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Menopausal hormone therapy informed consent

2003; Elsevier BV; Volume: 189; Issue: 4 Linguagem: Inglês

10.1067/s0002-9378(03)01097-4

1097-6868

Susan L. Hendrix,

Cancer Risks and Factors

A little over a year ago now, the large hormone therapy clinical trial of the Women's Health Initiative came to an abrupt halt. The publication of the results rocked the medical community and our patients because a class of drugs once thought to be associated overwhelmingly with benefit was found to cause more harm than good. Now doctors have the dilemma of how to inform patients of the results of the Women's Health Initiative in a way that will help them make the best decision for themselves of whether they should use of these agents for hot flashes, night sweats, vaginal dryness, or prevention of osteoporosis.In the thousands of daily conversations on this topic, the scenario used to look like this: The patient came to the office asking questions about menopause. When the practitioner determined the patient was going through the menopausal transition, the doctor wrote a prescription for hormone pills or patches, saying they would address her concerns by replacing the hormones her body used to make. They would abolish her hot flashes, slow her bone loss, and reduce her risk of a heart attack. The patient asked if the pills caused breast cancer. Probably in some women, the doctor would acknowledge, but argued that the benefits to the heart and bones were worth taking the chance.Now the patient comes to the office and asks about the confusing information she has been reading on the increased risk of heart attack, strokes, blood clots, and dementia with hormone use. The doctor acknowledges the information has changed and is very important, but the decision to use or not to use hormones is up to her. She has menopausal symptoms and wants a solution. However, she is looking for something safe that does not cause more problems than it solves.How do you take a 7-minute office visit and discuss the pros and cons of hormone therapy with your patient who is approaching menopause? That is after a comprehensive assessment for osteoporosis, cardiovascular disease, breast and colorectal cancer…and counseling about exercise, healthy dietary habits, smoking cessation, seat belt use, and a review of immunizations due. Where do you start?Doctors and patients find themselves today in this totally changed world of menopause management. If and when to start hormones, which ones, for how long and at what risk. Moreover, what is the responsibility of the provider to inform and protect their patients? What defines our culture of conscience? How do we present the ethical tensions that exist in modern medical research and practice, many of which originate from or are provoked by the incompleteness of our medical knowledge?The cornerstone of the physician-patient relationship is trust: trust between the person in the know and the person wanting to know. To preserve this trust, it is necessary to provide informed consent every time we initiate a therapy to protect our patients. In addition, it must be credible and accountable to the medical community. Exciting science carries with it the burden of responsibility.What are the elements of informed consent and how do we relay these to our patients? Informed consent is “the willing and uncoerced acceptance of a medical intervention by a patient after adequate disclosure by the physician of the nature of the intervention, its risks and benefits, as well as of alternatives with their risks and benefits.”1.Jonsen A.R. Siegler M. Winslade W.J. Clinical ethics: a practical approach to ethical decisions in clinical medicine.4th ed. McGraw-Hill, New York1998Google Scholar With continuing and open communication of relevant information (full disclosure), the physician enables the patient to exercise personal choice, protecting patient autonomy in decision making.So, how do I approach the patient in my office who is making the transition through menopause?I start by establishing the reason the patient is seeing me: is it her routine annual examination or is she actually experiencing some of the symptoms or signs of menopause? I try to understand what else is going on in her life, how she feels about the changes in her body and the changes in her life, and how she is handling it. It is important to establish with the patient what she has heard or believes about menopause and then review with her what is true. Many women believe that menopause causes chronic diseases such as osteoporosis, heart disease, and memory loss. Menopause does not cause chronic disease and it is important to help the patient understand that. Just because these conditions become more common as women age does not mean menopause is the cause. Many women experience mood changes and/or depression, but many of these complaints occur just as frequently in women who are beyond the menopausal transition. In fact, many men complain