a mosaic karyotype because, like tiles in mosaic floors or walls, there is more than one type of cell.

The clinical manifestations are highly variable, ranging from partial virilisation and ambiguous genitalia at birth, to patients with a completely male or female gonads. Most individuals with this karyotype have apparently normal male genitalia, and a minority with female genitalia, with a significant number of individuals showing genital abnormalities or intersex characteristics. A significantly higher than normal number of other developmental abnormalities are also found in individuals with X0/XY mosaicism. Psychomotor development is normal.

True hermaphroditism, clinically known as ovotesticular disorder of sex development, is a medical term for an intersex condition in which an individual is born with ovarian and testicular tissue. More commonly one or both gonads is an ovotestis containing both types of tissue.

Although similar in some ways to mixed gonadal dysgenesis, the conditions can be distinguished histologically.

Examples of symptoms of hypogonadism include delayed, reduced, or absent puberty, low libido, and infertility.

Hypergonadotropic hypogonadism (HH), also known as primary or peripheral/gonadal hypogonadism, is a condition which is characterized by hypogonadism due to an impaired response of the gonads to the gonadotropins, follicle-stimulating hormone (FSH) and luteinizing hormone (LH), and in turn a lack of sex steroid production and elevated gonadotropin levels (as an attempt of compensation by the body). HH may present as either "congenital" or "acquired", but the majority of cases are of the former nature.

On average, the ovaries supply a woman with eggs until age 51, the average age of natural menopause.

POF is not the same as a natural menopause, in that the dysfunction of the ovaries, loss of eggs, or removal of the ovaries at a young age is not a normal physiological occurrence.

Infertility is the result of this condition, and is the most discussed problem resulting from it, but there are additional health implications of the problem, and studies are ongoing. For example, osteoporosis or decreased bone density affects almost all women with POF due to an insufficiency of estrogen. There is also an increased risk of heart disease, hypothyroidism in the form of Hashimoto's thyroiditis, Addison's disease, and other auto-immune disorders.

Hormonally, POF is defined by abnormally low levels of estrogen and high levels of FSH, which demonstrate that the ovaries are no longer responding to circulating FSH by producing estrogen and developing fertile eggs. The ovaries will likely appear shriveled.

The age of onset can be as early as the teenage years, or can even exist from birth, but varies widely. If a girl never begins menstruation, it is called primary ovarian failure. The age of 40 was chosen as the cut-off point for a diagnosis of POF. This age was chosen somewhat arbitrarily, as all women's ovaries decline in function over time. However an age needed to be chosen to distinguish usual menopause from the abnormal state of premature menopause. Premature ovarian failure has components to it that distinguish it from normal menopause.

By the age of 40, approximately one percent of women have POF. Women suffering from POF usually experience menopausal symptoms that are more severe than the symptoms found in older menopausal women.

Because of the inability of the streak gonads to produce sex hormones (both estrogens and androgens), most of the secondary sex characteristics do not develop. This is especially true of estrogenic changes such as breast development, widening of the pelvis and hips, and menstrual periods. Because the adrenal glands can make limited amounts of androgens and are not affected by this syndrome, most of these girls will develop pubic hair, though it often remains sparse.

Evaluation of delayed puberty usually reveals the presence of pubic hair, but elevation of gonadotropins, indicating that the pituitary is providing the signal for puberty but the gonads are failing to respond. The next steps of the evaluation usually include checking a karyotype and imaging of the pelvis. The karyotype reveals XX chromosomes and the imaging demonstrates the presence of a uterus but no ovaries (the streak gonads are not usually seen by most imaging). At this point it is usually possible for a physician to make a diagnosis of XX gonadal dysgenesis.