Azoospermia is usually detected in the course of an infertility investigation. It is established on the basis of two semen analysis evaluations done at separate occasions (when the seminal specimen after centrifugation shows no sperm under the microscope) and requires a further work-up.

The investigation includes a history, a physical examination including a thorough evaluation of the scrotum and testes, laboratory tests, and possibly imaging. History includes the general health, sexual health, past fertility, libido, and sexual activity. Past exposure to a number of agents needs to be queried including medical agents like hormone/steroid therapy, antibiotics, 5-ASA inhibitors (sulfasalazine), alpha-blockers, 5 alpha-reductase inhibitors, chemotherapeutic agents, pesticides, recreational drugs (marijuana, excessive alcohol), and heat exposure of the testes. A history of surgical procedures of the genital system needs to be elicited. The family history needs to be assessed to look for genetic abnormalities.

Congenital absence of the vas deferens may be detectable on physical examination and can be confirmed by a transrectal ultrasound (TRUS). If confirmed genetic testing for cystic fibrosis is in order. Transrectal ultrasound can also assess azoospermia caused by obstruction, or anomalies related to obstruction of the ejaculatory duct, such as abnormalities within the duct itself, a median cyst of the prostate (indicating a need for cyst aspiration), or an impairment of the seminal vesicles to become enlarged or emptied.

Retrograde ejaculation is diagnosed by examining a postejaculatory urine for presence of sperm after making it alkaline and centifuging it.

Low levels of LH and FSH with low or normal testosterone levels are indicative of pretesticular problems, while high levels of gonadotropins indicate testicular problems. However, often this distinction is not clear and the differentiation between obstructive versus non-obstructive azoospermia may require a testicular biopsy. On the other hand, "In azoospermic men with a normal ejaculate volume, FSH serum level greater than two times the upper limit of the normal range is reliably diagnostic of dysfunctional spermatogenesis and, when found, a diagnostic testicular biopsy is usually unnecessary, although no consensus exists in this matter." But also, extremely high levels of FSH (>45 ID/mL) have been correlated with successful microdissection testicular sperm extraction.

Serum inhibin-B weakly indicates presence of sperm cells in the testes, raising chances for successfully achieving pregnancy through testicular sperm extraction (TESE), although the association is not very substantial, having a sensitivity of 0.65 (95% confidence interval [CI]: 0.56–0.74) and a specificity of 0.83 (CI: 0.64–0.93) for prediction the presence of sperm in the testes in non-obstructive azoospermia.

Seminal plasma proteins TEX101 and ECM1 were recently proposed for the differential diagnosis of azoospermia forms and subtypes, and for prediction of TESE outcome. Mount Sinai Hospital, Canada started clinical trial to test this hypothesis in 2016.

It is recommended that men primary hypopituitarism may be linked to a genetic cause, a genetic evaluation is indicated in men with azoospermia due to primary hypopituitarism. Azoospermic men with testicular failure are advised to undergo karyotype and Y-micro-deletion testing.

Unfortunately, the number of differentials to consider for PAIS is particularly large. Prompt diagnosis is particularly urgent when a child is born with ambiguous genitalia, as some causes are associated with potentially life-threatening adrenal crises. Determination of testosterone, testosterone precursors and dihydrotestosterone (DHT) at baseline and / or after human chorionic gonadotropin (hCG) stimulation can be used to exclude such defects in androgen biosynthesis.

Approximately one half of all 46,XY individuals born with ambiguous genitalia will not receive a definitive diagnosis. Androgen receptor (AR) gene mutations cannot be found in 27% to 72% of individuals with PAIS. As a result, genetic analysis can be used to confirm a diagnosis of PAIS, but it cannot be used to rule out PAIS. Evidence of abnormal androgen binding in a genital skin fibroblast study has long been the gold standard for the diagnosis of PAIS, even when an AR mutation is not present. However, some cases of PAIS, including AR-mutant-positive cases, will show normal androgen binding. A family history consistent with X-linked inheritance is more commonly found in AR-mutant-positive cases than AR-mutant-negative cases.

