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.

Several treatments have been found to be effective in managing AES, including aromatase inhibitors and gonadotropin-releasing hormone analogues in both sexes, androgen replacement therapy with non-aromatizable androgens such as DHT in males, and progestogens (which, by virtue of their antigonadotropic properties at high doses, suppress estrogen levels) in females. In addition, male patients often seek bilateral mastectomy, whereas females may opt for breast reduction if warranted.

Medical treatment of AES is not absolutely necessary, but it is recommended as the condition, if left untreated, may lead to excessively large breasts (which may necessitate surgical reduction), problems with fertility, and an increased risk of endometriosis and estrogen-dependent cancers such as breast and endometrial cancers later in life. At least one case of male breast cancer has been reported.

The root cause of AES is not entirely clear, but it has been elucidated that inheritable, autosomal dominant genetic mutations affecting "CYP19A1", the gene which encodes aromatase, are involved in its etiology. Different mutations are associated with differential severity of symptoms, such as mild to severe gynecomastia.

To date at least twenty five different genes have been implicated in causing Kallmann syndrome or other forms of HH through a disruption in the production or activity of GnRH. These genes involved cover all forms of inheritance and no one gene defect has been shown to be common to all cases which makes genetic testing and inheritance prediction difficult.

The number of genes known to cause cases of KS / CHH is still increasing. In addition it is thought that some cases of KS / CHH are caused by two separate gene defects occurring at the same time. Around 50% of cases have an unknown genetic origin.

Some of the genes known to be involved in cases of KS / CHH are listed in the Online Mendelian Inheritance in Man ((OMIM)) table at the end of this article.

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).

Many causes of early puberty are somewhat unclear, though girls who have a high-fat diet and are not physically active or are obese are more likely to physically mature earlier. "Obese girls, defined as at least 10 kilograms (22 pounds) overweight, had an 80 percent chance of developing breasts before their ninth birthday and starting menstruation before age 12 – the western average for menstruation is about 12.7 years." Exposure to chemicals that mimic estrogen (known as xenoestrogens) is a possible cause of early puberty in girls. Bisphenol A, a xenoestrogen found in hard plastics, has been shown to affect sexual development. "Factors other than obesity, however, perhaps genetic and/or environmental ones, are needed to explain the higher prevalence of early puberty in black versus white girls." While more girls are increasingly entering puberty at younger ages, new research indicates that some boys are actually starting later (delayed puberty). "Increasing rates of obese and overweight children in the United States may be contributing to a later onset of puberty in boys, say researchers at the University of Michigan Health System."

High levels of beta-hCG in serum and cerebrospinal fluid observed in a 9-year-old boy suggest a pineal gland tumor. The tumor is called a "chorionic gonadotropin secreting pineal tumor". Radiotherapy and chemotherapy reduced tumor and beta-hCG levels normalized.

In a study using neonatal melatonin on rats, results suggest that elevated melatonin could be responsible for some cases of early puberty.

Familial cases of idiopathic central precocious puberty (ICPP) have been reported, leading researchers to believe there are specific genetic modulators of ICPP. Mutations in genes such as LIN28, and LEP and LEPR, which encode leptin and the leptin receptor, have been associated with precocious puberty. The association between LIN28 and puberty timing was validated experimentally in vivo, when it was found that mice with ectopic overexpression of LIN28 show an extended period of pre-pubertal growth and a significant delay in puberty onset.

Mutations in the kisspeptin (KISS1) and its receptor, KISS1R (also known as GPR54), involved in GnRH secretion and puberty onset, are also thought to be the cause for ICPP However, this is still a controversial area of research, and some investigators found no association of mutations in the LIN28 and KISS1/KISS1R genes to be the common cause underlying ICPP.

The gene MKRN3, which is a maternally imprinted gene, was first cloned by Jong et al in 1999. MKRN3 was originally named Zinc finger protein 127. It is located on human chromosome 15 on the long arm in the Prader-Willi syndrome critical region2, and has since been identified as a cause of premature sexual development or CPP. The identification of mutations in MKRN3 leading to sporadic cases of CPP has been a significant contribution to better understanding the mechanism of puberty. MKRN3 appears to act as a "brake" on the central hypothalamic-pituitary access. Thus, loss of function mutations of the protein allow early activation of the GnRH pathway and cause phenotypic CPP. Patients with a MKRN3 mutation all display the classic signs of CCP including early breast and testes development, increased bone aging and elevated hormone levels of GnRH and LH.

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.

Secondary sexual development induced by sex steroids from other abnormal sources is referred to as "peripheral precocious puberty" or "precocious pseudopuberty." It typically presents as a severe form of disease with children. Symptoms are usually as a sequelae from adrenal insufficiency (because of 21-hydroxylase deficiency or 11-beta hydroxylase deficiency, the former being more common), which includes but is not limited to hypertension, hypotension, electrolyte abnormalities, ambiguous genitalia in females, signs of virilization in females. Blood tests will typically reveal high level of androgens with low levels of cortisol.

