Menopause is defined as the permanent cessation of menses. In the United States, the median age at which menopause occurs is 52 years, but it can vary between 40 and 58 years of age.1 The World Health Organization (WHO) and the Stages of Reproductive Aging Workshop have defined menopausal transition as the time of an increase in follicle-stimulating hormone and either increased variability in menstrual cycle length, two skipped menstrual cycles with 60 days or more of amenorrhea, or both.1 It concludes with the final menstrual period. Postmenopause begins at that time, although it is not recognized until after 12 months of amenorrhea.
|Clinical recommendation||Evidence rating||References||Comments|
|Extended use of hormone therapy in women who are aware of the risks and benefits and are under medical supervision is acceptable for the following: those who feel that the benefits of menopausal symptom relief outweigh the risks; those who have moderate to severe menopausal symptoms and are at high risk of osteoporotic fractures; and those with reduced bone mass who want to prevent further bone loss when alternate therapies are inappropriate.||C||9||Evidence-based guidelines|
|All postmenopausal women should have adequate intake of calcium (1,000 to 1,500 mg elemental calcium per day) and vitamin D (800 to 1,000 IU per day) to maintain bone health.||C||16||Evidence-based guidelines|
|Chemoprophylaxis with aspirin is recommended in women with high risk of coronary heart disease.||A||14,21||Evidence-based guidelines and USPSTF|
|Screen for breast cancer every one to two years, beginning at age 40 years.||B||28||USPSTF|
|Routinely screen for cervical cancer in women who are or have been sexually active and who have a cervix.||A||30||USPSTF|
|Screen for colorectal cancer beginning at age 50 years.||A||32, 33||Evidence-based guidelines and USPSTF|
With a life expectancy close to 80 years, the average woman is postmenopausal for one third of her life. The incidence of certain conditions (e.g., coronary artery disease, diabetes, breast cancer, colon cancer) increases after menopause. Family physicians have an opportunity to address preventive health care measures with postmenopausal women and encourage healthy lifestyle choices.
Many women go through menopause with few or no symptoms. Vasomotor symptoms and vaginal dryness are consistently associated with menopausal transition.1 According to a Cochrane review, oral hormone therapy is highly effective in relieving hot flashes and night sweats compared with placebo.2 Table 13 lists various hormonal preparations available to treat vasomotor symptoms. When estrogen is contraindicated, nonestrogen drugs may be considered (Table 23). Postmenopausal vaginal symptoms can be treated with topical estrogen therapy.4 Table 33 outlines selected vaginal estrogen preparations.
|Preparation||Drug||Dosages (mg per day)|
|Oral||Conjugated estrogens (Premarin)||0.3, 0.45, 0.625, 0.9, 1.25|
|Transdermal||17β-estradiol (Estrace)||0.5, 1.0, 2.0|
|17β-estradiol (Alora)||0.025, 0.05, 0.075, 0.1 (patch applied twice weekly)|
|17β-estradiol (Climara)||0.025, 0.0375, 0.05, 0.075, 0.1 (patch applied weekly)|
|Vaginal||Estradiol acetate (Femring vaginal insert†)||0.05, 0.1 (inserted every 90 days)|
|Oral||MPA (Provera)||2.5, 5.0, 10.0|
|Micronized progesterone (Prometrium)||100, 200 (in peanut oil)|
|Vaginal||Progesterone (Prochieve 4%)||45|
|Oral sequential‡||Conjugated estrogens and MPA (Premphase)||0.625 conjugated estrogens plus 5.0 MPA|
|Oral continuous§||Conjugated estrogens and MPA (Prempro)||0.625 conjugated estrogens plus 2.5 or 5.0 MPA;|
|0.45 conjugated estrogens plus 2.5 MPA;|
|0.3 or 0.45 conjugated estrogens plus 1.5 MPA|
|Transdermal continuous§||17β-estradiol–norethindrone acetate (Activella)||1.0 estradiol plus 0.5 norethindrone|
|17β-estradiol–levonorgestrel (Climara Pro)||0.045 estradiol plus 0.015 levonorgestrel (patch applied weekly)|
|17β-estradiol–norethindrone acetate (Combipatch)||0.05 estradiol plus 0.14 or 0.25 norethindrone (patch applied twice weekly)|
|Treatment||Oral dosage||Evidence of benefit||Outcome*||Side effects†|
|Progestins||Medroxyprogesterone acetate(Provera)||20 mg daily||Yes||Improvement of 48 percent over placebo||Nausea, vomiting, constipation, somnolence, depression, breast tenderness, and uterine bleeding; concern about increased risk of venous thromboembolism, cardiovascular events, and breast cancer|
