Tratamentul menopauzei

Dialogues in Menopause Management: Counseling Postmenopausal Women About Initiating Estrogen Use for

Severe Vasomotor Symptoms and Osteoporosis Prevention CME/CE

Steven R. Goldstein, MD

CME/CE Released: 06/04/2009; Valid for credit through 06/04/2010

The following test-and-teach case is an educational activity modeled on the interactive grand rounds approach. The questions within the activity are designed to test your current knowledge. After each question, you will be able to see whether you answered correctly and will then read evidence-based information that supports the most appropriate answer choice. Please note that these questions are designed to challenge you; you will not be penalized for answering the questions incorrectly. At the end of the case, there will be a short post-test assessment based on material covered in the activity.

Patient History


In this educational activity, the patient was played by a professional actor.

Alicia Baker is a 52-year-old African-American woman who presents for the first time at her clinician's office with a 2- to 3-month history of severe night sweats and hot flashes. These symptoms first began erratically about a year ago, but in the past few months Ms. Baker is awakening two to four times a night with drenched nightclothes. She estimates that she is experiencing four to eight hot flashes a day, which she describes as "extremely disruptive." Her worsening hot flashes and sleepless nights are now affecting her concentration at work.

The patient had a total abdominal hysterectomy 10 years ago for fibroids, but retained her ovaries. She exercises regularly, eats a low-fat diet, and does not smoke. She is not allergic to anything as far as she knows, and the only medications she takes daily are a multivitamin and a calcium supplement with vitamin D.

A physical examination is conducted. The results reveal:

  • Weight: 130 lb
  • Height: 5'8"
  • Blood pressure: 140/90 mm Hg; pulse 72
  • Breasts (lying and sitting): no masses or nipple discharge seen
  • Pelvis: external genitalia appear normal
  • Vagina: vaginal mucosa is slightly pale, there is diminished rugation, and the speculum exam is moderately uncomfortable
  • Cervix: surgically absent, and the vaginal cuff is well healed
  • Bimanual: no masses or tenderness noted

The patient's family history includes a mother who is alive and well at age 79. However, she has been recently diagnosed with osteoporosis and is currently taking bisphosphonate therapy. Ms. Baker's father died at age 74 of lung cancer. He smoked for almost 50 years. Her paternal aunt had breast cancer at age 55, but is now doing well. Her younger brother, age 46, has no significant medical problems.

 

What blood tests might the clinician order to confirm Ms. Baker's postmenopausal status?

       Your Colleagues Responded:
Follicle-stimulating hormone and serum estradiol Correct Answer  86%
  Follicle-stimulating hormone and dual energy x-ray absorptiometry (DXA)    6%
  Thyroid and vitamin D    2%
  Serum and saliva estradiol    3%
  • The correct answer is follicle-stimulating hormone and serum estradiol. These tests should reveal Ms. Baker's current hormone levels.

Diagnosis and Screening

From the patient's history and physical examination, the clinician has ascertained that she has recently reached menopause. The decrease in her estrogen levels are the cause of her increased vasomotor symptoms since her last checkup. She is confused because she had a hysterectomy 10 years ago, and did not have hot flashes then.

The clinician explains that even though she had a hysterectomy and her uterus was removed, her ovaries were not, and they continued to produce estrogen. As a result, she did not reach menopause at that time. The ovaries recently diminished in their production of estrogen and then the hot flashes started. The patient was counseled that hot flashes are a common response to menopause and the loss of estrogen.

Her speculum pelvic examination revealed that she is also experiencing vaginal discomfort. The clinician explains that this is related to vaginal dryness and lack of lubrication, also caused by the decrease in estrogen at menopause.

Menopause is confirmed when a woman has not had menstrual periods for 12 months consecutively in a row or when both ovaries are removed or damaged. However, in the case of this woman who had a hysterectomy 10 years ago, further tests to confirm her menopause status should be considered.

