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Women’s Health Issues Megan McNamara, MD, MSc, & Judith Walsh, MD, MPH

The field of women’s health encompasses more than the reproductive health issues commonly addressed by obstetricians and gynecologists; it evaluates diseases and conditions only seen or experienced in women or experienced by women in ways different than men, as well as the evidencebased prevention and treatment of risk factors and diseases in women. Hence, all primary care providers, including internists and family physicians, should be well versed in women’s health issues.

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PREVENTIVE HEALTH CARE

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 A. 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).

B. 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 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

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in women who do not already have CHD, the evidence of benefit is less clear. 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 0–1 risk factor, medication therapy is not initiated until the LDL cholesterol measures > 190 mg/dL.

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.

C. Diabetes

B. Exercise

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.

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.

D. 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.

E. 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 A. Aspirin Aspirin is clearly useful for secondary prevention of CHD in women. Among women who do not have CHD,

Berg AO et al. U.S. Preventive Services Task Force: screening for lipid disorders in adults: recommendations and rationale. Am J Nurs. 2002 Jun;102(6): 91,93,95. [PMID: 12394084] Centers for Disease Control and Prevention. National Center for Health Statistics, Health Data Interactive. Mortality by underlying cause, ages 18+: US/State, 1999–2007. http:// 205.207.175.93/ HDI/TableViewer/tableView.aspx?ReportId=673.

Mosca L et al. Effectiveness-based guidelines for the prevention of cardiovascular disease in women—2011 update: a guideline from the American Heart Association. Circulation. 2011 Mar 22;123(11):1243–62. [PMID: 21325087] National Cholesterol Education Program (NCEP) Expert Panel on Detection, Evaluation, and Treatment of High Blood Cholesterol in Adults (Adult Treatment Panel III). Third Report of the National Cholesterol Education Program (NCEP) Expert Panel on Detection, Evaluation, and Treatment of High Blood Cholesterol in Adults (Adult Treatment Panel III) final report. Circulation. 2002 Dec 17;106(25):3143–421.

[PMID: 12485966] U.S. Preventive Services Task Force. Aspirin for the prevention of cardiovascular disease: U.S. Preventive Services Task Force Recommendation Statement. Ann Intern Med. 2009 Mar 17;150(6):396–404. [PMID: 19293072] U.S. Preventive Services Task Force. Screening for Lipid Disorders in Adults: U.S. Preventive Services Task Force recommendation statement. http://www.uspreventiveservicestaskforce.org/ uspstf08/lipid/lipidrs.htm U.S. Preventive Services Task Force. Using nontraditional risk factors in coronary heart disease risk assessment: U.S. Preventive Services Task Force recommendation statement.

Ann Intern Med. 2009 Oct 6;151(7):474–82. [PMID: 19805770]

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CANCER PREVENTION 1. 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 chemo­ prevention. 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.

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):481–92. [PMID: 22007042] National Cancer Institute. Breast Cancer Risk Assessment Tool. http://www.cancer.gov/bcrisktool U.S. Preventive Services Task Force. Screening for breast cancer: U.S. Preventive Services Task Force recommendation statement. Ann Intern Med. 2009 Nov 17;151(10):716–26. [PMID: 19920272]

2. 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.

Holden DJ et al. Enhancing the use and quality of colorectal cancer screening. Evid Rep Technol Assess (Full Rep). 2010 Feb;(190):1–195. [PMID: 20726624] Levin B et al. Screening and surveillance for the early detection of colorectal cancer and adenomatous polyps, 2008: a joint guideline from the American Cancer Society, the US Multisociety Task Force on Colorectal Cancer, and the American College of Radiology. Gastroenterology. 2008 May;134(5): 1570–95. [PMID: 18384785] 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):627–37.

[PMID: 18838716]

Women’s Health Issues

3. 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

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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.

American College of Obstetricians and Gynecologists. ACOG Practice Bulletin no. 109: Cervical cytology screening. Obstet Gynecol. 2009 Dec;114(6):1409–20. [PMID: 20134296] U.S. Preventive Services Task Force. Screening for cervical cancer. http://www.uspreventiveservicestaskforce.org/uspstf/ uspscerv.htm U.S. Preventive Services Task Force. Screening for cervical cancer: U.S. Preventive Services Task Force recommendation statement. http://www.uspreventiveservicestaskforce.org/ uspstf11/cervcancer/cervcancerrs.htm

4. 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.

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National Lung Screening Trial Research Team; Aberle DR et al.

Reduced lung-cancer mortality with low-dose computed tomographic screening. N Engl Med. 2011 Aug 4;365(5): 395–409. [PMID: 21714641] U.S. Preventive Services Task Force. Lung cancer screening: recommendation statement. Ann Intern Med. 2004 May 4; 140(9):738–9. [PMID: 15126258]

5. 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.

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):2295–303. [PMID: 21642681] U.S. Preventive Services Task Force. Screening for ovarian cancer: recommendation statement. Am Fam Physician. 2005 Feb 15;71(4):759–62. [PMID: 15756773]

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 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.

``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.

Women’s Health Issues

Bischoff-Ferrari HA et al. Prevention of nonvertebral fractures with oral vitamin D and dose dependency: meta-analysis of randomized controlled trials. Arch Intern Med. 2009 Mar 23;169(6):551–6. [PMID: 19307517] World Health Organization Collaborating Centre for Metabolic Bone Diseases. Fracture Risk Assessment Tool (FRAX). http:// www.shef.ac.uk/FRAX/index.jsp Institute of Medicine (IOM). Dietary reference intakes for calcium and vitamin D. http://www.iom.edu/Reports/2010/ Dietary-Reference-Intakes-for-Calcium-and-Vitamin-D. aspx.

U.S. Preventive Services Task Force. Screening for osteoporosis: U.S. Preventive Services Task Force recommendation statement. Ann Intern Med. 2011 Mar 1;154(5):356–64. [PMID: 21242341] Watts NB et al; AACE Osteoporosis Task Force. American Association of Clinical Endocrinologists Medical Guidelines for Clinical Practice for the diagnosis and treatment of postmenopausal osteoporosis. Endocr Pract. 2010 Nov–Dec; 16(Suppl 3):1–37. [PMID: 21224201]

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.

Meyers D et al. U.S. Preventive Services Task Force recommendations for STI screening. Am Fam Physician. 2008 Mar 15; 77(6):819–24. [PMID: 18386598]

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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.

[PMID: 20807445] U.S. Preventive Services Task Force. Screening for depression in adults: U.S. Preventive Services Task Force recommendation statement. Ann Intern Med. 2009 Dec 1;151(11):784–92.

[PMID: 19949144] 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. [PMID: 21144018]

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SPECIFIC ISSUES & CONDITIONS

INTIMATE PARTNER VIOLENCE Intimate partner violence (IPV) is a pattern of abusive behavior by a person who is in some type of intimate relationship with the victim. The abuse can be physical, sexual, or emotional and can include economic deprivation.

