Sarcoidosis is a systemic disease of unknown cause that results in the formation of non-caseating granulomas in multiple organs. The prevalence is higher among blacks than whites by a ratio of 20:1. Usually the disease is localized to the chest, but urogenital involvement is found in 0.2% of clinically diagnosed cases and 5% of those diagnosed at necropsy. The kidney is the most frequently affected urogenital organ, followed in men by the epididymis. Testicular sarcoidosis can present as a diffuse painless scrotal mass or can mimic acute epididymo-orchitis. Usually it appears with systemic manifestations of the disease. Since it causes occlusion and fibrosis of the ductus epididymis, fertility may be affected. On ultrasound, the hypoechogenicity and ‘infiltrative’ pattern seen in the present case are recognized features. Opinions differ on the need for histological proof, with reports of limited biopsy and frozen section, radical orchiectomy in unilateral disease and unilateral orchiectomy in bilateral disease. The peak incidence of sarcoidosis and testicular neoplasia coincide at 20–40 years and this is why most patients end up having an orchiectomy. However, testicular tumours are much more common in white men, less than 3.5% of all testicular tumours being found in black men. These racial variations justify a more conservative approach in patients of descent with proven sarcoidosis elsewhere. Careful follow-up and ultrasonic surveillance may be preferable in certain clinical settings to biopsy and surgery, especially in patients with bilateral testicular disease.

Two main approaches to genitourinary sarcoidosis have been proposed. Based on the marked relationship between testicular cancer and sarcoidosis, orchiectomy is recommended, even if evidence of sarcoidosis in other organs is present. By contrast, others consider immediate orchiectomy as being quite aggressive because of several factors associated with a benign diagnosis, as well as the involvement of the epididymis or vas deferens and bilateral testicular involvement. If the malignant diagnosis is established by exploration and intraoperative ultrasound-guided biopsy, orchiectomy is performed in cases of diffuse involvement of a testis. Spontaneous resolution has been reported in 50% to 70% of patients with active sarcoidosis. If the diagnosis is not established unequivocally, immunosuppressive agents (frequently steroids) will resolve the inflammation in patients who wish to salvage their fertility; and in those with severely advanced disease, after careful consideration.

A new approach has been proposed recently, based on the absence of evidence for malignant transformation in pathologically confirmed benign diagnosed testicular sarcoidosis, and it involves the open exploration of both testes, with resection of the largest lesion (on the right tunica). In this technique, patient was not given steroids after the operation. Nevertheless, careful follow-up may be preferred to medication or surgery in certain clinical settings.

Links between maternal smoking and TDS are tenuous, but there are stronger associations between maternal alcohol consumption and incidences of cryptorchidism in sons. Smoking does however affect the growth of a fetus, and low birth weight is shown to increase the likelihood of all the disorders encompassed by TDS. Maternal obesity, resulting in gestational diabetes, has also been shown to be a risk factor for impaired testes development and TDS symptoms in sons.

Most cases of polyorchidism are asymptomatic, and are discovered incidentally, in the course of treating another condition. In the majority of cases, the supernumerary testicle is found in the scrotum.

However, polyorchidism can occur in conjunction with cryptorchidism, where the supernumerary testicle is undescended or found elsewhere in the body. These cases are associated with a significant increase in the incidence of testicular cancer: 0.004% for the general population vs 5.7% for a supernumerary testicle not found in the scrotum.

Polyorchidism can also occur in conjunction with infertility, inguinal hernia, testicular torsion, epididymitis, hydrocele testis and varicocele. However, it is not clear whether polyorchidism causes or aggravates these conditions, or whether the existence of these conditions leads sufferers to seek medical attention and thus become diagnosed with a previously undetected supernumerary testicle.

Of the phenomena occurring in neurosarcoid, only facial nerve involvement is known to have a good prognosis and good response to treatment. Long-term treatment is usually necessary for all other phenomena. The mortality rate is estimated at 10%

The disease can remit spontaneously or become chronic, with exacerbations and remissions. In some persons, it can progress to pulmonary fibrosis and death. About half of cases resolve without treatment or can be cured within 12–36 months, and most within five years. Some cases, however, may persist several decades. Two-thirds of people with the condition achieve a remission within 10 years of the diagnosis. When the heart is involved, the prognosis is generally less favourable, though corticosteroids appear effective in improving AV conduction. The prognosis tends to be less favourable in African Americans than in white Americans.

