Early puberty is believed to put girls at higher risk of sexual abuse, unrelated to pedophilia because the child has developed secondary sex characteristics; however, a causal relationship is, as yet, inconclusive. Early puberty also puts girls at a higher risk for teasing or bullying, mental health disorders and short stature as adults. Helping children control their weight is suggested to help delay puberty. Early puberty additionally puts girls at a "far greater" risk for breast cancer later in life. Girls as young as 8 are increasingly starting to menstruate, develop breasts and grow pubic and underarm hair; these "biological milestones" typically occurred only at 13 or older in the past. African-American girls are especially prone to early puberty. There are theories debating the trend of early puberty, but the exact causes are not known.

Though boys face fewer problems upon early puberty than girls, early puberty is not always positive for boys; early sexual maturation in boys can be accompanied by increased aggressiveness due to the surge of hormones that affect them. Because they appear older than their peers, pubescent boys may face increased social pressure to conform to adult norms; society may view them as more emotionally advanced, although their cognitive and social development may lag behind their appearance. Studies have shown that early maturing boys are more likely to be sexually active and are more likely to participate in risky behaviours.

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.

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.

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

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.

Factors that can cause male as well as female infertility are:

- DNA damage

- DNA damage reduces fertility in female ovocytes, as caused by smoking, other xenobiotic DNA damaging agents (such as radiation or chemotherapy) or accumulation of the oxidative DNA damage 8-hydroxy-deoxyguanosine

- DNA damage reduces fertility in male sperm, as caused by oxidative DNA damage, smoking, other xenobiotic DNA damaging agents (such as drugs or chemotherapy) or other DNA damaging agents including reactive oxygen species, fever or high testicular temperature

- General factors

- Diabetes mellitus, thyroid disorders, undiagnosed and untreated coeliac disease, adrenal disease

- Hypothalamic-pituitary factors

- Hyperprolactinemia

- Hypopituitarism

- The presence of anti-thyroid antibodies is associated with an increased risk of unexplained subfertility with an odds ratio of 1.5 and 95% confidence interval of 1.1–2.0.

- Environmental factors

- Toxins such as glues, volatile organic solvents or silicones, physical agents, chemical dusts, and pesticides. Tobacco smokers are 60% more likely to be infertile than non-smokers.

German scientists have reported that a virus called Adeno-associated virus might have a role in male infertility, though it is otherwise not harmful. Other diseases such as chlamydia, and gonorrhea can also cause infertility, due to internal scarring (fallopian tube obstruction).

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.

Prevalence of infertility varies depending on the definition, i.e. on the time span involved in the failure to conceive.

- Infertility rates have increased by 4% since the 1980s, mostly from problems with fecundity due to an increase in age.

- Fertility problems affect one in seven couples in the UK. Most couples (about 84%) who have regular sexual intercourse (that is, every two to three days) and who do not use contraception get pregnant within a year. About 92 out of 100 couples who are trying to get pregnant do so within two years.

- Women become less fertile as they get older. For women aged 35, about 94% who have regular unprotected sexual intercourse get pregnant after three years of trying. For women aged 38, however, only about 77%. The effect of age upon men's fertility is less clear.

- In people going forward for IVF in the UK, roughly half of fertility problems with a diagnosed cause are due to problems with the man, and about half due to problems with the woman. However, about one in five cases of infertility has no clear diagnosed cause.

- In Britain, male factor infertility accounts for 25% of infertile couples, while 25% remain unexplained. 50% are female causes with 25% being due to anovulation and 25% tubal problems/other.

- In Sweden, approximately 10% of couples wanting children are infertile. In approximately one third of these cases the man is the factor, in one third the woman is the factor, and in the remaining third the infertility is a product of factors on both parts.

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.

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.

Deficiency of sex hormones can result in defective primary or secondary sexual development, or withdrawal effects (e.g., premature menopause) in adults. Defective egg or sperm development results in infertility. The term hypogonadism usually means permanent rather than transient or reversible defects, and usually implies deficiency of reproductive hormones, with or without fertility defects. The term is less commonly used for infertility without hormone deficiency. There are many possible types of hypogonadism and several ways to categorize them. Hypogonadism is also categorized by endocrinologists by the level of the reproductive system that is defective. Physicians measure gonadotropins (LH and FSH) to distinguish primary from secondary hypogonadism. In primary hypogonadism the LH and/or FSH are usually elevated, meaning the problem is in the testicles, whereas in secondary hypogonadism, both are normal or low, suggesting the problem is in the brain.

Hypogonadism can involve just hormone production or just fertility, but most commonly involves both.

- Examples of hypogonadism that affect hormone production more than fertility are hypopituitarism and Kallmann syndrome; in both cases, fertility is reduced until hormones are replaced but can be achieved solely with hormone replacement.

- Examples of hypogonadism that affect fertility more than hormone production are Klinefelter syndrome and Kartagener syndrome.

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.

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.

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.

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.

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.

Familial male-limited precocious puberty, often abbreviated as FMPP, also known as familial sexual precocity or gonadotropin-independent testotoxicosis, is a form of gonadotropin-independent precocious puberty in which boys experience early onset and progression of puberty. Signs of puberty can develop as early as an age of 1 year.

The spinal length in boys may be short due to a rapid advance in epiphyseal maturation. It is an autosomal dominant condition with a mutation of the luteinizing hormone (LH) receptor. Treatment is with drugs that suppress gonadal steroidogenesis, such as cyproterone acetate, ketoconazole, spironolactone, and testolactone. Alternatively, the combination of the androgen receptor antagonist bicalutamide and the aromatase inhibitor anastrozole may be used.

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.

Presentations of low estrogen levels include hot flashes, headaches, lowered libido, and breast atrophy. Reduced bone density leading to secondary osteoporosis and atrophic changes such as pH change in the vagina is also linked to hypoestrogenism.

Low levels of estrogen can lead to dyspareunia and limited genital arousal because of changes in the four layers of the vaginal wall.

Hypoestrogenism is also considered one of the major risk factors for developing uncomplicated urinary tract infections (UTIs) in postmenopausal women who do not take hormone replacement therapy.

Hyperestrogenism can be caused by ovarian tumors, genetic conditions such as aromatase excess syndrome (also known as familial hyperestrogenism), or overconsumption of exogenous sources of estrogen, including medications used in hormone replacement therapy and hormonal contraception. Liver cirrhosis is another cause, though through lowered metabolism of estrogen, not oversecretion or overconsumption like the aforementioned.

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.

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.

Hypoestrogenism, or estrogen deficiency, refers to a lower than normal level of estrogen, the primary sex hormone in women. In general, lower levels of estrogen may cause differences in the breasts, genitals, urinary tract, and skin.

Hypoestrogenism is most commonly found in women who are postmenopausal, have premature ovarian failure, or are suffering from amenorrhea; however, it is also associated with hyperprolactinemia and the use of gonadotropin-releasing hormone (GnRH) analogues in treatment of endometriosis. It has also been linked to scoliosis and young women with type 1 diabetes mellitus.