Peri-menopause, hormone replacement, and GSM (genitourinary syndrome of menopause) Lecture presented by Dr. Jerome 9/13/2018
First, let’s define menopause.
When I talk about menopause, many women say, “I have done that already.”
The truth is that menopause begins the day after your last period is over, and lasts the rest of your life. Menopause means that your body has stopped producing estrogen. Your eggs have been spent, you can no longer become pregnant, and your intrinsic levels of estrogen decline. Your body can produce some estrogen in fatty tissue from the conversion of steroids produced in the adrenal gland. That is one of the theories of why women gain weight at menopause.
So, how to define the peri-menopause?
Sometime in your 40’s your cycles begin to change. The remaining eggs in your ovaries are not as healthy as they were when you were younger. That is why fertility declines in the 40’s.
Women notice at first subtle changes in their menstrual cycle. Instead of cycles being about 28 days apart, they occur closer together, somewhere between 21-28 days.
An occasional very short cycle can occur, perhaps two weeks from the last. The amount of bleeding can change, too. Many women notice that they get almost all of their bleeding on one or two days. Many women complain of changing a pad or tampon every hour or two on their first two days, with a marked decrease in bleeding for the next several days, and spotting than can go on for several more. After the cycles get closer together, then, in the next stage, the cycles become farther apart and erratic. The amount of bleeding can vary from cycle to cycle. Symptom wise, I think women feel more of the ups and downs of their hormone levels. Many women notice more bloating, breast tenderness, headaches, and irritability related to their cycles. Hot flashes can occur several days before the cycles begin. And, women with a history of depression may have more difficulty treating their depression during this time, or notice the new onset of depressive symptoms.
So how do we manage this?
I think that the first thing that we as physicians must realize is that this is a very significant time that women begin to see changes in their bodies and need support. We cannot be dismissive and chalk this up to getting older. Women can often benefit from treatment.
I think that low dose oral contraceptives are an excellent choice for many healthy women during this time. The birth control pill will regulate the frequency of cycles, decrease bleeding, and alleviate some of the ups and downs of hormone levels, thereby decreasing some of the symptoms related to hormonal changes.
What about cancer? There is very good news about the benefits of oral contraceptives and the risk of cancer. Women who take OC’s during peri-menopause can reduce their risk of getting ovarian cancer by up to 60% and the benefit can last up to 20 years. This is huge. Studies have also demonstrated a decrease in endometrial and colon cancers in women who took birth control pills. What about breast cancer? Although some studies have shown a small increase in breast cancer, the best study done did not show an increase in breast cancer.
A progesterone containing IUD is an excellent choice to deal with heavy cycles during the peri-menopause. The Mirena IUD is being used frequently in younger women now, and can really improve quality of life in women with heavy bleeding.
Of particular interest to me are women who undergo premature menopause. The average age of menopause is 51.5. Women who undergo menopause prematurely should be maintained on hormones at least until the age of natural menopause, because of the benefits for the heart and bones.
But we know that many of our cancer patients face early menopause due to surgery for cancer or chemotherapy. These patients require support in so many ways. The rapid decline in hormone levels can affect sleep, mood, cognition, productivity and quality of life. We do have non-hormonal options for women that include anti-depressants, gabapentin and clonidine that can relieve some of the vasomotor symptoms. We need to be very vigilant regarding a declining bone density , and use drugs specific to the bones to maintain density. Some of these drugs can also prevent bony metastases from breast cancer.
Decrease in sexual function and enjoyment due to dryness and pain can be very significant. I will talk about his more when we discuss GSM.
Hormone replacement therapy:
Most of us are aware of the results of the Women’s Health Initiative. This was the study whose results were published in 2002 that said that hormones increased the risk of breast cancer, strokes, heart attacks and blood clots in women. Many, many women stopped HRT that day, and the concerns about the results of this study and the negative feelings about hormone replacement remain to today.
As a practitioner, I saw so many women who suffered from the symptoms caused by lack of estrogen and were afraid to take hormones. I became more active in the North American Menopause Society and attend the conferences yearly to hear the scientists who study women’s health in menopause discuss their data. The good news is that there is comforting information in the subsequent studies and re-analysis of the data.
First, let’s understand why the Women’s Heath Initiative was proposed. When I first began practicing in the 80’s we gave women much higher doses of HRT with the thought that it protected the bones and heart, maybe the brain, and women would look and feel better. The data from a very large study called the Nurse’s Study, indicated that the women who took hormone replacement had less heart disease.