|Megestrol (Megace; brand available only as an oral suspension)||20 mg twice daily||Yes||Improvement of 47 percent over placebo in breast cancer survivors|
|Tibolone‡||1.25 to 5.0 mg||Yes||Improvement of 35 to 50 percent over placebo||Headache, weight gain, and uterine bleeding; unknown effects on venous thromboembolic events, cardiovascular disease, and breast and uterine cancers|
|SSRIs||Citalopram (Celexa)||30 mg||No||No benefit over placebo||Nausea, vomiting, diarrhea, insomnia, somnolence, anxiety, decreased libido, dry mouth, worsening depression, mania, suicidality, the serotonin syndrome, and the withdrawal syndrome; paroxetine and possibly other SSRIs decrease the activity of cytochrome P-450 enzymes, thereby decreasing the production of active metabolites of tamoxifen (Soltamox), which may interfere with the anti–breast cancer effects of tamoxifen|
|Fluoxetine (Prozac)||20 mg||Mixed||Improvement of 24 percent over placebo in breast cancer survivors|
|30 mg||Mixed||No benefit among women without breast cancer|
|Paroxetine (Paxil)||10 to 20 mg||Yes||Improvement of 30 percent over placebo in breast cancer survivors|
|12.5 to 25 mg, controlled release||Yes||Improvement of 25 percent over placebo in women without breast cancer|
|Sertraline (Zoloft)||25 to 100 mg||No||No benefit over placebo in breast cancer survivors|
|SNRIs||Venlafaxine (Effexor)||75 or 150 mg||Mixed||Improvement of 34 percent over placebo in breast cancer survivors||Same side effects as for SSRIs, but minimal effect on cytochrome P-450 enzymes (only slightly inhibits conversion of tamoxifen to active metabolites); possible hypertension|
|75 mg, extended release||Mixed||No benefit over placebo in women without breast cancer|
|Gabapentin (Neurontin)||300 mg three times daily||Yes||Improvement of 31 percent over placebo in breast cancer survivors and 23 percent over placebo in women without breast cancer||Nausea, vomiting, somnolence, dizziness, rash, ataxia, fatigue, and leukopenia|
|Clonidine (Catapres)||0.1 mg transdermal||Mixed||Little to no benefit or improvement of 27 percent over placebo||Drowsiness, dizziness, hypotension, and rebound hypertension|
|Methyldopa (Aldomet; brand no longer available in the United States)||375 to 1,125 mg daily in divided dosages||No||No benefit over placebo|
|Vaginal cream||Conjugated estrogens (Premarin)||0.625 mg per 2 g cream: 2 g per day for two weeks, then 1 to 2 g two to three times per week|
|17β-estradiol(Estrace)||0.1 mg per 2 g cream: 2 g per day for two weeks, then 1 to 2 g two to three times per week|
|Vaginal tablet||Estradiol hemihydrate (Vagifem)||0.025 mg per tablet: one tablet per day for two weeks, then one tablet two times per week|
|Vaginal ring||17β-estradiol (Estring)||0.0075 mcg per day (inserted every 90 days)|
Use of hormone therapy by menopausal women has declined since the results of the Women's Health Initiative (WHI) studies were published.5 The results found that women taking combined estrogen and progestin therapy have a higher risk of myocardial infarction (MI) and venous thromboembolism after one year, stroke after three years, and breast cancer after five years. However, there is a lower incidence of fractures and colon cancer in women who take combination hormone therapy continuously for five years. A recent updated analysis of the WHI findings concludes that estrogen alone does not increase the incidence of breast cancer in postmenopausal women with a previous hysterectomy.6
After carefully reviewing the data from the WHI study, the U.S. Food and Drug Administration (FDA) issued safety warnings on hormone therapy product labels.7 Hormone therapy should be prescribed at the lowest effective dose for the shortest duration necessary to control menopausal symptoms. The U.S. Preventive Services Task Force (USPSTF) recommends against the routine use of combined estrogen and progestin for the prevention of chronic conditions in postmenopausal women, such as cardiovascular disease, osteoporosis, and dementia.8
Based on the recent North American Menopause Society's update, hormone therapy is acceptable under the following circumstances: for women who feel that the benefits of menopausal symptom relief outweigh the risks; for women who have moderate to severe menopausal symptoms and are at high risk of osteoporotic fractures; and for women with reduced bone mass who want to prevent further bone loss when alternate therapies are inappropriate.9 All women on hormone therapy should be under clinical supervision and aware of the potential risks and benefits.
