Long-term nonprogressors (LTNPs), sometimes also called "elite controllers", are individuals infected with HIV, who maintain a CD4 count greater than 500 without antiretroviral therapy with a detectable viral load. Many of these patients have been HIV positive for 30 years without progressing to the point of needing to take medication in order not to develop AIDS. They have been the subject of a great deal of research, since an understanding of their ability to control HIV infection may lead to the development of immune therapies or a therapeutic vaccine. The classification "Long-term non-progressor" is not permanent, because some patients in this category have gone on to develop AIDS.

Long-term nonprogressors typically have viral loads under 10,000 copies RNA/ml blood, do not take antiretrovirals, and have CD4+ counts within the normal range. Most people with HIV not on medication have viral loads which are much higher.

It is estimated that around 1 in 300 people with HIV are long-term nonprogressors. Without the symptoms of AIDS, many LTNP patients may not know they are infected.

Genetic traits that confer greater resistance or more robust immune response to HIV are thought to explain why LTNP patients are able to live much longer with HIV than patients who are not LTNP. Some LTNP are infected with a weakened or inactive form of HIV, but it is now known that many LTNP patients carry a fully virulent form of the virus. Genetic traits that may affect progression include:

- Gene mutation. A mutation in the FUT2 gene affects the progression of HIV-1 infection. 20% of Europeans who have that mutation are called "non secretor" because of their absence of a certain type of antigen that also provides strong resistance against norovirus.

- Mitochondrial DNA. Different mitochondrial DNA haplotypes in humans may increase or decrease rates of AIDS progression. Haplotypes associated with more loosely coupled mitochondrial respiration, with reduced ATP and ROS generation, have been associated with faster progression and vice versa.

- Receptor mutations. A low percentage of long-term nonprogressors have been shown to have inherited mutations of the CCR5 receptor of T cell lymphocytes. HIV uses CCR5 to enter these cells. It is believed that the Δ32 (delta 32) variant of CCR5 impairs HIV ability to infect cells and cause disease. An understanding of this mechanism led to the development of a class of HIV medicines, the entry inhibitors. The presence of this mutation, however, is not a unifying theme among LTNPs and is observed in an exceedingly small number of these patients.

- HLA type has also been correlated with long-term non-progressor cohorts. In particular, strong correlations have been found between possessing the class 1 HLA-B*5701, HLA-B*5703, and/or HLA-B*2705 alleles and ability to exert control over HIV.

- Antibody production. All individuals with HIV make antibodies against the virus. In most patients, broadly neutralizing antibodies do not emerge until approximately 2–4 years after the initial infection. At this point, the latent reservoir has already been established and the presence of broadly neutralizing antibodies is not enough to prevent disease progression. In some rare patients, these antibodies emerge earlier and can result in a delayed disease course. These patients, however, are not typically classified as LTNPs, but rather as slow progressors, who will eventually develop AIDS. Induction of broadly neutralizing antibodies in healthy individuals is a potential strategy for a preventive HIV vaccine, as is the elicitation of these antibodies through rationally designed immunogens. Direct production of these antibodies in somatic tissue through plasmid transfection also pose a viable method for making these antibodies available in a large number of humans.

- APOBEC3G protein production. In a small number of people infected with HIV, the virus is naturally suppressed without medical treatment. These people may carry high quantities of a protein called APOBEC3G that disrupts viral replication in cells. APOBEC3G, or "A3" for short, is a protein that sabotages reverse transcription, the process HIV relies on for its replication. This process involves the virus transcribing its singe-stranded RNA genome into double-stranded DNA that is incorporated into the cell's genome. A3 usually stops dormant viruses in the human genome, called endogenous retroviruses, from reawakening and causing infections.

HIV is transmitted by three main routes: sexual contact, significant exposure to infected body fluids or tissues, and from mother to child during pregnancy, delivery, or breastfeeding (known as vertical transmission). There is no risk of acquiring HIV if exposed to feces, nasal secretions, saliva, sputum, sweat, tears, urine, or vomit unless these are contaminated with blood. It is possible to be co-infected by more than one strain of HIV—a condition known as HIV superinfection.