of these same problems as they age.Hormone therapy was previously called hormone replacement therapy because menopause was considered by many to be an estrogen-deficiency disease. Certainly, the estrogen level in a postmenopausal woman is lower than one who is premenopausal, but is this abnormal or just appropriate for her phase of life? There are many myths about menopause that still linger, but 1 indisputable fact: Hormone replacement for a deficiency disease should not cause harm if the replacement is physiologic. To me, this is confirmation menopause is not a disease, but a physiologic process that is certainly life changing and needs to be managed appropriately.Dr Barnett Kramer, Director of the Office of Disease Prevention at the National Institutes of Health (NIH) said it best just after a 2-day conference held at the NIH on Menopausal Hormone Therapy. With the old name, “it was almost as though language was corrupting thought,” he said.2.Kolata G. Replacing replacement therapy.The New York Times. October 27, 2002; PubMed Google Scholar “If you think that all you're doing is treating a deficiency, you can fool yourself into thinking you don't even need to test the hypothesis that the benefits of giving hormones would outweigh the harm.”Guided by the current evidence published in an International Position Paper on Women's Health and Menopause sponsored by the National Heart, Lung, and Blood Institute, the Office of Research on Women's Health, the National Institutes of Health, and the Giovanni Lorenzini Medical Science Foundation3.Available at: http://www.nhlbi.nih.gov/health/prof/heart/other/wm_menop.htm. Accessed.Google Scholar and the results of the Women's Health Initiative, I have attempted to create an informed consent document that may help us achieve the goal of best practice.4.Writing Group for the Women's Health Initiative Investigators Risks and benefits of estrogen plus progestin in healthy postmenopausal women: principal results from the Women's Health Initiative randomized controlled trial.JAMA. 2002; 288: 321-333Crossref PubMed Scopus (13856) Google Scholar, 5.Hays J. Ockene J. Brunner R. Kotchen J. Manson J. Patterson R. et al.Effects of estrogen plus progestin on quality of life: results from the Women's Health Initiative randomized clinical trial.N Engl J Med. 2003; 348: 1839-1854Crossref PubMed Scopus (659) Google Scholar, 6.Shumaker S.A. Legault C. Rapp S.R. Thal L. Wallace R.B. Ockene J.K. WHIMS Investigators et al.Estrogen plus progestin and the incidence of dementia and mild cognitive impairment in postmenopausal women: the Women's Health Initiative Memory Study: a randomized controlled trial.JAMA. 2003; 289: 2651-2662Crossref PubMed Scopus (1852) Google Scholar, 7.Rapp S.R. Espeland M.A. Shumaker S.A. Henderson V.W. Brunner R.L. Manson J.E. WHIMS Investigators et al.Effect of estrogen plus progestin on global cognitive function in postmenopausal women: the Women's Health Initiative Memory Study: a randomized controlled trial.JAMA. 2003; 289: 2663-2672Crossref PubMed Scopus (862) Google Scholar Undoubtedly, our approach to the patient has to be individualized, because there are many variations in menopausal symptoms, clinical practice, health care resources, effective and affordable interventions. However, I think we can provide a balanced discussion to help our patients make the personal best decision.Consent for menopausal hormone therapyFrom the viewpoint of Susan L. Hendrix, DOYou have reached menopause and are considering use of hormone therapy for menopausal symptoms of hot flashes, night sweats, vaginal dryness or prevention of osteoporosis. To help you make the best decision as to what is right for you, here is a summary of key points in the decision making process that may help guide you as you undergo that process.Menopause usually occurs around age 51 and the life expectancy for women is now greater than 80 years of age. We reach adulthood at 21, so that means you may live half of your adult years in menopause, so the health decisions you make have impact on your life for many years. It is important to remember, menopause is a normal physiologic event in every woman's life, not a disease. Although we still have many unanswered questions, women transitioning into menopause have more options and better interventions for healthy menopausal years than ever before. Menopause is a time in your life when you and your doctor have a unique opportunity to assess your health and discuss the best possible ways to promote it.Women view menopause in a variety of ways; some bothersome and maddening and many as upbeat and liberating. As we age, many women do have health complaints and may experience a decrease in quality of life and an increase in risk for illnesses, such as osteoporosis and coronary heart disease. Consideration needs to be given to these concerns when making decisions about hormone use. In years past, hormone therapy was thought to improve many of these problems. New information educates us that it does