Menopausal symptoms are becoming salient management
issues for cancer survivors, not because the menopausal experience of survivors
is significantly different from that of the general female population, but
rather, for several other reasons. First, the most effective treatment for
several menopausal symptomsestrogenis not usually offered to women
surviving estrogen-responsive cancer. Second, menopause can occur prematurely in
this population due to the effects of cancer therapies. Therefore, symptoms that
usually develop gradually around age 46 to 50 and last a few years may manifest
at age 40 or younger and last longer, particularly if the woman is taking
tamoxifen (Nolvadex). Third, in this setting, menopause often presents without
much advance preparation because the patient’s efforts are focused on coping
with cancer. In such cases, the symptoms of menopause can be particularly
Menopause marks a new phase in a woman’s life. It is defined as the
completion of menstrual cycles due to the cessation of ovarian function. Along
with a lack of ovarian functioning come decreased levels of estrogen. It is this
decrease in estrogen that is the basis for many of the changes and symptoms
women may experience in menopause. Some of the earliest signs of lowered
estrogen levels include hot flashes, night sweats, sleep disturbances, and mood
variability, with a tendency toward irritability.
Cancer survivors who are at risk for menopausal symptoms as a result of a
lack of ovarian functioning include those who have received pelvic irradiation (eg,
Hodgkin’s disease, gynecologic cancer, sarcoma, or pelvic neuroblastoma) or
chemotherapy. Other cancer survivors who are at risk for menopausal management
issues include those for whom hormone-replacement therapy following natural
menopause is not regarded as a safe option. This includes women with breast
and/or endometrial cancer.
Among women who receive radiation therapy and chemotherapy, age, dose,
duration, and type of chemotherapy agents used are the most significant risk
factors for premature menopause. A majority of women over age 40 become
amenorrheic after undergoing pelvic irradiation and some chemotherapy
Radiation therapy to the vaginal area can also cause decreased lubrication,
the development of fibrous tissue, shortening of the vaginal vault, and a
thinning of the epithelial tissue. This can result in dyspareunia and an overall
decrease in sexual functioning in up to 50% of patients.
Often prescribed as a treatment for breast cancer, tamoxifen is associated
with hot flashes (its major side effect) in at least 50% of women. Women who
experience moderate-to-severe hot flashes during natural menopause and/or had
been receiving estrogen therapy appear more likely to have problems with
tamoxifen-induced hot flashes.
Finally, when surgical oophorectomy is performed as part of cancer therapy,
it will cause a premature, abrupt menopause.
It is not known whether estrogen is a safe medication for women with a
history of breast cancer, and therefore, the standard of care as practiced by
most physicians is to avoid estrogen use in these women. Estrogen is also
contraindicated in women with uterine cancer. If such patients have a
symptomatic menopause, alternative treatments must be considered. It is worth
noting that, with regard to breast cancer, the "estrogen denial
pendulum" may be swinging away from denial toward permitting its
use.[10,11] Ongoing randomized, placebo-controlled trials will hopefully shed
more light on the safety of estrogen use in selected breast and endometrial
Estrogen affects many body systems, including temperature control, neuronal
and vascular functioning, bone strength, and tissue vitality. Changes in
temperature control and hormonal fluctuations may be responsible for a
constellation of vasomotor symptoms that include hot flashes, negative mood
swings (irritability and weeping), sleep disturbances, and muscle or joint
pain.[2,12,13] All of these symptoms can have a significant effect on each
other, as well as on a woman’s quality of life. Vasomotor symptoms are
experienced by more than half of all women in menopause.
Tissue changes include a loss of collagen, decreased secretions, and
epithelial atrophy. Results of these changes on the skin manifest as excessive
dryness, sagging, and wrinkling.[14,15] In the pelvis, there is a loss of
elasticity and lubrication of vaginal tissues, causing dyspareunia and
friability as well as a decreased response to sexual stimulation.[2,16] The
acidity of the vaginal environment diminishes, increasing the risk of infection.
Urogenital health also changes, with decreased muscle tone of the urinary
sphincter muscles contributing to stress incontinence. The urethra and
bladder may become more irritable.
Bone and vascular health may also be affected by lower estrogen levels. In
menopause, bones become more porous, with bone loss exceeding bone repair, thus
increasing the risk of osteoporosis and fractures.[2,15] Cardiac arteries become
less flexible, and fats circulating in the blood take on a less beneficial
profile; levels of low-density lipids increase, and levels of high-density
lipids decrease. Correspondingly, the risk of cardiac disease increases after
Neuronal health may also suffer. Preliminary descriptive and epidemiologic
evidence suggests that lowered estrogen levels may impair cognitive functioning.
Women undergoing menopause report difficulty with short-term memory and
concentration.[18,19] Additionally, epidemiologic research has shown that women
are at greater risk than men for earlier expression and development of Alzheimer’s
Preliminary data suggest that estrogen has a protective effect against
Alzheimer’s disease.[20,21] It is hypothesized that lowered estrogen levels
decrease the transport of glucose into the central nervous system. Therefore,
cells may be denied important nutrients and may end up with excessive neuron
loss in the hippocampus, the area of the brain that controls memory
function.[2,22] Estrogen is also thought to increase regional blood flow in the
brain. Much of this evidence comes from in vitro research. Therefore, the exact
interaction between estrogen and cognitive function in postmenopausal women has
not yet been elucidated.
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