Although anyone can be a victim of IPV, women are much more likely than men to be victims. Regardless of the type of abuse, the goal of the abuser is to gain control over the victim. IPV is common but is often not diagnosed, in part because patients try to hide the abuse.

The prevalence estimate of IPV varies depending on the setting. Rates are higher when measured in emergency departments than when measured in the general population. In a randomized controlled trial of IPV screening in emergency departments, the prevalence over 12-months ranged from 4% to 18%.

Risk factors for abuse include being young (under age 35 years); being pregnant; being single, divorced, or separated; alcohol or drug abuse in the victim or the partner; smoking; and being poor.

DEPRESSION SCREENING

``Evaluation

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?”

Since patients often do not volunteer that they have been abused, clinicians must be alert to clues that suggest abuse, including an explanation of the injuries that do not fit with what is being seen; frequent visits to the emergency department; and somatic complaint such as chronic headache, abdominal pain, and fatigue. The patient may be vague about some of her symptoms and may avoid eye contact. If the abusing partner is present, he or she may answer all the questions or may decline to leave the room. It is critical that the patient have the opportunity to speak with the clinician alone. The patient’s description of the events should be carefully detailed in case there are any subsequent legal issues.

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Physical examination often reveals injuries in the central area of the body. There may be injuries on the forearms as well if the patient tried to defend herself. As with any situation of expected abuse, bruises that are in various stages of healing may be an important clue. All physical examination findings should be well documented.

In addition to the physical consequences, abuse can have psychological consequences. Posttraumatic stress disorder, depression, anxiety, and alcohol or other substance abuse can develop in victims. Somatization is also very common among victims.

Several instruments have been developed to screen for IPV. These include the HITS (Hurt, Insult, Threaten, Screamed at) tool, the Women Abuse Screening tool (WAST), the Partner Violence Screen (PVS), the Abuse Assessment Screen (AAS), and the Women’s Experience with Battering (WEB) scale. A systematic review of these screening tools showed that most tools only had been evaluated in a relatively small number of studies and the sensitivities and specificities varied widely within and between the tools.

Inclusion of one question in the context of the medical history, “Have you ever been hit, kicked, punched or otherwise hurt by someone within the past year? If so, by whom?” has been shown to increase identification of IPV. Many studies have addressed how the questions about IPV are asked. In one randomized trial, women preferred written questionnaires over face to face interviewing.

Screening for IPV (in contrast to asking questions when IPV is suspected) has been advocated by many experts, although there is currently no evidence that it improves outcomes. In a randomized controlled trial conducted in emergency departments and other clinical sites, women in the screened group were assessed for IPV and if the screen was positive, the information was given to the clinician before the visit. At 18-month follow-up, there was no difference in recurrence of IPV among women in the screened compared with the non-screened groups. There were also no differences in quality of life, although there were no adverse effects of screening.

The USPSTF has concluded that there is insufficient evidence to recommend for or against universal screening for IPV, since there is currently no evidence that screening improves outcomes. However, clinicians should remain on high alert for clues to IPV among patients.

``Interventions for IPV Interventions can include encouraging the woman to leave the abusive situation, ensuring that she has a safe place to go, and counseling so that she can adequately assess her risk of danger and create a plan for safety. There is no evidence that treatment of the abuser changes abuser behavior.

``When to Refer • Victims should be referred to social services so that they can provide information on local resources. There is a national domestic violence hotline (1-800-799-SAFE) that can provide information on local resources.

• In general, mandatory reporting of IPV or suspicion of it in adult women who are competent is not required in

most states. However, mandatory reporting by physicians is required in California, Colorado, Kentucky, Mississippi, Ohio and Rhode Island.

Ahmad F et al. Computer-assisted screening for intimate partner violence and control: a randomized trial. Ann Intern Med. 2009 Jul 21;151(2):93–102. [PMID: 19487706] MacMillan HL et al; McMaster Violence Against Women Research Group. Screening for intimate partner violence in health care settings: a randomized trial. JAMA. 2009 Aug 5;302(5):493–501. [PMID: 19654384] Rabin RF et al. Intimate partner violence screening tools: a systematic review. Am J Prev Med. 2009 May;36(5):439–45.

[PMID: 19362697]

EATING DISORDERS Eating disorders are common in women. Anorexia nervosa and bulimia nervosa are described in detail in Chapter 29.

The female athlete triad, disordered eating in diabetics, and binge eating disorders are other eating disorders that should be considered in appropriate women.

1. Female Athlete Triad

``

E ssen t i a ls o f d i a g n o s i s

Disordered eating.

Menstrual disorders. `` Low BMD. `` ``

``General Considerations Female athletes who participate in sports and activities valuing thinness are at increased risk for developing the female athlete triad. The definition of the triad includes disordered eating (a spectrum of abnormal patterns of eating, including bingeing; purging; food restriction; prolonged fasting; and the use of diet pills, diuretics, or laxatives), menstrual disorders, and low BMD. Half of all athletes with amenorrhea have bone density at least 1.0 standard deviation below the mean. The bone density is decreased even in those areas subjected to stress during exercise. The diagnosis is made when the individual meets the three criteria of the triad.

``Clinical Findings A. Symptoms and Signs Individuals with the female athlete triad display some pattern of disordered eating and have some menstrual irregularities. Many women have amenorrhea but others have irregular menses. Typically, the patient has concerns about weight and body image. A history of stress fractures should also raise the clinician’s concern.

B. Laboratory Findings Depending on the severity of the symptoms and whether or not the patient is bingeing and purging, the laboratory

Women’s Health Issues abnormalities can be similar to those seen in anorexia nervosa or bulimia nervosa. BMD, if measured, is decreased.

``Differential Diagnosis The main differential diagnoses include anorexia nervosa, bulimia nervosa as well as endocrine disorders such as hyperthyroidism and diabetes mellitus.

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eating patterns. Other symptoms associated with eating disorders, such as disturbance of body image and menstrual irregularities, may also be present.

B. Laboratory Findings The main laboratory finding will be a trend of increasing levels of hemoglobin A1C.

``Treatment

``Differential Diagnosis

Little evidence is currently available about treatment of the female athlete triad. Strategies such as counseling, cognitive behavior therapy, and possibly exercise restriction may be helpful. A multidisciplinary approach, including consultation with a nutritionist and communication with the coach and trainers, may enable common goal setting. The desire to participate in sports and the lure of a performance enhancing diet may motivate some patients to pursue treatment.

The main differential diagnosis includes looking for other causes of worsening glycemic control such as underlying infection or metabolic disease such as hyperthyroidism.