not improve health conditions and may worsen them. The term hormone or estrogen therapy used in this document applies only to the prescription forms of these therapies.Because the use of hormone therapy affects many bodily systems, it is necessary to review both the potential risks and the benefits as they affect you as a whole person. As you consider what is best for you, it will be important to examine your beliefs about menopause, including your preferences for both medical and nonmedical therapies, your work situation, job satisfaction and stress levels, particularly with regard to personal relationships, your social supports, your cultural and ethnic influences/preferences, and your current use of any nonprescription (over-the-counter) remedies.This informed consent document was created with guidance from the current evidence published from the results of the recently published Women's Health Initiative (WHI) and an International Position Paper on Women's Health and Menopause sponsored by the National Heart, Lung, and Blood Institute, the Office of Research on Women's Health, the National Institutes of Health, and the Giovanni Lorenzini Medical Science Foundation.Potential benefitsHot flashes and night sweatsAlthough some women seem to make the menopausal transition without problems, others have considerable difficulty. Many women have complaints of a variety of problems that they attribute to the menopausal transition (dry skin, backache, forgetfulness, problems sleeping, irritability, mood swings). Instead, other conditions or other factors may be causing or worsening these conditions. The only symptoms of menopause that we know are due to the menopausal transition are hot flashes and night sweats, sleep disturbance (usually because of the night sweats), and vaginal dryness. About 80% of women experience hot flashes and night sweats, which are short episodes of intense heat of the face and neck. It is very difficult to predict how many years they will persist. Usually they begin to increase in the menopausal transition, peak 1 to 2 years after the final menstrual period, and may remain for several years or resolve shortly after. Avoidance of triggers, such as cigarette smoking, hot beverages, foods containing nitrites or sulphites, spicy foods, and alcohol, may help limit hot flushes.If you have hot flushes and/or night sweats, oral and transdermal estrogens are effective in reducing them. Estrogen must be combined with a progestin unless you have had a hysterectomy, in which case estrogen will be prescribed alone.Vaginal dryness and urinary incontinenceAll types of estrogen formulations reduce vaginal dryness and the pain that can occur during intercourse because of vaginal dryness. The hormone forms that can be used are oral preparations, topical estrogen creams, tablets, or a vaginal ring. The agents you put into the vagina appear to be as effective as the oral preparations for relieving these symptoms. Urinary incontinence (spontaneous urine loss) is not improved with estrogens or hormone therapy and may actually worsen the problem. The Food and Drug Administration (FDA) recommends when hormone products are being prescribed solely for the treatment of symptoms of vulvar and vaginal atrophy, topical vaginal products should be considered.Osteoporosis preventionWhether you have symptoms of menopause, you still must address your long-term health concerns. As you stop producing estrogen, your risk for osteoporosis grows. Osteoporosis is a disease that increases the fragility of your bones and makes them more likely to break. Osteoporosis can worsen without pain or other symptoms and result in bone fractures. Any bone can break, but fractures due to osteoporosis most commonly occur in the hip, spine, and wrist. Women are 4 times more likely than men to develop this disease.Knowing the factors that increase your risk may help you to focus on behaviors you need to change. Risk factors you cannot change are white race, increasing age, a family or personal history of osteoporosis, and early menopause, all of which increase your risk. Factors that may increase your risk, which you can change, are low weight or excessive weight loss, current smoking, low calcium intake or vitamin D deficiency, inadequate physical activity, or conditions that increase your risk for falling.A bone mineral density test (BMD) is the only way to diagnose osteoporosis and determine your risk for future fracture. There are many different ways to do a BMD test, but the standard we use to start therapy is to measure at the spine and hip. When you get your bone density report, look at the T-score. A T score of >−1 or greater means that you have begun to lose bone mass and may be at risk for developing osteoporosis. If it is >−2.5 or greater, then you have osteoporosis. For every 10% to 12% decrease in BMD from 1 test to the next, your fracture rate doubles; however, as we monitor your bone density, we often recommend some kind of medication to prevent further loss and