In 1994, scientists from the NIH began the study to determine if giving HRT to post-menopausal women would decrease heart disease, as 50% of women died of cardiovascular related causes. In the study, they gave women aged 50-80 Premarin ( an estrogen derived from horses' urine) and Provera ( a synthetic progesterone) , or placebo. It was a double-blinded study so the women did not know what they were getting. Many of these women had never taken HRT in the past. The study was terminated abruptly in 2002 because they found more cases of breast cancer, strokes, heart attacks, and blood clots in women who took HRT, and less cases of fractures and colon cancers. There were more negatives than positives, and the study was terminated prematurely, which gave hormone replacement a very bad name for years to follow. Those of us who were prescribing HRT at the time realized that the methodology of the study was not in line with how we practiced: we most often gave women HRT at menopause in their 50’s, but rarely would we begin HRT in the late 60’s or 70’s, and we did not appreciate the negative effects described in the study. But, the purpose of the study was to see if giving older women
hormone would prevent them from getting heart disease.
Some researchers looked deeper into the data. When they divided the women into groups by age: 50’s, 60’s and 70’s.. they found that the data varied . Women in their 50’s, or within the first 10 years of menopause, had less mortality if they took HRT. In the 60’s the risk and benefit were equal, and in the 70’s, HRT became more risky.
The researches proposed what is called the “timing hypothesis” which states that it truly depends on how soon after menopause hormones are initiated, and it is now felt that women should be started on HRT in the first ten years since the last menstrual cycle to achieve the most benefit.
This year, data was published after a 17 year follow-up to the initial date from the WHI, and that data did not show any increase in mortality in the women in the WHI who took HRT from any cause including cancer, no matter what age the hormones were started. This data did not get the same press as the initial results.
In the arm of the WHI which involved women who took estrogen only and not progesterone, because they had had hysterectomies, the data actually demonstrated less heart disease and breast cancer than women who did not take any hormones at all.
Since the WHI, we now often prescribe transdermal estrogen, often in patches, and bioidentical progesterone instead of synthetic, so more studies need to be done with these products which are expected to have even less risk.
The data regarding the benefits of estrogen for heart and bones is quite impressive.
I believe that I am seeing many more women with worrisome bone densities in their 50’s and 60’s than I used to see when more women were taking HRT. Now, the greatest contributor to how good our bones are is our genetics. To the great extent, our bone structure is inherited, and we can make some lifestyle changes which can be of some benefit. We worry about bone density in women because fractures, especially of the hip, can be the event which changes a women’s ability to live independently, which, for many of us, is our goal as we age. And we know that 25% of women who break a hip do not survive more than a year.
94% of women who break their hip, do so because of a fall. Prevention of falls is an important goal that we talk about with our patients. How do you prevent falls: the main contributor to falls is lack of muscle strength, so, here is another reason that exercise, especially weight bearing, which can help prevent falls and fractures.
Now you might be confused, are hormones right for me? We are cautioned that hormone should not be used to prevent chronic disease, although there are benefits to prevent cardiovascular disease, osteoporosis, and some recent studies have demonstrated a decrease in dementia in women who took HRT long term.
As we worry about our risks for cancer, we must also be concerned about diabetes, heart disease, fractures, and as a physician for women, it is important for me to look at the whole patient, and make decisions regarding HRT in light of all of a patients’s symptoms, risks and family history. We always need scientific data and not fears to guide us in making appropriate choices for each individual patient.
GSM: genitourinary syndrome of menopause
Although this sounds a bit scary, gynecologists now realize that it is not only the vagina, but the vulva and bladder that suffers from the lack of estrogen. The tissues become thin and less vascular, less elastic. Many, and probably most women who are not on HRT will experience vaginal dryness after menopause, and many will experience painful intercourse, vulvar dryness and discomfort, and in regards to the bladder, will notice more urgency, frequency and urinary tract infections. Along with the thinning of the vaginal epithelium there is also weakness in the vaginal muscles, and urinary incontinence becomes quite common.
As my patients age, I find that many women no longer have vaginal penetration and find other ways to be intimate, but mourn the loss of vaginal sex as a loss for their relationship. I have found that some of my elderly patients tell me that their difficulty with bladder function has affected their ability to exercise, and sometimes even socialize because their incontinence is unpredictable and embarrassing.
