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Healthy living after treatment of childhood, adolescent, and young adult cancer

Testicular and Reproductive Health after Cancer Treatment
The effects of childhood cancer therapy on reproductive function depend on many factors, including the specific typeand location of the cancer, and the treatment that was given. It is important to understand how the testes function andhow they may be affected by cancer treatment.
The reproductive system
The reproductive system contains many structures and is controlled by thepituitary gland in the brain. The testes are located in the scrotum (the loose
pouch of skin behind the penis). The testes are made up of leydig cells (cells
that produce the hormone—testosterone) and sertoli cells (cells that support
the sperm production). At the time of puberty, the pituitary gland in thebrain releases two hormones (FSH and LH) that signal the testes to begin
producing sperm and testosterone. As puberty progresses, testosterone
causes deepening of the voice, enlargement of the penis and testes, growthof facial and body hair, and muscular development of the body.

UreterVas deferens
SeminalVesicle
Prostate
GlandUrethraEpididymis

Testicle
Scrotum
Penis

How does cancer therapy affect the testes?
Cancer therapy can cause infertility (the inability to initiate a pregnancy).
Infertility can occur following treatment with certain types of chemotherapy,
radiation to the brain or testes, or surgery involving the reproductive system.
Another possible effect of cancer therapy is testosterone deficiency, also known as “hypogonadism”. When this occurs,
the testes are unable to produce enough testosterone hormone. If this happens before the age of puberty, puberty may
not start without hormone medication prescribed by a doctor. If it develops after puberty, testosterone therapy may beneeded to maintain muscular development, bone and muscle strength, proper distribution of body fat, sex drive, and theability to have erections.
What are the causes of male reproductive problems after childhood cancer treatment?
Chemotherapy of the “alkylator” type (such as cyclophosphamide, thiotepa, melphalan and busulfan) and heavy
metals (such as cisplatin and carboplatin) may cause testicular damage. The total dose of chemotherapy used duringcancer treatment is important in determining the likelihood of damage. The higher the total dose, the more potential fordeveloping problems such as infertility or testosterone deficiency. If alkylating or heavy metal chemotherapy was used in
combination with radiation, the risk for testicular damage is increased.
Radiation therapy can affect testicular function in two ways:•Radiation aimed directly at or near the testes. The sperm-producing cells are very sensitive to the effects ofradiation therapy. Most individuals who receive radiation to the testes at doses of 6 Gy (600 cGy/rads) or higher
will be infertile. The testosterone producing cells are more resistant to the effects of radiation and chemotherapy,
but if testicular radiation was given in doses of 12 Gy (1200 cGy/rads) or higher, the leydig cells may be damaged,
resulting in testosterone deficiency (in addition to infertility).

•Radiation to the hypothalamic and pituitary gland regions in the brain. The hypothalamus and pituitary gland
regulate the production of two hormones (LH and FSH) needed to signal the testes to make testosterone andsperm. People with low levels of these hormones will need to take testosterone hormone replacement. For some

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Healthy living after treatment of childhood, adolescent, and young adult cancer

survivors, it is possible to regain fertility with the use of specialized hormone treatments. Individuals who haveinfertility as a result of brain radiation and wish to achieve fertility should see a fertility specialist.
Surgery that involves removal of both testicles (bilateral orchiectomy) will result in infertility and testosterone
deficiency. Pelvic surgery, such as retroperitoneal lymph node dissection (RPLD), or spinal surgery sometimes results innerve damage that 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.
What types of cancer therapy increase the risk of problems with testicular function?
•Chemotherapy - the class of drugs called “alkylators” can cause infertility when given in high doses. Very highdoses may occasionally cause testosterone deficiency. Heavy metal chemotherapy can also affect testicularfunction. Examples of these drugs are:Alkylating agents:– Busulfan– Carmustine (BCNU)– Chlorambucil– Cyclophosphamide (Cytoxan®)– Ifosfamide
Heavy metals:– Carboplatin– Cisplatin•––––Lomustine (CCNU)
Mechlorethamine (nitrogen mustard)
Melphalan
Procarbazine– Thiotepa
Non-classical alkylators:– Dacarbazine (DTIC)– Temozolomide
Radiation therapy to any of the following areas may cause infertility:– Testes– Total body irradiation (TBI)– Head/brain especially if dose was 30 Gy (3000 cGy/rads) or higher
In addition to causing infertility, high doses of radiation to the testes (usually 12 Gy or higher) or brain (usually30 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)–