Bonci CM et al. National Athletic Trainers’ Association position statement: preventing, detecting and managing disordered eating in athletes. J Athl Train. 2008 Jan–Mar;43(1):80–108.

[PMID: 18335017] Nattiv A et al. American College of Sports Medicine position stand. The female athlete triad. Med Sci Sports Exerc. 2007 Oct;39(10):1867–82. [PMID: 17909417]

2. Disordered Eating in Diabetics

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E ssen t i a ls o f d i a g n o s i s

Binge eating. `` Purging with laxatives or vomiting. `` Insulin omission. `` Taking less insulin than prescribed to lose weight. ``

``Treatment There is currently no evidence to support any particular strategies for the treatment of disordered eating in diabetic patients. Proposed strategies for at risk diabetic patients include nutritional counseling to promote healthy eating instead of dietary restraint, regular (instead of fixed) meal and snack times, less intensive insulin therapy to reduce weight gain, and family counseling to improve communication.

No studies have evaluated the optimal treatment of diabetic patients with established eating disorders.

Presumably, strategies that are effective for patients without diabetes, such as cognitive behavioral therapy and medications, will be effective. In addition, diabetic management strategies that do not require the patient to constantly think about food may be beneficial.

Gobel-Fabbri AE et al. Disturbed eating behaviors and eating disorders in type 1 diabetes: clinical significance and treatment recommendations. Curr Diab Rep. 2009 Apr;9(2):133–9.

[PMID: 19323958]

3. Binge Eating Disorder

``General Considerations Eating disturbances have been estimated to be present in up to one-third of young women with diabetes. Eating disorders are more common in adolescents with diabetes than in their non-diabetic peers. Mortality is particularly high in individuals with both diabetes and eating disorders.

For diabetes, the dietary regimen emphasizes intense meal timing and consistency. In addition, the hunger associated with hypoglycemia encourages binge eating. Finally, weight gain is often associated with good glycemic control.

Diabetics with disordered eating have been shown to have an increased risk of retinopathy. Given the emphasis that young women often place on body weight, maintaining optimal diabetes control is a particular challenge. The diagnosis is typically made in a diabetic who has worsening diabetic control, when other causes of worsening control have been ruled out.

``Clinical Findings A. Symptoms and Signs Diabetics may report polydipsia, polyuria, or weight loss.

In addition, upon questioning, they may report disturbed

``

E ssen t i a ls o f d i a g n o s i s

Binge eating disorder consists of episodes of eating a large amount of food in a discreet period of time with a sense of lack of control. `` Binge episodes characterized by at least three of the following: – Eating large amounts of food when not feeling hungry.

– Eating more rapidly than normal.

– Eating until feeling uncomfortably full.

– Eating alone because of embarrassment about the amount of food consumed.

– Feeling disgusted, depressed, or guilty after eating. `` Episodes occur at least two times a week for at least 6 months. `` No compensatory behavior (purging, fasting, or excessive exercise) after eating. ``

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``General Considerations Binge eating disorder is more common than either anorexia nervosa or bulimia nervosa, but it is currently not recognized as a psychiatric diagnosis. Currently, the Diagnostic and Statistical Manual of Mental Disorders, fourth edition (DSM-IV) has criteria that are considered research criteria.

Individuals who meet these criteria are defined as having eating disorder, not otherwise specified.

Binge eating disorder is much more common in women and is associated with obesity, although not all individuals with binge eating disorder are obese. Obesity-related complications are likely to occur, and the disorder may be more common in weight cycling patients.

``Clinical Findings The patient may present with weight gain or may describe disordered eating patterns and binge eating episodes.

There are no specific laboratory findings for binge eating disorder.

``Differential Diagnosis The main differential diagnosis includes other psychiatric and eating disorders. Other diagnostic possibilities include hypothyroidism and Prader-Willi syndrome.

``Treatment Treatment goals focus on decreasing the patient’s binge eating episodes and may include weight loss and treatment of other psychiatric comorbidities. As in bulimia nervosa, cognitive behavioral therapy is the mainstay of treatment.

Interpersonal therapy has also been shown to be effective.

Pharmacotherapy with selective serotonin reuptake inhibitors is also helpful, but does not appear to be better than cognitive behavioral therapy.

National Institute for Health and Clinical Excellence. Eating disorders: core interventions in the treatment and management of anorexia nervosa, bulimia nervosa and related eating disorders. http://www.nice.org.uk/CG009 Vocks S et al. Meta-analysis of the effectiveness of psychological and pharmacological treatments for binge eating disorder. Int J Eat Disord. 2010 Apr;43(3):205–17. [PMID: 19402028] Wilson GT et al. Psychological treatments of binge eating disorder. Arch Gen Psychiatry. 2010 Jan;67(1):94–101. [PMID: 20048227]

SEXUALITY & SEXUAL HEALTH Sexual health is defined by the World Health Organization as a state of physical, emotional, mental, and social wellbeing in relation to sexuality. Healthy sexual functioning therefore depends on a complex interplay of physical, psychological, and societal factors. In the United States, sexual dysfunction is common, with more than 44% of surveyed women reporting a sexual problem and 12% experiencing distress from the problem. Six female sexual disorders have been identified in the DSM-IV and include hypoactive sexual desire disorder (HSDD), sexual aversion disorder, female sexual arousal disorder, female orgasmic

disorder, dyspareunia, and vaginismus; these are discussed in detail in Chapters 18 and 25. Notably, HSDD is most prevalent in middle-aged women. Several psychological and biological risk factors can contribute to female sexual dysfunction, including poor mental health, relationship difficulties, and hormonal changes that are associated with aging. In contrast, positive feelings about the partner and the relationship can be “protective.” Physicians should routinely assess patients’ sexual health during office visits; even a brief assessment provides patients with reassurance that this is an important topic. Providers can broach the subject using a broad question, such as “What concerns or questions do you have about your sexual functioning?” and then follow-up with more specific questions, including “Do you have difficulty with desire, arousal, or orgasm?” and “If you are not currently sexual, are there any particular problems that are contributing to your lack of sexual behavior?” Patient concerns can then be delineated more fully during the complete sexual assessment, which encompasses details about medical, surgical, and psychiatric problems, as well as medications and reproductive history. Treatment options depend on the diagnosed disorder and can include psychosexual and hormonal therapy (see Chapter 18).

Kingsberg S et al. Evaluation and treatment of female sexual disorders. Int Urogynecol J Pelvic Floor Dysfunct. 2009 May; 20(Suppl 1):S33–43. [PMID: 19440781] World Health Organization. Measuring sexual health: conception and practical considerations and related indicators.

World Health Organization, 2010, Geneva, Switzerland. http://www.who.int/reproductivehealth/publications/monitoring/who_rhr_10.12/en/index.html

CHRONIC PELVIC PAIN

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E ssen t i a ls o f d i a g n o s i s

Noncyclic pain.