So how do we manage these problems?
With the negative feelings about estrogen, many women decline to use vaginal or topical estrogen products to treat vaginal dryness and painful intercourse. So what does the data show? The level of estrogen in the bloodstream after the use of vaginal estrogens usually remains in the menopausal range. Most studies do not show an increase in cancers with normal doses of vaginal estrogen, even for women at high risk of breast cancer or those who have had breast cancer. Women currently being treated for breast cancer with aromatase inhibitors do have increased levels of estrogen with vaginal topical products and should not use them. Women who have had breast cancer do not show in increase in recurrence after the use of vaginal products. As in all decisions of this type, a women’s particular cancer, stage and treatment, must be included in decision making and in consultation with her oncologist.
What about non-hormonal treatments? Vaginal lubricants and moisturizers can be very helpful, There are many different types available. It may also be helpful to use vaginal dilators or vibrators to stretch the vaginal wall and maintain function.
A procedure that we at Foxhall have found very helpful to most patients who cannot use vaginal estrogen or find it inadequate is thevaginal laser. The laser penetrates the tissue and the laser energy causes tissue repair that increases blood vessels, collagen and elastic fibers, as well as increased layers of epithelium. These changes result in less dryness and painful intercourse for about 80-90% satisfaction rate in our patients. The FDA did put out warnings recently for various companies who have come out with lasers and radio frequency technologies that make claims that have not been substantiated in the literature. So if you decide to pursue one of these, please be certain that the data supports the benefits and the practitioner has the expertise to provide the service.
Another procedure we have found extremely helpful to our patients with incontinence and mild degrees of prolapse is called “pelvic floor muscle therapy”. Our nurse teaches patients how to best use the muscles of the pelvic floor to strengthen sphincters and improve incontinence of urine and bowels which is very common with aging.
Strengthening your pelvic floor has also helped patients with frequency, urgency, and frequent nighttime urination. Although pads are ubiquitous in the drug store , incontinence is not normal and often can be improved with exercise before medication or surgical correction needs to be considered.
So, for today, my take home message is that you do not have to live with symptoms of menopause that diminish your quality life. Don’t let anyone tell you that this is just aging and you will have to live with it. There is so much more we can do to make your life better.
Marilyn Jerome, MD
Foxhall OB-Gyn Associates
N.B. This lecture was presented on September 13, 2018, at the Woodmont Country Club as part of a benefit hosted by the Sibley Hospital Foundation to support the gynecologic cancer programs at Sibley Hospital
Decreasing hormone levels in the perimenopause and menopause can cause the physical symptoms of hot flashes, night sweats and vaginal dryness, but are also related to symptoms of anxiety and depression. Some women are very sensitive to hormonal changes manifested in PMS, pregnancy, postpartum, and during the menopausal transition.
Depressive symptoms include sadness, anxiety, fatigue, lack of energy, sleep disorders such as difficulty falling and staying asleep, and changes in appetite. More serious symptoms of hopelessness, worthlessness and suicidal ideation can occur. When depressive symptoms result in alterations of daily life and activities, it may be diagnosed as a clinical depression. The onset of clinical depression can occur at menopause.
Symptoms of menopause can include hot flashes, night sweats, sleep disturbances, weight gain, fatigue, decreased memory, and sexual dysfunction, and these symptoms can overlap with those of depression and anxiety, which is one reason why the diagnosis may be more difficult. This is often a time when women experience difficult life changes such as children leaving home, parents aging, job stresses and relationship issues which add difficult social components to the equation.
If you have suffered from depression in the past, have experienced PMS or postpartum depression, you are especially vulnerable during this time. If mood changes affect your ability to attend to normal daily activities, you should be appropriately evaluated and treated. Don’t be reluctant to recognize symptoms and ask for help.
So how do you treat depressive symptoms of menopause and clinical depression?
If diagnosed with clinical depression, certain antidepressants are effective in treating the mood disorder as well as vasomotor symptoms of hot flashes and night sweats. Gabapentin used at bedtime can alleviate night sweats and improve sleep. Cognitive behavioral therapy and psychotherapy can also be helpful in conjunction with medications.
Although hormone replacement therapy is not approved to treat mood disorders, research indicates that estrogen may be as effective as antidepressants in perimenopausal women, even if they are not experiencing hot flashes. Estrogen can benefit mood and well being in women who do not suffer depression. In postmenopausal women, estrogen is not effective in treating depression. There is less information about hormonal combinations such as estrogen and testosterone.