Causes can include:

- Endogenous sources

- gonadal tumors (such as arrhenoblastoma),

- adrenal tumors,

- germ cell tumor,

- congenital adrenal hyperplasia,

- McCune–Albright syndrome,

- Exogenous hormones

- Environmental exogenous hormones,

- As treatment for another condition.

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.

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

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.

It has been estimated that POF affects 1% of the female population.

In contrast to EIS, androgen insensitivity syndrome (AIS), a condition in which the androgen receptor (AR) is defective, is relatively common. This can be explained by the genetics of each syndrome. AIS is a X-linked recessive condition and thus carried over, by females, into future generations (although the most severe form, complete androgen insensitivity syndrome (CAIS), results in sterility, and hence cannot be passed on to offspring). EIS is not compatible with reproduction, thus each occurrence in humans would have to be a "de novo" mutation and is not transmitted to offspring.

IHH is divided into two syndromes: IHH with olfactory alterations or anosmia, Kallmann syndrome and IHH with normal smell (normosmic IHH).

Kallmann syndrome is responsible for approximately 50% of all cases of the condition. It is associated with mutations in "KAL1", "FGFR1/FGF8", "FGF17", "IL17RD", "PROKR2", "NELF", "CHD7"(which positively regulates GnRH secretion), HS6ST1, "FLRT3", "SPRY4", DUSP6, "SEMA3A", and "WDR11 (gene)", genes which are related to defects in neuronal migration.

Gene defects associated with IHH and normal smell include "PROKR2, FGFR1, FGF8, CHD7, DUSP6," and "WDR11", as in KS, but in addition

also mutations in "KISS1R", "TACR3", GNRH1/GNRHR, LEP/LEPR, HESX1, FSHB, and LHB.

GnRH insensitivity is the second most common cause of IHH, responsible for up to 20% of cases.

A minority of less than 5-10% is due to inactivating mutations in genes which positively regulate GnRH secretion such as ,"CHD7", "KISS1R", and "TACR3".

The causes of about 25% of all IHH cases are still unknown.

Isolated hypogonadotropic hypogonadism (IHH), also called idiopathic or congenital hypogonadotropic hypogonadism (CHH), as well as isolated or congenital gonadotropin-releasing hormone deficiency (IGD) constitutes a small subset of cases of hypogonadotropic hypogonadism (HH).

IHH is due to deficiency in or insensitivity to gonadotropin-releasing hormone (GnRH), where the function and anatomy of the anterior pituitary is otherwise normal, and secondary causes of HH are not present.

Hypogonadotropic hypogonadism (HH), also known as secondary or central hypogonadism, as well as gonadotropin-releasing hormone deficiency or gonadotropin deficiency (GD), is a medical condition characterized by hypogonadism due to an impaired secretion of gonadotropins, including follicle-stimulating hormone (FSH) and luteinizing hormone (LH), by the pituitary gland in the brain, and in turn decreased gonadotropin levels and a resultant lack of sex steroid production.

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).

The prevalence of PCOS depends on the choice of diagnostic criteria. The World Health Organization estimates that it affects 116 million women worldwide as of 2010 (3.4% of women). One community-based prevalence study using the Rotterdam criteria found that about 18% of women had PCOS, and that 70% of them were previously undiagnosed.

Ultrasonographic findings of polycystic ovaries are found in 8–25% of normal women. 14% women on oral contraceptives are found to have polycystic ovaries. Ovarian cysts are also a common side effect of intrauterine devices (IUDs).

A diagnosis of PCOS suggests an increased risk of the following:

- Endometrial hyperplasia and endometrial cancer (cancer of the uterine lining) are possible, due to overaccumulation of uterine lining, and also lack of progesterone resulting in prolonged stimulation of uterine cells by estrogen. It is not clear whether this risk is directly due to the syndrome or from the associated obesity, hyperinsulinemia, and hyperandrogenism.

- Insulin resistance/Type II diabetes. A review published in 2010 concluded that women with PCOS have an elevated prevalence of insulin resistance and type II diabetes, even when controlling for body mass index (BMI). PCOS also makes a woman, particularly if obese, prone to gestational diabetes.

- High blood pressure, in particular if obese or during pregnancy

- Depression and anxiety

- Dyslipidemia – disorders of lipid metabolism — cholesterol and triglycerides. Women with PCOS show a decreased removal of atherosclerosis-inducing remnants, seemingly independent of insulin resistance/Type II diabetes.

- Cardiovascular disease, with a meta-analysis estimating a 2-fold risk of arterial disease for women with PCOS relative to women without PCOS, independent of BMI.

- Strokes

- Weight gain

- Miscarriage

- Sleep apnea, particularly if obesity is present

- Non-alcoholic fatty liver disease, again particularly if obesity is present

- Acanthosis nigricans (patches of darkened skin under the arms, in the groin area, on the back of the neck)

- Autoimmune thyroiditis

Early diagnosis and treatment may reduce the risk of some of these, such as type 2 diabetes and heart disease.

The risk of ovarian cancer and breast cancer is not significantly increased overall.

Based on its cause, the type of hypogonadotropic hypogonadism (HH) may be classified as either "primary" or "secondary".

