Prevention of disease can be primary (preventing disease before it happens as well as identifying and modifying risk factors), secondary (identifying early disease), or tertiary (treating complications of the disease or limiting the impact of established disease). Important areas for primary prevention include encouraging women to exercise regularly to reduce the risk of coronary heart disease (CHD) and breast cancer as well as counseling women to discontinue smoking to reduce the risk of cardiac and lung diseases. Cancer screening in women focuses on secondary prevention, so that disease is detected early when prompt treatment improves outcome.

Cardiovascular Disease Prevention

Although cardiovascular disease is the leading cause of death in women, they are often more concerned about developing breast cancer (see below) than about developing heart disease. While some heart disease risk factors such as age and family history are not modifiable, as with men, other risk factors such as hypertension, hyperlipidemia, smoking, obesity, and diabetes are potentially modifiable. The Framingham risk calculator (http://hp2010.nhlbihin.net/atpiii/calculator.asp?usertype=prof) can be used to estimate a woman's 10-year risk of CHD based on her age, smoking status, blood pressure, and cholesterol levels.

Modifiable Risk Factors

Hypertension

Hypertension is a risk factor for CHD and stroke in both men and women. Approximately 70–80% of women over age 70 have hypertension. A woman with high blood pressure is at lower risk for CHD than a similar aged man. For many young and otherwise healthy women, drug treatment can be deferred, since their absolute risk of CHD in the next 10 years is likely to be low. When pharmacotherapy is started, the choice of medication is similar to those used in men (see Chapter 11: Systemic Hypertension).

Hyperlipidemia

Hyperlipidemia is a CHD risk factor in both men and women, but low levels of high-density lipoprotein (HDL) is more predictive of CHD risk in women. Elevated cholesterol is defined as a total cholesterol > 240 mg/dL (> 7.2 mmol/L) or low-density lipoprotein (LDL) cholesterol > 160 mg/dL (> 4.8 mmol/L). Borderline cholesterol is defined as a total cholesterol between 200 mg/dL and 240 mg/dL (6 mmol/L and 7.2 mmol/L) or an LDL cholesterol of 130–159 mg/dL (3.9–4.77 mmol/L). Ideal cholesterol is defined as a total cholesterol < 200 mg/dL (< 6 mmol/L) or an LDL < 130 mg/dL (< 3.9 mmol/L) and an HDL cholesterol > 50 mg/dL (> 1.5 mmol/L).

The US Preventive Services Task Force (USPSTF) recommends screening all women aged 45 and older for hyperlipidemia, whereas the National Cholesterol Education Program (NCEP) recommends screening all individuals aged 20 and over. Before screening a woman for hyperlipidemia, an important consideration is whether or not treatment recommendations will change based on the results. Since therapeutic lifestyle changes are recommended for all women, the question is at what point should drug treatment be considered.

There is clear evidence that drug treatment of hyperlipidemia reduces CHD events in women who already have CHD, but when lipid-lowering medications are used in women who do not already have CHD, the evidence of benefit is less clear. Decisions about when to initiate drug treatment should include an assessment of an individual's absolute risk of CHD in the next 10 years. Drug treatment should be targeted toward women with CHD and high-risk women who are most likely to benefit. The NCEP recommends different thresholds at which to initiate drug therapy based on individual CHD risk. For example, for a woman with known CHD, lipid-lowering drugs are initiated at an LDL cholesterol of > 130 mg/dL, whereas for a woman with 0–1 risk factor, drug therapy is not initiated until the LDL cholesterol measures > 190 mg/dL.

Diabetes

Diabetes is a CHD risk factor in both men and women. Studies have reached conflicting conclusions about the effect of tight control of diabetes on CHD outcomes in both men and women, although lipid lowering is clearly associated with a reduction in CHD events in diabetic women. All women should focus on primary prevention of diabetes with avoidance of obesity and maintenance of regular exercise.

Obesity

Obesity has been established as an independent risk factor for CHD in women. It is not known whether or not weight loss will decrease CHD risk. Since most obese women who lose weight gain it back, the overall goal should be ongoing avoidance of weight gain above normal weight.

