The history should include prior testicular or penile insults (torsion, cryptorchidism, trauma), infections (mumps orchitis, epididymitis), environmental factors, excessive heat, radiation, medications, and drug use (anabolic steroids, alcohol, smoking).

Sexual habits, frequency and timing of intercourse, use of lubricants, and each partner's previous fertility experiences are important.

Loss of libido and headaches or visual disturbances may indicate a pituitary tumor.

The past medical or surgical history may reveal thyroid or liver disease (abnormalities of spermatogenesis), diabetic neuropathy (retrograde ejaculation), radical pelvic or retroperitoneal surgery (absent seminal emission secondary to sympathetic nerve injury), or hernia repair (damage to the vas deferens or testicular blood supply).

A family history may reveal genetic problems.

The diagnosis of infertility begins with a medical history and physical exam by a physician, physician assistant, or nurse practitioner. Typically two separate semen analyses will be required. The provider may order blood tests to look for hormone imbalances, medical conditions, or genetic issues.

Aspermia is the complete lack of semen with ejaculation (not to be confused with azoospermia, the lack of sperm cells in the semen). It is associated with infertility.

One of the causes of aspermia is retrograde ejaculation, which can be brought on by excessive drug use, or as a result of prostate surgery. It can also be caused by alpha blockers such as tamsulosin and silodosin.

Another cause of aspermia is ejaculatory duct obstruction, which may result in a complete lack of or a very low-concentration semen (oligospermia), in which the semen contains only the secretion of accessory prostate glands downstream to the orifice of the ejaculatory ducts.

Aspermia can be caused by androgen deficiency. This can be the result of absence of puberty, in which the prostate gland and seminal vesicles (which are the main sources of semen) remain small due to lack of androgen exposure and do not produce seminal fluid, or of treatment for prostate cancer, such as maximal androgen blockade.

Low-volume, runny/fluid semen (oligospermia) or no semen at all (dry ejaculation/aspermia) are a logical consequence of an obstruction downstream of the seminal vesicles which contribute most to the volume of the semen. Usually, men will be able to observe a runny/fluid, low-volume semen by themselves during masturbation. Since the seminal vesicles contain a viscous, alkaline fluid rich in fructose, a chemical analysis of the semen of affected men will result in a low concentration of fructose and a low pH. A microscopic semen analysis will reveal aspermia/azoospermia.

In contrast, if both vasa deferentia are obstructed (which may be the result of intended sterilization), a semen analysis will also reveal aspermia/azoospermia, but an almost normal volume of the semen, since the efflux of the seminal vesicles is not hindered. This is because approx. 80% of the volume of the semen is the gel-like fluid originating from the seminal vesicles whereas the fraction from the testicles / epididymis, which contains the spermatozoa accounts for only 5–10% of the volume of the semen. In addition, if an obstruction of the vasa deferentia is the cause for the azoospermia, the concentration of fructose in the semen will also be normal, since the fructose comes primarily from the fluid stored in the seminal vesicles. If the seminal-vesicles contain spermatozoa, but the semen does not, the obstruction must be downstream of the seminal vesicles and the ejaculatory ducts are very likely to be obstructed, provided that other causes for a dry ejaculation/aspermia such as an retrograde ejaculation are ruled out.

Attempts are sometimes made to diagnose an ejaculatory duct obstruction by means of medical imaging, e.g. transrectal ultrasound or MRI, or by transrectal needle-aspiration of the seminal vesicles. However transrectal ultrasound has a relatively low sensitivity of approx. 50% and thus is only a tool to rule-out cysts in the region of the orifices but is not sufficient to rule out an obstruction of the ejaculatory ducts due to other causes. In approx. 50% of cases of unexplained low-volume azoospermia MRI and TRUS do not reveal any pathological findings, because it is difficult to see alterations in a narrowed, scarred duct with these methods. Due to the blockage of ejaculatory ducts, enlarged seminal vesicles are frequently seen in patients with ejaculatory duct obstructions. However, this is again neither a proof of an obstruction nor do normal-sized seminal vesicles rule-out an obstruction of the ejaculatory ducts. Since ejaculatory duct obstruction is a relatively rare cause of infertility, this possibility may be unfamiliar to some physicians, even some urologists.

A few cases of photosensitivity (hypersensitivity to ultraviolet light-induced skin redness and/or lesions) associated with bicalutamide have been reported. In one of the cases, bicalutamide was continued due to effectiveness in treating prostate cancer in the patient, and in combination with strict photoprotection (in the form of avoidance/prevention of ultraviolet light exposure), the symptoms disappeared and did not recur. Flutamide is also associated with photosensitivity, but much more frequently in comparison to bicalutamide.

Ejaculatory duct obstruction (EDO) is a congenital or acquired pathological condition which is characterized by the obstruction of one or both ejaculatory ducts. Thus, the efflux of (most constituents of) semen is not possible.

It is a cause of male infertility and / or pelvic pain. Ejaculatory duct obstruction must not be confused with an obstruction of the vas deferens.

Several case reports of interstitial pneumonitis (which can progress to pulmonary fibrosis) in association with bicalutamide treatment have been published in the medical literature. Interstitial pneumonitis with bicalutamide is said to be an extremely rare event, and the risk is far less relative to that seen with nilutamide (which has an incidence rate of 0.5–2% of patients). In a very large cohort of prostate cancer patients, the incidence of interstitial pneumonitis with was 0.77% for nilutamide but only 0.04% (4 per 10,000) for flutamide and 0.01% (1 per 10,000) for bicalutamide. An assessment done prior to the publication of the aforementioned study estimated the rates of pulmonary toxicity with flutamide, bicalutamide, and nilutamide as 1 case, 5 cases, and 303 cases per million, respectively. In addition to interstitial pneumonitis, a single case report of eosinophilic lung disease in association with six months of 200 mg/day bicalutamide treatment exists. Side effects associated with the rare potential pulmonary adverse reactions of bicalutamide may include dyspnea (difficult breathing or shortness of breath), cough, and pharyngitis (inflammation of the pharynx, resulting in sore throat).