Chapter 4: Disease Risk
Cardiovascular Health
Key Points
1. Cardiovascular disease (CVD) is the leading cause of death in women worldwide.
2. Major risk factors for CVD in women include age, hypertension, dyslipidemia, diabetes mellitus (DM), family history of premature CVD, smoking, sedentary lifestyle, and poor diet. Novel risk factors for CVD include a history of a pregnancy complicated by preeclampsia, gestational diabetes, or hypertension.
3. Hormonal changes associated with menopause can result in an accelerated increase in low-density lipoprotein cholesterol (LDL-C) in the year following menopause.
Recommendations for Clinical Care
1. All women should be encouraged to reduce their risk for CVD, including heart attack and stroke, by engaging in regular exercise, consuming a healthy diet, achieving a normal body weight, and not smoking.
2. Healthcare providers should evaluate all women for CVD risk using the American College of Cardiology-American Heart Association (ACC-AHA) risk assessment tool and manage risks accordingly. (Level II)
3. Treatment of blood pressure (BP) is recommended in women aged younger than 60 years for systolic BP (SBP)> 140 mm Hg or diastolic BP (DBP)> 90 mm Hg. In women aged older than 60 years, treatment is recommended for SBP> 150 mmHg or DBP> 90 mm Hg. (Level II)
4. Updated ACC-AHA guidelines on the treatment of dyslipidemia recommend statin therapy for women with 1) existing atherosclerotic CVD (ASCVD), 2) LDL-C 190 mg/dL or greater, 3) aged 40 to 75 years with DM, and 4) aged 40 to 75 years with an estimated 10-year ASCVD risk of 7.5% or higher, based on the use of a novel risk calculator for myocardial infarction and stroke. There is some controversy regarding use of the ASCVD risk calculator as an indication for statin therapy. (Level II)
5. Aspirin therapy should be considered for women 1) aged 65 years and older without known CVD, 2) any age with established CVD, and 3) any age with an estimated 10-year CVD risk of 10% or higher. (Level II)
6. Available evidence does not support the use of systemic hormone therapy for the prevention or treatment of CVD. However, age and time since menopause are critical modifiers of the effect of systemic HT on CVD, with more favorable effects observed for women aged 50 to 59 years and within 10 years of menopause at treatment initiation. (Level I)
Diabetes Mellitus
Key Points
1. Prediabetes and diabetes are highly prevalent in midlife women and the prevalence is increasing.
2. Glucose metabolism worsens with weight gain and aging. Evidence that hormonal changes at menopause contribute to a worsening of glucose metabolism is inconsistent.
3. Cardiovascular disease is the leading cause of death in women and the risk of CVD is higher in women with diabetes.
Recommendations for Clinical Care
1. Screening for diabetes with glycated hemoglobin (Hb A1c), fasting plasma glucose, or an oral glucose tolerance test should be considered for all women aged 45 years and is strongly recommended if women are overweight or obese. (Level I)
2. Optimal glucose control (eg, target Hb A1c <7%) is recommended to reduce the risk of vascular complications of diabetes. Lifestyle modifications addressing diet and exercise are first-line strategies for controlling glucose. Metformin therapy is the preferred initial pharmacologic strategy for type 2 diabetes. (Level I)
3. Regardless of LDL-C level, statins are recommended for all women with diabetes aged between 40 and 75 years to reduce atherosclerotic CVD risk. (Level I)
4. Controlling blood pressure through pharmacologic and nonpharmacologic means is also recommended to reduce cardiovascular events in women with diabetes. Target BP for women with diabetes is below 140/80 mm Hg. (Level I)
5. Women with diabetes should be advised to stop smoking.
Osteoporosis
Key Points
1. Postmenopausal osteoporosis is a common condition that leads to an increased risk of fracture. It can be diagnosed and treated before any fracture occurs.
2. The diagnosis of osteoporosis is established by measurement of bone mineral density by dual-energy x-ray absorptiometry (DXA) of the spine, hip, and/or forearm (T-score of −2.5 or lower) or by the presence of a low-trauma or fragility fracture.