Duration of 6 months or more. `` Localized to anatomic pelvis, anterior abdominal wall at or below the umbilicus, the lumbosacral back, or buttocks. `` Associated with functional disability. `` ``

``General Considerations Chronic pelvic pain is defined as noncyclic pain lasting at least 6 months that localizes to one of the following areas: the anatomic pelvis, the anterior abdominal wall at or below the umbilicus, the lumbosacral back, or the buttocks.

It must be of sufficient severity to cause functional disability or necessitate medical care. Endometriosis is diagnosed in up to two-thirds of women with chronic pelvic pain; other common etiologies include postoperative pelvic adhesions, pelvic varices, interstitial cystitis (IC), and

Women’s Health Issues irritable bowel syndrome (IBS). Musculoskeletal disorders such as fibromyalgia and levator ani syndrome have also been linked to chronic pelvic pain. Women with a history of physical and sexual abuse, pelvic inflammatory disease, abdominopelvic surgery, or difficult obstetric deliveries are at increased risk for developing chronic pelvic pain.

``Clinical Findings A. Symptoms and Signs Certain features of the history and physical examination can provide clues to the underlying diagnosis. Patients should be asked about the location, quality, and intensity of their pain as well as the relationship with the menstrual cycle, sexual activity, urination, and defecation.

Endometriosis, IC, and IBS may all worsen with hormonal changes, resulting in more pain during menses.

Dysmenorrhea and dyspareunia are often experienced by patients with endometriosis, whereas dysuria, urgency, and frequency in association with pelvic pain are characteristic of IC. Pain related to pelvic varices is usually postural, worsening with prolonged standing and improving with leg elevation. Patients with IBS often report abdominal pain, distention, and diarrhea or constipation. The physical examination, including the pelvic examination, is usually quite painful in the patient with chronic pelvic pain and should be done carefully. A single-digit internal vaginal examination should be done to localize the exact area of pain and to assess for trigger points along the pelvic floor muscles, which may indicate a musculoskeletal etiology for the pain. Tenderness with palpation of the anterior vaginal wall is consistent with IC, whereas discomfort with palpation of the cervix is suggestive of endometriosis or chronic pelvic infection. Women with pelvic congestion related to varices may have significant uterine tenderness. The external genitalia should also be examined carefully to identify areas of vulvar discomfort because vulvodynia often coexists in patients with chronic pelvic pain. Notably, the absence of physical examination findings does not rule out significant pathology.

B. Laboratory Findings Laboratory studies are useful if the history and physical examination do not identify an underlying cause for the pelvic pain. Laboratory tests can include a complete blood count, serum chemistry, erythrocyte sedimentation rate, urine microscopy and culture, and vaginal swabs for detecting chlamydia and gonorrhea.

C. Diagnostic Testing and Imaging Pelvic ultrasonography is useful for investigating any abnormalities detected on physical examination, for screening patients in whom pelvic varices are suspected, and for providing reassurance to the patient if the ultrasound is normal. Additional testing may be done to confirm a suspected diagnosis. Patients with IC often have a positive intravesical potassium chloride test or abnormalities detected on cystoscopy. Laparoscopy may be helpful for diagnosing endometriosis or pelvic adhesions, although

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40% of diagnostic laparoscopies are normal in patients with chronic pelvic pain.

``Differential Diagnosis Chronic pelvic pain is frequently a manifestation of another disease, as noted above. The history, physical examination, and diagnostic testing should be directed toward identifying patients with the most common “benign” underlying conditions, including endometriosis, pelvic adhesions, pelvic varices, IC, and IBS. Clinicians should be aware that patients frequently have more than one diagnosis contributing to the chronic pelvic pain syndrome. Less common but serious causes of chronic pelvic pain should also be considered in the differential diagnosis, including bladder malignancy, colon cancer, endometrial cancer, and inflammatory bowel disease. Accordingly, symptoms such as unexplained weight loss, hematochezia, and abnormal vaginal bleeding should be investigated thoroughly. Many patients have no clear pathologic basis for their symptoms, and are thus diagnosed with idiopathic chronic pelvic pain.

``Treatment A. Medical Treatment Medical treatment may focus on managing the chronic pain, the underlying condition, or both. Analgesics are commonly used, and nonsteroidal anti-inflammatory drugs (NSAIDs), such as diclofenac and naproxen, are typically helpful. However, patients and clinicians should be cautious about long-term use of these medications because long-term NSAID therapy can be associated with significant gastric toxicity. Antidepressants (eg, amitriptyline) and antiseizure medications (eg, gabapentin) (see Table 5–5), which have demonstrated efficacy in the treatment of other pain syndromes, may also be useful for chronic pelvic pain. Opioid therapy improves pain but not functional or psychological outcomes and should generally be avoided.

Hormonal therapies are used primarily for treating gynecologic sources of chronic pelvic pain. Women with endometriosis often benefit from treatment with combined oral contraceptive pills, which suppress ovulation and reduce dysmenorrhea. Gonadotropin-releasing hormone (GnRH) agonists and progestins improve pain associated with endometriosis and pelvic varices. The decrease in BMD associated with GnRH agonist treatment can be mitigated with estrogen or progesterone add-back therapy. Patients in whom endometriosis is suspected may also be treated with GnRH agonist therapy; improvement in symptoms may allow such patients to avoid laparoscopy.

Medical therapies directed at the treatment of nongynecologic sources of chronic pelvic pain, including IC and IBS, are discussed in Chapters 15 and 23. Notably, pelvic pain associated with IC and IBS frequently varies with the menstrual cycle, and GnRH agonist therapy may be helpful for treatment in these disorders as well.

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Physical therapy and injection of identified trigger points provide significant pain relief in patients with musculoskeletal sources of pain. Sacral nerve stimulation has been used in patients with IC but may also be effective in up to 60% of women with chronic pelvic pain but without urinary symptoms. Psychological evaluation and treatment should also be strongly considered in all patients, both to improve treatment outcomes (particularly in patients with pelvic varices) as well as to address a history of sexual or physical abuse.

B. Surgical Treatment Surgical treatment of chronic pelvic pain requires referral to a gynecologist. Surgical therapies that treat the pain itself include presacral neurectomy and laparoscopic uterosacral nerve ablation. These denervating interventions are typically used in the treatment of patients with severe dysmenorrhea. Condition-specific surgical treatments include adhesiolysis in patients with pelvic adhesions and laparoscopic surgical destruction of implants in patients with endometriosis. Importantly, the efficacy of adhesiolysis in the treatment of chronic pelvic pain is controversial.

Hysterectomy can be effective for relieving chronic pelvic pain and may also result in improved psychological and sexual outcomes.

