Ovaries are the main reproductive organs of the female. They are approximately 1½ inches in length when fully developed after puberty and are located in the abdomen on either side of the uterus. The major functions of the ovaries are development of eggs (ova) and production and release of sex hormones. Normal ovarian function is crucial for optimal growth, puberty, and fertility.

The ovaries of younger girls are more resistant to ovarian damage than those of older teens. However, each ovary contains a finite number of eggs, so any damage to them is irreparable. The good news is that the ovaries are very treatment resistant, and it takes a considerable amount of radiation or chemotherapy to damage them.

Organ damage

The ovaries’ functioning can be disrupted by radiation to the glands themselves or to their regulator—the HPA. Damage to the ovaries is called “primary failure” and damage to the HPA is called “secondary failure.”

Radiation to ovaries

Female children or teens who had radiation to the abdomen for Wilms tumor, Ewing sarcoma, or lymphoma (and some older protocols for leukemia), or had TBI, are at the highest risk for primary ovarian failure.

The effect of radiation on the ovaries is dependent on age and dosage. In older adolescents, the ovaries may be damaged at doses of 500 to 800 cGy. During puberty, radiation doses of 800 to 1000 cGy can cause the ovaries to shut down. Some prepubertal girls, however, can get 1000 to1200 cGy and still retain ovarian function. Once an ovary fails, it totally stops producing eggs and hormones. It is an “all-or-nothing” gland.

Older girls who stop having their periods after doses of up to 1000 cGy may resume their normal cycles months to years after treatment ends.

TBI prior to stem cell transplant can also cause ovarian failure. Young girls may not start puberty, and teens past puberty may stop having periods. Some female transplant survivors never develop secondary sexual characteristics (e.g., breasts, pubic hair) or start menstruating.

The preceding information concerns primary failure—damage to the glands themselves. Female survivors who had high-dose radiation to the pituitary or hypothalamus (for treatment of brain tumors or rhabdomyosarcoma) are at risk for secondary ovarian failure—reduction in hormones regulating the ovaries. The hypothalamus secretes GnRH, which stimulates the pituitary gland to release FSH and LH. FSH regulates ovarian follicular growth and LH regulates ovulation. Young girls who received cranial radiation for leukemia have a slightly increased risk for precocious or early puberty (see earlier section about the hypothalamic-pituitary axis).

Chemotherapy

Primary failure of the ovaries has been associated with chemotherapy, but it usually takes very high doses to cause damage. For instance, girls who haven’t gone through puberty can take up to 15 to 20 grams of cyclophosphamide (Cytoxan ^® ) and may still retain function, although they are at risk for premature ovarian failure in the future. After six cycles of MOPP, girls’ ovaries usually still function well. High doses of busulfan combined with cytoxan as a pretransplant regime often causes ovarian damage.

Sometimes older survivors of childhood cancer experience an early menopause (in other words, menopause begins in the 20s or 30s instead of the 40s or 50s). As this risk can affect when and if survivors are able to have children, it’s important to discuss this with your physician.

Girls treated for leukemia before or after puberty generally retain good ovarian function. However, a small percentage of girls treated in the 1970s and early 1980s with craniospinal radiation have damaged ovaries if the ovaries were in the radiation field. The majority of girls treated for ovarian germ cell tumors remain fertile if they have one intact ovary and their uterus.

A great concern of many female survivors is their ability to have healthy children if they become pregnant. The research is reassuring in this regard. The children of the vast majority of female survivors are just as healthy as those of the general population. For more information, see Chapter 3 .

Signs and symptoms

The signs and symptoms of ovarian problems depend on age. If ovaries fail before puberty, female survivors won’t start puberty. They may grow pubic hair, prompted by the adrenal glands, but they won’t develop breasts or begin menstruation.

Survivors who were treated after puberty may stop having periods, get hot flashes, and have decreased interest in sex.

Girls with precocious puberty begin to develop breasts and pubic hair before the age of 8. In addition to possible psychosocial problems, precocious puberty causes the growth of long bones to slow or stop. Girls whose precocious puberty is not stopped can be very short.

Screening and detection

Survivors who received chemotherapy or radiation that might have damaged the ovaries should get a thorough annual evaluation. Also, any girl showing signs of puberty before age 8 or who has not begun puberty by age 14 needs an examination by a pediatric endocrinologist. A full evaluation of ovarian function includes the following:

• A thorough history, including information about puberty (or lack thereof), menstruation (e.g., date of first period, date periods stopped), menstrual irregularities, pregnancies, difficulties becoming pregnant, libido, heights of parents, age at which mother and sisters began menstruating, and symptoms of hypothyroidism (e.g., dry skin, constipation, sensitivity to cold).

• A complete physical, including height, weight, stage of puberty, and uterine size.

• FSH, LH, and estradiol levels beginning at puberty.

• If a survivor does not have a period by age 14 and has few or no secondary sexual characteristics (e.g., breast growth, pubic or underarm hair), referral to a pediatric endocrinologist is necessary.

• If a survivor used to have periods, but they have stopped for more than 6 months, or if she have hot flashes or breast discharge, referral to an endocrinologist is necessary.

Teenagers who have never had a period or whose periods have stopped should also have the following tests:

• Bone age (x-ray of hand)

• Ultrasound of ovaries

• Blood tests: Free T4, TSH, DHEAS, testosterone, and prolactin

The levels of LH, FSH, and estradiol tell the story. If it’s a central problem—from the brain—the FSH, LH, and estradiol will all be low because the system was never turned on. If the ovaries are failing, FSH and LH will be high, and estradiol will be low.

Medical management

The medical management of girls whose ovaries have shut down is somewhat controversial. Consequently, it is extremely important that survivors be followed by a pediatric endocrinologist experienced in treating survivors of childhood cancer. An internist, family practice healthcare provider, or pediatrician may be able to provide care after a pediatric endocrinologist has thoroughly evaluated the situation and recommended treatment.

Some healthcare providers treat prepubertal girls experiencing ovarian failure with estrogen first, then add progesterone after a year. Growth hormone is suggested if the girl is growth-hormone deficient. When the girl is fully mature (with complete breast development, pubic and underarm hair), she is maintained on birth control pills.

Girls experiencing a precocious puberty are given medication to stop puberty so they will continue to grow normally. When the drug is discontinued, a normal puberty begins. Survivors at risk for premature ovarian failure may want to consider oocyte (egg) or embryo freezing if they may want to have a child in the future. In addition, post-pubertal girls who need a stem cell transplant can also undergo a procedure to procure oocytes for future use.

For information about fertility and pregnancy, see Chapter 3 , and the website of Fertile Hope at www.fertilehope.org .