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
Here is a lecture given in March at Sibley Hospital by Drs. Marilyn Jerome and Tara Abraham.
The video looks at the data regarding the risks and benefits of hormone replacement therapy. It discussed the options, and alternatives. Click on the link to view the lecture.
Should I have a hysterectomy, or are there other options?
Perhaps is was suggested that you consider a hysterectomy for heavy bleeding or fibroids. These problems are very common in women in their late 30’s and 40’s. You should know that there are non-surgical options that can control symptoms and avoid a major surgical procedure.
First of all, anyone with abnormal bleeding or a pelvic mass should be evaluated. Although uterine cancer is rare in women before the age of 50, a pelvic sonogram and/or an endometrial biopsy can evaluate the uterus and ovaries and decrease that concern.
Heavy menstrual cycles can be controlled often by using oral contraceptives. Birth control pills are very safe for women in their 40’s if they are not smokers or hypertensive. Birth control pills will manage the irregularity of the intervals between cycles that occurs in peri-menopause, and
markedly decrease the amount of flow. Additional benefits of oral contraceptives are that the pills can eliminate some of the hormonal irregularity of the peri-menopause which can cause hot flashes, mood changes, and insomnia.
If heavy bleeding is the issue, an IUD containing progesterone will often make the menstrual bleeding very light or absent, while also providing contraception. The progesterone IUD lasts for 5 years, and is inserted easily in the office.
Minor surgical procedures can also control heavy bleeding. A uterine ablation is a procedure that cauterizes the endometrial lining, so that bleeding is markedly reduced. Most often the procedure is performed in the hospital, but some doctors perform this in the office. A hysteroscopy and D&C (dilation and curettage) may be performed at the same time to evaluate the endometrial cavity. The results are permanent and should be performed after childbearing is completed.
If you have fibroids that are in the uterine cavity, a procedure can be done that resects these fibroids. There are several devices that shave off the portion of the fibroid which is in the cavity, and if most of the fibroid can be removed, bleeding can be markedly reduced. This procedure is most often done in the hospital as a same-day surgical procedure, and the recovery is minimal. Most patients would be able to go back to work in a day or two.
If you have large fibroids and they are causing symptoms of heavy bleeding or pressure on other organs, a minimally invasive procedure, a uterine artery embolization, can be done by a radiologist. The uterine artery is catheterized through a vessel in the groin, and the uterine artery is blocked by small pellets that block the vessels that supply blood to the fibroids. The result is that the blood supply to the fibroids is cut off, and the tissue undergoes necrosis or cell death. Most patients need pain killers for several days, but the size of the fibroids decrease over the next several months, and menstrual bleeding is often much decreased.
Although each case is individual and a physician who performs gynecologic procedures can help you decide which procedures are applicable to your situation, it is important to know your options so that you can make an informed decision.
Marilyn C. Jerome, MD
Foxhall OB-Gyn Associates
Genitourinary syndrome of menopause (GSM) is defined as symptoms of vaginal dryness, painful intercourse, vulvar discomfort, urinary frequency and urgency, incontinence, and increased frequency of bladder infections. These symptoms are caused by the thinning of the estrogen sensitive tissues of the vagina after menopause, due to the lack of estrogen in these tissues. The most effective treatments for these symptoms are topically applied vaginal estrogen products. Women who are at risk for breast cancer or who have had breast cancer are often very reluctant to use any products that contain estrogen, even if the dose is small.
The North American Menopause Society along with the International Society for the Study of Women’s Sexual Health have collaborated to review the literature in this area and have developed a consensus statement to guide physicians regarding the safety of prescribing vaginal estrogen for women who are at high risk for developing breast cancer, or who have already had breast cancer.
There are over 3 million breast cancer survivors in the US. Many survivors experience GSM symptoms, and often at a younger age because of treatments which decrease estrogen. It is important to discuss these symptoms with your health care provider and know your options. Some clinicians are reluctant to treat patients because of the lack of data that assures safety in particular populations.
In approaching the discussion with your physician, begin by noting your symptoms: vulvovaginal burning and dryness, painful intercourse, inability to have penetration, urinary frequency and urgency, incontinence, and increased frequency of urinary tract infections. Your physician should examine you to determine if there are any conditions such as a vaginal infection or inflammation that could lead to these symptoms.
Next, consider breast cancer risk which can be determined by several models that can be easily calculated. For women who are breast cancer survivors, consideration for risk of recurrence should take into consideration factors including the time since diagnosis, stage and grade of disease,
hormone receptor status, use of aromatase inhibitors, severity of GSM symptoms and their effect on quality of life. Consultation with your breast cancer oncologist should be included in decision making.