The use of dynamic endocrine tests is particularly helpful in isolating a diagnosis of PAIS. One such test is the human chorionic gonadotropin (hCG) stimulation test. If the gonads are testes, there will be an increase in the level of serum testosterone in response to the hCG, regardless of testicular descent. The magnitude of the testosterone increase can help differentiate between androgen resistance and gonadal dysgenesis, as does evidence of a uterus on ultrasound examination. Testicular function can also be assessed by measuring serum anti-Müllerian hormone levels, which in turn can further differentiate PAIS from gonadal dysgenesis and bilateral anorchia.

Another useful dynamic test involves measuring the response to exogenous steroids; individuals with AIS show a decreased response in serum sex hormone binding globulin (SHBG) after a short term administration of anabolic steroids. Two studies indicate that measuring the response in SHBG after the administration of stanozolol could help to differentiate individuals with PAIS from those with other causes of ambiguous genitalia, although the response in individuals with predominantly male phenotypes overlaps somewhat with the response in normal males.

CAIS can only be diagnosed in normal phenotypic females. It is not usually suspected unless the menses fail to develop at puberty, or an inguinal hernia presents during premenarche. As many as 1–2% of prepubertal girls that present with an inguinal hernia will also have CAIS.

A diagnosis of CAIS or Swyer syndrome can be made in utero by comparing a karyotype obtained by amniocentesis with the external genitalia of the fetus during a prenatal ultrasound. Many infants with CAIS do not experience the normal, spontaneous neonatal testosterone surge, a fact which can be diagnostically exploited by obtaining baseline luteinizing hormone and testosterone measurements, followed by a human chorionic gonadotropin (hGC) stimulation test.

The main differentials for CAIS are complete gonadal dysgenesis (Swyer syndrome) and Müllerian agenesis (Mayer-Rokitansky-Kuster-Hauser syndrome or MRKH). Both CAIS and Swyer syndrome are associated with a 46,XY karyotype, whereas MRKH is not; MRKH can thus be ruled out by checking for the presence of a Y chromosome, which can be done either by fluorescence in situ hybridization (FISH) analysis or on full karyotype. Swyer syndrome is distinguished by poor breast development and shorter stature. The diagnosis of CAIS is confirmed when androgen receptor (AR) gene sequencing reveals a mutation, although up to 5% of individuals with CAIS do not have an AR mutation.

Up until the 1990s, a CAIS diagnosis was often hidden from the affected individual and / or family. It is current practice to disclose the genotype at the time of diagnosis, particularly when the affected girl is at least of adolescent age. If the affected individual is a child or infant, it is generally up to the parents, often in conjunction with a psychologist, to decide when to disclose the diagnosis.

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.

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.

Some strategies suggested or proposed for avoiding male infertility include the following:

- Avoiding smoking as it damages sperm DNA

- Avoiding heavy marijuana and alcohol use.

- Avoiding excessive heat to the testes.

- Maintaining optimal frequency of coital activity: sperm counts can be depressed by daily coital activity and sperm motility may be depressed by coital activity that takes place too infrequently (abstinence 10–14 days or more).

- Wearing a protective cup and jockstrap to protect the testicles, in any sport such as baseball, football, cricket, lacrosse, hockey, softball, paintball, rodeo, motorcross, wrestling, soccer, karate or other martial arts or any sport where a ball, foot, arm, knee or bat can come into contact with the groin.

- Diet: Healthy diets (i.e. the Mediterranean diet) rich in such nutrients as omega-3 fatty acids, some antioxidants and vitamins, and low in saturated fatty acids (SFAs) and trans-fatty acids (TFAs) are inversely associated with low semen quality parameters. In terms of food groups, fish, shellfish and seafood, poultry, cereals, vegetables and fruits, and low-fat dairy products have been positively related to sperm quality. However, diets rich in processed meat, soy foods, potatoes, full-fat dairy products, coffee, alcohol and sugar-sweetened beverages and sweets have been inversely associated with the quality of semen in some studies. The few studies relating male nutrient or food intake and fecundability also suggest that diets rich in red meat, processed meat, tea and caffeine are associated with a lower rate of fecundability. This association is only controversial in the case of alcohol. The potential biological mechanisms linking diet with sperm function and fertility are largely unknown and require further study.

