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.
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 (see also Chapter 1: Disease Prevention & Health Promotion).
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.
Hypertension is a risk factor for CHD and stroke in both men
and women (see Chapter 1: Disease Prevention & Health Promotion). Approximately 7080% 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 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 130159 mg/dL
(3.94.77 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
medication treatment be considered.
There is clear evidence that medication 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 (see also Chapter 28: Lipid Disorders). Decisions about when to initiate medication treatment should include an assessment of an individual’s absolute risk of CHD in the next 10 years. Medication 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 medication therapy based on individual CHD risk. For example, for a woman with known CHD, lipid-lowering medication is initiated at an LDL cholesterol of > 130 mg/dL, whereas for a woman with 01 risk factor, medication therapy is not initiated until the LDL cholesterol measures > 190 mg/dL.
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. Women with diabetes also should focus on treatment of hypertension given the impact on CHD events (see Chapter 27: Diabetes Mellitus & Hypoglycemia).
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 (see Chapters 1: Disease Prevention & Health Promotion and 29: Nutritional Disorders).
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 has 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
Options for Reducing Risk Factors
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 5579 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 75325 mg/d is
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
2.53 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. See also Chapter 1: Disease Prevention & Health Promotion
|Centers for Disease Control and Prevention. National Center
for Health Statistics, Health Data Interactive. Mortality by underlying
cause, ages 18+: US/State, 19992007.
|Gutierrez J et al. Statin therapy in the prevention of recurrent cardiovascular events: a sex-based meta-analysis. Arch Intern Med. 2012 June 25;172(12):90919.
|Mosca L et al. Effectiveness-based guidelines for the prevention
of cardiovascular disease in women2011 update: a guideline
from the American Heart Association. Circulation. 2011 Mar 22;123(11):124362.
|U.S. Preventive Services Task Force. Screening for Lipid Disorders
in Adults: U.S. Preventive Services Task Force recommendation statement.
& Risk Assessment
Breast cancer is the most commonly detected cancer in women and
the second leading cause of cancer death (see also Chapter 17: Breast Disorders). 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.
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. Aromatase inhibitors, such as exemestane, show promise for breast cancer prevention but are not currently FDA approved for this indication. 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.
Traditional breast cancer screening modalities include screening
mammography, clinical breast examination, and breast self-examination (see also Chapter 17: Breast Disorders).
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 5074
years and routine mammographic screening is recommended for women
in this age group. For women aged 4049 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.
|Hubbard et al. Cumulative probability of false-positive recall or biopsy recommendation after 10 years of screening mammography: a cohort study. Ann Intern Med. 2011 Oct 18;155(8):48192.
|National Cancer Institute. Breast Cancer Risk
Assessment Tool. http://www.cancer.gov/bcrisktool
Colorectal cancer is the third leading cause of cancer death
in both men and women. In 2012, 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 5075, individualized
decision making about screening in individuals aged 7685,
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.
|Holden DJ et al. Enhancing the use and quality of colorectal cancer screening. Evid Rep Technol Assess (Full Rep). 2010 Feb;(190):1195.
|U.S. Preventive Services Task Force. Screening for Colorectal
Cancer: U.S. Preventive Services Task Force recommendation statement.
Ann Intern Med. 2008 Nov 4;149(9):62737.
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.
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 926 years to prevent disease associated with
these HPV types (see also Chapter 18: Gynecologic Disorders). 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 1118 but
states that there is insufficient evidence to recommend for or against
routine vaccination for women aged 1926. 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.
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. The USPSTF updated their screening recommendations in 2012 (see Chapter 18: Gynecologic Disorders). The 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. A multidisciplinary partnership among the American Cancer Society, the American Society for Colposcopy and Cervical Pathology and the American Society for Clinical Pathology also developed guidelines that are generally consistent with those of the USPSTF.