"Primary" HH, also called isolated hypogonadotropic hypogonadism, is responsible for only a small subset of cases of HH, and is characterized by an otherwise normal function and anatomy of the hypothalamus and anterior pituitary. It is caused by congenital disorders such as Kallmann syndrome, CHARGE syndrome, and gonadotropin-releasing hormone insensitivity.

"Secondary" HH, also known as acquired or syndromic HH, is far more common than primary HH, and responsible for most cases of the condition. It has a multitude of different causes, including brain or pituitary tumors, pituitary apoplexy, head trauma, ingestion of certain drugs, and certain systemic diseases and syndromes.

Primary and secondary HH can also be attributed to a genetic trait inherited from the biologic parents. For example, the male mutations of the GnRH coding gene could result in HH. Hormone replacement can be used to initiate puberty and continue if the gene mutation occurs in the gene coding for the hormone. Chromosomal mutations tend to affect the androgen production rather than the HPG axis.

Hirsutism can be caused by either an increased level of androgens, the male hormones, or an oversensitivity of hair follicles to androgens. Male hormones such as testosterone stimulate hair growth, increase size and intensify the growth and pigmentation of hair. Other symptoms associated with a high level of male hormones include acne, deepening of the voice, and increased muscle mass. The condition is called hyperandrogenism.

Growing evidence implicates high circulating levels of insulin in women for the development of hirsutism. This theory is speculated to be consistent with the observation that obese (and thus presumably insulin resistant hyperinsulinemic) women are at high risk of becoming hirsute. Further, treatments that lower insulin levels will lead to a reduction in hirsutism.

It is speculated that insulin, at high enough concentration, stimulates the ovarian theca cells to produce androgens. There may also be an effect of high levels of insulin to activate insulin-like growth factor 1 (IGF-1) receptor in those same cells. Again, the result is increased androgen production.

Signs that are suggestive of an androgen-secreting tumor in a patient with hirsutism is rapid onset, virilization and palpable abdominal mass.

The following are conditions and situations that have been associated with hyperandrogenism and hence hirsutism in women:

- Hyperinsulinemia (insulin excess) or hypoinsulinemia (insulin deficiency or resistance as in diabetes).

- Ovarian cysts such as in polycystic ovary syndrome (PCOS), the most common cause in women.

- Ovarian tumors such as granulosa tumors, thecomas, Sertoli–Leydig cell tumors (androblastomas), and gynandroblastomas, as well as ovarian cancer.

- Hyperthecosis.

- Pregnancy.

- Adrenal gland tumors, adrenocortical adenomas, and adrenocortical carcinoma, as well as adrenal hyperplasia due to pituitary adenomas (as in Cushing's syndrome).

- hCG-secreting tumors

- Inborn errors of steroid metabolism such as in congenital adrenal hyperplasia, most commonly caused by 21-hydroxylase deficiency.

- Acromegaly and gigantism (growth hormone and IGF-1 excess), usually due to pituitary tumors.

- Use of certain medications such as androgens/anabolic steroids, phenytoin, and minoxidil.

Causes of hirsutism not related to hyperandrogenism include:

- Porphyria cutanea tarda.

- Minoxidil

Hormone replacement therapy with estrogen may be used to treat symptoms of hypoestrogenism in females with the condition. There are currently no known treatments for the infertility caused by the condition in either sex.

Idiopathic azoospermia is where there is no known cause of the condition. It may be a result of multiple risk factors, such as age and weight. For example, 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. The review found no significant relation between oligospermia and being underweight.

Isolated hypogonadotropic hypogonadism (IHH), also called idiopathic or congenital hypogonadotropic hypogonadism (CHH), as well as isolated or congenital gonadotropin-releasing hormone deficiency (IGD), is a condition which results in a small subset of cases of hypogonadotropic hypogonadism (HH) due to deficiency in or insensitivity to gonadotropin-releasing hormone (GnRH) where the function and anatomy of the anterior pituitary is otherwise normal and secondary causes of HH are not present.

Approximately 10–25 percent of cases are estimated to result from the use of medications. This is known as non-physiologic gynecomastia. Medications known to cause gynecomastia include ketoconazole, cimetidine, gonadotropin-releasing hormone analogues, human growth hormone, human chorionic gonadotropin, 5α-Reductase inhibitors such as finasteride and dutasteride, estrogens such as those used in transgender women and men with prostate cancer, and antiandrogens such as bicalutamide, flutamide, and spironolactone. Medications that are probably associated with gynecomastia include calcium channel blockers such as verapamil, amlodipine, and nifedipine; risperidone, olanzapine, anabolic steroids, alcohol, opioids, efavirenz, alkylating agents, and omeprazole. Certain components of personal care products such as lavender or tea tree oil and certain supplements such as dong quai and "Tribulus terrestris" have been associated with gynecomastia.

Hirsutism affects members of any gender, since rising androgen levels can cause excessive body hair, particularly in locations where women normally do not develop terminal hair during puberty (chest, abdomen, back, and face). The medical term for excessive hair growth that affects any gender is hypertrichosis.