Some 1990s studies indicated that persons with sarcoidosis appear to be at significantly increased risk for cancer, in particular lung cancer, lymphomas, and cancer in other organs known to be affected in sarcoidosis. In sarcoidosis-lymphoma syndrome, sarcoidosis is followed by the development of a lymphoproliferative disorder such as non-Hodgkin lymphoma. This may be attributed to the underlying immunological abnormalities that occur during the sarcoidosis disease process. Sarcoidosis can also follow cancer or occur concurrently with cancer. There have been reports of hairy cell leukemia, acute myeloid leukemia, and acute myeloblastic leukemia associated with sarcoidosis.

Sometimes, sarcoidosis, even untreated, can be complicated by opportunistic infections.

Orchitis is not rare in bulls and rams.

It has also been described in roosters.

A major risk factor for the development of testis cancer is cryptorchidism (undescended testicles). It is generally believed that the presence of a tumor contributes to cryptorchidism; when cryptorchidism occurs in conjunction with a tumor then the tumor tends to be large. Other risk factors include inguinal hernias, Klinefelter syndrome, and mumps orchitis. Physical activity is associated with decreased risk and sedentary lifestyle is associated with increased risk. Early onset of male characteristics is associated with increased risk. These may reflect endogenous or environmental hormones.

Higher rates of testicular cancer in Western nations have been linked to the use of cannabis.

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

Exposure of a male fetus to substances that disrupt hormone systems, particularly chemicals that inhibit the action of androgens (male sex hormones) during the development of the reproductive system, has been shown to cause many of the characteristic TDS disorders. These include environmental estrogens and anti-androgens found in food and water sources that have been contaminated with synthetic hormones and pesticides used in agriculture. In historical cases, medicines given to pregnant women, like diethylstilbestrol (DES), have caused many of the features of TDS in fetuses exposed to this chemical during gestation. The impact of environmental chemicals is well documented in animal models. If a substance affects Sertoli and Leydig cell differentiation (a common feature of TDS disorders) at an early developmental stage, germ cell growth and testosterone production will be impaired. These processes are essential for testes descent and genitalia development, meaning that genital abnormalities like cryptorchidism or hypospadias may be present from birth, and fertility problems and TGCC become apparent during adult life. Severity or number of disorders may therefore be dependent on the timing of the environmental exposure. Environmental factors can act directly, or via epigenetic mechanisms, and it is likely that a genetic susceptibility augmented by environmental factors is the primary cause of TDS.

The heritability of sarcoidosis varies according to ethnicity. About 20% of African Americans with sarcoidosis have a family member with the condition, whereas the same figure for European Americans is about 5%. Additionally, in African Americans, who seem to experience more severe and chronic disease, siblings and parents of sarcoidosis cases have about a 2.5-fold increased risk for developing the disease. Investigations of genetic susceptibility yielded many candidate genes, but only few were confirmed by further investigations and no reliable genetic markers are known. Currently, the most interesting candidate gene is "BTNL2"; several "HLA-DR" risk alleles are also being investigated. In persistent sarcoidosis, the HLA haplotype "HLA-B7-DR15" are either cooperating in disease or another gene between these two loci is associated. In nonpersistent disease, there is a strong genetic association with HLA DR3-DQ2. Cardiac sarcoid has been connected to TNFA variants.

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.

Because polyorchidism is very uncommon, there is no standard treatment for the condition. Prior to advances in ultrasound technology, it was common practice to remove the supernumerary testicle. Several cases have been described where routine follow-up examinations conducted over a period of years showed that the supernumerary testicle was stable.

A meta-analysis in 2009 suggested removing non-scrotal supernumerary testicles because of the increased risk of cancer, and regular follow-up in the remaining cases to ensure that the supernumerary testicle remains stable.

Testicular microlithiasis is an unusual condition diagnosed on testicular ultrasound. It is found in between 1.5 to 5% of normal males, and may be found in up to 20% of individuals with subfertility. It is an asymptomatic, non-progressive disease. The cause is unknown, but this condition has been associated with testicular cancer in a small group of individuals, cryptorchidism, mumps, infertility and intraepithelial germ cell neoplasia. Classic testicular microlithiasis is defined as five or more echogenic foci per view in either or both testes, and limited testicular microlithiasis defined as one or more echogenic foci that do not satisfy the criteria for classic testicular microlithiasis. In 80% of cases, both testicles are affected.

Testicular microlithiasis is not associated with risk of testicular cancer in asymptomatic individuals with no risk factors for testicular germ cell tumor. However, a large meta-analysis has shown that in individuals with associated risk factors for testicular germ cell tumor, the increase in risk of concurrent diagnosis of testicular germ cell tumor, or testicular carcinoma-in-situ upon biopsy is approximately eight to ten-fold.

