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

Ovarian and Reproductive Health after Cancer Treatment
The effects of childhood cancer therapy on reproductive function depend on many factors, including age at the timeof cancer therapy, the specific type and location of the cancer, and the treatment that was given. It is important tounderstand how the ovaries function and how they may be affected by cancer treatment.
The reproductive system
At birth, the ovaries contain all the eggs they will ever have. When the time comes to begin puberty, the pituitary
gland in the brain signals the ovaries by releasing two hormones (FSH and LH). The ovaries secrete the estrogen andprogesterone, which are necessary for reproductive function. Normally, during a monthly menstrual cycle, one egg
matures and is released from the ovaries. If the egg is not fertilized, menstruation begins. The cycle then repeats itself
about every 28 days. With each menstrual cycle, the supply of eggs decreases. When most of the eggs are depleted
from the ovaries, menopause begins. During menopause, the menstrual cycles stop, the ovaries stop making hormones,
and pregnancy progressively becomes less likely.
How does cancer therapy affect the ovaries?
Certain chemotherapy drugs, radiation therapy, and surgery can sometimes damage the ovaries, decreasing ovarian
hormone production and reducing the reserve supply of eggs. When the ovaries are not able to produce sufficienthormones to regulate ovulation and menstruation, otherwise known as premature ovarian insufficiency (POI), an
individual may not begin puberty and menstruation, may have irregular menstrual cycles or menstrual cycles may stopearlier than expected (also known as premature menopause). Additionally, when the ovaries do not function properly,
this can result in infertility or difficulty becoming pregnant.
What are the causes of premature ovarian insufficiency (POI)?
Chemotherapy of the “alkylator” type (such as cyclophosphamide, thiotepa, melphalan and busulfan) is most likely
to affect ovarian function. The total dose of alkylators used during cancer treatment is important in determining the
likelihood of ovarian damage. With higher total doses, the likelihood of damage to the ovaries increases. Heavy metal
chemotherapy (cisplatin and carboplatin) may also damage the ovaries. If treatment for childhood cancer included a
combination of both radiation and these chemotherapies, the risk of POI may be higher .
Radiation therapy can affect ovarian function in two ways:
Radiation aimed at or near the ovaries. The age of the person at the time of radiation and the total radiation dosecan affect whether or not POI occurs. With lower doses of radiation, younger people tend to have less damage to theovaries than those who received equal doses but who were teenagers or young adults at the time of radiation. Highdoses of radiation usually result in a loss of ovarian function and infertility regardless of age.
Radiation to the hypothalamic and pituitary gland regions in the brain. The hypothalamus and pituitary gland
regulate the production of two hormones (FSH and LH) needed for proper ovarian function.
Radiation to the brain at higher doses can damage to these areas of the brain leading to low levels of these hormones.
Surgery. If both ovaries were removed (bilateral oophorectomy) during cancer therapy, this always results in a loss ofovarian function and infertility. This type of POI is sometimes called “surgical menopause.” If one ovary was removed(unilateral oophorectomy), menstruation may stop earlier than it otherwise would have.

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What types of cancer therapy increase the risk of POI?
Individuals who received the following therapy may be at risk for POI:•

Chemotherapy - the class of drugs called “alkylators” can cause POI when given in high doses. Heavy metal
chemotherapy can also affect ovarian function. 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:– Pelvis– Lower spine (sacral area)– Total body irradiation (TBI)– Head/brain especially if dose was 30 Gy (3000cGy/rads) or higher

Surgery:– Removal of one or both ovaries
What are the effects of childhood cancer therapy on the female reproductive system?
•

