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.

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.

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

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.

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.

One of the strongest arguments for early orchiopexy is reducing the risk of testicular cancer. About 1 in 500 men born with one or both testes undescended develops testicular cancer, roughly a 4 to 40 fold increased risk. The peak incidence occurs in the 3rd and 4th decades of life. The risk is higher for intra-abdominal testes and somewhat lower for inguinal testes, but even the "normally descended" testis of a man whose other testis was undescended has about a 20% higher cancer risk than those of other men.

The most common type of testicular cancer occurring in undescended testes is seminoma. It is usually treatable if caught early, so urologists often recommend that boys who had orchiopexy as infants be taught testicular self-examination, to recognize testicular masses and seek early medical care for them. Cancer developing in an intra-abdominal testis would be unlikely to be recognized before considerable growth and spread, and one of the advantages of orchiopexy is that a mass developing in a scrotal testis is far easier to recognize than an intra-abdominal mass.

It was originally felt that orchidopexy resulted in easier detection of testis cancer but did not lower the risk of actually developing cancer. However, recent data has resulted in a paradigm shift. The New England Journal of Medicine published in 2007 that orchidopexy performed before puberty resulted in a significantly reduced risk of testicular cancer than if done after puberty.

The risk of malignancy in the undescended testis is 4 to 10 times higher than that in the general population and is approximately 1 in 80 with a unilateral undescended testis and 1 in 40 to 1 in 50 for bilateral undescended testes. The peak age for this tumor is 15–45 yr. The most common tumor developing in an undescended testis is a seminoma (65%); in contrast, after orchiopexy, seminomas represent only 30% of testis tumors.

Testicular size as a proportion of body weight varies widely. In the mammalian kingdom, there is a tendency for testicular size to correspond with multiple mates (e.g., harems, polygamy). Production of testicular output sperm and spermatic fluid is also larger in polygamous animals, possibly a spermatogenic competition for survival. The testes of the right whale are likely to be the largest of any animal, each weighing around 500 kg (1,100 lb).

Among the Hominidae, gorillas have little female promiscuity and sperm competition and the testes are small compared to body weight (0.03%). Chimpanzees have high promiscuity and large testes compared to body weight (0.3%). Human testicular size falls between these extremes (0.08%).

Testis weight also varies in seasonal breeders like deer and horses. The change is related to changes in testosterone production.

Human testicles are smaller than chimpanzee testicles but larger than gorilla testicles.

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.

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).

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.

In the US, up to 20% of infertile couples have unexplained infertility. In these cases abnormalities are likely to be present but not detected by current methods. Possible problems could be that the egg is not released at the optimum time for fertilization, that it may not enter the fallopian tube, sperm may not be able to reach the egg, fertilization may fail to occur, transport of the zygote may be disturbed, or implantation fails. It is increasingly recognized that egg quality is of critical importance and women of advanced maternal age have eggs of reduced capacity for normal and successful fertilization. Also, polymorphisms in folate pathway genes could be one reason for fertility complications in some women with unexplained infertility. However, a growing body of evidence suggests that epigenetic modifications in sperm may be partially responsible.

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 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).

In posttesticular azoospermia sperm are produced but not ejaculated, a condition that affects 7–51% of azoospermic men. The main cause is a physical obstruction (obstructive azoospermia) of the posttesticular genital tracts. The most common reason is a vasectomy done to induce contraceptive sterility. Other obstructions can be congenital (example agenesis of the vas deferens as seen in certain cases of cystic fibrosis) or acquired, such as ejaculatory duct obstruction for instance by infection.

Ejaculatory disorders include retrograde ejaculation and anejaculation; in these conditions sperm are produced but not expelled.

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.

An individual having monorchism can be referred to as "monorchid".

Although extremely rare, monorchism has been observed to be characteristic of some animal species, notably in beetles.

Sex determination and differentiation is generalized with chromosomal sex during fertilization. At early stages, phenotypic sex does not match chromosomal sex—until later during intrauterine development, sexual maturation is reached. During intrauterine development, females change to male with the testes moving down from a blind vaginal pouch with a developing scrotum, as well as a penis which initially resembled a clitoris. What seems like a female phenotype is altered by increased testosterone levels secretion.

Mutations affecting the androgen receptor (AR) gene may cause either complete or partial androgen insensitivity syndrome. Androgen, a hormone used to describe a group of sex steroid hormones, is responsible for affecting male pseudohermaphroditism. The differentiation of the fetus as male takes place during the sixth or seventh week of gestation. The development is directed by the testicular determining factor: the gene SRY (sex determining region on Y chromosome). Throughout 9th to 13th week, the development of a male genitalia is dependent upon the conversion of testosterone to the more potent androgen by the action of 5α-reductase within the target tissues of the genitalia. A type of internal male pseudohermaphroditism is Persistent Müllerian duct syndrome, which is developed through synthesis of Müllerian-inhibiting factor defects. In such instances, duct derivatives are now in 46XY males—this includes the uterus, fallopian tubes, and upper vagina. These individuals with a hernia sac and bowel loops were found with duct derivatives as well as testes.

A study on a male pseudohermaphrodite kitten showed there was a combination of gastrointestinal and urogenital congenital abnormalities. It was confirmed to have type II atresia ani and rectovaginal fistula that is associated with male pseudohermaphroditism.

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 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.

Ultrasound is useful if the cause is not certain based on the above measures. If the diagnosis of torsion is certain, imaging should not delay definitive management such as physical maneuvers and surgery.

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.

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.