Administration of luteinizing hormone (LH) (or human chorionic gonadotropin) and follicle-stimulating hormone (FSH) is very effective in the treatment of male infertility due to hypogonadotropic hypogonadism. Although controversial, off-label clomiphene citrate, an antiestrogen, may also be effective by elevating gonadotropin levels.

Though androgens are absolutely essential for spermatogenesis and therefore male fertility, exogenous testosterone therapy has been found to be ineffective in benefiting men with low sperm count. This is thought to be because very high local levels of testosterone in the testes (concentrations in the seminiferous tubules are 20- to 100-fold greater than circulating levels) are required to mediate spermatogenesis, and exogenous testosterone therapy (which is administered systemically) cannot achieve these required high local concentrations (at least not without extremely supraphysiological dosages). Moreover, exogenous androgen therapy can actually impair or abolish male fertility by suppressing gonadotropin secretion from the pituitary gland, as seen in users of androgens/anabolic steroids (who often have partially or completely suppressed sperm production). This is because suppression of gonadotropin levels results in decreased testicular androgen production (causing diminished local concentrations in the testes) and because FSH is independently critical for spermatogenesis. In contrast to FSH, LH has little role in male fertility outside of inducing gonadal testosterone production.

Estrogen, at some concentration, has been found to be essential for male fertility/spermatogenesis. However, estrogen levels that are too high can impair male fertility by suppressing gonadotropin secretion and thereby diminishing intratesticular androgen levels. As such, clomiphene citrate (an antiestrogen) and aromatase inhibitors such as testolactone or anastrozole have shown effectiveness in benefiting spermatogenesis.

Low-dose estrogen and testosterone combination therapy may improve sperm count and motility in some men, including in men with severe oligospermia.

Treatments vary according to the underlying disease and the degree of the impairment of the male fertility. Further, in an infertility situation, the fertility of the female needs to be considered.

Pre-testicular conditions can often be addressed by medical means or interventions.

Testicular-based male infertility tends to be resistant to medication. Usual approaches include using the sperm for intrauterine insemination (IUI), in vitro fertilization (IVF), or IVF with intracytoplasmatic sperm injection (ICSI). With IVF-ICSI even with a few sperm pregnancies can be achieved.

Obstructive causes of post-testicular infertility can be overcome with either surgery or IVF-ICSI. Ejaculatory factors may be treatable by medication, or by IUI therapy or IVF.

Vitamin E helps counter oxidative stress, which is associated with sperm DNA damage and reduced sperm motility. A hormone-antioxidant combination may improve sperm count and motility. However there is only some low quality evidence from few small studies that oral antioxidants given to males in couples undergoing in vitro fertilisation for male factor or unexplained subfertility result in higher live birth rate. It is unclear if there are any adverse effects.

A method to treat ejaculatory duct obstruction is transurethral resection of the ejaculatory ducts (TURED). This operative procedure is relatively invasive, has some severe complications, and has led to natural pregnancies of their partners in approximately 20% of affected men. A disadvantage is the destruction of the valves at the openings of the ejaculatory ducts into the urethra such that urine may flow backwards into the seminal vesicles. Another, experimental approach is the recanalization of the ejaculatory ducts by transrectal or transurethral inserted balloon catheter. Though much less invasive and preserving the anatomy of the ejaculatory ducts, this procedure is probably not completely free of complications either and success rates are unknown. There is a clinical study currently ongoing to examine the success rate of recanalization of the ejaculatory ducts by means of balloon dilation.

Usually, affected men have a normal production of spermatozoa in their testicles, so that after spermatozoa were harvested directly from the testes e.g. by TESE, or the seminal vesicles (by needle aspiration) they and their partners are potentially candidates for some treatment options of assisted reproduction e.g. in-vitro fertilisation. Note that in this case, most of the treatment (e.g. ovarian stimulation and transvaginal oocyte retrieval) is transferred to the female partner.

Tamoxifen, a selective estrogen receptor modulator (SERM) with antiestrogenic actions in breast tissue and estrogenic actions in bone, has been found to be highly effective in preventing and reversing bicalutamide-induced gynecomastia in men. Moreover, in contrast to analogues (which also alleviate bicalutamide-induced gynecomastia), tamoxifen poses minimal risk of accelerated bone loss and osteoporosis. For reasons that are unclear, anastrozole, an aromatase inhibitor (or an inhibitor of estrogen biosynthesis), has been found to be much less effective in comparison to tamoxifen for treating bicalutamide-induced gynecomastia. A systematic review of -induced gynecomastia and breast tenderness concluded that tamoxifen (10–20 mg/day) and radiotherapy could effectively manage the side effect without relevant adverse effects, though with tamoxifen showing superior effectiveness. Surgical breast reduction may also be employed to correct bicalutamide-induced gynecomastia.

Combination of bicalutamide with medical (i.e., a analogue) or surgical castration modifies the side effect profile of bicalutamide. Some of its side effects, including breast pain/tenderness and gynecomastia, are far less likely to occur when the drug is combined with a analogue, while certain other side effects, including hot flashes, depression, fatigue, and sexual dysfunction, occur much more frequently in combination with a analogue. It is thought that this is due to the suppression of estrogen levels (in addition to androgen levels) by analogues, as estrogen may compensate for various negative central effects of androgen deprivation. If bicalutamide is combined with a analogue or surgical castration, the elevation of androgen and estrogen levels in men caused by bicalutamide will be prevented and the side effects of excessive estrogens, namely gynecomastia, will be reduced. However, due to the loss of estrogen, bone loss will accelerate and the risk of osteoporosis developing with long-term therapy will increase.

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.