Predictive Biomarkers and Clinical Tests

The use of high-sensitivity C-reactive protein (hsCRP) has increased in recent years. CRP is an inflammatory biomarker that has been shown to predict cardiovascular events. However, there is currently no evidence that screening for hsCRP improves cardiac outcomes. It has been suggested that measuring hsCRP may be useful in women for whom it would change treatment outcomes, but there is currently no evidence to support this. The USPSTF recently published guidelines outlining the use of nontraditional risk factors in the evaluation of CHD. The risk factors included in the recommendation were hsCRP, ankle-brachial index, leukocyte count, fasting blood glucose, periodontal disease, carotid intima media thickness, coronary artery calcification score, electron beam CT, homocysteine, and lipoprotein (a). The USPSTF concluded that there is insufficient evidence to balance the benefits and harms of screening asymptomatic men and women with no history of CHD to predict CHD events and did not recommend routine screening.

Therapeutic Options for Reducing Risk Factors

Aspirin

Aspirin is clearly useful for secondary prevention of CHD in women. Among women who do not have CHD, aspirin reduces the risk of stroke, whereas in men, it reduces the risk of CHD. Before starting an aspirin regimen to reduce the risk of the stroke, women should be assessed for their risk of gastrointestinal bleeding, which is the most common adverse side effect of aspirin use. The USPSTF recommends aspirin in women aged 55–79 years when the potential benefit of a reduction in ischemic strokes outweighs the potential harms of a gastrointestinal hemorrhage. For healthy or at-risk women, 81 mg/d or 100 mg every other day is the suggested dose. For high-risk women, a dose of 75–325 mg/d is recommended.

Exercise

Exercise has been associated with a reduction in all causes of cardiovascular mortality. Women often want to know how much exercise is necessary for health benefits. Studies have shown that walking 2.5–3 hours a week is associated with a reduction in cardiovascular disease. The Centers for Disease Control and Prevention and the American College of Sports Medicine recommend that all women accumulate at least 30 minutes a day of moderate intensity physical activity on most if not all days of the week. The Institute of Medicine recommends an hour a day for the goal of maintaining health and ideal body weight.

Cancer Prevention

Breast Cancer

Risk Factors & Risk Assessment

Breast cancer is the most commonly detected cancer in women and the second leading cause of cancer death. Breast cancer risk is increased with age and with a family history of breast cancer. Women who drink more than two alcoholic drinks per day are at increased risk for breast cancer, and exercise is associated with a decreased risk of breast cancer. Dietary intake has not been conclusively associated with breast cancer risk.

Various models have been used to predict a woman's risk for breast cancer. The National Cancer Institute has developed the Breast Cancer Risk Assessment Tool, which is based on the Gail Model, and calculates the woman's risk of developing breast cancer in the next 5 years by considering the following factors: (1) the woman's age, (2) age at which she had her first menstrual period, (3) age at delivery of first live child, (3) number of first-degree relatives with breast cancer, (4) history of any breast biopsies, and (5) history of atypical hyperplasia. The model has been validated in white women and has been evaluated in black women and found to be relatively accurate, although it may underestimate the risk in black women with a history of previous breast biopsies. It has yet to be validated in women of other ethnicities.

Primary Prevention

In addition to lifestyle modifications, such as exercise and moderation of alcohol intake, chemoprevention of breast cancer is an option for some women. The selective estrogen receptor modifiers (SERMS) tamoxifen and raloxifene have both been shown to reduce invasive breast cancer in high-risk women. However, there are risks associated with SERM treatment. Tamoxifen is associated with an increased risk of endometrial cancer and deep venous thrombosis (DVT). Although raloxifene is not associated with an increased risk of endometrial cancer, the risk of DVT remains. The USPSTF recommends that clinicians discuss chemoprevention with women at high risk for breast cancer and at low risk for the adverse effects of chemoprevention. Clinicians should inform patients of the potential benefits and harms of chemoprevention. Breast cancer risk increases with age, but the risk of adverse effects does as well. Since the clinical trials of tamoxifen and raloxifene for breast cancer prevention used a 1.66% 5-year risk, this risk level is often used as a guide for treatment.