Preventive Care Recommendations
Lifestyle modifications, screenings, early identification, and appropriate intervention may prevent many chronic conditions that cause morbidity and mortality during postmenopausal years. The USPSTF,10 the American Academy of Family Physicians,11 and other major organizations have published evidence-based recommendations for postmenopausal women.12–14 Table 48–11,13–34 summarizes these health maintenance recommendations.
|Hormone therapy||Same as USPSTF||Recommends against hormone therapy in postmenopausal women for management of chronic diseases, such as cardiovascular disease, osteoporosis, and dementia8||According to NAMS, extended use of estrogen or estrogen-progestogen therapy in women who are aware of the risks and benefits and are under medical supervision is acceptable for the following patients: those who feel that the benefits of symptom relief outweigh the risks; those who have moderate to severe symptoms and are at high risk of osteoporotic fractures; and those with reduced bone mass who want to prevent further bone loss when alternate therapies are inappropriate9|
|Osteoporosis||Screen women older than 65 years or starting at 60 years in women at high risk of osteoporotic fractures||Screen women older than 65 years15||NOF recommends routine screening of bone mineral density at 65 years of age and sooner in postmenopausal women at high risk of osteoporotic fractures13|
|Nutrition and lifestyle|
|Calcium and vitamin D||—||—||NOF recommends at least 1,200 mg of calcium and 800 to 1,000 IU of vitamin D per day for adult women13; NIH recommends 1,000 to 1,500 mg of calcium per day for postmenopausal women16|
|Obesity||Screen all adults for obesity; provide counseling and behavioral interventions more than once per month for at least three months||Screen and provide counseling and interventions to all adults to achieve sustained weight loss; BMI is a valid and reliable tool to identify persons at risk17||AHA recommends measurement of BMI and waist circumference as part of a periodic evaluation; encourage gradual and sustained weight loss in persons whose weight exceeds the ideal weight for their height14|
|Physical activity||Physical activity is important; no recommendations for counseling||Evidence is insufficient to recommend for or against counseling for exercise18||AGS recommends counseling older adults about an exercise program that balances the modalities of endurance, mobility, flexibility, strength, and gait19|
|Tobacco use||Same as USPSTF||Screen all adults for tobacco use and provide interventions for smoking cessation20||—|
|CHD and related medical conditions|
|Aspirin||Discuss risks and benefits of aspirin chemoprophylaxis in persons at high risk of CHD||Address aspirin chemoprevention in adults with CHD risk factors, keeping in mind the risk of gastrointestinal bleeding, and hemorrhagic stroke21||AHA recommends the use of low-dose aspirin in persons at high risk of coronary heart disease, especially those with a 10-year CHD risk of 20 percent or greater14|
|Blood pressure||—||Blood pressure screening is recommended in adults 18 years and older23||AHA recommends that all women receive periodic blood pressure screening14|
|Cholesterol||Screen women 45 years and older with a fasting lipid profile or nonfasting HDL and total cholesterol levels||Screen women 45 years and older who are at increased cardiovascular risk with HDL and total cholesterol levels; insufficient evidence for triglyceride measurement24||NCEP–ATP III recommends a fasting lipoprotein profile (LDL, HDL, and total cholesterol levels; and triglycerides) every five years in women25|
|Diabetes||Screen adults with hypertension and hyperlipidemia||Screen adults with hypertension and hyperlipidemia26; insufficient evidence for routine screening in asymptomatic adults||ADA recommends that all adults 45 years and older be screened every three years for diabetes with a fasting glucose test, particularly in those with a BMI ≥ 25 kg per m2 Earlier or frequent screening is recommended for overweight patients (BMI > 25 kg per m2) if diabetes risk factors are present27|
|Breast cancer||Mammography every one to two years in women 40 years and older||Mammography, with or without clinical breast examination, every one to two years in women 40 years and older; screen women older than70 years who have a reasonable life expectancy 28||ACS recommends yearly mammography and clinical breast examination in women 40 years and older 29|
