Case studies and clinical considerations in menopausal management
CASE 2: A SYMPTOMATIC 47-YEAR-OLD WITH A HISTORY OF BREAST CANCER
Dr. McKenzie: A 47-year-old postmenopausal woman with a 7-year history of breast cancer presents for the management of hot flashes, irritability, and reduced sleep. In addition, recent onset of vaginal dryness is causing dyspareunia that is not alleviated by lubricants. Her breast cancer was estrogen receptor (ER)/progesterone receptor (PR)–positive, and she received tamoxifen therapy for 5 years (now completed) following the initial diagnosis and management. How would you approach the management of this patient?
Dr. Marjorie Jenkins: I would first try to determine the severity of her hot flashes and how much her symptoms are affecting her quality of life. She may say that she is still having hot flashes, but how frequent are they? Do they cause nighttime awakening and subsequent fatigue?
Dr. McKenzie: The reason this patient presented was to ask for some form of relief because her symptoms were affecting her quality of life. Her dyspareunia was getting worse. She was trying various lubricants without success. At the same time, she expressed fear because her tumor was ER/PR-positive. Most cancer survivors have recurrence in the back of their mind even though they are in remission.
Dr. Jenkins: Was she asking specifically about HT or about help to relieve her symptoms?
Dr. McKenzie: She was asking for help for her symptoms.
Dr. Jenkins: I would consider low-dose vaginal estrogen to address her dyspareunia. I would also consider a serotonin-norepinephrine reuptake inhibitor, such as venlafaxine, to treat her hot flashes and irritability, along with lifestyle modifications, although the latter do not have evidence-based support. If these measures failed to offer relief, I would reconsider the risks and benefits of low-dose HT. I would call her oncologist for input if I planned to start vaginal estrogen, low-dose topical testosterone, or any type of hormonal treatment. I would make sure that the patient knew that her oncologist was working as part of the team responsible for her management.
Dr. Thacker: I concur. When I see hormonally sensitive breast cancer patients with vaginal symptoms, particularly when they are taking tamoxifen, I often talk to them about local estrogen before vaginal atrophy becomes severe. Once the atrophy becomes severe, local estrogen, even in low doses, may be absorbed systemically (increasing the risk of endometrial hyperplasia) until the the vagina becomes re-estrogenized and stratified with healthy squamous epithelium. Once this restratification takes place, there are generally no systemic hormonal effects with low-dose local vaginal estrogen, but it is best to avoid severe atrophy in the first place. I like to start local estrogen early if I know that the oncologist wants to use an aromatase inhibitor in a breast cancer survivor. I prescribe the low-dose vaginal form frequently in my practice, and order transvaginal ultrasonography liberally if there is concern about the endometrium.
Additionally, I would offer this patient venlafaxine or, more specifically, desvenlafaxine, as the literature has shown that the latter agent is associated with an improvement in sleep.4 (Currently, desvenlafaxine has been approved by the US Food and Drug Administration [FDA] solely to treat major depression; however, it has been studied in nondepressed women with hot flashes and is expected to be the first nonhormonal agent to receive FDA approval specifically to treat hot flashes.)
Dr. Gass: This patient still has her uterus in place. Data show that estrogens have a first-pass uterine effect, and this gives me pause because estrogen levels could well be higher in the uterus than in the bloodstream. Because of those data, as well as the absence of long-term safety data, the use of estrogen in this patient would cause me concern.
With breast cancer patients in particular, I try everything else to treat vaginal dryness before adding estrogen. I believe that if a patient is having dyspareunia despite the use of adequate lubricants, something else is the problem. In many cases these women have not had intercourse for months because they have been undergoing treatment for breast cancer, and they can have hallmark pain syndromes or constriction of the vagina that may require treatments besides just estrogen. If all else failed, I would prescribe vaginal estrogen on a temporary basis. Women who stay sexually active after menopause can do perfectly fine without treatment, but those who have periods of abstinence and then try to resume sexual activity typically run into problems.
Dr. Hodis: Would you have concern about breast cancer recurrence with estrogen reinitiation, based on the literature?
Dr. Gass: I have seen recurrences out to 20 years after the initial cancer. If the cancer does recur, the woman will always have a nagging doubt that it could have been avoided if she had not used estrogen.
Dr. Thacker: We have many breast cancer survivors in our practice. It is an easier decision to give estrogen to women who have had bilateral mastectomy with reconstruction for a stage I breast cancer and have already had a hysterectomy or bilateral salpingooophorectomy. But we otherwise try to avoid it unless the patient has first tried everything else and is miserable from her vaginal symptoms.
Dr. Gass: When a patient is diagnosed with breast cancer, I gently encourage her to continue sexual activity through the course of treatment, explaining that she may be far better off later. It may avoid a lot of problems if we can proactively get that message across.
Dr. Jenkins: That is a great point, and there is evidence that increased sexual activity decreases vaginal atrophy and assists in maintaining vaginal elasticity and the ability of urogenital congestion with arousal. Although lubricants and moisturizers do work well, they may require repeated application, and inelasticity is still a problem for some patients. It is somewhat of a “use it or lose it” proposition.
Dr. Thacker: Recurrent urinary tract infections (UTIs) are a problem as well. Patients see urologists, undergo multiple endoscopies, and are treated with antibiotics, sometimes chronically, yet often they are not even offered local vaginal estrogen, which reduces recurrent UTIs. Local estrogen should be considered in any woman with vaginal atrophy and recurrent UTIs.
Case continued
Dr. McKenzie: To return to our case, this patient’s vagina was, in fact, severely constricted because she had not been sexually active for a while. Her BMI was initially greater than 25 kg/m2, but she lost weight and became more symptomatic as she did so. She then stopped having sex because it was painful.
When she presented initially, she had a package of black cohosh with her and was willing to try it for her symptoms but was apprehensive after reading the disclaimers in the package. A 47-year-old who has already been diagnosed with ER-positive breast cancer is generally anxious about using any therapies that may be associated with an increased risk of breast cancer.
After examination of her vagina, her oncologist was consulted and suggested that her serum estradiol levels be measured; they were less than 20 pg/mL. We then agreed to a trial of estradiol vaginal tablets, vaginal dilators, and an increase in her sexual activity. She has been on vaginal estradiol for 2 years and is functioning very well. Her hot flashes improved spontaneously as her body adapted to her new weight.