There is little data to support the use of complementary medical treatments such as herbal remedies or supplements to treat depression in menopause. Exercise may be helpful in alleviating depressive symptoms.
As with all medical decisions, your individual symptoms and medical history must be taken into account to decide on which treatment is best for your situation.
MenoNote, MenoNotes Task Force of the North American Menopause Society,
What does the data tell us about the effect of hormone therapy on the incidence of Alzheimer’s disease? Conflicting data has appeared in the literature for many years.
The WHI (Women’s Health Initiative) data demonstrated that women over 65 who were given oral Premarin and medroxyprogesterone acetate had cognitive decline, while the younger women did not. Perhaps, similar to cardiovascular disease, timing is important.
Data from a Finnish study which followed women for 25 years had different findings. Of the 8000 women who were followed, 227 eventually developed Alzheimer’s disease, with a mean age of 72. The analysis controlled for the following risk factors: age, alcohol use, smoking, exercise, occupation, and parity ( the number of children a women has had). The data demonstrated that if hormone therapy was taken for 5 years, there was no increased risk of developing Alzheimer’s. If hormones were taken 5-10 years, the risk ration was .89, or an 11% decrease in the incidence of Alzheimer’s, although this did not reach statistical significance.
What was significant was that women who took hormones for more than 10 years had an almost 50% reduction in Alzheimer’s disease.
Three other large randomized trials in which women took HRT for less than 7 years did not demonstrate a change in cognitive function. In contrast, the Cache County study from Utah did demonstrate a significant reduction in Alzheimer’s disease if HRT was started early in menopause and continued for at least 10 years.
Mortality date from the WHI calculated 18 years after the study was completed demonstrated a decreased risk of dementia in estrogen and progesterone uses, with a larger decrease in risk in those women who took estrogen alone.
Since the WHI, there have been changes in hormone prescribing, with more use of transdermal preparations and bio-identical progesterone. It is possible that these preparations would
provide improved results.
At this point, the North American Menopause Society does not recommend that HRT be given for the prevention of dementia until more definitive data is available. Hormones given soon after surgical menopause may improve cognitive function, and should be considered at least until the age of natural menopause.
It is not likely that long-term randomized clinical trials will be done to put this issue to rest.
What can be concluded from the data as provided is that hormone therapy started soon after menopause and continued for ten years or more may reduce the incidence of Alzheimer’s disease.
Update Menopause. OBG Management, Volume 30, Number 6, June 2018
What’s the impact of long-term use of systemic hormone therapy on Alzheimer disease risk?
Andrew Kaunitz, MD, JoAnn Pinkerton, MD, JoAnn Manson, MD
Imtiaz, et al., Post-menopausal hormone therapy and Alzheimer’s disease: a prospective cohort study, Neurology, 2017; 88 (11) pp 1062-1068
Women over the age of 40 know that it is unlikely that they will conceive spontaneously, however, gynecologists recommend that women use contraception until one year after the last menstrual period.
Although conception over 40 may be difficult, US census data demonstrated 26 births per 1000 women over the age of 40. Of these, one-third are unintended. Therefore, there is a need for contraception during this age group. Additionally, women over 40 experience a high risk of spontaneous miscarriage: 34% up to age 44, and 53% over the age of 45. Increased maternal complications include hypertension and diabetes, For the fetus, there is a high risk of chromosomal defects. Therefore, the need for effective contraception in this age group is an important consideration.
So what does the data tell us?
The CDC (Center for Disease Control) has important data regarding safety considerations and contraindications to contraceptive use.
IUD’s are considered in the top tier of recommended contraceptives. There are two types of IUD’s, those with progesterone, and those with no hormones. IUD’s are placed in the office and there are few contraindications. They are highly effective and remain in place for 5 or 10 years. They are easily reversible. Risk of infection and expulsion are quite small, and the continuation rate is higher than oral contraceptives.
The copper IUD is considered to be effective for 10-12 years. The failure rate is less than !%. It is the recommended IUD for women who have had breast cancer and should not be exposed to progesterone. Although in the first 6 months of use menstrual bleeding can be heavier, the bleeding tends to normalize in the first year of use.