Here are the options for treatment:
1. Vaginal moisturizes are used for symptoms of dryness and must be used frequently and independently of intercourse.
2. Lubricants are used during intercourse to reduce pain from penetration and friction. The ideal lubricant has the same pH and osmolality of the vaginal tissue and should not include parabens, flavors or scents, glycerin and spermicides that can be irritating.
3. Vaginal dilators in graduated sizes can be used to maintain the caliber of the vagina and stretching of the tissues.
4. Vaginal vibrators can be used independently or with other sexual activity.
5. Pelvic floor physical therapy can relieve pain from pelvic floor muscle spasm and vaginismus (involuntary muscle spasm of the vagina which makes penetration difficult).
6. Vaginal estrogen can be inserted as a cream, pill or vaginal ring. Because of the difference in products, methods of administration, amount of cream administered and site of administration (lower vagina vs. upper vagina), and the quality of the vaginal tissue (thinner vaginal epithelium is more absorptive than thicker tissue), the amount of systemic absorption varies. Observational studies including data from the Women’s Health Initiative have not shown any evidence of an increased risk of breast cancer in women who used vaginal estrogens. One study did not find an increased risk of recurrent breast cancer in women who used vaginal estrogen products after the diagnosis of breast cancer. The message here is that the available evidence is reassuring, but in making a decision, risk should be considered.
7. Vaginal DHEA, prasterone, has shown evidence of improvement in sexual function. The suppositories are used daily, at least in the first month of use. The DHEA is converted to estrogen and testosterone in the body, although the levels are small and in the postmenopausal range, the difference is significant. It has not been tested in breast cancer survivors.
8. SERMs: Ospemifene if a selected estrogen receptor modulator which acts like estrogen on the vaginal tissue. It is an oral table taken daily. It is not approved in the US for use by women with breast cancer, and its effect on breast tissue has not been studies.
9. Topical lidocaine 4% applied to the vaginal opening prior to penetration can reduce pain, but it can also reduce sensation.
10. Vaginal testosterone can be compounded for use as a vaginal gel, but is not FDA approved. Testosterone is converted to estrogen in the body, and there is evidence that use of vaginal testosterone increases serum estrogen levels.
11. Estriol is considered a weaker estrogen produced in women during pregnancy. It can be compounded but is not FDA approved and there is not data to determine its safety in patients with breast cancer.
12. Vaginal lasers are now being used to improve the integrity of the vaginal epithelium.The effect of the vaginal laser is to increase vascularization of the vaginal epithelium which increases lubrication with sexual excitation. It also increases the thickness of the vaginal epithelium as well as increased collagen and elastic fibers in the submucosa.Studies in breast cancer survivors demonstrated significant improvement in GSM symptoms and improved sexual function.
As with other medical conditions, an evaluation with a gynecologist is the best way to evaluate risks and determine which treatment is appropriate for your individual situation.
Consensus Recommendations: Management of genitourinary syndrome of menopause in women with
or at high risk for breast cancer: consensus recommendations from the North American Menopause
Society and the International Society for the Study of Women's Sexual Health,
Menopause. The Journal of the American Menopause Society, Volume 25, No. 4, 2018
This lecture was given at Sibley Memorial Hospital in February by Dr. Shawn Davis-Wilensky and Dr. Shannon Green.
Some women go through menopause with severe symptoms and are advised not to use hormonal therapy. Women who have had breast cancer or deep vein thrombosis are at increased risk if they use hormones. So, how do you treat menopausal symptoms if you cannot use hormones?
The North American Menopause Society has collected data on which treatments work and which do not. Most women, 50-80%, try some type of non-hormonal treatment for menopausal symptoms. Most women are not fully informed about the benefits and risk of herbal therapies. Because of these uncertainties, many women use the wrong supplements or inadequate dosing, and suffer from bothersome symptoms when they could be using more successful treatments. Many supplements have risks which are not well known.
What does work?
Two mind-body therapies have proved to be successful in clinical studies. Cognitive behavioral therapy has good evidence of efficacy by reducing the discomfort of symptoms, while not really decreasing the frequency of symptoms. Hypnosis, using the Elkins protocol, has also proved effective. This protocol involves in-person hypnosis and at-home self-hypnosis. In women with more than 50 episodes of vasomotor symptoms per week, the frequency and severity of symptoms were reduced. When breast cancer survivors were treated, there was a significant decrease in symptoms, as well as in improvement in sleep and mood.