Low testosterone can be identified through a simple blood test performed by a laboratory, ordered by a health care provider. Blood for the test must be taken in the morning hours, when levels are highest, as levels can drop by as much as 13% during the day and all normal reference ranges are based on morning levels. However, low testosterone in the absence of any symptoms does not clearly need to be treated.

Normal total testosterone levels depend on the man's age but generally range from 240–950 ng/dL (nanograms per deciliter) or 8.3-32.9 nmol/L (nanomoles per liter). Some men with normal total testosterone have low free or bioavailable testosterone levels which could still account for their symptoms. Men with low serum testosterone levels should have other hormones checked, particularly luteinizing hormone to help determine why their testosterone levels are low and help choose the most appropriate treatment (most notably, testosterone is usually not appropriate for secondary or tertiary forms of male hypogonadism, in which the LH levels are usually reduced).

Treatment is often prescribed for total testosterone levels below 230 ng/dL with symptoms. If the serum total testosterone level is between 230 and 350 ng/dL, free or bioavailable testosterone should be checked as they are frequently low when the total is marginal.

The standard range given is based off widely varying ages and, given that testosterone levels naturally decrease as humans age, age-group specific averages should be taken into consideration when discussing treatment between doctor and patient. In men, testosterone falls approximately 1 to 3 percent each year.

- Blood testing

A position statement by the Endocrine Society expressed dissatisfaction with most assays for total, free, and bioavailable testosterone. In particular, research has questioned the validity of commonly administered assays of free testosterone by radioimmunoassay. The free androgen index, essentially a calculation based on total testosterone and sex hormone-binding globulin levels, has been found to be the worst predictor of free testosterone levels and should not be used. Measurement by equilibrium dialysis or mass spectroscopy is generally required for accurately results, particularly for free testosterone which is present normal in such small concentrations.

Ultrasonography of the scrotum is useful when there is a suspicion of some particular diseases. It may detect signs of testicular dysgenesis, which is often related to an impaired spermatogenesis and to a higher risk of testicular cancer. Scrotum ultrasonography may also detect testicular lesions suggestive of malignancy. A decreased testicular vascularization is characteristic of testicular torsion, whereas hyperemia is often observed in epididymo-orchitis or in some malignant conditions such as lymphoma and leukemia. Doppler ultrasonography useful in assessing venous reflux in case of a varicocele, when palpation is unreliable or in detecting recurrence or persistence after surgery, although the impact of its detection and surgical correction on sperm parameters and overall fertility is debated.

Dilation of the head or tail of the epididymis is suggestive of obstruction or inflammation of the male reproductive tract. Such abnormalities are associated with abnormalities in sperm parameters, as are abnormalities in the texture of the epididymis. Scrotal and transrectal ultrasonography (TRUS) are useful in detecting uni- or bilateral congenital absence of the vas deferens (CBAVD), which may be associated with abnormalities or agenesis of the epididymis, seminal vesicles or kidneys, and indicate the need for testicular sperm extraction. TRUS plays a key role in assessing azoospermia caused by obstruction, and detecting distal CBAVD or anomalies related to obstruction of the ejaculatory duct, such as abnormalities within the duct itself, a median cyst of the prostate (indicating a need for cyst aspiration), or an impairment of the seminal vesicles to become enlarged or emptied.

Management of AIS is currently limited to symptomatic management; no method is currently available to correct the malfunctioning androgen receptor proteins produced by "AR" gene mutations. Areas of management include sex assignment, genitoplasty, gonadectomy in relation to tumor risk, hormone replacement therapy, genetic counseling, and psychological counseling.