Removal of one testicle or a portion of one testicle–

Retroperitoneal lymph node dissection (RPLD)–

Removal of tumor in the retroperitoneal area–

Pelvic surgery–

Cystectomy (removal of the bladder)–

Prostatectomy (removal of the prostate)

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Healthy living after treatment of childhood, adolescent, and young adult cancer–

Spinal surgery–

Removal of tumor near the spinal cord

In addition, removal of both testicles will result testosterone deficiency, and removal of one testicle or a portion of
one testicle may result in low testosterone levels.
What monitoring is recommended?
Individuals whose treatment places them at risk for problems with the reproductive system should have a yearly
check-up that includes careful evaluation of their sexual development. Blood may be tested for hormone levels (AMtestosterone, LH, FSH, and inhibin). If any problems are detected, a referral to an endocrinologist (hormone specialist),urologist (specialist in the reproductive system) and/or fertility specialist may be recommended. Individuals who have
had both testes removed should begin seeing an endocrinologist starting at about age 11 for hormone replacement.
People who have had fertility preservation procedures (saving sperm outside of the body or “cryopreserved”), should
review previous fertility counseling and current options for family building with a fertility specialist.
What can be done for testosterone deficiency?
Individuals with low testosterone levels should receive testosterone replacement therapy. Testosterone is available inseveral forms, including skin patches, injections, and topical gel. Your endocrinologist will determine which form of
therapy is best for you.
How will I know if I am infertile?
Infertility, the inability to initiate a pregnancy after a year of unprotected intercourse, can occur after cancer treatment.
Recovery of the ability to make sperm may occur in some survivors. When recovery occurs, it usually happens in thefirst few years after completion of cancer treatment. The best way to assess the ability to make sperm is a semen
analysis which evaluates the number of sperm produced, the motility (movement of the sperm) and morphology (whatthe sperm look like). The specimen is produced after several days of abstinence. If the patient is unable to produce asemen specimen or prefers not to, an FSH and inhibin level may provide some insight into the ability to make sperm. A
high FSH or low inhibin suggest impaired ability to make sperm.
A semen analysis that shows azoospermia (no sperm in the semen sample) on more than one sample is an indicatorof infertility. Patients with oligospermia (low sperm count) may still be able to have children with the help of fertility
specialists.
In general, contraception should be used unless pregnancy is desired.
What if only one testicle or a portion of one testicle was surgically removed?
Although fertility and testosterone production are not usually affected if only one testicle or a portion of 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 thegroin area (such as contact sports, baseball, etc.).
What are the risks if pregnancy occurs after childhood cancer treatment?
Fortunately, in most cases, there is no increased risk of cancer or birth defects in children born to childhood cancer
survivors. In rare cases, if the type of cancer in childhood was a genetic (inherited) type, then there may be a risk ofpassing that type of cancer on to a child. You should check with your oncologist if you are not sure whether the type ofcancer you had is associated with a genetic risk that can be passed on.
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Written by Marcia S. Leonard, RN, CPNP, C.S. Mott Children’s Hospital, Ann Arbor, MI.
Reviewed by Katy Tomlinson, RN, BSN; Lillian R. Meacham, MD; Melissa Acquazzino, MD, MS; and Kayla L. Foster, MD, MPH.

Additional health information for childhood cancer survivors is available atwww.survivorshipguidelines.org
Note: Throughout this Health Links series, the term “childhood cancer” is used to designate pediatric cancers that may occur during childhood, adolescence, or young adulthood.
Health Links are designed to provide health information for survivors of pediatric cancer, regardless of whether the cancer occurred during childhood, adolescence, or youngadulthood.
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