Although the patient is of African-American heritage, which is associated with reduced osteoporosis risk, the patient is thin for her height and has a strong family history of osteoporosis.

Ms. Baker's examination, along with her complaint about disruptive menopausal symptoms, suggest postmenopausal status. Further tests are recommended, including a dual energy x-ray absorptiometry (DXA) scan with FRAX (Fracture Risk Assessment Tool)[1,2] to get a baseline measurement of her bone density and risk of fracture; vitamin D level to rule out any nutritional deficiency; and follicle-stimulating hormone and serum estradiol to corroborate what is clinically apparent about her status.

 

All of the following are government-approved indications for systemic menopausal estrogen therapy, EXCEPT:

       Your Colleagues Responded:
Treatment of vaginal atrophy    5%
  Improvement of cognitive function and memory Correct Answer  88%
  Relief of vasomotor symptoms    2%
  Prevention of osteoporosis    3%

    Which of the following statements are NOT true about Ms. Baker's treatment options?

           Your Colleagues Responded:
    Because Ms. Baker had a hysterectomy, she could be prescribed estrogen plus progestogen for her menopausal symptoms.    14%
      Because Ms. Baker had a hysterectomy, she could be prescribed estrogen plus androgen therapy for her menopausal symptoms.    11%
      Because Ms. Baker had a hysterectomy, she is not a good candidate for any hormone therapy.    10%
      All of the above. Correct Answer  63%

      Relief for Menopause-Related Symptoms

      If the patient's vasomotor symptoms were less severe, the clinician might recommend nonhormonal alternative options, such as gabapentin or an antidepressant. But systemic postmenopausal estrogen therapy (ET) is the only treatment proven to work quickly and satisfactorily for severe hot flashes. It is also the only treatment that's approved by the US Food and Drug Administration[3] for treating these menopause conditions.

      Government-approved and scientifically proven indications for systemic ET use include treatment of moderate to severe vasomotor and vulvar symptoms, and prevention of postmenopausal osteoporosis. Women suffering solely from vulvar and vaginal atrophy are commonly prescribed local vaginal ET. Similarly, if a woman is being treated solely for osteoporosis prevention, other agents would be recommended unless she is unable to use nonestrogen medications.

      Because the patient does not need progestogen for endometrial protection, unopposed systemic ET in a low dose would be appropriate, and can be expected to be safer than doses studied in the Women's Health Initiative (WHI).

       


      The greatest influence on a woman's peak bone mass is:

             Your Colleagues Responded:
      Ethnicity    5%
        Menopause status    17%
        Inadequate intake of calcium and vitamin D    15%
        Heredity Correct Answer  61%

        The following tests should be ordered to assess Ms. Baker's risk of osteoporosis, EXCEPT:

               Your Colleagues Responded:
        Vitamin D    4%
          DXA    3%
          FRAX    3%
          Magnetic resonance imaging (MRI) Correct Answer  88%

           

           

          Osteoporosis Risk

          The patient's family history of osteoporosis is a concern for her. Everyone loses bone strength as they age, but because her mother has osteoporosis, this patient is at higher risk for the disease. She might already have significant bone loss, and is thus more likely to suffer a bone fracture.

          Osteoporosis is characterized by a reduction in bone mass and bone strength, and results in an increased risk of fracture from a relatively minor trauma. Most cases of fracture occur more frequently in the elderly, but the pathogenesis of the disease begins earlier. Although bone loss starts in the fourth decade at the hip, loss from the spine is more closely related to estrogen deficiency and starts about 2 years before the last period.[4]

          The increased rate of bone resorption immediately after menopause clearly indicates a hormonal influence on bone mineral density (BMD) in women. The most likely explanation for this increased resorption is the drop in ovarian estrogen production that accompanies menopause. As BMD decreases, every standard deviation of reduction results in a twofold or greater risk of fracture compared with other women of the same age.[4] However, increased fracture risk depends on many factors, including age.

