The effects of children’s cancer therapy on male reproductive function depend on many factors, including the person’s age at the time of cancer therapy, the specific type and location of the cancer, and the treatment that was given. It is important to understand how the male reproductive organs function and how they may be affected by therapy given to treat cancer during childhood.
Male Reproductive Organs
The male reproductive system is made up of the scrotum, testicles, vas deferens, epididymis, seminal vesicles, prostate gland, penis, and urethra. The reproductive system is controlled by the pituitary gland in the brain. The testicles are located in the scrotum (the loose pouch of skin that hangs behind the penis). The testicles are made up of Leydig cells (cells that produce the male hormone – testosterone) and germ cells (cells that produce sperm).
When a boy enters puberty, the pituitary gland releases two hormones (FSH and LH) that signal the testicles to begin producing sperm and testosterone. As puberty progresses, testosterone causes deepening of the voice, enlargement of the penis and testicles, growth of facial and body hair, and muscular development of the body. Sperm produced by the testicles mature in the epididymis (a coiled tube that sits on top of each testicle) and then travel into the vas deferens (sperm storage area). The seminal vesicles and prostate gland produce fluids that mix with the sperm to create semen. When a man ejaculates, sperm are pumped out through the vas deferens, mixed with fluids from the prostate and seminal vesicles, and exit the body through the urethra (tube that carries fluids out of the penis).
Cancer Therapies’ Affect on the Male Reproductive System
The most common effect of cancer therapy on the male reproductive system is infertility (the inability to initiate a pregnancy). Infertility can occur as a result of certain types of chemotherapy, radiation to the brain or testicles, or surgery involving the male reproductive system.
Another possible effect of cancer therapy on the male reproductive system is testosterone deficiency, also known as “hypogonadism” or “Leydig cell failure.” This is the inability to produce enough of the male hormone, testosterone, and can result from damage to the Leydig cells or pituitary gland caused by radiation to the testicles or brain. If this occurs in a young boy, he will not be able to go into puberty without the help of hormones prescribed by a doctor. Males who develop testosterone deficiency after puberty will need hormonal therapy in order to maintain their muscular development, bone and muscle strength, proper distribution of body fat, sperm production, sex drive, and potency.
Causes of Male Reproductive Problems After Children’s Cancer Treatment
Chemotherapy of the “alkylator” type (such as cyclophosphamide, nitrogen mustard and procarbazine) may cause infertility. The total dose of alkylators used during cancer therapy is important in determining the likelihood of damage to spermproducing cells. The higher the total dose, the more potential for developing infertility. If alkylating chemotherapy was used in combination with radiation, the risk of infertility may be increased.
Radiation therapy can affect testicular function in two ways:
- Radiation aimed directly at or near the testicles. The sperm-forming cells (germ cells) are very sensitive to the effects of radiation therapy. Most males who receive radiation to the testicles at doses of 6 Gy (600 cGy/rads) or higher will be infertile. Even radiation doses of 3 Gy (300 cGy/rads) or lower may cause a drop in the number and quality of sperm produced. This reduction in sperm production may be temporary, but infertility can sometimes occur even at very low radiation doses. Testosterone production often continues even if the sperm-forming cells are no longer functioning, because the cells that produce testosterone (Leydig cells) are not as sensitive to radiation. However, testicular radiation in doses of 20 Gy (2000 cGy/rads) or higher often causes the Leydig cells to stop functioning, resulting in testosterone deficiency.
- Radiation to the pituitary gland in the brain. Brain radiation can result in damage to the pituitary gland leading to low levels of the hormones (FSH and LH) needed to signal the testicles to make sperm and testosterone. Males with low levels of these hormones will need to take testosterone for the rest of their lives. However, it is sometimes possible for these men to attain fertility with the use of specialized hormone treatments. Men who have infertility as a result of brain radiation and wish to achieve fertility should see a fertility specialist.
- Surgery that involves removal of both testicles will result in infertility and testosterone deficiency. Surgery such as retroperitoneal lymph node dissection (RPLD) may cause damage to the nerves in the pelvic area and may prevent the ejaculation of sperm. Removal of the prostate or bladder may result in difficulties achieving an erection and/or ejaculation. In these situations, sperm production may be unaffected and fertility may still be possible by using specialized techniques, such as sperm harvesting and artificial insemination. If fertility is desired, consultation with a fertility specialist is recommended.