HIV can be transmitted from mother to child during pregnancy, during delivery, or through breast milk, resulting in the baby also contracting HIV. This is the third most common way in which HIV is transmitted globally. In the absence of treatment, the risk of transmission before or during birth is around 20% and in those who also breastfeed 35%. As of 2008, vertical transmission accounted for about 90% of cases of HIV in children. With appropriate treatment the risk of mother-to-child infection can be reduced to about 1%. Preventive treatment involves the mother taking antiretrovirals during pregnancy and delivery, an elective caesarean section, avoiding breastfeeding, and administering antiretroviral drugs to the newborn. Antiretrovirals when taken by either the mother or the infant decrease the risk of transmission in those who do breastfeed. However, many of these measures are not available in the developing world. If blood contaminates food during pre-chewing it may pose a risk of transmission.

If a woman is untreated, two years of breastfeeding results in an HIV/AIDS risk in her baby of about 17%. Treatment decreases this risk to 1 to 2% per year. Due to the increased risk of death without breastfeeding in many areas in the developing world, the World Health Organization recommends either: (1) the mother and baby being treated with antiretroviral medication while breastfeeding being continued (2) the provision of safe formula. Infection with HIV during pregnancy is also associated with miscarriage.

The CDC recommends that sexually active men who have sex with men be tested at least yearly. The USPSTF also recommends screening among those at high risk.

Syphilis is a notifiable disease in many countries, including Canada the European Union, and the United States. This means health care providers are required to notify public health authorities, which will then ideally provide partner notification to the person's partners. Physicians may also encourage patients to send their partners to seek care. Several strategies have been found to improve follow-up for STI testing, including email and text messaging as reminders of appointments.

Condom use reduces the likelihood of transmission during sex, but does not completely eliminate the risk. The Centers for Disease Control and Prevention (CDC) states, "Correct and consistent use of latex condoms can reduce the risk of syphilis only when the infected area or site of potential exposure is protected. However, a syphilis sore outside of the area covered by a latex condom can still allow transmission, so caution should be exercised even when using a condom."

Abstinence from intimate physical contact with an infected person is effective at reducing the transmission of syphilis. The CDC states, "The surest way to avoid transmission of sexually transmitted diseases, including syphilis, is to abstain from sexual contact or to be in a long-term mutually monogamous relationship with a partner who has been tested and is known to be uninfected."

The following increase an individual's chances for acquiring VCD:

- Upper airway inflammation (allergic or non-allergic rhinitis, chronic sinusitis, recurrent upper respiratory infections)

- Gastroesophageal reflux disease

- Past traumatic event that involved breathing (e.g. near-drowning, suffocation)

- Severe emotional trauma or distress

- Female gender

- Playing a wind instrument

- Playing a competitive or elite sport

There have been reports of pulmonary venous thromboembolism in pregnant women with sickle cell trait, or men during prolonged airflight, and mild strokes and abnormalities on PET scans in children with the trait.

Sickle cell trait appears to worsen the complications seen in diabetes mellitus type 2 (retinopathy, nephropathy and proteinuria) and provoke hyperosmolar diabetic coma nephropathy, especially in male patients.

The exact cause of VCD is not known, and it is unlikely that a single underlying cause exists. Several contributing factors have been identified, which vary widely among VCD patients with different medical histories. Physical exercise (including, but not limited to, competitive athletics) is one of the major triggers for VCD episodes, leading to its frequent misdiagnosis as exercise-induced asthma. Other triggers include airborne pollutants and irritants such as smoke, dust, gases, soldering fumes, cleaning chemicals such as ammonia, perfumes, and other odours. Gastroesophageal reflux disease (GERD) and rhinosinusitis (inflammation of the paranasal sinuses and nasal cavity) may also play a role in inflaming the airway and leading to symptoms of VCD as discussed below.

