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.

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

Because hyperandrogenism can appear as a symptom of numerous different genetic and medical conditions, it is difficult to make a general statement on whether hyperandrogenic symptoms can be passed from parent to offspring. However, a collection of the conditions with hyperandrogenic symptoms, including polycystic ovary syndrome, have been observed as hereditary in certain cases. One potential cause of polycystic ovary syndrome is maternal hyperandrogenism, where the hormonal irregularities of the mother can affect the development of the child during gestation, resulting in the passing of polycystic ovary syndrome from mother to child.

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.

Treatment of HH is usually with hormone replacement therapy, consisting of androgen and estrogen administration in males and females, respectively.

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

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.

During embryogenesis, without any external influences for or against, the human reproductive system is intrinsically conditioned to give rise to a female reproductive organisation.

As a result, if a gonad cannot express its sexual identity via its hormones—as in gonadal dysgenesis—then the affected person, no matter whether their chromosomes are XY or XX, will develop external female genitalia. Internal female genitalia, primarily the uterus, may or may not be present depending on the cause of the disorder.

In both sexes, the commencement and progression of puberty require functional gonads that will work in harmony with the hypothalamic and pituitary glands to produce adequate hormones.

For this reason, in gonadal dysgenesis the accompanying hormonal failure also prevents the development of secondary sex characteristics in either sex, resulting in a sexually infantile female appearance and infertility.

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.

Twelve percent of all infertility cases are a result of a woman either being underweight or overweight. Fat cells produce estrogen, in addition to the primary sex organs. Too much body fat causes production of too much estrogen and the body begins to react as if it is on birth control, limiting the odds of getting pregnant. Too little body fat causes insufficient production of estrogen and disruption of the menstrual cycle. Both under and overweight women have irregular cycles in which ovulation does not occur or is inadequate. Proper nutrition in early life is also a major factor for later fertility.

A study in the US indicated that approximately 20% of infertile women had a past or current eating disorder, which is five times higher than the general lifetime prevalence rate.

A review from 2010 concluded that overweight and obese subfertile women have a reduced probability of successful fertility treatment and their pregnancies are associated with more complications and higher costs. In hypothetical groups of 1000 women undergoing fertility care, the study counted approximately 800 live births for normal weight and 690 live births for overweight and obese anovulatory women. For ovulatory women, the study counted approximately 700 live births for normal weight, 550 live births for overweight and 530 live births for obese women. The increase in cost per live birth in anovulatory overweight and obese women were, respectively, 54 and 100% higher than their normal weight counterparts, for ovulatory women they were 44 and 70% higher, respectively.

There are a multitude of different etiologies of HH. Congenital causes include the following:

- Chromosomal abnormalities (resulting in gonadal dysgenesis) - Turner's syndrome, Klinefelter's syndrome, Swyer's syndrome, XX gonadal dysgenesis, and mosaicism.

- Defects in the enzymes involved in the gonadal biosynthesis of the sex hormones - 17α-hydroxylase deficiency, 17,20-lyase deficiency, 17β-hydroxysteroid dehydrogenase III deficiency, and lipoid congenital adrenal hyperplasia.

- Gonadotropin resistance (e.g., due to inactivating mutations in the gonadotropin receptors) - Leydig cell hypoplasia (or insensitivity to LH) in males, FSH insensitivity in females, and LH and FSH resistance due to mutations in the "GNAS" gene (termed pseudohypoparathyroidism type 1A).

Acquired causes (due to damage to or dysfunction of the gonads) include ovarian torsion, vanishing/anorchia, orchitis, premature ovarian failure, ovarian resistance syndrome, trauma, surgery, autoimmunity, chemotherapy, radiation, infections (e.g., sexually-transmitted diseases), toxins (e.g., endocrine disruptors), and drugs (e.g., antiandrogens, opioids, alcohol).

Most XY children are so undervirilized that they are raised as girls. The testes are uniformly nonfunctional and undescended; they are removed when the diagnosis is made due to the risk of cancer development in these tissues.