MAIS is only diagnosed in normal phenotypic males, and is not typically investigated except in cases of male infertility. MAIS has a mild presentation that often goes unnoticed and untreated; even with semenological, clinical and laboratory data, it can be difficult to distinguish between men with and without MAIS, and thus a diagnosis of MAIS is not usually made without confirmation of an AR gene mutation. The androgen sensitivity index (ASI), defined as the product of luteinizing hormone (LH) and testosterone (T), is frequently raised in individuals with all forms of AIS, including MAIS, although many individuals with MAIS have an ASI in the normal range. Testosterone levels may be elevated despite normal levels of luteinizing hormone. Conversion of testosterone (T) to dihydrotestosterone (DHT) may be impaired, although to a lesser extent than is seen in 5α-reductase deficiency. A high ASI in a normal phenotypic male, especially when combined with azoospermia or oligospermia, decreased secondary terminal hair, and/or impaired conversion of T to DHT, can be indicative of MAIS, and may warrant genetic testing.

The diagnosis is often one of exclusion found during the workup of delayed puberty.

A paper published in 2012 by Prof. Jacques Young highlights a typical example of the diagnostic work up involved in a suspected case of KS/CHH.

One of the biggest problems in the diagnosis of KS and other forms of CHH is the ability to distinguish between a normal constitutional delay of puberty and KS or CHH.

The main biochemical parameters in men are low serum testosterone and low levels of the gonadotropins LH and FSH, and in women low serum oestrogen and low levels of LH and FSH.

For both males and females with constitutional delay of puberty, endogenous puberty will eventually commence without treatment. However a delay in treatment in a case of KS/HH will delay the physical development of the patient and can cause severe psychological damage. The "wait and see" approach applied to "late bloomers" is probably counterproductive to the needs of the patient whereas a step-by-step approach with hormone replacement therapy used with slowly increasing doses can be used as a diagnostic tool.

Post natal diagnosis of KS / CHH before the age of 6 months is sometimes possible. The normal post natal hormonal surge of gonadotropins along with testosterone or oestrogen is absent in babies with KS / CHH. This lack of detectable hormones in the blood can be used as a diagnostic indicator, especially in male infants.

Normally testicular enlargement is the key sign for the onset of puberty in boys however the use of nighttime LH sampling can help predict the onset of puberty.

In females diagnosis is sometimes further delayed as other causes of amenorrhoea normally have to be investigated first before a case of KS/CHH is considered. KS/CHH can still occur in females in cases when menstruation has begun but stopped after one or two menstrual bleeds. A study of GnRH deficient women in 2011 showed that 10% had experienced one or two bleeds before the onset of amenorrhoea.

In males, treatment with age-appropriate levels of testosterone can be used to distinguish between a case of KS/CHH from a case of delayed puberty. If just delayed the testosterone can "kick-start" endogenous puberty, as demonstrated by testicular enlargement, whereas in the case of KS/CHH there will be no testicular enlargement while on testosterone therapy alone. If no puberty is apparent, especially no testicular development, then a review by a reproductive endocrinologist may be appropriate. Dr Richard Quinton, a leading UK expert on KS/CHH, suggests that if puberty is not apparent by the age of 16 then the patient should be referred for endocrinological review.

A full endocrine workup will be required to measure the levels of the other pituitary hormones, especially prolactin, to check that the pituitary gland is working correctly. There can be other general health issues such as being overweight or having an underlying chronic or acute illness which could cause a delay of puberty. This makes it essential for a patient to get a full endocrine review to distinguish between a case of KS/CHH and another cause for the pubertal delay.

Bone age can be assessed using hand and wrist X-rays. If the bone age is significantly lower than the chronological age of the patient, this could suggest delayed puberty unless there is another underlying reason for the discrepancy.

A karyotype may be performed to rule out Klinefelter syndrome and Turner syndrome, although the hormones levels would also rule out both these relatively common reasons for hypogonadism.

A magnetic resonance imaging (MRI) scan can be used to determine whether the olfactory bulb is present and to check for any physical irregularities of the pituitary gland or hypothalamus.

A standard smell test can be used to check for anosmia, but it must be remembered that even in total anosmia various substances (such as menthol and alcohol) can still be detected by direct stimulation of the trigeminal nerve.

Genetic screening can be carried out, but in light of the unknown genes involved in the majority of KS and CHH cases, a negative result will not rule out a possible diagnosis.