Medications that improve menopausal symptoms include antidepressants and gabapentin.
The FDA has approved low-dose paroxetine for the treatment of vasomotor symptoms. Other SSRI’s and SNRI’s have been proven to be effective in case controlled studies. The drugs that have been shown to significantly decrease menopausal symptoms are paroxetine, escitalopram, citalopram, venlaflaxine, and desvenlaflaxine. Your physician can best determine which of these drugs would be best for you while taking into account past history and use of medication, and other medical problems and prescription therapies . If a mood disorder is a significant menopausal symptom, these drugs can be very helpful. These medications are often started at lower doses and titrated up the the most effective dose. The benefits and side effects should be monitored every 6-12 months. It is important when trying to go off of these medications, the dose is tapered over two weeks to minimize side effects.
Gabapentin, which is a drug used for seizures and pain, is also effective. When given before bed, it can be very helpful for patients who suffer from insomnia and night sweats.
Other therapies that show some evidence of benefit include weight loss, mindfulness based stress reduction, the s-equol derivative of soy, and stellate ganglion block (although I have yet to find a practitioner who performs this).
What doesn’t work?
The therapies that have proven to provide not benefit through studies that look at their effectiveness include vitamins, over-the-counter supplements, herbal remedies, chiropractic therapy, and relaxation techniques. For many years, black cohash has been recommended for hot flashes with some anecdotal evidence of success. Although it could be a placebo effect, studies have not shown it to be effective.
Cooling techniques and avoiding triggers are often recommended and may provide some symptomatic relief, but do not actually decrease the frequency and severity of symptoms.
Although providing other health benefits, yoga, exercise and acupuncture have not been found to be effective strategies for the treatment of symptoms.
The bottom line is that there are useful strategies for the prevention of menopausal symptoms in women who cannot or choose not to take hormones, You do not need to suffer, so ask for help and your physician can determine which treatment might be most successful for you.
Marilyn C. Jerome, MD
Foxhall OB-Gyn Associates
North American Menopause Society: Key Points from the 2015 Position Statement of the North American Menopause Society
The November, 2017, issue of the American Journal of Obstetrics and Gynecology
discussed the benefits of removing fallopian tubes at the time of vaginal hysterectomy. Removal of the tubes at the time of abdominal or laparoscopic hysterectomy done for benign disease is becoming more routine. It was thought that removing the tubes during a vaginal hysterectomy would lead to more complications and blood loss, but the study recently published demonstrated that the risks were quite low when compared to the decrease in ovarian cancer and deaths. The authors recommended that prophylactic removal of the fallopian tubes be considered when a vaginal hysterectomy is done. This can be accomplished in about 80% of patients, while in 20% it may not be possible to remove both tubes. Why take out the tubes when not planning to remove the ovaries?
As more prophylactic salpingo-oophorectomies (removal of the tubes and ovaries for prevention) have been performed, largely due to increased testing for the BRCA gene, pathologists have noted that women at high risk for ovarian cancer have been found to have more serous intraepithelial cancers in the fallopian tubes. These are felt to be the precursor lesions for high grade ovarian and peritoneal cancers. The removal of the fallopian tubes can lower the risk of a subsequent diagnosis of ovarian cancer. In women with the BRCA gene, it is recommended that the ovaries be removed after childbearing. Removing ovaries in a premenopausal women can have serious health consequences including menopausal symptoms, vaginal dryness and painful intercourse, and an increased risk of heart disease and osteoporosis. Removal of the fallopian tubes, with subsequent removal of the ovaries after menopause, is a strategy that may reduce ovarian cancer risk, but optimize the benefits of estrogen for women in their 40's who are at risk for ovarian cancer. Although more studies are in progress, the current data points to a favorable risk/benefit ratio in favor of removing fallopian tubes during hysterectomy for benign disease.
Marilyn Jerome, MD
Foxhall Ob-Gyn Associates
American Journal of Obstetrics and Gynecology, November 2017
Risks and benefits of opportunistic salpingectomy during vaginal hysterectomy: a decision analysis. Cadish, et al.
Feasibility of prophylactic salpingectomy during vaginal hysterectomy. Antosh, et al.
Prophylactic bilateral salpingectomy at vaginal hysterectomy: time for a "policy"?,
Rosanne Kho, MD
Drs. Nicole Pardo and Lauren Messinger provided a comprehensive discussion of the transition into menopause in February, 2017. Take a look!