3. Many conditions, diseases, and medications contribute to bone loss and increased fracture risk.
4. Current FDA-approved pharmacologic options for the prevention of postmenopausal osteoporosis include estrogen therapy, estrogen-progestogen therapy, and an estrogen agonist/antagonist (bazedoxifene) combined with estrogen (BZA-CE). Pharmacologic options approved for the treatment of postmenopausal osteoporosis include denosumab, teriparatide, and calcitonin. Pharmacologic options approved for the prevention and treatment of postmenopausal osteoporosis include bisphosphonates and the estrogen agonist/antagonist raloxifene. There are no prospective studies comparing these drugs for antifracture efficacy.
5. Pharmacotherapy reduces fracture risk in patients with osteoporosis, but the antifracture efficacy of pharmacotherapy in women with low bone mass (osteopenia) without fractures is less strong.
6. Pharmacologic therapy must be individualized based on risk-benefit assessments and patient preference.
Recommendations for Clinical Care
1. It is important to identify and address potential factors that contribute to bone loss and increased fracture risk by a careful history, physical examination, and basic laboratory testing. (Level II)
2. All postmenopausal women should be encouraged to obtain adequate calcium and vitamin D, engage in regular exercise, stop smoking, limit alcohol intake, and modify their environments to reduce the risk of falls. (Level I)
3. Bone mineral density testing is recommended for all women aged 65 years and older, with consideration for earlier testing in women with clinical risk factors for fracture, including low body weight, history of prior fracture, family history of osteoporosis, smoking, excessive alcohol intake, or long-term use of high-risk medications (eg, glucocorticoids). (Level I)
4. After initial BMD testing, the need for additional testing and the optimal interval for repeat testing should be individualized based on the baseline BMD, therapeutic interventions initiated, and fracture risk. (Level II)
5. Healthcare providers should consider treating women with osteoporosis or low bone mass who have either a 10-year probability of a hip fracture of 3% or higher or a 10-year probability of a major osteoporosis-related fracture of 20% or higher, based on the US-adapted World Health Organization algorithm (ie, using the FRAX® Web-based tool). (Level I)
6. There is considerable controversy regarding the optimal duration of bisphosphonate therapy and the length of a drug holiday, both of which should be based on an individualized assessment of risk and benefit. (Level II)
7. Healthcare providers should individualize treatment based on an assessment of the potential benefits and risks of therapy for each patient and the effectiveness of a given osteoporosis treatment on reduction of vertebral and nonvertebral fractures. (Level I)
Gallbladder Disease
Key Points
1. Gallbladder disease occurs twice as frequently in women as in men.
2. Risk factors for gallstones include obesity, increased parity, weight-loss diets, bariatric surgery, and oral estrogen use.
3. Oral contraceptives and oral menopausal hormone therapy increase biliary cholesterol saturation, a prerequisite for cholesterol gallstone formation.
4. Warning signs for gallbladder disease include abdominal pain, nausea, vomiting, fever, jaundice, dark urine, and light stools.
5. In the Women's Health Initiative (WHI), combined estrogen-progestogen therapy (EPT) was associated with an increased absolute risk of 27 cases of gallbladder disease per 1,000 women after 5.6 years' use, whereas estrogen-only therapy resulted in an increased absolute risk of 45 additional cases per 1,000 women after 7 years.
6. The risk of gallbladder disease associated with HT appears greater with oral than with transdermal estrogen use.
Recommendations for Clinical Care
1. Hormone therapy should be administered with caution to women who have gallstones or a history of gallbladder disease. (Level I)
2. An increased risk of gallbladder disease should be included in discussions of the risks and benefits of HT. (Level II)
3. Transdermal ET is associated with lower risk of gallbladder disease than oral ET. (Level II)
Arthritis and Arthralgia
Key Points
1. Osteoarthritis is predominantly a degenerative arthritis and a disease of aging. It is not associated with involvement of organs outside of the musculoskeletal system or systemic symptoms. Treatment is directed at palliating pain and maintaining function.
2. Rheumatoid arthritis is a systemic inflammatory arthritis that requires aggressive treatment with immunomodulating drugs. Current therapies generally can control the disease and progression to disabling joint destruction is uncommon.
3. Fibromyalgia is a chronic, painful process that does not affect the joints but rather is characterized by diffuse pain felt largely in the musculature. Treatment requires multiple modalities, including exercise, physical therapy, and neuroactive medications.