reduce your risk for fracture. If you had adequate calcium intake and physical activity and did not smoke, you may have achieved your bone mass at around age 25.Life style changes that you can make to maximize your bone health are to eat a balanced diet rich in calcium and vitamin D, to avoid extreme weight loss, to add weight-bearing and muscle-building exercises, and to avoid smoking, sedatives, and excess alcohol. To prevent falls, correct any visual impairment and fall-proof your home.Depending on your age, the combined diet and supplement intake of calcium should be approximately 1000 to 1200 mg each day. Vitamin D is needed to absorb calcium. Vitamin D intake should be 400 to 800 IU/d and can be obtained from fortified dairy products, egg yolks, saltwater fish, and liver.Combined hormone therapy prevents osteoporosis-related fractures. Of the women in the WHI on hormone therapy, 10 had a hip fracture each year compared with 15 of every 10,000 women taking placebo pills each year. The FDA recommends when hormone products are being prescribed solely for the prevention of postmenopausal osteoporosis, approved nonestrogen treatments should be carefully considered, and estrogens and combined estrogen-progestin products should only be considered for women with significant risk of osteoporosis that outweighs the risks of the drug.Colorectal cancerCancer that begins in the colon is called colon cancer, and cancer that begins in the rectum is called rectal cancer. Cancers affecting either of these organs may also be called colorectal cancer. The exact causes of colorectal cancer are not known. However, studies show the risk factors for colon cancer are increasing age, high fat and low fiber diets, polyps, and ulcerative colitis and may increase a person's chances of having colorectal cancer develop. Women with a history of cancer of the ovary, uterus, or breast have a somewhat increased chance of having colorectal cancer develop. Parents, siblings, or children of a person who has had colorectal cancer are somewhat more likely to have this type of cancer develop, especially if the relative had the cancer at a young age. Having 1 or more of these risk factors does not guarantee that a person will have colorectal cancer develop. It just increases the chances.Of the women in the WHI on hormone therapy, 10 had colon cancer develop each year compared with 16 of every 10,000 women taking placebo pills.Quality of lifeQuality of life is a measure of how someone's health affects perceived well-being and the ability to function (physically, mentally, and socially). To assess quality of life, women in the WHI were given questions about their general health, physical functioning, bodily pain, energy, social functioning, mental health, depression, sleep disturbances, sexual satisfaction, and symptoms associated with menopause.The results showed there were no clear benefits for those taking estrogen plus progestin on any of the quality of life measures. There were no significant improvements on perceptions of general health, energy, social functioning, mental health, depression, or sexual satisfaction. There were slight improvements in women's physical functioning, bodily pain, and sleep disturbances at 1 year. These effects were very small and did not translate into meaningful effects. The average increase in physical functioning, for example, was less than 1 point on a 100-point scale. Most women would not notice such small differences in everyday life.In younger women (50-54 years) who reported having hot flashes and night sweats, the symptoms that cause some women to seek treatment, there were no improvements in quality of life for these 574 women except a small improvement (1 point on a 20-point scale) in sleep disturbance.Potential risksUntil recently, hormone therapy was thought to have little if any risk associated with its use. Recent research shows that for women taking estrogen plus progestin combined hormone therapy, overall, the risks (increased breast cancer, heart attacks, strokes, and blood clots in the lungs and legs) outweigh the benefits (fewer hip fractures and colon cancers).Breast cancerIf you have a family history of breast, ovarian, or colorectal cancer, especially in a first-degree relative, you may be at increased risk for breast cancer. Most cancer rates increase with age. Starting your menses early and going through menopause late, increases the risk for breast cancer. However, early first pregnancy and multiple pregnancies decrease the risk for breast cancer.Heavier postmenopausal women are at increased risk for cancer of the breast. A low-fat diet that is high in fruits, vegetables, and fiber, as well as physical activity, may reduce the risk for breast, endometrial, and colorectal cancer. Excessive alcohol use increases your risk for breast cancer. After age 50, mammography is usually performed annually or every other year because the risk for breast cancer continues to increase with age. Mammographic screening remains appropriate even