A new video from the North American Menopause Society discussing current data regarding how hormones affect the cardiovascular system.
Dr. Marla Shapiro, Immediate Past President of NAMS interviews Dr. Maria Stuenkel, Clinical Professor of Medicine, University of California at San Diego
Treating vulvovaginal atrophy in postmenopausal breast cancer survivors: efficacy of the fractional carbon dioxide laser
Many women experience symptoms of vulvovaginal atrophy after the menopause transition.
The symptoms include vaginal dryness, painful intercourse, vaginal itching and burning, vaginal bleeding with intercourse, painful urination, and decreased sensitivity with intercourse. Women can be prone to more vaginal and urinary infections. The cause is lack of estrogen in the vaginal and vulvar tissues, which are very sensitive to estrogen. The result of lack of estrogen is decreased lubrication which comes from the blood vessels beneath the epithelium of the vaginal wall. There is also a decrease in the collagen and elastic fibers of the vaginal wall, which leads to decrease elasticity, and narrowing and shortening of the vagina.
In women being treated for breast cancer, chemotherapy can cause premature menopause and a decrease in estrogen levels. Anti-estrogen drugs such as tamoxifen and aromatase inhibitors also decrease estrogen levels. The vulvovaginal atrophy in breast cancer patients is often worse than in women who transition to menopause naturally. Quality of life is often severely impacted by inability to have a normal sexual relationship, as well as other bothersome symptoms. These symptoms can be so bothersome that some women might consider discontinuing anti-estrogen treatments early, which can affect survival.
Treatments for women who have not experienced breast cancer include lubricants, local and systemic hormone therapy. Vaginal testosterone and DHEA are metabolized in the body to estrogen, although the level is very low. Many women are concerned about any treatment that might increase the estrogen level in the body.
In women who have had breast cancer, the treatments include vaginal moisturizers, vaginal dilators, and pelvic floor physical therapy. Many women resort to non-penetrative sexual activity, and become resigned to not having intercourse again. In 2014, the fractional carbon dioxide laser was introduced in the US, and was approved by the FDA for the treatment of vaginal dryness and painful intercourse. In women who experienced natural menopause, studies demonstrated that the affect of the laser was to increase vascularity of the vaginal wall, which increased lubrication. It also increased collagen and elastic fibers, which restored the integrity of the vaginal wall. Data regarding the benefit to women who have experienced menopause because of breast cancer chemotherapy or hormonal treatments had not been studied in any large trials.
In the latest issue of Menopause, a study was published from the University of Naples in Italy.
The study looked at 82 women who were affected by breast cancer and vulvovaginal atrophy, made worse by chemotherapy or anti-estrogen treatments. Almost two-thirds of these patients were younger than age 50. All of the women studied had failed treatment with non-estrogenic lubricants or moisturizers.
Patients in the study were treated with the vaginal laser three times, 30-40 days apart. A number of symptoms were evaluated with each treatment, including pain, dryness, painful intercourse, vulvar itching, and reduced sensation.
The results of the study demonstrated that many of the symptoms (vaginal dryness, itching, vaginal sensitivity, bleeding, painful intercourse, and pain with penetration with the laser probe) were significantly improved, although not completely in many patients. It is possible that more than three cycles should be used in these patients. The study did not demonstrate any systemic adverse effects. Although patients do not experience pain with administration of the laser treatment, the initial discomfort with the insertion of the laser probe appears to improve with subsequent treatments. There was evidence that starting treatments before symptoms are more severe, produced a greater reduction in symptoms.
Further studies should look at whether additional treatments will benefit women who continue to have symptoms after the initial three treatments, and how long the benefits lasts. It is recommended that women have a touch-up yearly, but in this unique population, a different treatment schedule might be more effective. Stay tuned as more data is collected and reported.
Marilyn C. Jerome, MD
Fractional microablative CO2 laser in breast cancer survivors affected by iatrogenic vulvovaginal atrophy after failure of nonestorgenic local treatments: a retrospective study.
Pagano, et al. Menopause, alum 25, Number 6, June 2018
New data on breast cancer and chemotherapy: more women with early stage disease do not need chemotherapy
More than 300,000 women were diagnosed in the US with breast cancer in 2017. Of those, approximately 63,000 were diagnosed with ductal carcinoma in situ, DCIS, or non-invasive breast caner. The remaining 250,000 had breast cancer that was invasive. Of those, 60,000 were diagnosed with early stage breast cancer that had intermediate Oncotype DX score, and the decision about whether to recommend chemotherapy was unclear.
The Oncotype DX test analyzes the activity of a group of genes that describes the behavior of cancer and its response to treatment, and whether it is likely to grow and spread. This test is used in patients who have been diagnosed with Stage 1 or 2 breast cancer that is estrogen-receptor positive and lymph node negative for cancer cells. The test is used to determine if chemotherapy would be useful to prevent recurrence. It is also used to determine if DCIS is likely to be recurrent or progress to invasive cancer, and whether radiation would be helpful.
It is typical that tamoxifen or aromatase inhibitors (endocrine therapy) are used after surgical removal of the tumor to prevent recurrences, but some women are more at risk of having recurrences, and the Oncotype DX is used to determine who would benefit from chemotherapy.
The results of the Oncotype DX will provide a recurrence score, between 0 and 100. If the recurrence score is less that 18, the cancer’s risk of recurrence is low and the benefits of chemotherapy may not outweigh the risks of the treatment. If the score is 18-30, the risk of recurrence is considered intermediate, and it was not clear whether the benefits of chemotherapy would outweigh the risks. If the score is 31 or greater, it is felt that the benefits outweigh the risks, and chemo is offered to the patient.