``Prognosis Cohort studies provide some information on the prognosis of women who undergo hysterectomy as definitive treatment for chronic pelvic pain. In a comparative study of women with chronic pelvic pain, abnormal uterine bleeding, or leiomyomas, women who had a hysterectomy experienced significant improvement in symptoms compared with those treated medically after 1 year. However, among younger patients with chronic pelvic pain who do not have obvious anatomic pathology, the benefits of surgery are less clear, and up to 40% of patients may still have persistent pain after hysterectomy.

``When to Refer Patients should be referred to a gynecologist for diagnostic or therapeutic surgical procedures, if the underlying diagnosis is unclear, or if the provider feels uncomfortable managing side effects associated with medical treatments (ie, GnRH agonist therapy).

American College of Obstetricians and Gynecologists (ACOG).

ACOG Practice Bulletin No. 51. Chronic pelvic pain. Obstet Gynecol. 2004 Mar;103(3):589–605. [PMID: 14990428] Daniels JP et al. Chronic pelvic pain in women. BMJ. 2010 Oct 5;341:c4834. [PMID: 20923840] Vercellini P et al. Chronic pelvic pain in women: etiology, pathogenesis, and diagnostic approach. Gynecol Endocrinol. 2009 Mar;25(3):149–58. [PMID: 19347704] Vercellini P et al. Medical, surgical, and alternative treatments for chronic pelvic pain in women: a descriptive review. Gynecol Endocrinol. 2009 Apr;25(4):208–21. [PMID: 19296329]

MASTALGIA

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E ssen t i a ls o f d i a g n o s i s

Infection, malignancy, and extramammary conditions can cause breast pain. `` Benign mastalgia is diagnosed once other causes of breast pain have been excluded and is characterized as cyclical or noncyclical. `` Abnormal physical examination findings, such as a breast mass or skin abnormalities, should prompt radiographic imaging. ``

``General Considerations Breast pain, or mastalgia, is categorized as cyclical, noncyclical, or extramammary. Although minor breast discomfort is commonly associated with the normal menstrual cycle, women with cyclical mastalgia typically have moderate to severe pain that can last more than 5 days. Cyclical mastalgia can be diagnosed only in reproductive-age women who experience breast pain as a result of the hormonallymediated proliferation in breast tissue that occurs with ovulation. In contrast, noncyclical mastalgia has no relationship to the menstrual cycle and can occur in premenopausal or postmenopausal women. Causes of noncyclical mastalgia include large breast size (with stretching of Cooper ligaments), medications, pregnancy, thrombophlebitis, or inflammatory breast cancer. Extramammary mastalgia is caused by pain that is referred from other anatomic locations, including the chest wall, heart, gallbladder, or spine. Trauma or previous surgery may also produce extramammary pain.

``Clinical Findings A. Symptoms and Signs Cyclical mastalgia is often described as a deep, heavy, aching pain, which is typically diffuse and bilateral and is clearly associated with the menstrual cycle. Conversely, noncyclical pain, which may be constant or intermittent, is often well localized and can involve one or both breasts.

Chest wall pain, a frequent cause of extramammary mastalgia, typically causes unilateral, burning pain that may be either localized or diffuse. Malignancy-associated mastalgia is often severe, progressive, and unilateral.

Breast cancer may be associated with mastalgia, and thus a careful physical examination is essential in all women who report breast pain. Large, pendulous breasts may be observed in women who have noncyclical pain caused by stretching of Cooper ligaments. Chest wall pain is usually related to inflammation or injury to the pectoralis major muscle; it may be reproduced by palpation or by having the patient place her hand on her hip and push inward. Any palpable breast mass must be evaluated further with radiologic imaging.

Women’s Health Issues B. Imaging An ultrasound or mammogram or both should be obtained in women who have a palpable breast mass. Clinicians should also ensure that patients with mastalgia are up to date on routine screening mammography, as appropriate for their age and personal risk factors.

``Differential Diagnosis Malignancy must be ruled out in all patients with mastalgia, and this is usually accomplished through a careful history, physical examination, and diagnostic imaging in patients with clinical abnormalities, such as a palpable breast mass. Extramammary causes of breast pain include chest wall pain, spinal or gallbladder disease, and myocardial ischemia. Cyclical and noncyclical mastalgia are easily differentiated by assessing the temporal relationship between the patient’s pain and her menstrual cycle.

``Treatment Women with cyclical mastalgia who have a normal physical examination and are up to date on routine mammographic screening should be reassured about the benign nature of their symptoms and monitored closely. Cyclical and noncyclical mastalgia often improve with use of a supportive bra. Although there is conflicting evidence regarding the benefit of vitamin E, some experts advocate its use (at a dose of 2000–3000 mg daily) for women with cyclical breast pain. Topical NSAIDs, such as diclofenac gel, improve localized breast pain.

Women who experience severe and persistent cyclical mastalgia despite adherence to conservative measures may be offered hormonal treatment. Commonly used hormonal therapies for cyclical mastalgia include danazol, bromocriptine, and tamoxifen. Danazol, a synthetic androgen that inhibits ovulation, is the only medication that has been approved by the Food and Drug Administration (FDA) for the treatment of cyclical mastalgia. However, side effects associated with treatment are common and include weight gain, menstrual irregularities, voice deepening, and hot flashes. Similarly, in a study of patients with cyclical mastalgia who were treated with bromocriptine, 40% of patients experienced adverse reactions, including nausea, dizziness, and headache. Tamoxifen therapy is tolerated well by most women, and many experts recommend it as first-line therapy for the treatment of cyclical mastalgia. Patients treated with tamoxifen should be counseled about the possibility of hot flashes and menstrual irregularities (experienced by up to 10% of women), as well as the risk for more serious adverse events, such as thromboembolic disease and endometrial cancer.

``Prognosis Symptoms of cyclical and noncyclical mastalgia improve without pharmacologic treatment in most women. In addition, most women with cyclical mastalgia have resolution of their pain with menopause. Observational studies examining the association between cyclical mastalgia

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and the subsequent development of breast cancer have produced conflicting results. Two case-control studies suggested an increased risk of breast cancer, while a third observational study suggested a decreased risk. Based on this evidence, guidelines indicate that all women with mastalgia should have an individual assessment of their breast cancer risk, and that this should guide subsequent management.

Women in whom mastalgia develops while receiving hormone replacement therapy may have an increased risk of breast cancer. In a recent analysis of data from the Women’s Health Initiative, women in whom new-onset breast tenderness developed after initiating treatment with conjugated equine estrogen plus medroxyprogesterone had a 48% higher risk of developing breast cancer compared with those who did not experience breast pain. Thus, women in whom mastalgia develops in the setting of hormone-replacement therapy should have a thorough discussion with their clinician regarding the risks and benefits of continued treatment as well as screening and preventative strategies for breast cancer.

``When to Refer Patients with mastalgia and a palpable breast mass should be referred to a breast surgeon, even if the results of diagnostic imaging are normal.