Recommendations for Clinical Care
1. With more than 100 forms of arthritis, a specific diagnosis is the first step toward appropriate treatment. As many forms of arthritis have similar features and gold standard diagnostic tests generally are lacking, the diagnosis is determined on the basis of clinical experience and may require observation over time. (Level III)
2. Effective therapy of osteoarthritis includes palliation of pain and maintenance of function and mobility, with assist devices when necessary. Treatment should incorporate appropriate exercise regimens and analgesic medications, which may include nonsteroidal antiinflammatory drugs and neuroactive medications. Complementary approaches are widely used and may provide significant pain relief, although their incremental benefit beyond placebo remains controversial. (Level I)
3. Rheumatoid arthritis is a serious progressive disease that should be treated with the intention of achieving remission. With the use of appropriate modern medications and biologics, most patients can expect to live a normal functional life. (Level I)
4. Fibromyalgia and myofascial pain syndromes require multidisciplinary therapeutic plans, including exercise regimens, physical therapy, and neuroactive medications; conventional analgesics and opiates have little efficacy for this condition. (Level II)
Thyroid Disease
Key Points
1. Thyroid disorders are common in women and often are associated with symptoms similar to those of the menopause transition.
2. As women age, thyroid disorders can be associated with significant morbidity and potentially increased mortality.
3. Subclinical thyroid disorders are common, although clinical trial evidence justifying benefits of treatment is lacking.
4. Overtreatment of hypothyroidism or hyperthyroidism can result in untoward effects and undesired extremes of thyroid hormone.
Recommendations for Clinical Care
1. Current recommendations do not consistently support screening of all women for thyroid disorders; however, a high index of suspicion is merited in midlife and postmenopausal women. Measurement of thyroid stimulating hormone is the initial step in assessing thyroid function. (Level II)
2. Treatment of hypothyroidism includes administration of thyroxine (dose depending on age and comorbidities) with TSH monitoring every 6 to 8 weeks, targeting the TSH to within the normal range. (Level I)
3. Treatment of hyperthyroidism is more complex and is probably best approached in consultation with an endocrinologist. (Level II)
4. Diagnosis of subclinical thyroid disorders requires repeated monitoring because laboratory testing often returns to normal with continued observation. (Level II)
5. When treating subclinical thyroid disorders, care must be exercised not to overtreat and induce the opposite thyroid condition. (Level I)
6. The thyroid examination should evaluate for the presence of thyroid nodules. If present, referral for further evaluation is usually indicated. (Level I)
Epilepsy
Key Points
1. Menopause generally occurs earlier in women with epilepsy than in women in the general population. The earlier occurrence of menopause correlates with the total number of lifetime seizures but also may be affected by antiepileptic drugs, especially those that may affect estrogen levels by inducing the hepatic CYP450 isoenzyme (eg, phenytoin, phenobarbital).
2. Because reproductive steroids have neuroactive properties, and a subset of women with epilepsy have seizures that are hormonally sensitive (eg, catamenial epilepsy), clinicians should be aware that hormonal changes that occur during perimenopause and menopause may result in changes in seizure frequency and patterns.
3. Anovulatory cycles that characterize perimenopause and feature unopposed estrogen effects are associated with a greater frequency of generalized convulsive seizures than are ovulatory cycles.
Recommendations for Clinical Care
1. Cyclic natural progesterone supplementation and cycle suppression with gonadotropin-releasing hormone agonists or depomedroxyprogesterone acetate have been proposed as interventions to reduce the frequency of hormonally sensitive seizures, but efficacy remains unproven. (Level II)
2. One antiepileptic drug, gabapentin, may be particularly effective in lessening some autonomic symptoms of menopause such as warmth, hot flashes, and night sweats. (Level I)
3. Because antiepileptic drugs can accelerate vitamin D metabolism and contribute to osteoporosis, postmenopausal women with epilepsy require adequate intake of calcium and vitamin D and may benefit from closer monitoring of bone mineral density. (Level II)
Asthma
Key Points
1. Asthma is more prevalent in women than men, and its severity can vary with the menstrual cycle in women prior to menopause.
2. The incidence of asthma does not clearly increase after menopause, but lung volumes tend to decline, and pulmonary symptoms, including wheezing, become more prevalent.
3. Asthma that has its onset after menopause tends not to be associated with atopy and can be particularly severe.
4. The effect of hormone therapy on asthma is unclear. Several large observational studies have shown an association between current HT use and asthma risk, whereas several small interventional trials have demonstrated neutral to beneficial effects of HT on airway function and clinical course.