|Cervical cancer||Pap smear at least every three years in women who have a cervix and who have ever had sexual intercourse||Pap smear at least every three years in women who have ever had sexual intercourse and have a cervix; discontinue after age 65 years if the patient has had regular normal Pap smears30||ACS recommends annual Pap smear beginning within three years after first sexual intercourse; screen every two to three years in women older than 30 years who have had three consecutive normal results31; stop screening at age 70 years|
|Colorectal cancer*||Screen adults 50 years and older||Screen adults 50 years and older; age of discontinuation is uncertain32||ACS recommends screening adults beginning at age 50 years33|
|Influenza vaccine||Recommends as per CDC||Recommends as per CDC||CDC recommends annual in.uenza vaccine for all persons 50 years and older 34|
|Pneumococcal(Pneumovax) vaccine||Recommends as per CDC||Recommends as per CDC||CDC recommends immunizing all adults 65 years and older, and before age 65 years in persons with chronic medical problems34|
|Td/Tdap vaccines||Recommends as per CDC||Recommends as per CDC||Administer a booster dose every 10 years in adults who have completed a primary series; Tdap or Td vaccine may be used; Tdap should replace a single dose of Td for adults younger than 65 years who have not previously received a dose of Tdap34|
One half of all postmenopausal women will have an osteoporotic fracture during their lifetime.35 Guidelines from the National Osteoporosis Foundation (NOF)13 and the USPSTF15 recommend routine bone mineral density screening to detect osteoporosis in women older than 65 years. The NOF also recommends screening younger postmenopausal women at increased risk of osteoporotic fractures. Recent NOF guidelines incorporate the WHO absolute fracture prediction algorithm (FRAX), a computer-based tool to estimate a patient's 10-year fracture risk. This tool takes into account bone mineral density score and other clinical risk factors for osteoporosis, including personal and family history of fracture, age, weight, race, sex, steroid use, smoking, and excessive alcohol intake. Treatment is recommended for women with osteoporosis, and those with low bone mass and a 10-year hip fracture probability of 3 percent or more, or a 10-year major fracture risk of 20 percent or more based on the WHO absolute fracture risk model.
CALCIUM AND VITAMIN D
Evidence suggests that adequate calcium and vitamin D intake reduces bone loss in peri- and postmenopausal women.16 Calcium also potentiates the effects of exercise on bone mineral density in postmenopausal women.
The National Institutes of Health (NIH) recommends 1,000 mg of calcium per day for postmenopausal women younger than 65 years who take estrogen, and 1,500 mg per day for those who do not take estrogen.16 The NIH recommends that all women 65 years and older take 1,500 mg of calcium per day.16 The NOF recommends at least 1,200 mg of calcium per day.13 The average dietary calcium intake for postmenopausal women in the United States is approximately 600 mg per day. Therefore, most women need calcium supplementation to ensure adequate calcium intake. Although calcium carbonate products are typically less expensive than most other types of calcium supplements, they should be taken with a meal to ensure optimal absorption. Calcium citrate can be taken without food and is the preferred supplement for patients with achlorhydria or who are taking long-term histamine H2 blockers or proton pump inhibitors.36 Consumption of calcium in divided doses, typically 500 mg or less at one time, can maximize absorption.
Vitamin D plays a major role in calcium absorption and bone health.13 Vitamin D is formed in the skin following direct exposure to sunlight. Usually 10 to 15 minutes of exposure of hands, arms, and face two to three times per week satisfies the body's vitamin D requirement. Other sources include vitamin D–fortified foods, such as milk, yogurt, cheese, bread, orange juice, and oily fish (e.g., sardines, salmon, tuna). The current recommendation for daily vitamin D3 intake is 800 to 1,000 IU per day13 Serum 25(OH)D levels should be measured in women at high risk of vitamin D deficiency (e.g., older women, women with malabsorption [celiac disease], women who are homebound or institutionalized, women with dark skin). Vitamin D should be supplemented enough to maintain serum 25(OH)D levels of 30 ng per mL (75 nmol per L) or higher.13
Regular weight-bearing exercise can reduce the risk of developing osteoporotic fractures in postmenopausal women. A recent randomized controlled trial (RCT) revealed that brisk walking combined with moderate resistance training improved muscle strength, balance, and walking performance in women who recently went through menopause.37 Dividing the walking into two daily sessions was found to be more feasible than continuous walking,38 and is easy to incorporate into everyday life.