in old age. Hormone therapy increases the density of the breasts as seen with mammography and may delay diagnosis of breast cancer by making mammograms more difficult to read. Twice as many women on hormone therapy have abnormal mammograms than women who are not taking hormones. An abnormal mammogram is a breast radiograph that results in a recommendation for additional medical evaluation (most often, a shorter time between mammograms, but sometimes, a breast biopsy or other tests). This translates into 1 more otherwise avoidable abnormal mammogram for 25 women per year with estrogen plus progestin use. Although we have known from other studies that estrogen plus progestin use increases the density of breast tissue on mammograms, the increase in abnormal mammograms with estrogen plus progestin use seen in the WHI is a new finding.The increased risk of breast cancer caused by hormones is 8 additional cases of breast cancer for every 10,000 women over 1 year (from 30 women to 38 per 10,000).The breast cancers in the estrogen plus progestin group had similar characteristics (as seen under a microscope) to those in the placebo group. However, the tumors in the hormone group tended to be larger and more advanced (had spread to the lymph nodes or elsewhere in the body). A more advanced stage is usually associated with poorer outcome. At this time, no direct statements can be made about the prognosis of the breast cancer found in women taking combined hormones until more information is collected.Coronary heart diseaseCardiovascular disease is a more common cause of illness and death in women than osteoporosis and cancer combined. The main risk factors for coronary heart disease are high blood pressure, high blood cholesterol, diabetes, and cigarette smoking. As you age, for every 10-year increase in age, the risk for heart disease increases about 3-fold. If there is a family history of early heart disease such as a heart attack in your father before the age of 55 or your mother before the age of 65, this increases your risk for heart attack approximately 2-fold. All these factors are increased in women who smoke cigarettes.Behaviors that you can change to improve your risk for heart disease include smoking cessation, increase in physical activity to at least 3 hours a week (which will reduce the risk to approximately one third), and eating a diet low in saturated and trans-fats and high in unsaturated fats, as well as high in fiber, fruits, and vegetables. This will reduce the risk for heart attack by half.Keeping your body size leaner will reduce your risk half to one quarter the rate of women who are overweight or obese. If your waist circumference is less than 28 inches, you will have one third the risk of a heart attack compared with women who are more than 38 inches. It is important to keep your blood pressure in the normal range. The systolic pressure (the top number) should be less than 140 mm Hg.Blood cholesterol is a very important risk factor and the low density lipoprotein (LDL) cholesterol levels should be below 130 mg/dL and triglyceride levels below 150 mg/dL. Women with high density lipoprotein (HDL) cholesterol levels, above 60 mg/dL, have a lower risk than women with a level less than 40 mg/dL; however, contrary to popular belief, women with high HDL cholesterol levels are not immune to heart attack.In the WHI, there were 7 more heart attacks annually per 10,000 women who used estrogen plus progestin (from 30 to 37). The risk for women on combined hormones was greatest in the first year and was almost double the women on placebo. Women who had higher baseline LDL cholesterol levels at the beginning of the study were at particularly high risk of chronic heart disease with estrogen plus progestin use. The use of medications such as aspirin or statins did not prevent women from having heart attacks.StrokeStroke is a type of cardiovascular disease. It affects the arteries leading to and within the brain. A stroke occurs when a blood vessel that carries oxygen and nutrients to the brain is either blocked by a clot or bursts. When that happens, part of the brain cannot get the blood (and oxygen) it needs, so it starts to die.Clots that block an artery can cause ischemic strokes and are the most common type of stroke. Ruptured blood vessels cause hemorrhagic or bleeding strokes. When part of the brain dies from lack of blood flow, the part of the body it controls is affected. Strokes can cause paralysis, affect language and vision, and cause other problems. The risk factors for stroke are similar to those for coronary heart disease.The excess risk of stroke caused by estrogen plus progestin was 8 for every 10,000 women over 1 year. For every 10,000 women followed for 1 year, we would expect to see 29 strokes in women on estrogen plus progestin compared with 21 in women on placebo. Most of these strokes were caused by blood clots in the brain. The less common type of stroke, caused by bleeding into the brain, did not seem to be affected by