Laryngeal hyperresponsiveness is considered the most likely physiologic cause of VCD, brought on by a range of different triggers that cause inflammation and/or irritation of the larynx (voice box). The glottic closure reflex (or laryngeal adductor reflex) serves to protect the airway, and it is possible that this reflex becomes hyperactive in some individuals, resulting in the paradoxical vocal fold closure seen in VCD. Two major causes of laryngeal inflammation and hyperresponsiveness are gastroesophageal reflux disease (GERD) and postnasal drip (associated with rhinosinusitis, allergic or nonallergic rhinitis, or a viral upper respiratory tract infection (URI)). Rhinosinusitis is very common among patients with VCD and for many patients, VCD symptoms are ameliorated when the rhinosinusitis is treated. GERD is also common among VCD patients, but only some experience an improvement in VCD symptoms when GERD is treated. Other causes of laryngeal hyperresponsiveness include inhalation of toxins and irritants, cold and dry air, episodic croup and laryngopharyngeal reflux (LPR).

VCD has long been strongly associated with a variety of psychological or psychogenic factors, including conversion disorder, major depression, obsessive-compulsive disorder, anxiety (especially in adolescents), stress (particularly stress relating to competitive sports), physical and sexual abuse, post-traumatic stress disorder, panic attacks, factitious disorder and adjustment disorder. It is important to note that anxiety and depression may occur in certain patients as a "result" of having VCD, rather than being the cause of it. Psychological factors are important precipitating factors for many patients with VCD; although exercise is also a major trigger for episodes of VCD, some patients experience VCD co-occurring with anxiety regardless of whether or not they are physically active at the time of the VCD/anxiety episode. Experiencing or witnessing a traumatic event related to breathing (such as a near-drowning or life-threatening asthma attack, for example), has also been identified as a risk factor for VCD.

VCD has also been associated with certain neurologic diseases including Arnold-Chiari malformation, cerebral aqueduct stenosis, cortical or upper motor neuron injury (such as that resulting from stroke), amyotrophic lateral sclerosis (ALS), parkinsonism syndromes and other movement disorders. However, this association occurs only rarely.

Cholera has been found in two animal populations: shellfish and plankton.

Transmission is usually through the fecal-oral route of contaminated food or water caused by poor sanitation. Most cholera cases in developed countries are a result of transmission by food, while in the developing world it is more often water. Food transmission can occur when people harvest seafood such as oysters in waters infected with sewage, as "Vibrio cholerae" accumulates in planktonic crustaceans and the oysters eat the zooplankton.

People infected with cholera often have diarrhea, and disease transmission may occur if this highly liquid stool, colloquially referred to as "rice-water", contaminates water used by others. A single diarrheal event can cause a one-million fold increase in numbers of "V. cholerae" in the environment. The source of the contamination is typically other cholera sufferers when their untreated diarrheal discharge is allowed to get into waterways, groundwater or drinking water supplies. Drinking any contaminated water and eating any foods washed in the water, as well as shellfish living in the affected waterway, can cause a person to contract an infection. Cholera is rarely spread directly from person to person.

Both toxic and non-toxic strains exist. Non-toxic strains can acquire toxicity through a temperate bacteriophage.

5α-Reductase is an enzyme that converts testosterone to 5α-dihydrotestosterone (DHT) in peripheral tissues. These enzymes also participate in the creation of such neurosteroids as allopregnanolone and THDOC, convert progesterone into dihydroprogesterone (DHP), and convert deoxycorticosterone (DOC) into dihydrodeoxycorticosterone (DHDOC). 5-ARD is biochemically characterized by low to low-normal levels of testosterone and decreased levels of DHT, creating a higher testosterone/DHT ratio.

DHT is a potent androgen, and is necessary for the development of male external genitalia in utero.

About 100million bacteria must typically be ingested to cause cholera in a normal healthy adult. This dose, however, is less in those with lowered gastric acidity (for instance those using proton pump inhibitors). Children are also more susceptible, with two- to four-year-olds having the highest rates of infection. Individuals' susceptibility to cholera is also affected by their blood type, with those with type O blood being the most susceptible. Persons with lowered immunity, such as persons with AIDS or malnourished children, are more likely to experience a severe case if they become infected. Any individual, even a healthy adult in middle age, can experience a severe case, and each person's case should be measured by the loss of fluids, preferably in consultation with a professional health care provider.

The cystic fibrosis genetic mutation known as delta-F508 in humans has been said to maintain a selective heterozygous advantage: heterozygous carriers of the mutation (who are thus not affected by cystic fibrosis) are more resistant to "V. cholerae" infections. In this model, the genetic deficiency in the cystic fibrosis transmembrane conductance regulator channel proteins interferes with bacteria binding to the intestinal epithelium, thus reducing the effects of an infection.