Crandall CJ et al. New-onset breast tenderness after initiation of estrogen plus progestin therapy and breast cancer risk.

Arch Intern Med. 2009 Oct 12;169(18):1684–91. [PMID: 19822825] Rosolowich V et al; Society of Obstetricians and Gynecologists of Canada (SOGC). Mastalgia. J Obstet Gynaecol Can. 2006 Jan;28(1):49–60. [PMID: 16533457] Rungruang B et al. Benign breast diseases: epidemiology, evaluation, and management. Clin Obstet Gynecol. 2011 Mar;54(1): 110–24. [PMID: 21278510]

THE PALPABLE BREAST MASS

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Diagnostic imaging is essential for any women with a palpable dominant breast mass, regardless of her age. `` Ultrasound is the initial test of choice for women under the age of 30; diagnostic mammography with or without ultrasonography is performed initially in women over the age of 30. ``

``General Considerations Palpable breast masses may be detected by a patient on a breast self-examination, or may be identified by the provider during a routine physical examination. Approximately 10% of breast masses are malignant, and thus a thorough work-up of any palpable breast mass is essential, regardless of age and personal risk factors for breast cancer.

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Common benign causes of palpable breast masses include fibrocystic condition, cysts, and fibroadenomas (see also Chapter 17).

``Clinical Findings

because of increased breast vascularity. Surgical consultation should be obtained to evaluate persistent areas of concern that are identified on clinical breast examination and ultrasound.

A. Symptoms and Signs

``Differential Diagnosis

Clinicians should ask patients about temporal changes in the mass shape and size, as well as associated symptoms, including pain, skin thickening, and nipple discharge. A patientâ&#x20AC;&#x2122;s personal risk for breast cancer should be assessed, including age, previous breast biopsies, family history, and age at menarche and first pregnancy.

The location of the mass should be described using the clock-face position and distance from the nipple, as this aids the radiologist in the diagnostic evaluation. Examiners should also note the size, site, mobility, and texture of the mass, as well as areas of skin dimpling, retraction, or erythema. Benign masses are typically mobile with welldefined margins; conversely, malignant lesions may be fixed and have indistinct borders. Some women may have areas of indeterminate thickening in the absence of a discrete and well-defined palpable mass; if this finding is asymmetric it should be evaluated further with diagnostic imaging.

The differential diagnosis of palpable masses includes benign etiologies, such as cysts, fibroadenomas, fibrocystic condition, lymph nodes, galactoceles, lipomas, and hematomas. Breast cancer, including ductal carcinoma in situ, invasive lobular carcinoma, and invasive ductal carcinoma, can also initially present with a palpable breast mass.

Certain history and physical examination features may be suggestive of a particular diagnosis. Cysts are fluid-filled structures that are commonly found in women aged 35â&#x20AC;&#x201C;50 years; acute enlargement of the cysts may cause abrupt and severe pain. Fibroadenomas are typically diagnosed in reproductive age women between the ages of 15 and 35 years and present as firm, nontender, and mobile masses on physical examination. Fibrocystic condition describes a pathologic diagnosis that may be accompanied by clinical symptoms and signs, including cyclical pain that is bilateral and poorly localized as well as tender, multifocal nodules.

These fibrocystic changes, which include macrocysts, microcysts, fibrosis, and ductal hyperplasia, are most common among premenopausal women.

B. Diagnostic Tests and Imaging As noted above, all women with a dominant palpable breast mass require diagnostic imaging. Approved imaging techniques include diagnostic mammography and ultrasonography. Diagnostic mammography consists of the standard views that are used in screening mammography, plus additional views, such as spot-compression and magnification, to better delineate the area of concern. The breast ultrasound is the most sensitive test for distinguishing a cystic from a solid lesion, and also provides detailed information regarding the shape, borders, and acoustic properties of an identified mass. In addition, ultrasonography can be used to guide the biopsy of suspicious lesions.

Women over the age of 30 with a palpable breast mass should initially be evaluated with diagnostic mammography. Features of a benign lesion include a round shape with well-circumscribed borders; a suspicious finding may have an irregular shape with spiculated margins. Ultrasonography may be coupled with diagnostic mammography if the mass is mammographically occult or has concerning mammographic features. For women under the age of 30, ultrasonography is the initial diagnostic test of choice because the dense breast tissue found in younger women limits the sensitivity of mammography. Abnormal findings on ultrasound include posterior acoustic shadowing, microlobulations, and a spiculated margin. A mass which has a thin, echogenic capsule, an ellipsoid shape, and homogenous echogenicity is more likely to be benign.

In women who are pregnant, ultrasonography is the initial diagnostic test of choice; the sensitivity of mammography is limited by the loss of contrasting fatty tissue in the breast during pregnancy. Fine-needle aspiration (FNA) biopsy does not have the same accuracy in pregnant women as a result of the increased cellularity of the breast tissue, and breast biopsy may be technically difficult

``Treatment Management of the palpable breast mass depends on the results of diagnostic imaging. If ultrasonography or mammography suggests that the mass is related to a simple cyst, fine-needle aspiration (FNA) may be offered to symptomatic women to relieve associated pain. Characteristics of the aspirated fluid guides further work-up. If benign fluid, which is typically yellow, straw-colored, green, or brown, is aspirated and the mass resolves, the patient can be monitored expectantly. Conversely, if bloody fluid is aspirated, or if the mass persists after aspiration, further intervention with either core biopsy or excision may be indicated. A complex cyst should always be aspirated because there is a small chance (0.4%) that it may be malignant.

Core-needle biopsy, which provides a sample of tissue for histologic diagnosis, is typically used to evaluate breast masses that have a suspicious appearance on diagnostic imaging. Ultrasonography, mammography, or MRI may be used to guide the biopsy, thereby resulting in few complications and minimal trauma to the breast tissue. Excisional biopsy may be necessary if the mass is not amenable to coreneedle biopsy (because of location or imaging characteristics) or if additional tissue is needed to confirm a benign diagnosis.

Women who have palpable masses that are associated with normal ultrasound or mammographic imaging should be referred to a breast surgeon, with consideration given to performing a diagnostic core-needle biopsy. Benign biopsy results are reassuring but require close clinical follow-up for at least 1â&#x20AC;&#x201C;2 years.

The radiologist may categorize certain breast masses as probably benign after review of ultrasound or mammographic

Women’s Health Issues images. In rare cases, these masses may be associated with malignancy, and so two diagnostic options may be considered.

The patient may opt to forgo biopsy at that time and have imaging performed again in 6 months. Alternatively, diagnostic core excisional biopsy may be performed immediately (after consultation with a breast surgeon) if there are worrisome findings on physical examination or if there is a high clinical suspicion for malignancy. All masses categorized as probably benign require follow-up imaging at 6-month intervals for at least 2 years.