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.

The human breast cancer susceptibility gene 2 (BRCA2) is employed in homologous recombinational repair of DNA damages during meiosis. A common single-nucleotide polymorphism of BRCA2 is associated with severe oligospermia.

Men with mild oligospermia (semen concentration of 15 million to 20 million sperm/ml) were studied for an association of sperm DNA damage with life style factors. A significant association was found between sperm DNA damage and factors such as age, obesity and occupational stress.

The 2006 Consensus statement on the management of intersex disorders states that individuals with 17β-hydroxysteroid dehydrogenase III deficiency have an intermediate risk of germ cell malignancy, at 28%, recommending that gonads be monitored. A 2010 review put the risk of germ cell tumors at 17%.

The management of 17β-hydroxysteroid dehydrogenase III deficiency can consist, according to one source, of the elimination of gonads prior to puberty, in turn halting masculinization.

Hewitt and Warne state that, children with 17β-hydroxysteroid dehydrogenase III deficiency who are raised as girls often later identify as male, describing a "well known, spontaneous change of gender identity from female to male" that "occurs after the onset of puberty." A 2005 systematic review of gender role change identified the rate of gender role change as occurring in 39–64% of individuals with 17β-hydroxysteroid dehydrogenase III deficiency raised as girls.

Sexually transmitted infections are a leading cause of infertility. They often display few, if any visible symptoms, with the risk of failing to seek proper treatment in time to prevent decreased fertility.

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.

In about 30% of infertile men no causative factor is found for their decrease in sperm concentration or quality by common clinical, instrumental, or laboratory means, and the condition is termed "idiopathic" (unexplained). A number of factors may be involved in the genesis of this condition, including age, infectious agents ( such as "Chlamydia trachomatis"), Y chromosome microdeletions, mitochondrial changes, environmental pollutants, and "subtle" hormonal changes.

A review in 2013 came to the result that oligospermia and azoospermia are significantly associated with being overweight (odds ratio 1.1), obese (odds ratio 1.3) and morbidly obese (odds ratio 2.0), but the cause of this is unknown. It found no significant relation between oligospermia and being underweight.

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.

The incidence varies geographically. In the United States, congenital adrenal hyperplasia is particularly common in Native Americans and Yupik Eskimos (incidence ). Among American Caucasians, the incidence is approximately ).

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).

The androgen receptor gene contains two polymorphic trinucleotide microsatellites in exon 1. The first microsatellite (nearest the 5' end) contains 8 to 60 repetitions of the glutamine codon "CAG" and is thus known as the polyglutamine tract. The second microsatellite contains 4 to 31 repetitions of the glycine codon "GGC" and is known as the polyglycine tract. The average number of repetitions varies by ethnicity, with Caucasians exhibiting an average of 21 CAG repeats, and Blacks 18. Disease states are associated with extremes in polyglutamine tract length; prostate cancer, hepatocellular carcinoma, and mental retardation are associated with too few repetitions, while spinal and bulbar muscular atrophy (SBMA) is associated with a CAG repetition length of 40 or more. Some studies indicate that the length of the polyglutamine tract is inversely correlated with transcriptional activity in the AR protein, and that longer polyglutamine tracts may be associated with infertility and undermasculinized genitalia. However, other studies have indicated that no such correlation exists. A comprehensive meta-analysis of the subject published in 2007 supports the existence of the correlation, and concluded that these discrepancies could be resolved when sample size and study design are taken into account. Longer polyglycine tract lengths have also been associated with genital masculinization defects in some, but not all, studies.

This condition will occur if there is an absence of both Müllerian inhibiting factor and testosterone. The absence of testosterone will result in regression of the Wolffian ducts; normal male internal reproductive tracts will not develop. The absence of Müllerian inhibiting factor will allow the Müllerian ducts to differentiate into the oviducts and uterus. In sum, this individual will possess female-like internal and external reproductive characteristics, lacking secondary sex characteristics. The genotype may be either 45,XO, 46,XX or 46,XY.

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.