5α-Reductase deficiency (5-ARD) is an autosomal recessive intersex condition caused by a mutation of the 5α reductase type II gene.

Obesity is one of the leading preventable causes of death worldwide. A number of reviews have found that mortality risk is lowest at a BMI of 20–25 kg/m in non-smokers and at 24–27 kg/m in current smokers, with risk increasing along with changes in either direction. This appears to apply in at least four continents. In contrast, a 2013 review found that grade 1 obesity (BMI 30-35) was not associated with higher mortality than normal weight, and that overweight (BMI 25-30) was associated with "lower" mortality than was normal weight (BMI 18.5-25). Other evidence suggests that the association of BMI and waist circumference with mortality is U- or J-shaped, while the association between waist-to-hip ratio and waist-to-height ratio with mortality is more positive. In Asians the risk of negative health effects begins to increase between 22–25 kg/m. A BMI above 32 kg/m has been associated with a doubled mortality rate among women over a 16-year period. In the United States, obesity is estimated to cause 111,909 to 365,000 deaths per year, while 1 million (7.7%) of deaths in Europe are attributed to excess weight. On average, obesity reduces life expectancy by six to seven years, a BMI of 30–35 kg/m reduces life expectancy by two to four years, while severe obesity (BMI > 40 kg/m) reduces life expectancy by ten years.

A pregnant woman may have intercurrent diseases, defined as disease not directly caused by the pregnancy, but that may become worse or be a potential risk to the pregnancy.

- Diabetes mellitus and pregnancy deals with the interactions of diabetes mellitus (not restricted to gestational diabetes) and pregnancy. Risks for the child include miscarriage, growth restriction, growth acceleration, fetal obesity (macrosomia), polyhydramnios (too much amniotic fluid), and birth defects.

- Thyroid disease in pregnancy can, if uncorrected, cause adverse effects on fetal and maternal well-being. The deleterious effects of thyroid dysfunction can also extend beyond pregnancy and delivery to affect neurointellectual development in the early life of the child. Demand for thyroid hormones is increased during pregnancy which may cause a previously unnoticed thyroid disorder to worsen.

- Untreated celiac disease can cause spontaneous abortion (miscarriage), intrauterine growth restriction, small for gestational age, low birthweight and preterm birth. Often reproductive disorders are the only manifestation of undiagnosed celiac disease and most cases are not recognized. Complications or failures of pregnancy cannot be explained simply by malabsorption, but by the autoimmune response elicited by the exposure to gluten, which causes damage to the placenta. The gluten-free diet avoids or reduces the risk of developing reproductive disorders in pregnant women with celiac disease. Also, pregnancy can be a trigger for the development of celiac disease in genetically susceptible women who are consuming gluten.

- Systemic lupus erythematosus in pregnancy confers an increased rate of fetal death "in utero," spontaneous abortion, and of neonatal lupus.

- Hypercoagulability in pregnancy is the propensity of pregnant women to develop thrombosis (blood clots). Pregnancy itself is a factor of hypercoagulability (pregnancy-induced hypercoagulability), as a physiologically adaptive mechanism to prevent "post partum" bleeding. However, in combination with an underlying hypercoagulable states, the risk of thrombosis or embolism may become substantial.

Obesity increases the risk of many physical and mental conditions. These comorbidities are most commonly shown in metabolic syndrome, a combination of medical disorders which includes: diabetes mellitus type 2, high blood pressure, high blood cholesterol, and high triglyceride levels.

Complications are either directly caused by obesity or indirectly related through mechanisms sharing a common cause such as a poor diet or a sedentary lifestyle. The strength of the link between obesity and specific conditions varies. One of the strongest is the link with type 2 diabetes. Excess body fat underlies 64% of cases of diabetes in men and 77% of cases in women.

Health consequences fall into two broad categories: those attributable to the effects of increased fat mass (such as osteoarthritis, obstructive sleep apnea, social stigmatization) and those due to the increased number of fat cells (diabetes, cancer, cardiovascular disease, non-alcoholic fatty liver disease). Increases in body fat alter the body's response to insulin, potentially leading to insulin resistance. Increased fat also creates a proinflammatory state, and a prothrombotic state.