Progesterone containing IUD’s have become very popular. They are effective for 3-5 years, depending the the type used. There are therapeutic benefits beside the contraceptive one. The progesterone in the IUD thins the lining of the uterus, therefore making menstrual bleeding less. The effectiveness of the decrease in bleeding is similar to an endometrial ablation, and therefore reduces the need for surgery in women with bothersome, heavy bleeding. The progesterone containing IUD can also be used in postmenopausal women on estrogen therapy to protect the endometrium.
Progesterone only contraceptive products can be used in women in whom estrogen is contraindicated. Contraindications to the use of estrogen would be tobacco use, obesity, migraines with aura, long-standing diabetes, hypertension, and a history of thromboembolism.
Options include the progesterone only oral contraceptive, the progesterone implant, and injections of depo-progesterone which are administered every 3 months. Contraindications to progesterone contraceptives are a recent history of breast cancer.
The progesterone implant is inserted in the office with local anesthesia. It is effective for at least three years, and the failure rate is less than !%. The shots of depo-progesterone are administered every three months. The longer the injections are given, the more likely that menses will stop. After stopping the injections, it can take more than 6 months for menses to resume. Users of this form of contraception were noted to have an 80% decreased risk of endometrial cancer, and a 40% deceased risk of ovarian cancer. Most studies have not demonstrated an increased risk of breast cancer.
What about combined estrogen and progesterone contraceptives? Oral contraceptives are safe in most patients, except for those with the medical problems mentioned previously. The failure rate for OC’s is stated to be 9%, but with close to perfect use, the risk is much lower. OC’s are often used in the peri-menopausal women to control irregular cycles and heavy bleeding. OC’s can also treat the symptoms or irregular hormone levels often found in the peri-menopause. These symptoms can include headaches, hot flashes, and mood changes. The risk of thromboembolism is increased with OC users, and the risk if about 8-10 per 10,000 women/years of use. The greatest risk is in the first 3 months of use.
When oral contraceptives are used in women over 40, careful considerations must be given to medical situations that might increase the risk of heart attack and stroke, since these are rare but significant side effects. OC’s should be avoided in smokers and hypertensives, and also in women who have migraines with aura.
Combined estrogen and progesterone can also be administered as a patch or intra-vaginal ring. The patch is considered to provide higher levels of estrogen and an increased risk of blood clots than a similar OC.
The benefit of reducing cancer risk is impressive and lasts for at least 15 years after discontinuation. The decreased risk of endometrial cancer is 56% after 4 years of use, and 72% after 12 years of use. Women who used OC’s more than 10 years reduced their risk of ovarian cancer by more than 50%, and the benefit lasted 20 years. A reduction of colon cancer was found to be 18%. The most reliable study done on OC effect on breast cancer risk was done by the NIH, which demonstrated no increased risk, although several other studies have demonstrated a small increased risk. Women who carry the BRCA gene did not have an increased risk of breast cancer if the formulation contained 35 mcg or less of estrogen, while the OC also decreases the risk of ovarian cancer in this high risk group.
As far as peri-menopausal symptom control, contraception has significant medical benefits.
The progesterone IUD controls heavy bleeding better than oral contraceptives, and can be used to decrease bleeding in women with fibroids, although the expulsion rate is higher. For vasomotor symptoms of hot flashes and night sweats, oral contraceptives are very effective, especially if giving continuously. Standard hormone replacement will not provide contraception.
Permanent sterilization is always an option for women after childbearing is complete. Traditional tubal ligation performed laparoscopically or after a vaginal delivery or at the time of C-section has been found to reduce the risk of ovarian cancer. Many doctors are now performing bilateral removal of the fallopian tubes, as many ovarian cancers are thought to begin the the tubes.
Another option is a metal coil placed through the uterus into the fallopian tubes.
Emergency contraception is an option after unprotected intercourse. Progesterone emergency contraceptive can be used within 72 hours of intercourse, and a copper IUD can be inserted within 5 days of intercourse. Inserting an IUD is 99% effective in preventing pregnancy if inserted within 5 days.
Use of contraception can be continued until age 55, or sooner if a blood test, FSH, demonstrates evidence of menopause. The FSH should be checked at least 14 days after discontinuation of oral contraceptives.
This article provides general considerations, but medical decisions regarding the best contraception options should be made with your personal physician who can consider your history, examination, family history, and your goals.
Menopause: The Journal of the North American Menopause Society, value 25, Number 7, July 2018. Contraception for midlife women: a review. Miller, et al.
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
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