          Influences on osteoporosis risk[4]:

          • The greatest influence on a woman's peak bone mass (ie, the maximum BMD gained during the skeletal development and maturation phase) is heredity.
          • Studies have suggested that up to 80% of the variability in peak bone density might be attributable to genetic factors.
          • Female children of women who have osteoporotic fractures have lower BMD than would be expected for their age.
          • First-degree relatives (ie, mother, sister) of women with osteoporosis also tend to have lower BMD than those with no family history.
          • It has also been shown that in general African-American women have a lower risk of osteoporosis than white women. In one large study of postmenopausal women from five ethnic groups (white Americans, African Americans, Asian Americans, Hispanic Americans, and Native Americans),[5] African Americans had the highest BMD, while Asian Americans had the lowest.
          • The BMD differences for African Americans were not explained by differences in weight. The differences may be related more to body size than to race.

          For women at high risk for osteoporosis who do not exhibit other menopausal symptoms, treatments such as bisphosphonates or selective estrogen-receptor modulators (SERMs) are recommended. But for women who have established reduction in bone mass, menopausal symptoms, and cannot tolerate alternate osteoporosis therapies, hormone therapy (HT) is an option. However, HT use must be extended for osteoporosis prevention, as stopping therapy results in bone loss.

          Ms. Baker works out and eats a healthy diet, unlike her mother. The clinician explains that healthy living certainly helps lower her risk of osteoporosis, as perhaps does being African-American, but her strong family history and her thinness probably trump these benefits.

          Research shows that unopposed systemic ET helps reduce osteoporosis risk and prevent fractures.[6] Adequate calcium and vitamin D are also encouraged for her bone health.[7]

          Here is a current list of approved postmenopausal osteoporosis drugs available in the United States and Canada. (Table Set 1)

           

          Which statement best explains the evidence on timing of initiation of hormone therapy?

                 Your Colleagues Responded:
            Hormone therapy may increase breast cancer risk when initiated in younger women.    12%
          Hormone therapy may reduce coronary heart disease risk when initiated in younger, more recently postmenopausal women. Correct Answer  64%
            Timing of initiation of hormone therapy has no effect on either coronary heart disease or breast cancer.    6%
            None of the above    16%
          • The correct answer is hormone therapy may reduce coronary heart disease risk when initiated in younger, more recently postmenopausal women. Initiating therapy younger than age 55 and within 2 to 3 year after menopause is safer than starting several years after menopause.

           

           

          Timing of ET Initiation

          Disparity in data from observational studies and randomized controlled trials (RCTs) -- including the large WHI -- seems to be related in part to the timing of initiation of HT in relation to age and proximity to menopause.[8] Most women studied in observational studies were younger than age 55 and within 2 to 3 years after menopause at the time HT was initiated. On the other hand, women enrolled in RCTs were an average of 63 to 64 years old and more than 10 years beyond menopause. When analyzed by age and time since menopause at initiation of HT, RCTs are in general agreement with observational studies indicating that HT may reduce coronary heart disease (CHD) risk when initiated in younger and more recently postmenopausal women.[9, 10]

          Research shows[11]:

          • In a secondary analysis of WHI data, there was a statistically significant reduction in myocardial infarction, coronary artery revascularization, and coronary death in women who were randomized to ET alone during ages 50 to 59.

          • Combined data from both ET and estrogen-progestogen therapy (EPT) WHI trials showed a statistical trend of an HT effect relative to placebo on CHD by time since menopause, indicating that women who initiate HT more than 10 years beyond menopause are at increased risk for CHD. Those women who initiate HT within 10 years of menopause tend to have a decreased risk for CHD.

          • How soon HT is begun after menopause seems to have a strong impact on long-term health outcomes (eg, early initiation may reduce total mortality rates and CHD risk).

          • Women older than age 60 who experienced natural menopause at the typical age and never used HT will have elevated baseline risks of CHD, stroke, venous thromboembolism, and breast cancer, and HT should therefore not be initiated in this population without a strong indication.