The “triple test,” which is composed of the findings on physical examination, the results of diagnostic imaging, and the pathologic diagnosis obtained from FNA or coreneedle biopsy, helps clinicians determine the likelihood that a palpable breast mass is malignant. In all cases, the results of each of these tests should be concordant. For example, the diagnostic imaging should identify the palpable area of concern, and if benign features are noted, the results of the FNA biopsy or core-needle biopsy should confirm a benign diagnosis, such as a fibroadenoma. If the results of any of the tests are discordant, further evaluation is warranted. Thus, if the results of FNA biopsy or coreneedle biopsy suggest a benign diagnosis, but the radiographic imaging indicates a suspicious lesion, it may be appropriate to repeat the biopsy or perform an excisional biopsy. Similarly, if there is a palpable breast mass that is not identified on radiographic imaging, referral to a breast surgeon is necessary to document resolution or persistence of the mass. If the mass is persistent, the surgeon may elect to perform a biopsy to obtain a definitive diagnosis.

``Prognosis In general, the benign causes of a palpable breast mass have a favorable prognosis. Many women with breast pain and palpable masses due to fibrocystic condition have spontaneous resolution or have improvement in their symptoms with menopause. Benign simple cysts that are asymptomatic may be followed clinically, and symptomatic cysts should resolve with aspiration.

Certain pathologic diagnoses increase the risk of breast cancer, including papillary lesions, radial scars, atypical ductal or lobular hyperplasia, and lobular carcinoma in situ. FNA biopsy or core-needle biopsy results that indicate one of these diagnoses necessitate referral to a breast surgeon for further evaluation and management.

``When to Refer • Women with a palpable breast mass should be referred to a breast surgeon in the following situations: – If diagnostic imaging indicates that the mass has suspicious features.

– If the mass persists and diagnostic imaging is normal.

– If the mass is categorized as probably benign on diagnostic imaging, but there are worrisome features on physical examination or there is a high clinical suspicion for malignancy.

– If diagnostic imaging demonstrates a complex cyst, or aspiration of a simple cyst reveals a bloody aspirate.

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– If the biopsy demonstrates a lesion with an increased risk of breast cancer (papillary lesions, radial scars, atypical hyperplasia, lobular carcinoma in situ).

– If the biopsy results are discordant with the physical examination and radiographic findings.

• It may also be prudent to refer pregnant women with a palpable breast mass to a breast surgeon, because of the limitations noted above with radiographic imaging and biopsy.

Pearlman MD et al. Benign breast disease. Obstet Gynecol. 2010 Sep;116(3):747–58. [PMID: 20733462] Rungruang B et al. Benign breast diseases: epidemiology, evaluation, and management. Clin Obstet Gynecol. 2011 Mar;54(1): 110–24. [PMID: 21278510] Stein L et al. The radiologic workup of a palpable breast mass.

Cleve Clin J Med. 2009 Mar;76(3):175–80. [PMID: 19258464]

NIPPLE DISCHARGE Nipple discharge is a common breast complaint but is rarely indicative of malignancy. In one retrospective study, invasive breast cancer was subsequently diagnosed in only 5% of women in whom nipple discharge was the presenting symptom. Nipple discharge that comes from multiple ducts, is bilateral, and is produced only with squeezing is considered physiologic, and no further work-up is necessary. Milky discharge that is bilateral and spontaneous is consistent with galactorrhea caused by an elevated prolactin level. Investigation should focus on identifying the underlying causes of the hyperprolactinemia, including pregnancy, pituitary tumors, and certain medications. Women who have bloody discharge or persistent spontaneous unilateral discharge from a single duct, should be referred for mammography and surgical consultation. These features are suggestive of a pathologic diagnosis, such as papilloma, duct ectasia, or malignancy. In addition, the presence of a palpable breast mass in association with the nipple discharge significantly increases the likelihood of underlying malignancy. Surgical excision of the involved duct is the gold standard for diagnosis. See also Chapter 17.

Dolan RT et al. Nipple discharge and the efficacy of duct cytology in establishing breast cancer risk. Surgeon. 2010 Oct; 8(5):252–8. [PMID: 20709281] Rungruang B et al. Benign breast diseases: epidemiology, evaluation, and management. Clin Obstet Gynecol. 2011 Mar;54(1): 110–24. [PMID: 21278510]

FEMALE PATTERN HAIR LOSS Androgenetic alopecia, also known as female pattern hair loss, is the most common cause of alopecia in women; up to 50% of females will be affected in their lifetime. This type of alopecia is mediated by the effects of androgen on the hair follicle and is characterized by shortening of the anagen (growth) phase and follicle miniaturization.

Clinically, presenting signs include diffuse thinning over the central scalp and a prominent midline part; the frontal

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hairline is typically preserved. Although serum androgen levels are typically normal, androgen excess disorders can present with female pattern hair loss. If irregular menses, hirsutism, or acne accompany the female pattern hair loss, the patient should be evaluated for an underlying hyperandrogenic condition with measurements of total and free testosterone, prolactin, and dehydroepiandrosterone.

Topical minoxidil is currently the only medication that has been approved by the FDA for the treatment of female pattern hair loss. Randomized trials have confirmed the efficacy of this therapy, compared with placebo, for inducing minimal to moderate hair regrowth in the majority of treated women (NNT = 8). In patients with suspected female pattern hair loss, minoxidil 2% is applied directly onto the scalp twice daily while symptoms persist. The most common side effect of minoxidil is facial hypertrichosis, which can affect 3–5% of women, but this typically resolves after 1 year of treatment. In women who have excess androgen levels, the addition of spironolactone (an anti-androgen) to minoxidil treatment may result in additional clinical benefit. Similarly, an oral contraceptive pill containing drosperinone, which is a spironolactone analogue, is an appropriate choice in women desiring hormonal contraception.

Harrison S et al. Diffuse hair loss: its triggers and management.

Cleve Clin J Med. 2009 Jun;76(6):361–7. [PMID: 19487557] Mounsey AL et al. Diagnosing and treating hair loss. Am Fam Physician. 2009 Aug 15;80(4):356–62, 373–4. [PMID: 19678603]

TREATMENT OF VARICOSE VEINS Varicose veins result from weakness in the vein wall and may involve obstruction to, or reversal of, normal blood flow. Approximately 30–40% of women are affected, and the clinical presentation ranges from asymptomatic to severe, with lower extremity pain, swelling, and nocturnal cramps. Medical complications can include venous ulceration, abnormal skin pigmentation, and eczema.

Treatment may be considered to relieve symptoms or for cosmetic purposes. Conservative therapy is generally recommended for asymptomatic patients or those who experience only mild to moderate discomfort. The principle behind conservative therapy is to limit disease progression: weight loss and physical exercise will improve circulation, and avoidance of prolonged standing will reduce the pressure on affected valves. Compression stockings improve venous hemodynamics and reduce symptoms of pain and swelling.