Recommendations for Clinical Care
1. Healthcare providers should be aware that asthma presenting after menopause is not necessarily associated with atopy and may be less responsive to anti-inflammatory treatments than asthma that presents earlier in life. (Level II)
2. Hormone therapy should not be initiated or withheld because of asthma. (Level II)
Breast Cancer
Key Points
1. Breast cancer incidence rates have been increasing in North America for decades, and the most important risk factor, other than being a woman, is age.
2. Nulliparity, late age at first birth, excess alcohol consumption, obesity, a family history of breast cancer in first-degree relatives, BRCA gene mutations, biopsied benign breast disease, and atypical ductal hyperplasia all increase the risk of breast cancer.
3. Breast cancer risk is increased in postmenopausal women by the use of combined estrogen-progestogen hormone therapy for more than 3 to 5 years. The use of estrogen-alone therapy in women without a uterus for up to 7 years does not increase breast cancer risk, although long-duration estrogen-alone use appears to increase breast cancer risk.
4. Selective estrogen receptor modulators (estrogen agonist/antagonists) reduce the incidence of primary breast cancer in high-risk women. Tamoxifen reduces the risk of breast cancer in premenopausal and postmenopausal women. Raloxifene reduces the risk of breast cancer in postmenopausal women.
5. In postmenopausal women, aromatase inhibitors (AIs), including anastrozole and exemestane, reduce breast cancer recurrence, improve survival, and reduce breast cancer risk in women at high risk. Aromatase inhibitors are not yet approved for breast cancer prevention.
6. Breast cancer mortality has been declining for several decades due to early detection through wider application of mammographic screening, more effective use of hormone-modulating therapies for early disease, and adjuvant chemotherapy for advanced disease.
Recommendations for Clinical Care
1. Routine screening for breast cancer is indicated for midlife women. There is considerable controversy regarding the age at which breast cancer screening should begin and end and the frequency of screening. Current guidelines generally include mammograms every 1 to 2 years, starting at age 40 to 50 years and continuing until age 70. Magnetic resonance imaging is recommended for women at high risk for breast cancer. (Level I)
2. Genetic testing for BRCA mutations should be recommended for women at high risk for breast cancer on the basis of family history. (Level I)
3. Weight gain is associated with an increased risk of breast cancer recurrence, and a low-fat diet is associated with improved survival in women with certain types of breast cancer, so weight control and a low-fat diet may be advised for women with breast cancer. (Level II)
4. Women at increased risk for breast cancer should be counseled regarding the potential benefits and risks of tamoxifen and raloxifene for breast cancer risk reduction. (Level I)
Endometrial Cancer
Key Points
1. Endometrial cancer (endometrioid, type-I) is a relatively common cancer among postmenopausal women.
2. In the United States, survival after diagnosis of endometrial cancer is lower in black women than in white women.
3. The presenting symptom of endometrial cancer is typically abnormal uterine bleeding.
4. The principal risk factors for endometrial cancer are age (>50 years), hyperestrogenic endometrial milieu, diabetes mellitus, and obesity.
5. The precursor of endometrial cancer is atypical endometrial hyperplasia.
6. The main route of spread for endometrial cancer is contiguous extension into the myometrium.
7. Posttreatment recurrences occur in women with highgrade tumors or with deep myometrial invasion and usually involve the vaginal apex.
Recommendations for Clinical Care
1. In postmenopausal women, any bleeding should be promptly and thoroughly evaluated. A thickened endometrium must be biopsied. Transvaginal ultrasonography, hysteroscopy, and sonohysterography are useful to identify focal abnormalities. (Level I)
2. Postmenopausal woman with an intact uterus using systemic estrogen-only therapy are at risk of developing endometrial hyperplasia and cancer. Treatment with adequate progestogen reduces the risk of endometrial cancer in women using ET. Women using estrogen combined with bazedoxifene do not require a progestogen. (Level I)
3. Atypical endometrial hyperplasia should be treated with hysterectomy and bilateral salpingo-oophorectomy. Conservative management with progestogen therapy and close follow-up may be an option for reliable younger women seeking to preserve fertility or for poor surgical candidates. (Level I)
4. Endometrial cancer is treated with hysterectomy, bilateral salpingo-oophorectomy, and dissection of pelvic and para-aortic lymph nodes. Staging and projected prognosis are based on surgical findings. Women with advanced endometrial cancer (≥50% myometrial invasion) will usually require adjuvant therapy. (Level I)
Cervical Cancer
Key Points
1. When detected at an early stage, the 5-year survival rate for women with cervical cancer is 92%. In women aged older than 65 years with cervical cancer, 42% had never been screened.