There is extensive controversy over whether testicular microlithiasis in individuals with testicular germ cell tumor, or risk factors for such, should undergo testicular biopsy to exclude the presence of testicular carcinoma-in-situ, also known as intratubular germ cell neoplasia of unclassified type. Additionally, whether the presence of testicular microlithiasis should influence decision for adjuvant chemotherapy or surveillance in individuals with testicular germ cell tumor remains unclear. A recent review in Nature Reviews Urology has comprehensively evaluated these topics.

There is no cure or treatment for testicular microlithiasis, however, patients may be monitored via ultrasound to make sure that other conditions do not develop. Emphasis on testicular examination is the recommended follow up for asymptomatic men incidentally identified with testicular microlithiasis. For men with risk factors for testicular germ cell tumor such as subfertility however, individualized discussion with their urologists is necessary.

Sarcoidosis has a prevalence of 40 per 100,000 in the general population. However, though those with the GG genotype at rs1049550 in the ANXA11 gene were found to have 1.5-2.5 times higher odds of sarcoidosis compared to those with the AG genotype, while those with the AA genotype had about 1.6 times lower odds. Furthermore, those with Common Variable Immunodeficiency (CVID) may be at even higher risk. One study of 80 CVID patients found 8 of these had sarcoidosis, suggesting as high a prevalence in CVID populations as 1 in 10. Given that less than 10% of those with sarcoidosis will have neurological involvement, and possibly later on in their disease course, neurosarcoidosis has a prevalence of less than 4 per 100,000.

Sarcoidosis most commonly affects young adults of both sexes, although studies have reported more cases in females. Incidence is highest for individuals younger than 40 and peaks in the age-group from 20 to 29 years; a second peak is observed for women over 50.

Sarcoidosis occurs throughout the world in all races with an average incidence of 16.5/100,000 in men and 19/100,000 in women. The disease is most prevalent in Northern European countries and the highest annual incidence of 60/100,000 is found in Sweden and Iceland. In the United States sarcoidosis is more common in people of African descent than Caucasians, with annual incidence reported as 35.5 and 10.9/100,000, respectively. Sarcoidosis is less commonly reported in South America, Spain, India, Canada, and the Philippines. There may be a higher susceptibility to sarcoidosis in those with coeliac disease. An association between the two disorders has been suggested.

The differing incidence across the world may be at least partially attributable to the lack of screening programs in certain regions of the world and the overshadowing presence of other granulomatous diseases, such as tuberculosis, that may interfere with the diagnosis of sarcoidosis where they are prevalent.

There may also be differences in the severity of the disease between people of different ethnicities. Several studies suggest that the presentation in people of African origin may be more severe and disseminated than for Caucasians, who are more likely to have asymptomatic disease.

Manifestation appears to be slightly different according to race and sex. Erythema nodosum is far more common in men than in women and in Caucasians than in other races. In Japanese patients, ophthalmologic and cardiac involvement are more common than in other races.

Sarcoidosis is one of the few pulmonary diseases with a higher prevalence in non-smokers.

Epididymitis makes up 1 in 144 visits for medical care (0.69 percent) in men 18 to 50 years old or 600,000 cases in males between 18 and 35 in the United States.

It occurs primarily in those 16 to 30 years of age and 51 to 70 years. As of 2008 there appears to be an increase in incidences in the United States that parallels an increase in reported cases of chlamydia and gonorrhea.

Fournier's gangrene ( an aggressive and rapidly spreading infection of the perineum ) usually presents with fever and intense pain. It is a rare condition but fatal if not identified and aggressively treated with a combination of surgical debridement and broad spectrum antibiotics.

Most testicular germ cell tumors have too many chromosomes, and most often they are triploid to tetraploid. An isochromosome 12p (the short arm of chromosome 12 on both sides of the same centromere) is present in about 80% of the testicular cancers, and also the other cancers usually have extra material from this chromosome arm through other mechanisms of genomic amplification.

Though urinary tract infections in men are rare, bacterial infection is the most common cause of acute epididymitis. The bacteria in the urethra back-track through the urinary and reproductive structures to the epididymis. In rare circumstances, the infection reaches the epididymis via the bloodstream.

In sexually active men, "Chlamydia trachomatis" is responsible for two-thirds of acute cases, followed by "Neisseria gonorrhoeae" and "E. coli" (or other bacteria that cause urinary tract infection). Particularly among men over age 35 in whom the cause is "E. coli", epididymitis is commonly due to urinary tract obstruction. Less common microbes include "Ureaplasma", Mycobacterium, and "cytomegalovirus", or "Cryptococcus" in patients with HIV infection. "E. coli" is more common in boys before puberty, the elderly, and men who have sex with men. In the majority of cases in which bacteria are the cause, only one side of the scrotum or the other is the locus of pain.