Current guidelines from the American College of Obstetricians and Gynecologists (ACOG) state that screening should start at age 21 regardless of the onset of sexual activity. ACOG recommends screening every 2 years in women aged 2129 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.
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.
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 (see Chapters 1: Disease Prevention & Health Promotion and 39: Cancer). 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 lung cancer screening, although many organizations are in the midst of reassessing their recommendations for lung cancer screening based on the results of the National Lung Screening Trial (NLST). In 2012, the American Academy of Chest Physicians and the American Society of Clinical Oncology issued a joint recommendation. They recommended that smokers and former smokers who have smoked for 30 pack years or more and either continue to smoke or have quit within the past 15 years be offered annual screening with low-dose CT scanning, but only in settings that can provide the comprehensive care provided to NLST participants. They do not recommend screening for individuals who do not meet the NLST criteria.
|National Lung Screening Trial Research Team; Aberle DR et al. Reduced lung-cancer mortality with low-dose computed tomographic screening. N Engl J Med. 2011 Aug 4;365(5):395409.
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 (see also Chapter 18: Gynecologic Disorders). 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.
|Buys SS et al. Effect of screening on ovarian cancer mortality: the Prostate, Lung, Colorectal and Ovarian (PLCO) Cancer Screening Randomized Controlled Trial. JAMA. 2011 Jun 8;305(22):2295303.
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). See also Chapter 26: Endocrine Disorders. 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
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 and other research has highlighted potential risks of calcium supplementation. Calcium appears to be necessary but not sufficient for fracture prevention. The USPSTF draft recommendations in June 2012 state that the evidence is insufficient to assess the balance of benefits and harms for the combination of vitamin D and calcium for primary prevention of fractures in men or postmenopausal women. They recommend against daily supplementation with < 400 international units of vitamin D3 and 1000 mg calcium for primary prevention of fractures in noninstitutionalized postmenopausal women, and state that there is insufficient evidence for daily supplementation with > 400 international units of vitamin D3 and 1000 mg of calcium for fracture prevention. Recommended calcium intake for women younger than 50 years is 1000 mg/d and for women aged 51 and over, it is 1200 mg/d. Dietary calcium may be safer than calcium supplements, but calcium supplements 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 70 and younger 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.
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. The USPSTF recommends screening women aged 65 and older and only screening younger women whose fracture risk is equal to or greater than that of a 65-year-old white woman who has no additional risk factors. The Fracture Risk Assessment tool (FRAX) tool can be used to calculate 10-year risk of osteoporotic fracture. Most guidelines do not specifically address how often a woman should undergo BMD testing. However, decisions about when to rescreen should probably be based on the results of initial screening. Analysis of a large cohort of women showed that osteoporosis would develop in < 10% of women during rescreening intervals of 15 years for women with normal BMD at baseline 5 years for women with moderate osteopenia (t score 1.5 to 1.990 and 1 year for women with advanced osteopenia (t score 2.00 to 2.49).
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.
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 (see Chapter 30: Common Problems in Infectious Diseases & Antimicrobial Therapy). Screening should continue in women over age 25 and in women who have high-risk sexual behaviors. The USPSTF recommends screening all women for HIV, including adolescents and women age 1565, others at high risk, as well as pregnant women. All patients who have a sexually transmitted infection or who seek testing for a sexually transmitted infection should be offered HIV testing. The CDC currently recommends screening all women born between 1945 and 1965 for hepatitis C infection.
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 (see also Chapter 25: Psychiatric Disorders). Low energy or fatigue is a particularly common symptom
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.
|Phelan E et al. A study of the diagnostic accuracy
of the PHQ-9 in primary care elderly. BMC Fam Pract. 2010 Sept 1;11:63.
|Zuithoff NP et al. The Patient Health Questionnaire-9 for detection
of major depressive disorder in primary care: consequences of current
thresholds in a cross-sectional study. BMC Fam Pract. 2010 Dec 13;11:98.