          In a discussion of the potential risks associated with ET, the good news is that Ms. Baker is young. Initiating ET at the age of 52 and newly postmenopausal is safer than starting several years after menopause.

           

          Which of the following family members with breast cancer constitute a major risk to relatives?

                 Your Colleagues Responded:
            Aunt or sister    0%
          Mother or sister Correct Answer  98%
            Grandmother or grandfather    0%
            None of the above    0%
          • The answer is mother or sister. One of the greatest risk factors for breast cancer is having a first-degree relative (ie, mother, sister, daughter) with the disease.

           

           

          ET and Breast Cancer

          Ms. Baker's fear of breast cancer is not as great as she may perceive because she has a second-degree relative (aunt) with the disease, and only a first-degree relative would increase her risk. And, not needing progestogen in addition to estrogen may further lesson her risk.[12]

          But for many women, breast cancer is their primary health concern. It is the second major cause of cancer mortality in US and Canadian women. A woman's lifetime risk of developing breast cancer is approximately 1 in 8, and the risk increases with age; it is not specifically affected by menopause. Nearly one half of all breast cancer cases occur in women aged 65 years and older.

          Among racial/cultural groups in the United States, white non-Hispanic women have the highest incidence of breast cancer, although African-American women have the highest mortality from the disease, possibly related to later stages of diagnosis, more estrogen-receptor negative tumors, and more aggressive tumors. The 5-year survival rate for African Americans is 71% versus 86% for Caucasians.[13]

          Although the incidence of breast cancer has increased in recent years, mortality rates have decreased, perhaps due to earlier intervention. Smaller, less-advanced tumors that would have been missed without mammography can now be detected. After the WHI reports in 2002 documented risks of HT for postmenopausal women, HT use in the United States dropped substantially.[14] The incidence of breast cancer also dropped, suggesting a cause-and-effect relationship.[15] But the cause of this decline remains controversial.

          The latest report from the WHI[16] confirmed that the increased risk of breast cancer in EPT users declined soon after discontinuation. It has also been confirmed that this decrease was unrelated to changes in frequency of mammography. Moreover, experts have noted that the rapid decline in breast cancer rates after HT discontinuation may not be biologically plausible, because breast cancers normally take several years to develop. Instead, it has been postulated that stopping HT could quickly influence hormone-sensitive tumor growth in much the same ways that tamoxifen and aromatase inhibitors can cause tumor regression in women with metastatic breast cancer after only a few months of treatment.[17]

          Diagnosis of breast cancer increases with EPT use beyond 3 to 5 years. In the WHI, the increase in breast cancer risk was significantly related to EPT use before enrollment in the trial. Available evidence suggests that use of ET alone for more than 5 years has little impact on breast cancer risk.[18]

          For Ms. Baker, regular breast exams and mammograms are other safety nets against breast cancer. A major finding of the WHI was that many of the reported HT risks -- including breast cancer and stroke -- were associated with the use of progestogen added to ET for uterine protection. Ms. Baker, who had a hysterectomy, does not need progestogen.

           

          Which of the following statements reflects the current recommendations for prescribing postmenopausal hormone therapy?

                 Your Colleagues Responded:
            Using systemic hormone therapy for less than 5 years is completely safe.    2%
            Continue hormone therapy for more than 10 years if needed to ensure a woman's quality of life.    2%
          Begin hormone therapy with the lowest effective dose for the shortest duration consistent with treatment goals. Correct Answer  93%
            None of the above    1%
          • The correct answer is begin hormone therapy with the lowest effective dose for the shortest duration consistent with treatment goals.

          Lowest Dose for Shortest Duration

          Systemic ET for 2 to 3 years would more than likely relieve Ms. Baker's hot flashes, night sweats, and vaginal discomfort. It would also prevent osteoporosis while she takes the medication. Her prescription would be for the lowest effective dose. ET in lower, probably safer doses seems to provide as much relief as the higher doses.