Breast Cancer Screening

Traditional breast cancer screening modalities include screening mammography, clinical breast examination, and breast self-examination. Teaching women to do routine breast self-examination has not been shown to reduce breast cancer mortality. The USPSTF recommends against teaching women to do breast self-examination. The American Cancer Society states that it is acceptable not to do it, but that if women are performing breast self-examination, it is important to ensure that they are doing it correctly. The combination of breast examination done by a clinician and mammography is associated with a decrease in breast cancer mortality, but there is insufficient evidence to recommend clinical breast examination alone.

Mammography reduces breast cancer mortality in women aged 50–74 years and routine mammographic screening is recommended for women in this age group. For women aged 40–49 years, screening has been more controversial. Recent guidelines published by the USPSTF recommend that clinicians not routinely order mammography among 40- to 49-year-old women but rather that they individualize the decision to begin screening, since the number needed to invite to screen to prevent one breast cancer death is much higher in younger women and the number of false-positive and false-negative test results are much higher. Since women over age 75 have not been included in clinical trials and since the likelihood of comorbid diseases limiting life expectancy increases, routine screening of women in this age group is not recommended, but rather the decision making should be individualized.

Colorectal Cancer

Colorectal cancer is the third leading cause of cancer death in both men and women. In 2010, an estimated 9% of cancer deaths in women were caused by colorectal cancer. Since the risk of colorectal cancer increases with age, all women should be screened for colorectal cancer starting at the age of 50. The USPSTF recommends routine screening in men and women age 50–75, individualized decision making about screening in individuals aged 76–85, and no screening after the age of 85. Details of the screening options and suggested screening intervals are described in Chapter 1: Disease Prevention & Health Promotion.

Cervical Cancer

In contrast to most other cancers for which routine screening is recommended, the incidence of cervical cancer is higher in younger women and decreases with age. The major risk factor for cervical cancer is exposure to the human papillomavirus (HPV). Primary prevention of cervical cancer includes avoidance of smoking, postponing sexual debut, and limiting the number of sexual partners. Condom use may also be protective.

Primary Prevention

A quadrivalent HPV vaccine that includes capsid proteins against four HPV types (6, 11, 16, and 18) has been approved for use in girls and women aged 9–26 years to prevent disease associated with these HPV types. A bivalent vaccine (Cervarix) is also available. The published studies, which are based on interim results, show a high degree of efficacy of prevention of vaccine-associated genital warts, persistent infections, and cervical intraepithelial neoplasia. Protection has not been shown against strains that are not in the vaccine or strains that were present before vaccination. The Advisory Committee on Immunization Practices (ACIP) recommends routine vaccination for girls aged 11 or 12 up to age 26, whereas the American Cancer Society recommends the vaccine for girls aged 11–18 but states that there is insufficient evidence to recommend for or against routine vaccination for women aged 19–26. The ACIP also recommends that all 11- and 12-year-old boys get vaccinated against HPV. Unanswered questions about the vaccine include the long-term effects and the length of protection. Receipt of vaccine should not change cervical cancer screening intervals in women.

Secondary Prevention

An important focus of cervical cancer prevention is screening using the Papanicolaou smear. Cervical cancer screening is the biggest success in the history of cancer screening. Cervical cancer mortality has been reduced by about 70% with routine cervical cancer screening. One of the reasons that screening has been so successful is that there is a long preclinical phase where early changes can be detected and treated so as to avoid the development of cancer. In a 2012 update, the US Preventive Services Task Force (USPSTF) recommends screening for cervical cancer in women age 21 to 65 years with cytology (Papanicolaou smear) every 3 years or, for women age 30 to 65 years who want to lengthen the screening interval, screening with a combination of cytology and HPV testing every 5 years. Screening may be done with either liquid-based or conventional cytology. The USPSTF recommends against screening for cervical cancer with HPV testing, alone or in combination with cytology, in women younger than age 30 years. The USPSTF recommends against screening for cervical cancer in women older than age 65 years who have had adequate prior screening and are not otherwise at high risk for cervical cancer. Women with risk factors that place them at higher risk for cervical intraepithelial neoplasia may require more frequent screening. Guidelines from the American College of Obstetricians and Gynecologists (ACOG) state screening should start at age 21 regardless of the onset of sexual activity. ACOG recommends screening every 2 years in women aged 21–29 and every 3 years in women aged 30 and older who have had at least three normal smears. All organizations agree that older women (over age 65 or 70) can stop screening.