Cigarette smoking has been associated with earlier onset of natural menopause. The annual risk of death for women who continue to smoke is more than double that of persons who have never smoked in every age group from 45 through 74 years.39 Postmenopausal women who currently smoke have lower bone mineral density and an increased risk of hip fracture compared with women who do not smoke.39 Smoking cessation reduces the risk of certain cancers, coronary artery disease, and premature death among women.39 At each office visit, smokers should be encouraged to quit smoking. Physicians should offer appropriate support, pharmacologic therapy, and follow-up to achieve success with smoking cessation.
CORONARY HEART DISEASE PREVENTION
Coronary heart disease (CHD) is the most common cause of death in women. Approximately one in two women develops CHD, and one in three dies from it.40 Early mortality following MI is higher and long-term prognosis is worse in women than in men.
The USPSTF strongly recommends routinely screening women 45 years and older for lipid disorders and treating abnormal lipid levels in persons who are at increased risk of CHD. Screening for diabetes with fasting plasma glucose is indicated for women with risk factors for CHD, such as hypertension and hyperlipidemia.26 Data suggest that smoking cessation after an MI and treatment of hypertension and hyperlipidemia lower the risk for CHD events in women.40
The USPSTF21 and the American Heart Association14 recommend aspirin therapy in women at high risk of CHD. However, the use of aspirin for primary prevention in healthy women is controversial. A recent study followed 39,876 healthy women 45 years and older who were randomized to receive 100 mg of aspirin or placebo on alternate days.22 The women were monitored for 10 years for a first major cardiovascular event. Aspirin lowered the risk of ischemic stroke by 24 percent, but no significant effect was noted on the risk of fatal or nonfatal MI. Another RCT that evaluated the risks and benefits of aspirin prevention for CHD in women found a beneficial effect only in women 65 years and older.41 Aspirin use is associated with an increased risk of hemorrhagic stroke and major gastrointestinal hemorrhage, particularly in older women.21 Its use should be individualized for each patient.
Breast cancer is the most common non-skin malignancy diagnosed in women and the second leading cause of cancer-related death.28 The risk of breast cancer increases with age. The USPSTF recommends screening for breast cancer every one to two years, with mammography alone or mammography and annual clinical breast examination, for women 40 years and older. The evidence that screening reduces mortality from breast cancer is strongest for women 50 to 69 years of age.28 There is no evidence of benefit for women older than 75 years, but the task force recommends screening women older than 70 years who have a reasonable life expectancy.
There is evidence that early detection through routine Papanicolaou (Pap) testing and treatment of precursor cervical intraepithelial neoplasia can lower mortality from cervical cancer.42 The USPSTF recommends routine screening with Pap testing for all women who have a cervix and are or have been sexually active.30 Screening can be discontinued after 65 years of age if the patient has had regular normal Pap smears. The American College of Obstetricians and Gynecologists recommends two options for low-risk women 30 years and older: Perform three consecutive annual cervical cytology tests and, if they are negative, rescreen at intervals of two to three years, or perform cervical cytology testing in conjunction with an FDA–approved human papillomavirus (HPV) DNA test for high-risk HPV types.12 Patients with negative results on both tests do not need to be rescreened for at least three years. Screening is not required for women who have had a total hysterectomy for benign indications.30
Early detection of colorectal cancer improves outcomes. The five-year survival rate is approximately 91 percent with localized disease, but drops to 6 percent among persons presenting with distant metastasis.43 The USPSTF and the American Cancer Society recommend screening for colorectal cancer for all persons 50 years and older.32,33 The screening options include the following: fecal occult blood testing every year, flexible sigmoidoscopy every five years, fecal occult blood testing every year plus flexible sigmoidoscopy every five years, double-contrast barium enema every five years, or colonoscopy every 10 years.44
Annual influenza vaccine should be administered to women 50 years and older.34 A tetanus and diphtheria toxoid (Td) booster is recommended every 10 years after the primary series is completed. The 2007–2008 Advisory Committee on Immunization Practices (ACIP) guideline recommends that a tetanus toxoid, reduced diphtheria toxoid, and acellular pertussis vaccine (Tdap) should replace a single dose of Td for adults younger than 65 years who have not previously received a dose of Tdap.34 Women 65 years and older should also be immunized against pneumococcal disease. The current recommendation is that the vaccine be repeated for those 65 years and older who received their first dose when they were younger than 65 years, and if five or more years have passed since that dose. A single dose of zoster vaccine is recommended for adults 60 years and older, whether or not they report a previous episode of herpes zoster.