          In the WHI, participants were taking daily 0.625 mg oral conjugated estrogens (CE), and women with a uterus also took 2.5 mg daily progestin.[19] Today, however, lower daily doses are available in 0.3 mg CE, 0.45 mg CE, 0.5 mg oral micronized 17beta-estradiol, or a 0.014 mg to 0.025 mg transdermal 17beta-estradiol patch. For women with a uterus, typical lowest doses of progestogen are 1.5 mg oral medroxyprogesterone acetate, 0.1 mg oral norethindrone acetate, 0.5 mg oral drospirenone, or 50 mg to 100 mg oral micronized progesterone.

          Side effects are also reduced with the lower doses. The "standard" ET dose might provide an 85% reduction in vasomotor symptoms, but a 30% increase in breast tenderness and a 50% increase in vaginal bleeding. Low ET doses might provide a 75% reduction in vasomotor symptoms, but a 15% increase in breast tenderness and a 25% increase in vaginal bleeding. The ultralow ET dose might provide a 55% reduction in vasomotor symptoms, with only a 5% increase in breast tenderness and a 12% increase in vaginal bleeding.[20]

          For women who have had a hysterectomy, clinicians should explain that some of the estrogen products being used today, such as 17beta-estradiol, are not the same as the CE used in the WHI trials. Also, some of the components of CE may in fact have a property similar to SERMs, and the 20% nonstatistically significant reduction in breast cancer seen in the estrogen-only WHI study may or may not be unique to the product used. The FDA labels are organized by class, not individual product -- a distinction that should be noted.

          There are several different types of estrogens to choose from, as well as several different ways to deliver this systemic therapy -- from pills to patches to sprays. There is no conclusive evidence comparing types of estrogens or types of regimens.

          Here is a current list of approved ET products in the United States and Canada. (Table Set 2).

           

          Clinical Summary

          Ms. Baker understands now that she will be prescribed systemic estrogen alone because she doesn't need the uterine protection of progestogen. She has also been counseled about lower, possibly safer doses and short duration of use. The clinician recommends some lifestyle modifications that will also help relieve her vasomotor symptoms, such as lowering the ambient temperature, dressing in layers, using a fan, increasing regular exercise, paced respiration, and avoiding any personal hot flash triggers (eg, hot drinks, spicy foods, alcohol).

          The clinician orders a few more tests to confirm her menopause status and assess her BMD and vitamin D level. After receiving the results of the blood work within 24 hours, the patient and clinician will choose a suitable product for her symptom relief. They will schedule regular visits to monitor her progress and adjust her treatment plan, if necessary, to assure optimal relief with the lowest possible risk.

          Assessment: Measuring CME Effectiveness

          One of the goals of continuing healthcare education is to acquire and retain new knowledge that will ultimately affect clinical practice and patient outcomes. The following survey is a planned change assessment instrument associated with the learning objectives. Data from this survey will help facilitate recommendations for future activities that will best meet the educational and clinical performance gaps identified. We encourage you to complete this survey.

           

          When managing menopausal symptoms, what will you do differently in your practice as a result of your participation in this activity? (check all that apply)

                 Your Colleagues Responded:
          Use follicle-stimulating hormone and serum estradiol blood tests to confirm menopausal status.    42%
            Utilize FRAX, vitamin D, and/or DXA testing to assess osteoporosis risk.    41%
            Consider systemic menopausal estrogen therapy to prevent postmenopausal osteoporosis.    34%
            Consider patient age when assessing risks of breast cancer or coronary heart disease with hormone therapy.    45%
            Incorporate risk education into my counseling on treatment of menopausal symptoms.    44%
            Tailor my counseling strategies to patients' current clinical situation and history.    41%
            This program confirmed my current practices.    39%
            I do not plan to make any changes to my practice.    12%

            This activity is supported by an independent educational grant from Wyeth.

             

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