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.

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.

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.

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.

Around 15% of all adult males, up to 35% of men who are evaluated for male infertility, and around 80% of men who are infertile due to some other cause, have varicocele.

Often the greatest concern with respect to varicocele is its effect on male fertility. The relationship between varicocele and infertility is unclear; some men with the condition are fertile, some have sperm that are normal in shape and move normally, but are compromised in function, and some have sperm with abnormal shapes or that do not move well. Theories as to how variocele affects sperm function include damage via excess heat caused by the blood pooling and oxidative stress on sperm (ROS).

Tobacco smoking and mutations in the gene expressing glutathione S-transferase Mu 1 both put men at risk for infertility; these factors may also exacerbate the risk that varicocele will affect fertility.

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.

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.

A retrospective postal survey of 396 men found that 4% had significant genital pain for more than one year that required surgical intervention.

Another study contacted 470 vasectomy patients and received 182 responses, finding that 18.7% of respondents experienced chronic genital pain with 2.2% of respondents experiencing pain that adversely affected quality of life.

The most robust study of post-vasectomy pain, according to the American Urology Association's Vasectomy Guidelines 2012 (amended 2015) found a rate of 14.7% reported new-onset scrotal pain at 7 months after vasectomy with 0.9% describing the pain as "quite severe and noticeably affecting their quality of life".

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).

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.

Treatment is often with NSAIDs and antibiotics however, this is not always effective.

Testing for gonorrhea and chlamydia should be routinely performed.

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.

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

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.

Spermatoceles can originate as diverticulum from the tubules found in the head of the epididymis. Sperm formation gradually causes the diverticulum to increase in size, causing a spermatocele. They are due to continuity between the epididymis and tunica vaginalis.

They are also believed to result from epididymitis, physical trauma, or vasectomy. Scarring of any part of the epididymis can cause it to become obstructed and in turn form a spermatocele.

A hydrocele testis is not generally thought to affect fertility. However, it may be indicative of other factors that may affect fertility.

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.

Treatment depends on the proximate cause. In one study, it was reported that 9 of 13 men who underwent vasectomy reversal in an attempt to relieve post-vasectomy pain syndrome became pain-free, though the followup was only one month in some cases. Another study found that 24 of 32 men had relief after vasectomy reversal.

Nerve entrapment is treated with surgery to free the nerve from the scar tissue, or to cut the nerve. One study reported that denervation of the spermatic cord provided complete relief at the first follow-up visit in 13 of 17 cases, and that the other four patients reported improvement. As nerves may regrow, long-term studies are needed.

One study found that epididymectomy provided relief for 50% of patients with post-vasectomy pain syndrome.

Orchiectomy is recommended usually only after other surgeries have failed.

90% of ruptured testes are successfully repaired when treated surgically within 72 hours; the percentage of successful treatment drops to 45% after this period. Though not typically fatal, testicular rupture can cause hypogonadism, low self-esteem, and infertility.

A hydrocele testis is an accumulation of clear fluid in the tunica vaginalis, the most internal of membranes containing a testicle. A primary hydrocele causes a painless enlargement in the scrotum on the affected side and is thought to be due to the defective absorption of fluid secreted between the two layers of the tunica vaginalis (investing membrane). A secondary hydrocele is secondary to either inflammation or a neoplasm in the testis.

A hydrocele usually occurs on one side, but can also affect both sides. The accumulation can be a marker of physical trauma, infection, tumor or varicocele surgery, but the cause is generally unknown. Indirect inguinal hernia indicates increased risk of hydrocele.

A hydrocele is normally seen in infant boys, as an enlarged scrotum. In infant girls, it appears as enlarged labia. However, hydroceles are more common in boys than girls.

To some extent, it is possible to change testicular size. Short of direct injury or subjecting them to adverse conditions, e.g., higher temperature than they are normally accustomed to, they can be shrunk by competing against their intrinsic hormonal function through the use of externally administered steroidal hormones. Steroids taken for muscle enhancement (especially anabolic steroids) often have the undesired side effect of testicular shrinkage.

Similarly, stimulation of testicular functions via gonadotropic-like hormones may enlarge their size. Testes may shrink or atrophy during hormone replacement therapy or through chemical castration.

In all cases, the loss in testes volume corresponds with a loss of spermatogenesis.

Small cysts are best left alone, as are larger cysts that are an asymptomatic condition. Only when the cysts are causing discomfort and are enlarging in size, or the patient wants the spermatocele removed, should a spermatocelectomy be considered. Pain may persist even after removal.

Spermatocelectomy can be performed on an outpatient basis, with the use of local or general anesthesia.

A spermatocelectomy will not improve fertility.