A review paper published in 2014 highlighted the need for doctors to be aware of the possible diagnosis of KS / HH if pubertal delay is found alongside associated "red flag" symptoms. The symptoms listed in the paper were split into two categories; reproductive symptoms associated with the lack of mini puberty seen between birth and six months of age and non-reproductive symptoms which are associated with specific forms of HH. As with other review papers the authors also warned against the "wait and see" approach when puberty appears to be delayed.

Testing serum LH and FSH levels are often used to assess hypogonadism in women, particularly when menopause is believed to be happening. These levels change during a woman's normal menstrual cycle, so the history of having ceased menstruation coupled with high levels aids the diagnosis of being menopausal. Commonly, the post-menopausal woman is not called hypogonadal if she is of typical menopausal age. Contrast with a young woman or teen, who would have hypogonadism rather than menopause. This is because hypogonadism is an abnormality, whereas menopause is a normal change in hormone levels. In any case, the LH and FSH levels will rise in cases of primary hypogonadism or menopause, while they will be low in women with secondary or tertiary hypogonadism.

Hypogonadism is often discovered during evaluation of delayed puberty, but ordinary delay, which eventually results in normal pubertal development, wherein reproductive function is termed constitutional delay. It may be discovered during an infertility evaluation in either men or women.

In cases where the individual is being evaluated for ambiguous genitalia, such as a small phallus, hypospadias, or labioscrotal folds, exploratory surgery may be used to determine if male and/or female internal genitalia is present.

A standard karyotype can be completed to cytogenetically determine that an individual with a partial or complete male phenotype has a XX genotype.

FISH analysis determines the presence or absence of the SRY gene.

Localization of the SRY gene can by determined using fluorescent "in situ" hybridization.

Indicators include two testes which have not descended the inguinal canal, although this is seen in a minority of XX males, and the absence of Müllerian tissue.

Preimplantation genetic diagnosis (PGD or PIGD) refers to genetic profiling of embryos prior to implantation (as a form of embryo profiling), and sometimes even of oocytes prior to fertilization. When used to screen for a specific genetic sequence, its main advantage is that it avoids selective pregnancy termination, as the method makes it highly likely that a selected embryo will be free of the condition under consideration.

In the UK, AIS appears on a list of serious genetic diseases that may be screened for via PGD. Some ethicists, clinicians, and intersex advocates have argued that screening embryos to specifically exclude intersex traits are based on social and cultural norms as opposed to medical necessity.

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.

Since the Sertoli cells are not affected by Leydig cell hypoplasia, anti-Müllerian hormone is secreted normally and so there are no Müllerian structures. Wolffian structures, such as the prostate, vasa deferentia, and epidydimides are present. In type I, abdominal testes are revealed on ultrasound; in type II testes may be descended or undescended.

People with Leydig cell hypoplasia type I display no response to the hCG stimulation test; there is no increase in serum levels of testosterone and dihydrotestosterone. Leydig cell hypoplasia type II can display either a pronounced rise of testosterone levels or no rise.

In any case, the diagnosis is confirmed on biopsy of the testes, revealing either absent or hypoplastic Leydig cells. The inside of the testis will be grayish and mucous, displaying arrested spermatogenesis and the presence of Sertoli cells. The diagnosis can also be confirmed by looking for mutations in the gene for the LH receptor.

A diagnosis of Leydig cell hypoplasia is usually made in the neonatal period, following the discovery of ambiguous genitalia, or at puberty, when secondary sex characteristics fail to develop. Puberty is the most common time for Leydig cell hypoplasia to be diagnosed.

Conditions justifying newborn screening for any disorder include (1) a simple test with an acceptable sensitivity and specificity, (2) a dire consequence if not diagnosed early, (3) an effective treatment if diagnosed, and (4) a frequency in the population high enough to justify the expense. In the last decade more states and countries are adopting newborn screening for salt-wasting CAH due to 21-hydroxylase deficiency, which leads to death in the first month of life if not recognized.

