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

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.

Hypospermia is a condition in which a man has an unusually low ejaculate (or semen) volume, less than 1.5 ml. It is the logical opposite of hyperspermia. It should not be confused with oligospermia, which means low sperm count.

Normal ejaculate when a man is not drained from prior sex and is suitably aroused, is around 1.5-6 ml, although this varies greatly with mood, physical condition and sexual activity. Of this, around 1% by volume is sperm cells. Hypospermia would only usually be a factor in infertility if the two conditions (hypospermia and oligospermia) are combined. The U.S. based National Institutes of Health defines hypospermia as a semen volume lower than 2 mL on at least two semen analyses.

The presence of high levels of fructose (a sugar) is normal in the semen and this comes almost entirely from the seminal vesicle. The seminal vesicles, major contributors to ejaculate volume, render semen pH basic. Thus, low fructose may indicate problems in the prostatic pathway, while low semen pH may indicate problems related to the seminal vesicles. Obstruction of the seminal vesicles result in low semen volumes since they normally produce 70% of the seminal plasma.

A case report of male breast cancer subsequent to bicalutamide-induced gynecomastia has been published. According to the authors, "this is the second confirmed case of breast cancer in association with bicalutamide-induced gynaecomastia (correspondence AstraZeneca)." It is notable, however, that gynecomastia does not seem to increase the risk of breast cancer in men. Moreover, the lifetime incidence of breast cancer in men is approximately 0.1%, the average age of diagnosis of prostate cancer and male breast cancer are similar (around 70 years), and millions of men have been treated with bicalutamide for prostate cancer, all of which are potentially in support of the notion of chance co-occurrences. In accordance, the authors concluded that "causality cannot be established" and that it was "probable that the association is entirely coincidental and sporadic."

Because bicalutamide blocks the , like all antiandrogens, it can interfere with the androgen-mediated sexual differentiation of the genitalia (and brain) during prenatal development. In pregnant rats given bicalutamide at a dosage of 10 mg/kg/day (resulting in circulating drug levels approximately equivalent to two-thirds of human therapeutic concentrations) and above, feminization of male offspring, such as reduced anogenital distance and hypospadias, as well as impotence, were observed. No other teratogenic effects were observed in rats or rabbits receiving up to very high dosages of bicalutamide (that corresponded to up to approximately two times human therapeutic levels), and no teratogenic effects of any sort were observed in female rat offspring at any dosage. As such, bicalutamide is a selective reproductive teratogen in males, and may have the potential to produce undervirilization/sexually ambiguous genitalia in male fetuses.

In medicine, hyperspermia is a condition in which a male has an abnormally large ejaculate (or semen) volume. Males with hyperspermia usually have higher sex drives than males that do not. It is the opposite of hypospermia, and is generally defined in humans when the ejaculate is over 5.5 ml.