Prior to the most recent data, patients who found themselves in the intermediate category found themselves in a conundrum. The decision on whether to offer chemotherapy was a shared decision between doctor and patient, taking into account many factors including age, other medical problems, and the patient’s wishes. Data were needed to further clarify the benefits in this group of patients.
The TailorRx was a prospective clinical trial that enrolled 10,000 women between 2010 and 2016. These women had estrogen-receptor positive, HER2 negative, lymph node negative breast cancer. If the recurrence score was less than 11, the women received only endocrine therapy. If the score was greater than 26, the women received chemotherapy and endocrine therapy. If the score was between 11 and 25, the women were randomized to receive either endocrine therapy only, or endocrine therapy plus chemo. These women were followed on average 8-9 years. The results were published last week in the New England Journal of Medicine.
There were 6711 women who were in the mid-range, and who were randomized. In that group, there were 836 events, which included recurrence, a new primary, or death. The study demonstrated that the women who had undergone chemotherapy and endocrine therapy did no better than those who had endocrine therapy alone. The exception to this were women who were diagnosed with breast cancer at age 50 or younger. If the recurrence score in this group was 16 or greater, they received substantial benefit from chemotherapy. This could be accounted for by the fact that chemotherapy induced early menopause.
In women with a score of 10 or less, the risk of recurrence at 9 years was 3%. In the intermediate score group (11-25) the nine year risk of recurrence was 5% for those who did and did not have chemotherapy.
There are other gene assays besides the Oncotype DX that can be used, and it is expected the further research will identify and analyze additional genes that will be useful.
All medical decisions, including those that regarding the treatment of cancer, must take into account an individual’s specific disease and medical situation. Medical oncologists should be consulted to get an accurate assessment of risks and benefits.
Marilyn C. Jerome, MD
Foxhall Ob-Gyn Associates
The Washington Post: Health and Science, June 3, 2018
Most women with a common type of early-stage breast cancer can skip chemo, a new report finds, by Laurie McGinley
The New England Journal of Medicine. June 3, 2018
Adjuvant Chemotherapy Guided by a 21-Gene Expression Assay in Breast Cancer, Sparano, et al.
Breast cancer.org. Oncotype DX
Gynecologists often prescribe oral contraceptives to manage the perimenopausal symptoms of irregular cycles, heavy and prolonged bleeding, and hormonal variations that can result in mood changes, irritability, headaches and hot flashes. The data regarding the risks of oral contraception increasing breast cancer incidence has been confusing.
An editorial published in the May, 2018, issue of the journal Menopause, addressed this controversy.
The New England Journal of Medicine published a Danish study recently that demonstrated a small but statistically significant increase in breast cancer in women who currently or recently used birth control pills. The relative risk was in the range of 1.2, and was similar to the increased risk of women who used the progesterone containing IUD. Because this was on observational study and looked at women only below the age of 50 (most breast cancers occur in women over the age of 50), the authors noted that the study did not control for other factors that also increase the risk of breast cancer such as age at first menses, alcohol intake, exercise. and a history of lactation. The study also did not take into account the surveillance for breast cancer such as clinical breast exams and mammograms. it is probable that women receiving regular exams and being prescribed medication would have greater surveillance than women not seeing a physician as regularly. Because the elevated risk was modest and this was an observational study, the study does not prove cause-and-effect, and the data should be interpreted within its limitations.
Several studies published prior to this one differed in conclusions. The NIH funded a population-based study looking at women ages 35 to 64, performed by the CDC and published in 2002. The study was felt be rigorously conducted and detailed regarding oral contraceptive use and breast cancer incidence. The results of this study did not demonstrate an increase in breast cancer in uses of birth control pills, progesterone only pills, and progesterone implants or injections. The doses of oral contraceptives were often higher prior to 2002 than they are now.
The follow-up analysis done in 2012 did not demonstrate a difference between the ten most commonly prescribed formulations of oral contraceptives. A different study did show in increase of breast cancer in formulations with higher doses of estrogen and the progestin ethynodial acetate which is rarely used today. Lower dose OC’s did not demonstrate an increased risk of breast cancer.
A study which came from the UK and published in 2017 was the longest-term study published to date. On average, they followed women for 40 years since 1968. Many of the women were in their 70’s, and the results were impressive. There was no increase in breast cancer for women who ever used oral contraceptives vs. never users, but the risks of colon, endometrial, and ovarian cancer were significantly decreased!! The risk of cervical cancer was increased but not statistically significant.
When multiple studies were analyzed, there was not found to be an increased all-cause mortality or breast cancer specific mortality for women who ever took OC’s, despite length of use or time since discontinuation.Women who ever took OC’s demonstrated a reduced mortality of ovarian cancer to RR 0.58.
Women at risk of breast cancer because of family history do not further increase their risk by taking oral contraceptives, when pooled data were evaluated.
What about carriers of the BRCA genes? The data varies, but multiple studies do demonstrate an increased incidence of breast cancer which is moderate, and not always statistically significant, but a very definite decrease in ovarian cancer which is significant.
The use of hormonal contraception to manage peri-menopause must take into account multiple variables. Women in this age group with untreated hypertension are at increased risk of stroke, heart attacks, and peripheral vascular disease. Healthy, normal weight, non-smokers can use oral contraceptives until menopause or the age of 55 to manage the menopausal transition. Available data demonstrated no increase in breast cancer or all-cause mortality of this intervention, while offering protection against endometrial, ovarian and colon cancer.
As will similar medical decisions, consult your gynecologist to choose the best intervention for your particular situation.
Marilyn C. Jerome, MD
Foxhall Ob-Gyn Associates
Editorial: Hormonal contraception and the risk of breast cancer: a closer look, Andrew M. Kunitz, MD, JoAnn V. Pinkerton, MD, JoAnn Manson, MD
Menopause: The Journal of the North American Menopause Society, Volume 25, Number 5, May 2018