Invasive therapy may be indicated to treat patients with more severe symptoms, or those who desire significant cosmetic results. The gold standard for treating varicose veins is surgical ligation and vein stripping. If the greater saphenous vein is involved, both ligation and stripping are typically performed; smaller saphenous veins may be treated only with ligation. Surgical techniques are effective in the short-term, but recurrence is common, ranging from 30% to 50% after 5 years. Moreover, patients who receive surgical therapy are exposed to the risks of general

or epidural anesthesia and may experience postoperative pain and neurologic damage.

Minimally invasive techniques for treating varicose veins have been increasing in popularity and are often associated with faster recovery times and fewer complications when compared with surgical treatment. Currently available therapies include ultrasound-guided foam sclerotherapy (UGFS), radiofrequency ablation (RFA), and endovenous laser ablation (EVLA). Sclerotherapy is usually done in the ambulatory setting and involves injecting a chemical through a catheter into the abnormal vein to induce scarring and collapse. UGFS mixes air or gas with the sclerosing substance to produce foam, which allows for coverage of a larger surface area. Injection sclerotherapy is most beneficial for small and medium-size veins; rare complications include embolization of foam to the brain or retina. RFA and EVLA both use the principles of thermolysis to selectively induce vessel-wall damage and collapse.

Laser (EVLA) or radiofrequency (RFA) energy is used to generate a heated fiber, which is inserted into the abnormal vein and slowly advanced along its length. Endothelial and vessel wall damage results, with contraction of the vein wall and ultimate collapse of the entire vessel. A minority of patients may experience local bruising, tenderness, or paresthesias as a result of these procedures.

Meta-analysis evaluating the efficacy of each of these techniques compared with surgical intervention demonstrated that success rates, as measured by complete obliteration of the vessel at 5 years, were highest for EVLA and RFA (95.4 % and 79.9%, respectively) and were similar for UGFS and surgery (73.5% and 75.7% respectively).

Moreover, the efficacy of RFA, UGFS, and surgery declined substantially over time, but remained relatively constant for EVLA. The authors of this study concluded that EVLA was the most effective of the minimally invasive techniques and was associated with fewer side effects and faster improvement in health-related quality of life when compared with surgical therapy. However, more studies that directly compare these methods to each other are needed.

Leopardi D et al. Systematic review of treatments for varicose veins. Ann Vasc Surg. 2009 Mar;23(2):264–76. [PMID: 19059756] Raju S et al. Clinical practice. Chronic venous insufficiency and varicose veins. N Engl J Med. 2009 May 28;360(22):2319–27.

[PMID: 19474429] Van den Bos R et al. Endovenous therapies of lower extremity varicosities: a meta-analysis. J Vasc Surg. 2009 Jan;49(1):230–9.

[PMID: 18692348]

AGE-RELATED FACIAL CHANGES Minimally invasive aesthetic procedures are now commonly used to treat mild to moderate age-related changes in the face. These procedures are generally safe and are associated with high rates of patient satisfaction. In 2008, more than 80% of aesthetic plastic surgery treatments involved minimally invasive techniques. Thus, primary care clinicians should be familiar with the efficacy and safety of these treatment modalities in order to best counsel their patients.

Women’s Health Issues Visible signs of aging in the face result from loss of subcutaneous fat, gravitational changes, and alterations in skin elasticity. Various areas of the face respond differently to each of these changes and at different times. In the upper one-third of the face, hyperdynamic wrinkles, manifested as frown lines, crow’s feet, and horizontal forehead lines, typically develop as a result of repetitive muscle contraction. Conversely, volume changes are more prominent in the mid-face, as gravitational descent of the malar fat pad and volume loss leads to deepening of the nasolabial folds. Changes in the lower one-third of the face are characterized both by hyperdynamic changes resulting in deep furrows and lines, as well as flattening and loss of fullness in the lips.

Clostridium botulinum is an organism that produces potent neurotoxins with various serotypes, ranging from A to G. These serotypes vary in both their mechanism of action and clinical use, and only serotype A is used for cosmetic purposes. Botox and Dysport are two formulations of botulinum serotype A that the FDA has approved for treating hyperactivity of the glabellar muscles, which produces frown lines. Both of these products work by inhibiting the release of acetylcholine at the neuromuscular junction, thereby resulting in a chemical denervation and an overall relaxation of hyperdynamic facial muscles.

Botox and Dysport are also commonly used off-label to treat horizontal frown lines and crow’s feet, as the restriction of muscular movement in these areas also reduces the appearance of fine wrinkles. The onset of action of these treatments is immediate, and results typically last 3–4 months. In one study, only 5% of studied patients who had been treated with Botox experienced adverse effects, the most common of which was local bruising.

Whereas Botox and Dysport are the treatments of choice in the upper one-third of the face to treat fine wrinkles, dermal fillers are commonly used in the mid- and lower face to restore volume and fullness. Several filler substances are currently used, including collagen, hydroxylapatite,

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hyaluronic acid, and injectable poly-L-lactic acid. Among these, hyaluronic acid fillers have become increasingly popular and have been approved by the FDA for treatment of nasolabial folds. They are also frequently used off-label to volumize and shape the lips. Several formulations are currently available, and they differ in their degree of crosslinking, gel hardness, and ability to resist dilution. Clinically, these differences result in various degrees of longevity, with the effects of Restylane and Perlane lasting approximately 6 months, and the effects of Juvederm Ultra and Juvederm Ultra Plus lasting approximately 12 months. The effects of injection are immediately apparent, and complications are typically mild and local, including bruising, redness, and swelling. If necessary, the injection of hyaluronidase can reverse any significant adverse effects. Notably, the clinical improvement associated with hyaluronic acid injections seems to be closely associated with the expertise of the practitioner.

Combination therapy with botulinum toxin and hyaluronic acid is now commonly being used to achieve more satisfying cosmetic results. However, serious complications can result from the injection of hyaluronic acids in the upper face, including skin necrosis, which occurs when the injection inadvertently involves a blood vessel. A thorough knowledge of the anatomy in this area is essential for avoiding this adverse event. Similarly, only experienced practitioners should use botulinum toxin in the lower face, to avoid the drooling, speech problems, and mouth incompetence that result from over-injection or misplaced treatment.

Berbos ZJ et al. Update on botulinum toxin and dermal fillers.

Curr Opin Opthalmol. 2010 Sep;21(5):387–95. [PMID: 20703120] Small R. Aesthetic procedures in office practice. Am Fam Physician. 2009 Dec 1;80(11):1231–7. [PMID: 19961136] Wollina U et al. Aging well—the role of minimally invasive aesthetic dermatological procedures in women over 65. J Cosmet Dermatol. 2010 Mar;9(1):50–8. [PMID: 20367673]