Cancer Therapies that Increase Risk of Male Reproductive Problems
Chemotherapy – the class of drugs called “alkylators” – can cause infertility when given in high doses. Examples of these drugs are:
- Cyclophosphamide (Cytoxan)
- Nitrogen mustard
- Lomustine (CCNU)
- Carmustine (BCNU)
- Dacarbazine (DTIC)
Radiation therapy to any of the following areas may cause infertility:
- “Inverted Y” or total nodal radiation
- Inguinal/femoral areas
- TBI (total body irradiation)
- Spinal – if dose was 24 Gy (2400 cGy/rads) or higher
- Cranial (brain) – if dose was 30 Gy (3000 cGy/rads) or higher
In addition to causing infertility, high doses of radiation to the testicles (usually 20 Gy or higher) or brain (usually 30 Gy or higher) may also cause testosterone deficiency. Surgeries that may cause infertility or disrupt normal sexual functioning include:
- Removal of both testicles (this surgery will always result in infertility)
- Retroperitoneal lymph node dissection (RPLD)
- Cystectomy (removal of the bladder)
- Prostatectomy (removal of the prostate)
In addition, removal of both testicles will also result in testosterone deficiency.
Males who have had cancer treatments that place them at risk for reproductive problems should have a yearly check-up that includes careful evaluation of their hormone and puberty status. Blood may be tested for hormone levels (FSH, LH, and testosterone). If any problems are detected, a referral to an endocrinologist (hormone specialist), urologist (specialist in the male reproductive organs) and/or fertility specialist may be recommended.
Males with low testosterone levels should receive testosterone replacement therapy. Testosterone is available in several forms, including gels, skin patches, and injections. Your endocrinologist will determine which form of therapy is best for you.
Infertility is not related to sexual function. In some men with infertility, there may be a decrease in the size or firmness of the testicles, but in others, there are no physical indications of infertility.
Males who had surgical removal of both testicles will not be able to make sperm, and infertility will be permanent. In other males, the only sure way to check for sperm production is to have a semen analysis performed, which checks the appearance, movement and concentration of sperm in the semen. A semen analysis that shows azoospermia (no sperm in the semen sample) on more than one sample is a likely indicator of infertility.
In men who have azoospermia as a result of radiation, return of sperm production is unlikely. However, in men who have azoospermia as a result of chemotherapy, the effect on male fertility is highly variable. Recovery of sperm production may occur months or years after the completion of chemotherapy. For others, the damage may be permanent. It may be impossible to determine if sperm production will resume at some time in the future, especially if chemotherapy ended only a few years prior to the semen analysis. For this reason, males who have azoospermia from chemotherapy should always assume they can make a woman pregnant.
When to Have a Semen Analysis
Any sexually mature male who is concerned about fertility should have a semen analysis performed. Most hospitals or clinics with an adult urology or obstetric/gynecology department have the facilities to perform a semen analysis. If the results are within normal limits, there is no need to do anything further.
Low Sperm Count
If the results show no sperm (azoospermia) or very low sperm counts, the test should be repeated several times. Sperm recovery following chemotherapy may take as long as 10 years, so if you have had chemotherapy that may cause low sperm counts, it may be important to check periodically over several years. Also, men’s sperm counts vary considerably from day to day, so sub-normal test results may improve if additional samples are checked after waiting for a month or two. Sperm production and quality may continue to improve as more time passes from the chemotherapy treatment. Men who have low sperm counts cannot rely on this to prevent pregnancy. Pregnancy can occur with low sperm counts therefore, some method of birth control must be used if pregnancy is not desired. If pregnancy is desired, men with low sperm counts may benefit from various assisted reproductive techniques such as artificial insemination or in-vitro fertilization (IVF).
Options for Men with No Sperm
If semen analysis shows no sperm, and fertility is desired, consult with a doctor who specializes in male infertility. Medical advancements dealing with male infertility are being made. Recently, surgeons have been able to locate areas of active sperm production in the testes of men who were thought to be azoospermic. Surgical harvesting of the sperm has allowed conception with techniques devised for men with absent or very low sperm counts. Occasionally, azoospermia may be unrelated to chemotherapy altogether, and treatment for another disorder may be indicated.
Options for using banked sperm depend on the amount and quality of material saved. Men who banked sperm prior to cancer treatment will need to work with a doctor specializing in reproductive medicine, so that the cryo-preserved (frozen) sperm can be used in an optimal manner.
Another option for males who produce no sperm may be donor insemination. This results in pregnancy with a child that is biologically related only to the mother. Additional options include adoption of a biologically unrelated child or child-free living.
Removal of One Testicle
Although fertility and testosterone production are not usually affected if only one testicle was surgically removed, you should take precautions to protect the remaining testicle from injury by always wearing an athletic supporter with a protective cup when participating in any activities that may potentially cause injury to the groin area (such as contact sports, baseball, etc.). If your remaining testicle was treated with radiation, or if you received chemotherapy that can affect testicular function, the effects of these treatments are the same as discussed above.