1. Failure to enter puberty. Pre-pubertal individuals who received cancer therapy that results in ovarian failure willneed hormonal therapy (hormones prescribed by a doctor) to progress through puberty. If this occurs, referral to an
endocrinologist (hormone doctor) should be made for further evaluation and management.
2. Temporary cessation of menstrual cycles. Many who were already menstruating will stop having monthly
periods during their cancer therapy. In most cases, menstrual cycles will resume sometime after cancer treatment
ends, although the timing of this is unpredictable. In some cases, it may take up to several years to restart
menstruation. Since eggs are released before the menstrual cycles, pregnancy can occur before the menstrual
periods resume. If pregnancy is undesired, birth control (contraception) should be used, even if the menstrual
cycles have not resumed.
3. Permanent cessation of menstrual cycles (premature menopause). Menopause (the permanent cessation of
menstrual cycles) occurs at an average age of 51. People who were already menstruating prior to their cancer
therapy sometimes develop ovarian failure as a result of their cancer treatment and never resume menstrual
cycles. Others may resume menstrual cycles, but then stop menstruating much earlier than would normally be
expected. If a person is currently having menstrual periods but received chemotherapy or radiation that can affectovarian function or had one ovary removed, they may still be at risk for entering menopause at an early age. If aperson at risk for premature menopause desires to have children, it is best not to delay childbearing beyond theearly thirties, because the period of fertility may be shortened after having cancer therapy.
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4. Lack of sex hormones. People with ovarian failure do not make enough estrogen. Estrogen is needed forfunctions other than reproduction—it is very important for maintaining strong healthy bones, a healthy heart,and overall well-being. Young people with ovarian failure should see an endocrinologist (hormone specialist) for
hormone replacement therapy, which will be necessary until they reach middle age.
5. Infertility. Infertility is the inability to achieve a pregnancy after at least one year of unprotected intercourse.
Infertility occurs when the ovaries cannot produce eggs (ovarian failure), or when the reproductive organs areunable to sustain a pregnancy. Infertility may be the result of surgery, radiation therapy, chemotherapy, or any
combination of these. There may also be other reasons for infertility that are unrelated to cancer therapy.
If a person has regular monthly menstrual periods and normal hormone levels (FSH, LH and estradiol), they arelikely to be fertile and able to have a baby. If they do NOT have monthly menstrual periods, or if they have monthly
menstrual periods ONLY with the use of supplemental hormones, or if they had to take hormones in order to enteror progress through puberty, they are likely to be infertile.
People who had surgical removal of both ovaries will be infertile. Those who had surgical removal of the uterus(hysterectomy) but still have functioning ovaries can become a parent with the use of a gestational surrogate(another person who carries the pregnancy to term). People who are infertile should discuss their options with afertility specialist and their oncologist. The use of donor eggs may be an alternative for some. Additional options
may include adoption of a biologically unrelated child or child-free living.
6. Pregnancy risks. Certain therapies used during treatment for childhood cancer can sometimes increase therisk of problems that a person may experience during pregnancy, labor, and childbirth. The following may be atincreased risk:–

Those who had radiation to the pelvis, lower spine, or total body (TBI) may have an increased risk of
miscarriage, premature delivery, or problems during labor.

–Those who received anthracycline chemotherapy (such as doxorubicin or daunorubicin), and those who
received radiation to the abdomen, chest or thoracic spine may be at risk for heart problems that can worsenwith pregnancy and labor (see related Health Link: “Heart Health”).

People with these risk factors should be followed closely by an obstetrician who is qualified to care for high-risk
pregnancies.
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 was genetic.
What monitoring is recommended?
Those who have had any of the cancer treatments that may affect ovarian function should have a yearly checkup that includes careful evaluation of progression through puberty, menstrual and pregnancy history, and sexualfunction. Blood may be tested for hormone levels (FSH, LH, and estradiol) if a problem is suspected. If any problems
are detected, a referral to an endocrinologist (hormone specialist) and/or other specialists may be recommended. For
people with ovarian failure, a bone density test (special type of x-ray) to check for thinning of the bones (osteoporosis)
may also be recommended.

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

Written by: Marcia S. Leonard, RN, CPNP, C.S. Mott Children’s Hospital, Ann Arbor, MI.
Reviewed by Katy Tomlinson, BSN, RN; 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 young
adulthood.
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Introduction to Late Effects Guidelines and Health Links: The Long-Term Follow-Up Guidelines for Survivors of Childhood, Adolescent, and Young Adult Cancers and accompanying Health
Links were developed by the Children’s Oncology Group as a collaborative effort of the Late Effects Committee and Nursing Discipline and are maintained and updated by the Children’s
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To cancer patients (if children, their parents or legal guardians): Please seek the advice of a physician or other qualified health provider with any questions you may have regarding a
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