The salt-wasting form of CAH has an incidence of 1 in 15,000 births and is potentially fatal within a month if untreated. Steroid replacement is a simple, effective treatment. However, the screening test itself is less than perfect. While the 17α-hydroxyprogesterone level is easy to measure and sensitive (rarely missing real cases), the test has a poorer specificity. Screening programs in the United States have reported that 99% of positive screens turn out to be false positives upon investigation of the infant. This is a higher rate of false positives than the screening tests for many other congenital metabolic diseases.

When a positive result is detected, the infant must be referred to a pediatric endocrinologist to confirm or disprove the diagnosis. Since most infants with salt-wasting CAH become critically ill by 2 weeks of age, the evaluation must be done rapidly despite the high false positive rate.

Levels of 17α-hydroxyprogesterone, androstenedione, and cortisol may play a role in screening.

Pre- and post-testicular azoospermia are frequently correctible, while testicular azoospermia is usually permanent. In the former the cause of the azoospermia needs to be considered and it opens up possibilities to manage this situation directly. Thus men with azoospermia due to hyperprolactinemia may resume sperm production after treatment of hyperprolactinemia or men whose sperm production is suppressed by exogenous androgens are expected to produce sperm after cessation of androgen intake. In situations where the testes are normal but unstimulated, gonadotropin therapy can be expected to induce sperm production.

A major advancement in recent years has been the introduction of IVF with ICSI which allows successful fertilization even with immature sperm or sperm obtained directly from testicular tissue. IVF-ICSI allows for pregnancy in couples where the man has irreversible testicular azoospermia as long as it is possible to recover sperm material from the testes. Thus men with non-mosaic Klinefelter's syndrome have fathered children using IVF-ICSI. Pregnancies have been achieved in situations where azoospermia was associated with cryptorchism and sperm where obtained by testicular sperm extraction (TESE).

In men with posttesticular azoospermia a number of approaches are available. For obstructive azoospermia IVF-ICSI or surgery can be used and individual factors need to be considered for the choice of treatment. Medication may be helpful for retrograde ejaculation.

Due to its mild presentation, MAIS often goes unnoticed and untreated. Management of MAIS 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. Treatment includes surgical correction of mild gynecomastia, minor hypospadias repair, and testosterone supplementation. Supraphysiological doses of testosterone have been shown to correct diminished secondary sexual characteristics in men with MAIS, as well as to reverse infertility due to low sperm count. As is the case with PAIS, men with MAIS will experience side effects from androgen therapy (such as the suppression of the hypothalamic-pituitary-gonadal axis) at a higher dosage than unaffected men. Careful monitoring is required to ensure the safety and efficacy of treatment. Regular breast and prostate examinations may be necessary due to comorbid association with breast and prostate cancers.

If both partners are young and healthy and have been trying to conceive for one year without success, a visit to a physician or women's health nurse practitioner (WHNP) could help to highlight potential medical problems earlier rather than later. The doctor or WHNP may also be able to suggest lifestyle changes to increase the chances of conceiving.

Women over the age of 35 should see their physician or WHNP after six months as fertility tests can take some time to complete, and age may affect the treatment options that are open in that case.

A doctor or WHNP takes a medical history and gives a physical examination. They can also carry out some basic tests on both partners to see if there is an identifiable reason for not having achieved a pregnancy. If necessary, they refer patients to a fertility clinic or local hospital for more specialized tests. The results of these tests help determine the best fertility treatment.

Since CAH is an autosomal recessive disease, most children with CAH are born to parents unaware of the risk and with no family history. Each child will have a 25% chance of being born with the disease. Families typically wish to minimize the degree of virilization of a girl. There is no known prenatal harm to a male fetus from CAH, so treatment can begin at birth.

Adrenal glands of female fetuses with CAH begin producing excess testosterone by the 9th week of gestation. The most important aspects of virilization (urogenital closure and phallic urethra) occur between 8 and 12 weeks. Theoretically, if enough glucocorticoid could be supplied to the fetus to reduce adrenal testosterone production by the 9th week, virilization could be prevented and the difficult decision about timing of surgery avoided.

