Understanding the relationship between menopause and cardiovascular disease
Cardiovascular disease will kill more than 400,000 women this year, more than all cancer deaths combined. The good news is that mortality for deaths from coronary artery disease decreased 68% from 1979-2011. Unfortunately, there has been a larger decline for men than women. There is certainly less awareness and recognition of coronary disease in women than men, and this can be contributory. It is important to understand the gender differences when studying heart disease. For example, there is believed to be a larger burden in women of disease of the tiny blood vessels in the heart, which leads to heart failure without major coronary obstruction. Also,certain medical problems unique to women such as gestational diabetes, pre-eclampsia, recurrent early pregnancy loss, polycystic ovarian syndrome, and certain breast cancer treatments all increase the risk of heart disease in women.
Whether menopause itself or simply aging is associated with the increase in heart disease is still being debated. It is certain that surgical menopause, especially in women younger than 45, is associated with increased heart disease and all cause mortality. Because of this, it is recommended that women who undergo surgical menopause continue estrogen at least until the average age of menopause, but more importantly, it is recommended that the ovaries remain at hysterectomy unless involved in the disease progress.
Premature menopause is also associated with increased risk of cardiovascular disease, but now some researchers are considering the hypothesis that the underlying cardiovascular disease may contribute to the shortened reproductive life span.
In the 1990’s it was widely accepted, even by internal medicine doctors, that hormone replacement after menopause would decrease the risk of heart disease and HRT was offered to almost all women during the transition. Studies during this time demonstrated that markers for cardiovascular disease were favorable with HRT, including cholesterol, glucose, blood pressure, and markers of thrombosis. Another studied published in 1998, which gave women with heart disease hormones, was unable to show a definite benefit, and actually found an increase in heart attacks in the first year of treatment.
Next came the Women’s Health Initiative (WHI) which gave hormones to women who did not have heart disease. The study was abruptly terminated in 2002 when the researchers found more heart attacks, strokes, blood clots, and breast cancer in women who were taking HRT. The widely publicized results of the study was the impetus for many women stopping HRT immediately and many more in the next 15 years refusing to begin treatment. If hormones were to be used for the prevention of vasomotor symptoms, the lowest dose for the shortest period of time was recommended.
By 2007, the WHI data was further analyzed, and it was found that women in their 50’s, within the first ten years of menopause, had minimal cardiovascular risk, with risk increasing for women greater than age 60. The women who took estrogen only in the WHI had significant reductions in heart attacks while they were taking hormones, and no increase in CV mortality when followed 18 years later. The timing hypothesis was born, which said that it mattered how soon after menopause hormones were started.
Lessons learned from the WHI demonstrated that early use of HRT in menopausal women had less risks, and use of estrogen alone was even safer. The current use of transdermal estrogen and micronized progesterone may have less risks, but have not been studied to prove this.
Current practice today involves evaluating women for cardiac risks, and avoiding HRT in women at increased risk of CV disease. For women of intermediate risk, transdermal estrogen is thought to have less cardiovascular risk, and lower doses expected to be less risky. Instead of limiting use of HRT for a certain number of years, current recommendations suggest yearly evaluations and tailoring duration of use depending on symptoms and current health concerns.
Prescribing HRT today deserves a detailed discussion of symptoms, risk factors, family history, and treatment goals with a physician who is knowledgeable about the risks and benefits of hormone replacement.
Marilyn Jerome, MD
Foxhall Ob-Gyn Associates
Editorial: Deciphering the complex relationship between menopause and heart disease: 25 years and counting. Cynthia A. Stuenkel, MD
Menopause: The Journal of the North American Menopause Society, Vol. 25, No. 9, September, 2018.
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,