The chronology of pregnancy is, unless otherwise specified, generally given as gestational age, where the starting point is the woman's last normal menstrual period (LMP), or the corresponding age of the gestation as estimated by a more accurate method if available. Sometimes, timing may also use the fertilization age which is the age of the embryo.

A study of a population of French women from 1670 and 1789 shows that those who married at age 20–24 had 7.0 children on average and 3.7% remained childless. Women who married at age 25–29 years had a mean of 5.7 children and 5.0% remained childless. Women who married at 30–34 years had a mean of 4.0 children and 8.2% remained childless. The average age at last birth in natural fertility populations that have been studied is around 40.

In 1957, a study was done on a large population (American Hutterites) that never used birth control. The investigators measured the relationship between the age of the female partner and fertility. (Infertility rates today are believed to be higher in the general population than for the population in this study from the 1950s.)

This 1957 study found that:

- By age 30, 7% of couples were infertile

- By age 35, 11% of couples were infertile

- By age 40, 33% of couples were infertile

- At age 45, 87% of couples were infertile

Sickle cell trait provides a survival advantage over people with normal hemoglobin in regions where malaria is endemic. The trait is known to cause significantly fewer deaths due to malaria, especially when "Plasmodium falciparum" is the causative organism. This is a prime example of natural selection, evidenced by the fact that the geographical distribution of the gene for hemoglobin S and the distribution of malaria in Africa virtually overlap. Because of the unique survival advantage, people with the trait become increasingly numerous as the number of malaria-infected people increases. Conversely, people who have normal hemoglobin tend to succumb to the complications of malaria.

Although the precise mechanism for this phenomenon is not known, a several factors are believed to be responsible.

- Infected erythrocytes (red blood cells) tend to have lower oxygen tension, because it is significantly reduced by the parasite. This causes sickling of that particular erythrocyte, signalling the phagocytes to get rid of the cell and hence the parasite within.

- Since the sickling of parasite-infected cells is higher, these selectively get removed by the reticulo-endothelial system, thus sparing the normal erythrocytes.

- Excessive vacuole formation occurs in those parasites infecting sickle cells.

- Sickle trait erythrocytes produce higher levels of the superoxide anion and hydrogen peroxide than normal erythrocytes do, both are toxic to malarial parasites.

The sickle cell trait was found to be 50% protective against mild clinical malaria, 75% protective against admission to the hospital for malaria, and almost 90% protective against severe or complicated malaria.

The average age of a young woman's first period (menarche) is 12 to 13 (12.5 years in the United States, 12.72 in Canada, 12.9 in the UK) but, in postmenarchal girls, about 80% of the cycles are anovulatory in the first year after menarche, 50% in the third and 10% in the sixth year. A woman's fertility peaks in her early and mid-20s after which it starts to decline. However, the exact estimates of the chances of a woman to conceive after a certain age are not clear, and are subject to debate.

According to the National Institute for Health and Clinical Excellence over 80 out of every 100 women aged under 40 who have regular unprotected sexual intercourse will get pregnant within 1 year of trying. In the second year the percentage rises to over 90%.

According to a 2004 study by Henri Leridon, PhD, an epidemiologist with the French Institute of Health and Medical Research of women trying to get pregnant, without using fertility drugs or in vitro fertilization.

- At age 30

- 75% will have a conception ending in a live birth within one year

- 91% will have a conception ending in a live birth within four years

- At age 35

- 66% will have a conception ending in a live birth within one year

- 84% will have a conception ending in a live birth within four years

- At age 40

- 44% will have a conception ending in a live birth within one year

- 64% will have a conception ending in a live birth within four years

According to a study done on a sample of 782 healthy European couples ages 19–39, fertility starts declining after age 27 and drops at a somewhat greater rate after age 35. The women were divided into four age groups: 19–26, 27–29, 30–34 and 35–39. Statistical analysis showed that the women in the 27–29 age group had significantly less chance on average of becoming pregnant than did the 19- to 26-year-olds. Pregnancy rates did not change notably between the 27–29 age group and the 30–34 age group, but dropped significantly for the 35–39 age group. The age of the male partner had a significant impact on female fertility among the women who had reached their mid-30s, but not among the younger women. However, experts said the new study was too small and there were too many variables which were too difficult to sort out, for a clear conclusion to be drawn. Some experts suggested that the main change in fertility in the older women was the fact that it took them "longer" to conceive, not necessary that they were significantly more unlikely to eventually succeed. David Dunson, a biostatistician at the U.S. National Institute of Environmental Health Sciences, said that: "Although we noted a decline in female fertility in the late 20s, what we found was a decrease in the probability of becoming pregnant per menstrual cycle, not in the probability of eventually achieving a pregnancy."