The challenge of preventing severe virilization of girls is twofold: detection of CAH at the beginning of the pregnancy, and delivery of an effective amount of glucocorticoid to the fetus without causing harm to the mother.

The first problem has not yet been entirely solved, but it has been shown that if dexamethasone is taken by a pregnant woman, enough can cross the placenta to suppress fetal adrenal function.

At present no program screens for risk in families who have not yet had a child with CAH. For families desiring to avoid virilization of a second child, the current strategy is to start dexamethasone as soon as a pregnancy has been confirmed even though at that point the chance that the pregnancy is a girl with CAH is only 12.5%. Dexamethasone is taken by the mother each day until it can be safely determined whether she is carrying an affected girl.

Whether the fetus is an affected girl can be determined by chorionic villus sampling at 9–11 weeks of gestation, or by amniocentesis at 15–18 weeks gestation. In each case the fetal sex can be determined quickly, and if the fetus is a male the dexamethasone can be discontinued. If female, fetal DNA is analyzed to see if she carries one of the known abnormal alleles of the "CYP21" gene. If so, dexamethasone is continued for the remainder of the pregnancy at a dose of about 1 mg daily.

Most mothers who have followed this treatment plan have experienced at least mild cushingoid effects from the glucocorticoid but have borne daughters whose genitalia are much less virilized.

Surgery is sometimes performed to alter the appearance of the genitals. However many surgeries performed on intersex people lack clear evidence of necessity, can be considered as mutilating, and are widely considered to be human rights violations when performed without the informed consent of the recipient.

Testicular biopsy would confirm the absence of spermatozoa. Seminal plasma protein TEX101 was proposed for differentiation of Sertoli cell-only syndrome from maturation arrest and hypospermatogenesis. And a clinical trial at Mount Sinai Hospital, Canada started testing this hypothesis in 2016.

Reversal of symptoms have been reported in between 15% to 22% of cases. The causes of this reversal are still under investigation but have been reported in both males and females.

Reversal appears to be associated with 14 of the known gene defects linked to KS/CHH. The study suggests no obvious gene defect showing a tendency to allow reversal. There is a suggestion that the TAC3 and TACR3 mutations might allow for a slightly higher chance of reversal, but the numbers involved are too low to confirm this. The ANOS1 mutations appear to be least likely to allow reversal with to date only one recorded instance in medical literature. Even male patients who previous had micro-phallus or cryptorchidism have been shown to undergo reversal of symptoms.

The reversal might not be permanent and remission can occur at any stage; the paper suggests that this could be linked to stress levels. The paper highlighted a reversal case that went into remission but subsequently achieved reversal again, strongly suggesting an environmental link.

Reversal cases have been seen in cases of both KS and normosmic CHH but appear to be less common in cases of KS (where the sense of smell is also affected). A paper published in 2016 agreed with the theory that there is a strong environmental or epigenetic link to the reversal cases. The precise mechanism of reversal is unclear and is an area of active research.

Reversal would be apparent if testicular development was seen in men while on testosterone therapy alone or in women who menstruate or achieved pregnancy while on no treatment. To date there have been no recorded cases of the reversal of anosmia found in Kallmann syndrome cases.

Female patients may show symptoms of hyperandrogenism in their early life, but physicians become more concerned when the patient is in her late teens or older.

Hyperandrogenism is most often diagnosed by checking for signs of hirsutism according to a standardized method that scores the range of excess hair growth.

Checking medical history and a physical examination of symptoms are used for an initial diagnosis. Patient history assessed includes age at thelarche, adrenarche, and menarche; patterns of menstruation; obesity; reproductive history; and the start and advancement of hyperandrogenism symptoms. Patterns of menstruation are examined since irregular patterns may appear with hirsutism. Family history is also assessed for occurrences of hyperandrogenism symptoms or obesity in other family members.

A laboratory test can also be done on the patient to evaluate levels of FSH, LH, DHEAS, prolactin, 17OHP, and total and free testosterone in the patient's blood. Abnormally high levels of any of these hormones help in diagnosing hyperandrogenism.