Female Reproductive System Problems in Childhood Cancer Survivors

Some female childhood cancer survivors may have problems with their reproductive health — menstrual periods, pregnancy, and childbearing — because of certain treatments they received.

The effect, if any, depends on the:

Tissues and organs involved in the cancer
Type, dosage, and combination of treatments
Age at the time of therapy

Treatments are available for many conditions that affect the reproductive system.

This illustration shows a teen with her uterus, fallopian tubes, ovaries, cervix, and vagina labeled. To the right of the main image, the endocrine system organs are also shown against the silhouette of the young woman’s body: pineal gland, hypothalamus, pituitary gland, thyroid and parathyroid, thymus, adrenal gland, and pancreas. — The organs of the female reproductive system work together so a woman can get pregnant, carry a developing human until time for delivery, and give birth.

How the female reproductive system works

It is important to understand how the female reproductive system functions and how it may be affected by cancer treatment.

The organs of the female reproductive system work together so a woman can:

Get pregnant
Carry a developing human until time for delivery
Give birth

Females have two ovaries. During puberty, the pituitary gland in the brain signals the ovaries to start making more estrogen and progesterone. These are hormones necessary for the reproductive system to work.

Once a month, the ovaries typically release at least 1 egg. If the egg is fertilized by sperm, the female becomes pregnant. If it is not fertilized, the woman will have her menstrual period. This cycle repeats about every 28 days. With each menstrual cycle, the supply of eggs decreases.

A girl is born with all the eggs she will ever have. When her supply becomes low, a woman begins menopause. When menstrual periods stop, a woman usually cannot get pregnant anymore. Menopause can occur in a woman’s 40s or 50s. The average age is 51. Menopause is considered early if it happens before the age of 40.

Cancer treatments that can affect female health

Chemotherapy

Alkylating Drugs	Heavy Metal Drugs
Busulfan Carmustine (BCNU) Chlorambucil Cyclophosphamide (Cytoxan®) Ifosfamide Lomustine (CCNU) Mechlorethamine (nitrogen mustard) Melphalan Procarbazine Thiotepa	Carboplatin Cisplatin
	Non-classical alkylators
	Dacarbazine (DTIC) Temozolomide

Radiation

Radiation therapy that affects a patient’s pelvic area, reproductive organs, and pituitary gland in the brain may affect a patient’s fertility. The treatment may decrease the number of eggs or affect the quality of the eggs.

Abdomen/ pelvic/ total body radiation

Radiation directly to or near the ovaries can cause them to stop working. Radiation therapy to the abdomen, pelvis, and lower spine can affect the uterus and increase the risk of miscarriage, premature labor, low birth weight, and problems during labor.

Brain/ hypothalamus/ pituitary gland

Brain radiation can damage the pituitary gland in the brain. The pituitary gland produces two hormones needed for the ovaries to function correctly – FSH (follicle-stimulating hormone) and LH (luteinizing hormone.) FSH stimulates the ovarian follicles to produce eggs. LH signals the follicles to release eggs. High levels of radiation to this area of the brain can lead to low levels of these hormones.

Pelvic radiation and alkylating agent combination

The combination of pelvic radiation and high doses of alkylating agents causes the highest risk of damage to reproductive function.
Surgery

Tumors and/or surgery that result in damage to the pituitary gland can cause the ovaries to stop working due to deficiency in LH and FSH. This condition is called central hypogonadism.

Surgery that removes both ovaries before the normal age of menopause causes premature ovarian failure.

Removal of one ovary before the normal age of menopause may cause menopause to happen a few years earlier than normal.

Other factors that may increase the risk of female health problems

Age

In general, females who are adolescents and young adults at the time of treatment are at higher risk for problems than younger girls.

Problems that may occur

Failure to enter or progress through puberty

Damage to ovaries can cause puberty to be delayed (no signs of breast development after age 13 years) or to stall (no progress in signs of puberty, no onset of periods past the age of 16 years). Affected girls will need hormone treatment prescribed by a doctor to experience puberty and have a menstrual period.
Temporary stopping of menstrual periods

Many females will temporarily stop having their period during treatment, but it may return later. That timing is unpredictable. It could take several years. It is important that women take birth control if they are sexually active and don’t want to become pregnant.
Premature menopause

Cancer treatment can cause women to stop menstruating earlier than expected (before the age of 40.) Heath care professionals recommend that women at risk for early menopause not put off trying to have children beyond the early 30s if they are able.
Lack of female hormones

Women with ovarian failure don’t produce enough estrogen, which is needed for healthy bones, a healthy heart, and overall well-being. Girls at risk for this problem may need to consult an endocrinologist and/or gynecologist.

Lack of female hormones represents a problem with the endocrine system.
Infertility

Infertility is defined as not being able to get pregnant and have a biologic child after 1 year of unprotected sexual intercourse. Women at risk for infertility may want to see a fertility specialist.
Pregnancy risks

Women who had radiation to the pelvis, lower spine or total body (TBI) may be at increased risk for miscarriage, premature delivery, low birthweight infants, or problems during labor. Survivors who received these treatments and who are planning to become pregnant or are already pregnant should ask to see an obstetrician/ gynecologist (OB/GYN) who specializes in high-risk pregnancies.

Women who had chemotherapy with anthracyclines could have heart problems during pregnancy and labor. Survivors are encouraged to talk to their OB/GYN about the possible need to have a heart muscle function evaluation.