Testing for high-risk HPV types is routinely used for the evaluation of abnormal Papanicolaou smears, but their use in routine screening is controversial. Since the prevalence of exposure to high risk HPV types is very high, the potential utility of HPV testing would be finding no evidence of HPV. ACOG and the American Cancer Society recommend co-testing with high risk HPV types as an option, and then rescreening in 3 years if the HPV testing is negative. The USPSTF concludes that the evidence is insufficient to assess the balance of benefits and harms of HPV testing, alone or in combination with cytology for screening for cervical cancer in women aged 30 and older. Given that women with a normal Papanicolaou smear can be rescreened in 3 years, it is not clear what high risk HPV testing for primary screening adds. However, given that the vast majority of cervical cancers occur in women who have never been screened, or who have not been screened in the past 5 years, efforts for cervical cancer prevention should primarily focus on those women.

Lung Cancer

Although lung cancer is not typically considered a “women’s cancer,” it is the leading cause of cancer mortality in both men and women. Primary prevention of lung cancer should be a high priority with encouragement of tobacco cessation among women who smoke. The use of chest radiographs and sputum cytology for cancer screening have not been shown to reduce lung cancer mortality. The National Lung Screening Trial (NLST) compared screening with low-dose CT to screening with chest radiography. High-risk participants (either current or former smokers) received either annual CT or chest radiography for 3 years and were then monitored for 6.5 years. There was a significant reduction in both lung cancer mortality and total mortality with CT screening. However, there were a very large number of false-positive test results, many of which led to additional testing. The USPSTF does not currently recommend any of these modalities for lung cancer screening, although many organizations are in the midst of reassessing their recommendations for lung cancer screening based on the results of the NLST.

Ovarian Cancer

Ovarian cancer is a relatively rare but dreaded cancer, with a lifetime incidence of about 1.2% in women with no family history of ovarian cancer. Because it is often detected late, treatment options may be limited.

Many of the risk factors for ovarian cancer such as age and family history are not modifiable, but there are protective factors, including having more than one full-term pregnancy, breast-feeding, and oral contraceptive use. Women at high-risk for ovarian cancer should consider the use of oral contraceptives for as long as it is feasible.

Although screening for ovarian cancer with either the serum marker CA-125 or with transvaginal ultrasound is theoretically appealing, the rarity of the disease limits their use and leads to many false-positive test results. The Prostate, Lung, Colorectal and Ovarian Cancer Screening Trial, where women were screened for ovarian cancer with annual CA-125 and transvaginal ultrasound and monitored for 12.4 years, resulted in no reduction in ovarian cancer mortality. In addition, there were a large number of false-positive test results, some leading to surgical follow-up and resultant surgical complications. The USPSTF does not recommend screening for ovarian cancer.

Osteoporosis Prevention

Osteoporotic fractures are increasing as the population ages. Age and female sex are major risk factors for osteoporotic fractures. Hip and vertebral fractures are associated with premature mortality. Osteoporosis risk can be assessed by measuring bone mineral density (BMD). Normal BMD is no lower than 1.0 standard deviation below the mean for young adult women (t score). Osteopenia is defined as BMD between 1.0 and 2.5 standard deviations below the mean for young adults (t score of -1.0 to -2.5) and osteoporosis is defined as a BMD more than 2.5 standard deviations below the young adult mean (t score < -2.5).