A French study found no difference between the fertility rate of women under 25 and those ages 26–30, after which fertility started to decrease. Estimating the "fertility of a woman" is quite difficult because of the male factor (quality of sperm). This French study looked at 2,193 women who were using artificial insemination because their husbands were azoospermic. The cumulative success rates after 12 cycles of insemination were 73% for women under age 25, 74% in women ages 26–30, 61% for ages 31–35, and 54% in the over 35 age group. (Note that the study is from 1982; artificial insemination techniques and success rates have evolved greatly since then.)

In Hungary, a study by the (Central Statistics Office) estimated that 7%–12% of Hungarian women younger than 30 were infertile; 13%–22% of women age 35 were infertile; and 24%–46% of women age 40 were infertile.

The below is a table containing estimates of the percentage of women who, if starting to conceive at a certain age, will fail to obtain a live birth. Note that while for the young ages researchers tend to agree, for older ages there is discrepancy.

Gastrointestinal (GI) complaints and low intensity GI bleeding frequently occur in marathon runners. Strenuous exercise, particularly in elite athlete runners and less frequently in other exercise activities, can cause acute incapacitating gastrointestinal symptoms including heartburn, nausea, vomiting, abdominal pain, diarrhea and gastrointestinal bleeding. Approximately one third of endurance runners experience transient but exercise limiting symptoms, and repetitive gastrointestinal bleeding occasionally causes iron deficiency and anaemia. Runners can sometimes experience significant symptoms including hematemesis. Exercise is associated with extensive changes in gastrointestinal (GI) tract physiology, including diversion of blood flow from the GI tract to muscle and lungs, decreased GI absorption and small intestinal motility, increased colonic transit, neuroimmunoendocrine changes in hormones and peptides such as vasoactive intestinal peptide, secretin and peptide-histidine-methionine. Substantial changes occur in stress hormones including cortisol, in circulating concentrations and metabolic behavior of various leucocytes, and in immunoglobulin levels and major histocompatibility complex expression. Symptoms can be exacerbated by dehydration or by pre-exercise ingestion of certain foods and hypertonic liquids, and lessened by adequate training.

Ingestion of 800 mg of cimetidine 2 hr before running a marathon did not significantly affect the frequency of gastrointestinal symptoms or occult gastrointestinal bleeding. Conversely, 800 mg of cimetidine 1 hr before the start and again at 50 miles of a 100-mile running race substantially decreased GI symptoms and postrace guaiac test positivity but did not affect race performance.

In 2007 the nomenclature of overt, obscure and occult bleeding was clarified.

The common pathway of sexual differentiation, where a productive human female has an XX chromosome pair, and a productive male has an XY pair, is relevant to the development of intersex conditions.

During fertilization, the sperm adds either an X (female) or a Y (male) chromosome to the X in the ovum. This determines the genetic sex of the embryo. During the first weeks of development, genetic male and female fetuses are "anatomically indistinguishable", with primitive gonads beginning to develop during approximately the sixth week of gestation. The gonads, in a "bipotential state", may develop into either testes (the male gonads) or ovaries (the female gonads), depending on the consequent events. Through the seventh week, genetically female and genetically male fetuses appear identical.

At around eight weeks of gestation, the gonads of an XY embryo differentiate into functional testes, secreting testosterone. Ovarian differentiation, for XX embryos, does not occur until approximately Week 12 of gestation. In normal female differentiation, the Müllerian duct system develops into the uterus, Fallopian tubes, and inner third of the vagina.