estrogen plus progestin. The increased risk of stroke caused by estrogen plus progestin was seen in all groups of women studied, including those closest to the menopausal change and those with symptoms such as hot flashes.Pulmonary embolismPulmonary embolism is the sudden blockage of an artery in the lung. Pulmonary embolism caused by large clots can cause sudden death, usually within 30 minutes of when symptoms begin. Smaller clots may cause permanent damage to the heart and lungs. A blood clot in the deep leg veins (deep vein thrombosis) is the greatest risk factor for pulmonary embolism. Inactivity, especially long periods of bed rest, long flights, or car trips, increases your risk of pulmonary embolism because of reduced blood circulation. Recent surgery, stroke, heart attack, being overweight, use of birth control pills, heart failure, cancer, chronic lung disease, and smoking are also risk factors for pulmonary embolism.The excess risk of pulmonary embolism caused by estrogen plus progestin was 18 for every 10,000 women over 1 year. For every 10,000 women followed for 1 year, we would expect to see 34 pulmonary emboli in women on estrogen plus progestin compared with 16 in women on placebo.DementiaIn the past, we thought hormones might protect against Alzheimer's disease, other dementias, and cognitive decline. The results from the women aged 65 and older in WHI show hormones do not protect women from normal declines in cognitive function when compared with placebo. Women taking the hormone combination tested slightly worse on the yearly cognitive function questions and developed mild cognitive impairment at the same rate as women in the placebo group. This finding indicates that combined hormone therapy does not protect postmenopausal women from the milder type of abnormal cognitive decline.Women taking combined hormones had the risk for developing dementia doubled compared with those taking placebo. They were twice as likely to have this more severe type of abnormal cognitive decline develop over the course of the study. This finding translates into 23 more cases of dementia per year for every 10,000 women 65 and older taking the combination hormone therapy (from 22 in women on placebo compared with 45 in women on hormone therapy).AlternativesHot flashes and night sweatsThere are some simple things that you can do to try to manage hot flashes and night sweats: wearing layered clothing that can be removed or added as needed, avoiding hot, spicy foods and beverages, and reducing caffeine and alcohol. Relaxation techniques such as deep, slow breathing may also help hot flashes.Other prescription medications that may considerably help hot flushes are the selective serotonin and/or norepinephrine reuptake inhibitors that include medications such as venlafaxine, paroxetine, sertraline, and fluoxetine. High-dose progestins may also reduce hot flushes, but may have other side effects and risks. Clonidine is a blood pressure medication that reduces the frequency and intensity of hot flashes in some women.There are many “alternative” and so-called “natural” products for sale that claim to help menopausal symptoms. These products are not regulated through any government agency like medications and in the majority of cases, there is no qualified research to backup their claims. Phytoestrogens or plant estrogens have not been shown in most clinical trials to reduce hot flushes better than placebo. The best single dietary source of a phytoestrogen is soy. Soy may have a modest effect on hot flashes, but there is no conclusive evidence for benefit and no long-term safety studies. Soy protein at a dose of 25 g/d reduces cholesterol levels and may be associated with a lower risk of cardiovascular disease. Dong quai, evening primrose oil, vitamin E, red clover, and acupuncture have been shown in clinical trials not to be any more effective than placebo for the treatment of hot flushes. There is some evidence black cohosh may be effective for hot flashes, but the lack of adequate long-term safety data (mainly on estrogenic stimulation of the breast or endometrium) precludes recommending long-term use.Vaginal drynessNonhormone over-the-counter vaginal lubricants and moisturizers are reasonably effective in reducing symptoms of vaginal dryness.Osteoporosis preventionIf your practitioner recommends medication treatment for either bone loss or osteoporosis, you have many options. If your goal is to prevent bone loss and prevent fractures, raloxifene, alendronate, or risedronate can be used. If you have stopped estrogen or hormone therapy, discuss other alternatives for bone protection with your practitioner. The FDA recommends hormone treatment be reserved for management of hot flushes and night sweats and not used primarily for its bone-preserving effects.Complementary and alternative therapies for osteoporosis prevention and treatment are few. Soy protein isolate has little or no benefit for the skeleton and ipriflavone has shown some reduction of bone loss,