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 symptoms—estrogen—is 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(Drug information on 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 noxious.[1]
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.[2]
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.
Treatment-Induced Menopause
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 regimens.[3-5]
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.[6]
Often prescribed as a treatment for breast cancer, tamoxifen is associated with hot flashes (its major side effect) in at least 50% of women.[7] 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.[7]
Finally, when surgical oophorectomy is performed as part of cancer therapy, it will cause a premature, abrupt menopause.
Estrogen Denial
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.[8] Estrogen is also contraindicated in women with uterine cancer.[9] 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 cancer survivors.
Effects of Estrogen Deficiency on Body Tissues
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(Drug information on 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.[17] 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 menopause.[15]
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 disease.[2]
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.
A 48-year-old female presents with complaints of irregular vaginal bleeding and postcoital bleeding. Images from a PET/CT and pelvis MRI reveal characteristic findings. What is your diagnosis?