2. Risk factors for cervical cancer include human papillomavirus (HPV) infection, sexual intercourse at an early age, multiple sexual partners, smoking, and immunocompromised states, including HIV infection.
3. Almost all cervical cancers are related to infection by the sexually transmitted, high-risk (oncogenic) types of HPV. Two vaccines are available to prevent infection with the HPV types that cause most cervical cancers.
Recommendations for Clinical Care
1. Vaccination for HPV is recommended for girls aged 13 to 26 years and for boys aged 13 to 21 years. Women immunized against HPV should follow routine cervical cancer screening guidelines. (Level I)
2. Cervical cancer screening should start at age 21 and is recommended every 3 years for women aged 21 to 29 years. For women aged 30 to 65 years, co-testing with cervical cytology and HPV testing every 5 years is advised, although screening with cytology alone every 3 years is acceptable. (Level I)
3. Women who have had a hysterectomy for benign disease with removal of the cervix should no longer be screened for cervical cancer, unless there is a history of cervical dysplasia (cervical intraepithelial neoplasia [CIN] 2 or higher). (Level I)
4. Women with a history of cervical cancer, HIV infection, immunocompromised state, or diethylstilbestrol exposure in utero require increased screening. (Level I)
5. Screening should be discontinued after age 65 years in women with adequate negative prior screening and no history of CIN2 or higher in the past 20 years. (Level I)
6. Abnormal uterine bleeding or a cervical abnormality identified during a pelvic examination may be a sign of cervical cancer and should be promptly evaluated. (Level I)
Ovarian Cancer
Key Points
1. Ovarian cancer is the tenth most common cancer in US women, but the fifth most common cause of cancer death.
2. Risk factors for epithelial ovarian cancer include genetic predisposition (BRCA mutations, Lynch syndrome), older age, nulligravidity, endometriosis, early menarche, and late menopause.
3. Protective factors include oral contraceptives and tubal sterilization, each of which decrease risk by 50%.
4. In normal-risk women, ovarian cancer screening with cancer antigen-125 or ultrasound is not effective and is not recommended.
5. Signs of ovarian cancer are subtle and include early satiety, abdominal bloating, abdominal pain, pelvic pain, and urinary frequency occurring daily for weeks.
6. Women with suspected ovarian cancer should undergo definitive surgical procedures with gynecologic oncologists as outcomes are superior.
Recommendations for Clinical Care
1. Women should be informed of the symptoms of ovarian cancer and advised to inform their healthcare providers if daily symptoms persist. (Level III)
2. Family history of breast, ovarian, colon, and pancreatic cancers suggestive of increased hereditary risk should prompt referral for genetic counseling. (Level II)
3. Ovarian cancer screening should not be performed in normal-risk women. In high-risk women, screening may be offered, but risk-reducing surgery (bilateral salpingooophorectomy or possibly bilateral salpingectomy) or medications (eg, oral contraceptives) should be considered to decrease ovarian cancer risk. (Level I)
Lung Cancer
Key Points
1. Smoking prevalence has been decreasing as a result of increased tobacco control, increased tobacco prices, and more laws prohibiting smoking in many locations.
2. Lung cancer takes many years to develop, with an average age of diagnosis of 71 years. It is the leading cause of cancer death among white, black, Asian/Pacific Islander, and American Indian/Alaska Native women and the second most common cause of cancer death among Hispanic women.
3. Most lung cancers are believed to be caused by cigarette smoking. Other risk factors include exposure to asbestos, radon, second-hand smoke, and other environmental agents. Among nonsmokers, women are more likely than men to develop lung cancer. Smoking cessation reduces lung cancer incidence.
4. Studies on the effect of hormone use on lung cancer incidence and survival are limited, with inconsistent results. Large observational studies have shown protective effects of oral contraceptives and hormone therapy on lung cancer risk. However, in the Women's Health Initiative, use of estrogen-progestogen therapy was associated with an increased risk of death from lung cancer, with an additional 9 cases per 1,000 women after 5.6 years of use plus 2.4 years of additional follow-up. An increased risk of lung cancer was not seen with the use of estrogen alone. Additional research is needed on the association between hormones and lung cancer.