Non-infectious causes are also possible. Reflux of sterile urine (urine without bacteria) through the ejaculatory ducts may cause inflammation with obstruction. In children, it may be a response following an infection with enterovirus, adenovirus or "Mycoplasma pneumoniae". Rare non-infectious causes of chronic epididymitis include sarcoidosis (more prevalent in black men) and Behçet's disease.

Any form of epididymitis can be caused by genito-urinary surgery, including prostatectomy and urinary catheterization. Congestive epididymitis is a long-term complication of vasectomy. Chemical epididymitis may also result from drugs such as amiodarone.

Epididymitis occurs when there is inflammation of the epididymis (a curved structure at the back of the testicle). This condition usually presents with gradual onset of varying degrees of pain, and the scrotum may be red, warm and swollen. It is often accompanied by symptoms of a urinary tract infection, fever, and in over half of cases it presents in combination with orchitis. In those between the ages of 14 to 35 it is usually caused by either gonorrhea or chlamydia. In people either older or younger E. coli is the most common bacterial infection. Treatment involves the use of antibiotics.

Orchitis can be related to epididymitis infection that has spread to the testicles (then called "epididymo-orchitis"), sometimes caused by the sexually transmitted diseases chlamydia and gonorrhea. It has also been reported in cases of males infected with brucellosis. Orchitis can also be seen during active mumps, particularly in adolescent boys.

Ischemic orchitis may result from damage to the blood vessels of the spermatic cord during inguinal herniorrhaphy, and may in the worst event lead to testicular atrophy.

In most full-term infant boys with cryptorchidism but no other genital abnormalities, a cause cannot be found, making this a common, sporadic, unexplained (idiopathic) birth defect. A combination of genetics, maternal health, and other environmental factors may disrupt the hormones and physical changes that influence the development of the testicles.

- Severely premature infants can be born before descent of testes. Low birth weight is also a known factor.

- A contributing role of environmental chemicals called endocrine disruptors that interfere with normal fetal hormone balance has been proposed. The Mayo Clinic lists "parents' exposure to some pesticides" as a known risk factor.

- Diabetes and obesity in the mother.

- Risk factors may include exposure to regular alcohol consumption during pregnancy (5 or more drinks per week, associated with a 3x increase in cryptorchidism, when compared to non-drinking mothers. Cigarette smoking is also a known risk factor.

- Family history of undescended testicle or other problems of genital development.

- Cryptorchidism occurs at a much higher rate in a large number of congenital malformation syndromes. Among the more common are Down syndrome Prader–Willi syndrome, and Noonan syndrome.

- In vitro fertilization, use of cosmetics by the mother, and preeclampsia have also been recognized as risk factors for development of cryptorchidism.

In 2008 a study was published that investigated the possible relationship between cryptorchidism and prenatal exposure to a chemical called phthalate (DEHP) which is used in the manufacture of plastics. The researchers found a significant association between higher levels of DEHP metabolites in the pregnant mothers and several sex-related changes, including incomplete descent of the testes in their sons. According to the lead author of the study, a national survey found that 25% of U.S. women had phthalate levels similar to the levels that were found to be associated with sexual abnormalities.

A 2010 study published in the European medical journal "Human Reproduction" examined the prevalence of congenital cryptorchidism among offspring whose mothers had taken mild analgesics, primarily over-the-counter pain medications including ibuprofen (e.g. Advil) and paracetamol (acetaminophen). Combining the results from a survey of pregnant women prior to their due date in correlation with the health of their children and an "ex vivo" rat model, the study found that pregnant women who had been exposed to mild analgesics had a higher prevalence of baby boys born with congenital cryptorchidism.

New insight into the testicular descent mechanism has been hypothesized by the concept of a male programming window (MPW) derived from animal studies. According to this concept, testicular descent status is "set" during the period from 8 to 14 weeks of gestation in humans. Undescended testis is a result of disruption in androgen levels only during this programming window.

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.

Torsion is most frequent among adolescents with about 65% of cases presenting between 12–18 years of age. It occurs in about 1 in 4,000 to 1 per 25,000 males per year before 25 years of age; but it can occur at any age, including infancy.

Torsion is due to a mechanical twisting process. It is also believed that torsion occurring during fetal development can lead to so-called neonatal torsion or vanishing testis, and is one of the causes of an infant being born with monorchism (one testicle).

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

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