In males, the Müllerian duct-inhibiting hormone MIH causes this duct system to regress. Next, androgens cause the development of the Wolffian duct system, which develops into the vas deferens, seminal vesicles, and ejaculatory ducts.

By birth, the typical fetus has been completely "sexed" male or female, meaning that the genetic sex (XY-male or XX-female) corresponds with the phenotypical sex; that is to say, genetic sex corresponds with internal and external gonads, and external appearance of the genitals.

Clitoromegaly is a rare condition and can be either present by birth or acquired later in life.

If present at birth, congenital adrenal hyperplasia can be one of the causes, since in this condition the adrenal gland of the female fetus produces additional androgens and the newborn baby has ambiguous genitalia which are not clearly male or female. In pregnant women who received norethisterone during pregnancy, masculinization of the fetus occurs, resulting in hypertrophy of the clitoris; however, this is rarely seen nowadays due to use of safer progestogens. It can also be caused by the autosomal recessive congenital disorder known as Fraser syndrome.

In acquired clitoromegaly, the main cause is endocrine hormonal imbalance affecting the adult woman, including polycystic ovarian syndrome (PCOS) and hyperthecosis. Acquired clitoromegaly may also be caused by pathologies affecting the ovaries and other endocrine glands. These pathologies may include virulent (such as arrhenoblastoma) and neurofibromatosic tumors. Another cause is clitoral cysts. Sometimes there may be no obvious clinical or hormonal reason.

Female bodybuilders and athletes who use androgens, primarily to enhance muscular growth, strength and appearance , may also experience clearly evident enlargement of the clitoris and increases in libido. Women who use testosterone for therapeutic reasons (treating low libido, averting osteoporosis, as part of an anti-depressant regimen, etc.) experience some enlargement of the clitoris, although the dosages warranted for these conditions are much lower. Pseudoclitoromegaly or pseudohypertrophy of the clitoris "has been reported in small girls due to masturbation: manipulations of the skin of prepuce leads to repeated mechanical trauma, which expands the prepuce and labia minora, thus imitating true clitoral enlargement".

Intersex people are born with any of several variations in sex characteristics including chromosomes, gonads, sex hormones, or genitals that, according to the UN Office of the High Commissioner for Human Rights, "do not fit the typical definitions for male or female bodies". Such variations may involve genital ambiguity, and combinations of chromosomal genotype and sexual phenotype other than XY-male and XX-female.

Intersex people were previously referred to as hermaphrodites, "congenital eunuchs", or congenitally "frigid". Such terms have fallen out of favor; in particular, the term "hermaphrodite" is considered to be misleading, stigmatizing, and scientifically specious. Medical description of intersex traits as disorders of sex development has been controversial since the label was introduced in 2006.

Intersex people may face stigmatization and discrimination from birth or discovery of an intersex trait. In some countries, documented in parts of Africa and Asia, this may include infanticide, abandonment and the stigmatization of families. Globally, some intersex infants and children, such as those with ambiguous outer genitalia, are surgically or hormonally altered to create more socially acceptable sex characteristics. However, this is considered controversial, with no firm evidence of good outcomes. Such treatments may involve sterilization. Adults, including elite female athletes, have also been subjects of such treatment. Increasingly these issues are considered human rights abuses, with statements from international and national human rights and ethics institutions. Intersex organizations have also issued statements about human rights violations, including the Malta declaration of the third International Intersex Forum.

In 2011, Christiane Völling became the first intersex person known to have successfully sued for damages in a case brought for non-consensual surgical intervention. In April 2015, Malta became the first country to outlaw non-consensual medical interventions to modify sex anatomy, including that of intersex people.

Some intersex persons may be assigned and raised as a girl or boy but then identify with another gender later in life, while most continue to identify with their assigned sex.

In "Atlas of Human Sex Anatomy (1949)" by Robert Latou Dickinson, the "typical" clitoris is defined as having a crosswise width of 3 to 4 mm (0.12 - 0.16 inches) and a lengthwise width of 4 to 5 mm (0.16 - 0.20 inches). On the other hand, in Obstetrics and Gynecology medical literature, a frequent definition of clitoromegaly is when there is a clitoral index (product of lengthwise and crosswise widths) of greater than 35 mm (0.05 inches), which is almost twice the size given above for an "average" sized clitoral hood.