Recommendations for Clinical Care
1. Women should be asked about smoking at all comprehensive visits and smoking cessation advised. (Level I)
2. Women using HT, particularly those who smoke, should be informed that EPT was associated with a small increased risk of death from lung cancer in the WHI, with no increased risk associated with the use of estrogen alone. (Level II)
3. The US Preventive Services Task Force recommends annual screening for lung cancer with low-dose computed tomography in women aged 55 to 80 years who have a 30 pack-year smoking history and currently smoke or have quit within the past 15 years. Screening should be discontinued once a person has not smoked for 15 years or develops a health problem that substantially limits life expectancy or the ability to have curative lung surgery. (Level I)
Colorectal Cancer
Key Points
1. Colorectal cancer is a leading cause of death for women.
2. Risk factors for colorectal cancer include age, smoking, presence of colorectal polyps, inflammatory bowel disease (eg, ulcerative colitis or Crohn disease), family history of colorectal cancer, personal history of breast cancer, and certain genetic diseases (eg, Lynch syndrome/ hereditary nonpolyposis colorectal cancer or familial adenomatous polyposis).
3. Colon cancer has been linked to a high-fat, low-fiber diet and to a high intake of red or processed meat.
4. Screening for colorectal cancer has been shown to detect asymptomatic, early stage disease and improve mortality. Colonoscopy is the most accurate diagnostic test for colorectal cancer and allows for concurrent removal of polyps and biopsy of suspicious lesions. General screening guidelines include an initial colonoscopy at age 50, with repeat testing every 10 years until age 75. If polyps or other abnormalities are identified during screening, more frequent surveillance is recommended. Other methods to screen for colorectal cancer include annual high-sensitivity fecal occult blood testing, sigmoidoscopy, computed tomographic colonography, and double-contrast barium enema.
Recommendations for Clinical Care
1. Women should be advised to not smoke and to eat a low-fat, high-fiber diet with limited intake of red or processed meat for overall health and possible colorectal cancer risk reduction (Level II)
2. Women should be screened for colorectal cancer, generally with an initial colonoscopy at age 50 and repeat testing every 10 years, until age 75. (Level I)
3. Women at increased risk for colorectal cancer, including those with inflammatory bowel disease, colorectal polyps, or a family history of colorectal cancer, should be screened more frequently. (Level I)
Pancreatic Cancer
Key Points
1. Pancreatic cancer is the fourth leading cause of cancer death in US women.
2. There is no clear association between pancreatic cancer risk and reproductive factors or use of oral contraceptives or hormone therapy.
3. Smoking is the only well-established risk factor for pancreatic cancer, but other probable risk factors include age, high-fat diet, alcohol intake, type 2 diabetes mellitus, chronic pancreatitis, and obesity.
4. Pancreatic cancer does not cause symptoms until advanced stages, and there are no effective methods for early detection; presenting signs include jaundice and thromboembolic events.
Recommendations for Clinical Care
1. Encourage smoking cessation and a healthy lifestyle for overall health and possible pancreatic cancer risk reduction. (Level II)
2. A midlife woman presenting with thromboembolic disease should be evaluated for the possibility of pancreatic cancer. (Level II)
Skin Cancer
Key Points
1. Skin cancer is the most common form of cancer and includes basal and squamous cell carcinomas and melanoma.
2. Common risk factors for skin cancer include advancing age, chronic or intense exposure to ultraviolet radiation (typically from the sun or tanning beds), family history of skin cancer, and chronic immunosuppression.
3. Sun exposure is the most preventable risk factor for all types of skin cancer, including melanoma.
4. Some common benign skin growths associated with maturing skin such as seborrheic keratoses and capillary hemangiomas can mimic skin cancers.
Recommendations for Clinical Care
1. All women should be assessed for skin cancer risk and be examined regularly for skin cancer and skin cancer precursors. (Level I)
2. Women should be instructed in skin self-examination to promote early detection of skin cancer. Potential signs of skin cancer include new or changing moles and lesions that bleed, ulcerate, or fail to heal. (Level II)
3. Photoprotective measures should be advised to reduce a woman's risk of skin cancer, including avoiding midday sun, using sunscreen consistently, wearing protective hats and clothing, and avoiding tanning salons. (Level I)