The World Health Organization has developed a fracture risk assessment tool (FRAX, available at http://www.shef.ac.uk/FRAX/index.jsp) that can predict a woman's 10-year risk of having any osteoporotic fracture and the 10-year risk of hip fracture. Risk factors used in the FRAX tool include age, gender, personal history of fracture, parental history of hip fracture, low body mass index, use of oral corticosteroids, secondary osteoporosis, current smoking, and alcohol intake of three or more drinks per day. It can be used with or without BMD. The FRAX tool is particularly helpful in determining which women with osteopenia are most likely to benefit from treatment. Based on the World Health Organization algorithm adopted for the United States, treatment is recommended when there is a 10-year risk of hip fracture 3% or a 10-year risk of a major osteoporotic fracture 20%.

Primary Prevention

Although calcium supplementation is routinely recommended, evidence from the Women's Health Initiative showed that calcium supplementation did not reduce fracture risk in healthy postmenopausal women. Calcium appears to be necessary but not sufficient for fracture prevention. Recommended calcium intake for women younger than 50 years is 1000 mg/day and for women aged 51 and over, it is 1200 mg/day. Calcium can be given as either calcium citrate or calcium carbonate and should be given with vitamin D. Regular weight bearing exercise has also been associated with an increase in bone density although the effect is lost when the exercise is not continued.

Increasing evidence suggests that vitamin D supplementation is associated with a reduction in fracture risk. Vitamin D can be given as either D₂ or D₃ formulations. Recommendations are that women aged 1–70 should consume 600 international units of vitamin D per day, whereas women aged 71 and older should consume 800 international units per day. Individuals with vitamin D deficiency (25-OH vitamin D < 20 mg/mL) may require higher doses, although most recommendations for vitamin D supplementation are based on achieving a serum 25-OH vitamin D concentration of a particular level, rather than on a clinical outcome. Whether or not women should be routinely screened for vitamin D deficiency remains an ongoing question. However, given the association of vitamin D and fractures, checking a 25-OH vitamin D level in women with osteoporosis is reasonable.

Bone Mineral Density Screening

The biggest risk factor for developing osteoporosis is increasing age. Although many women expect to be screened around the time of menopause, routine BMD screening is not recommended until the age of 65. The National Osteoporosis Foundation recommends screening all women age 65 and older and screening younger postmenopausal women if there is a concern based on their risk-factor profile, if they have had a fracture, or if they are discontinuing hormone therapy. The USPSTF recommends screening women aged 65 and older and only screening women aged 60–64 who are at increased risk.

Treatment is generally recommended in women who have a t score < -2.5, who have already had a fracture or who have a t score in the osteopenic range but are at high risk for fracture. Treatment options for osteoporosis are described in Chapter 26: Endocrine Disorders.

Prevention of Sexually Transmitted Infections

Many sexually transmitted infections are asymptomatic in women and some can lead to significant consequences. Primary prevention of sexually transmitted infections includes postponing sexual debut, limiting number of sexual partners, and regular condom use.

The USPSTF and the Centers for Disease Control and Prevention recommend annual screening for Chlamydia trachomatis and gonorrhea in sexually active women age 25 and younger. Screening should continue in women over age 25 and in women who have high-risk sexual behaviors. The Centers for Disease Control and Prevention recommends screening all women for HIV, whereas the USPSTF recommends focusing screening efforts on high-risk individuals. All patients who have a sexually transmitted infection or who seek testing for a sexually transmitted infection should be offered HIV testing.

Depression Screening

Since depression is approximately two times more common in women than in men, clinicians should be alert to symptoms suggesting depression in women. Symptoms include depressed mood, loss of interest in activities, sleep disturbance, change in appetite or weight, psychomotor retardation, difficulty concentrating, feelings of worthlessness, and thoughts of suicide. Low energy or fatigue is a particularly common symptom in women.

There are several clinical surveys for depression screening. The two question screen appears to be effective. Patients are asked "Over the past 2 weeks, have you felt down, depressed or hopeless?" and "Over the past 2 weeks, have you felt little interest or pleasure in doing things?" There is no evidence to suggest that any particular screening tool is superior. A positive screening test should lead to more extensive evaluation.

The USPSTF recommends screening for depression if staff-assisted depression care supports are in place to ensure accurate diagnosis, effective treatment, and follow-up. If these supports are not in place, screening is not recommended.