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This chapter should be cited as follows:
Utian, W, Sultana, C, Glob. libr. women's med.,
(ISSN: 1756-2228) 2008; DOI 10.3843/GLOWM.10080
This chapter was last updated:
January 2008

Gynecologic Care of the Older Woman

Authors

INTRODUCTION

Office management of the gynecologic problems of elderly female patients requires sensitivity to the special needs of this group. The general gynecologist can expect to see more geriatric women as the U.S. population continues to age. In 1990, 12.6% of the population was older than 65 years of age. By the year 2050, this figure will almost double to 22.9%, or 100 million elderly.1 These changing demographics raise the problem of providing gynecologic care for these women and the issue of the role of gynecologist as their primary care physician. This chapter addresses both areas in sections on screening and disease prevention and on management of gynecologic problems in this age group.

SCREENING

What should be the role of the gynecologist in screening elderly women for disease? The answer depends on the clinical situation in which the patient presents. Ideally, disease prevention and screening should be done at regular visits to a primary care physician. Last defined primary care as “continuity of care and ongoing relationship between patient and physician, superseding issues of medical specialty, to provide for health maintenance and disease prevention.”2 An otherwise healthy woman whose obstetrician or gynecologist is her only physician has needs that are different from those of the patient with comprehensive geriatric care who is being referred for a specific complaint. Many aspects of gynecologic and medical screening may not be addressed by the patient's primary care provider. For example, 14% of women between the ages of 65 and 74 years and 39% of those older than 75 have never had a Papanicolaou (Pap) smear.3 Gynecologists can ensure with annual examinations that this type of basic health maintenance screening is not overlooked.

Primary care stresses counseling on healthy lifestyles, avoidance of risks, and early disease detection. Periodic examinations should concentrate on conditions that cause morbidity and mortality, are detectable when asymptomatic, and have better treatment outcomes with early detection. The physician should assess the status of chronic illnesses. Polypharmacy is an iatrogenic problem that affects many of the elderly. Adverse drug reactions are responsible for many of this group's hospital admissions,4 and the more medications the patient is taking, the more likely is an adverse reaction.5 The annual checkup can be an opportunity to review continuing need for all prescription drugs, and also to ask about over the counter and herbal remedies that the patient may not mention. Typical problem medications are psychotropics, antihypertensives, digoxin, nonsteroidal antiinflammatory drugs, steroid preparations, theophylline, and warfarin.

The elderly woman's diet and level of physical activity can significantly affect her health. Nutritional status can be affected by slowing metabolic rate, loss of dentition, loss of smell and taste receptors, and the effects of poverty, isolation, and depression. Aging typically is associated with a decrease in lean body mass and a corresponding increase in the percent of body fat; however, these changes may be the result of inactivity. The practitioner should encourage physical activity tailored to the patient's medical problems and level of fitness. Exercise has been shown to improve cardiopulmonary and muscular fitness in the elderly6 and preserve functional capacity. It can benefit glucose control, prevent osteoporosis, and benefit preservation of cognitive function, possibly through increased oxygen transport.

Visits should also present opportunities for review of vaccinations and assessment of activities of daily living (ADLs), social supports, and substance abuse screening. Social vulnerability, economic problems, and psychiatric illnesses put older patients at risk. Asking patients about tobacco, alcohol, and prescription medication abuse is important because these problems are not rare and can be treated. For example, studies7 suggest that 10–15% of women older than 65 years of age abuse alcohol. Structured interviews such as Michigan Alcohol Screening Test (MAST) and CAGE (for ‘cut down, annoyed by criticism, guilty about drinking, eye-opener drinks”) are reliable screening instruments. Women are more likely to be prescribed psychoactive medication,7 especially in the institutional setting. Cigarette smoking carries a relative mortality risk of 1.8 for women age 65 and older in the National Institute on Aging Epese study.8 Quitting appears to decrease mortality within 1–2 years. This visit is also an opportunity to screen for common mental disorders such as depression, anxiety, and sleep disorders, all of which are more common in elderly women than in elderly men.9

Screening for gynecologic and nongynecologic cancer is a critical part of annual checkups. Fifty percent of all malignancies occur in the 11% of the population older than 65 years of age.10, 11 When does early detection improve morbidity, mortality, and quality of life for the elderly? An effective strategy requires common diseases with an early symptomatic period, significant burden of disease, an accurate and low-risk screening test, and the availability of effective and acceptable treatment.12 Based on these criteria, screening for breast, colon, cervical, and endometrial (by evaluation of any bleeding) cancer makes sense in this population. These issues are well addressed elsewhere; Table 1 offers suggested screening protocols.12

Table 1. Age 65 and older: interventions considered and recommended for the periodic health examination*

Interventions for the general population

Motorcycle and bicycle helmets

Screening

Fall prevention

Blood pressure

Safe storage/removal of firearms

Height and weight

Smoke detector

Fecal occult blood test and/or sigmoidoscopy

Set hot water heater to <120–130°F

Mammogram ± clinical breast examination (women ≤69 years)

CPR training for houshold members

Papanicolaou (Pap) test (women)

Dental health

Vision screening

Regular visits to dental care provider

Assess for hearing impairment

Floss, brush with fluoride toothpaste daily

Assess for problem drinking

Sexual behavior

Counseling

STD prevention: avoid high-risk sexual behavior; use condoms

Substance abuse

Immunizations

Tobacco cessation

Pneumococcal vaccine

Avoid alcohol/drug use while driving, swimming, boating, etc.

Influenza

Diet and exercise

Tetanus-diphtheria (Td) boosters

Limit fat & cholesterol; maintain caloric balance; emphasize grains, fruits, vegetables

Chemoprophylaxis

Adequate calcium intake (women)

Discuss hormone prophylaxis (perimenopausal and menopausal women)

Regular physical activity

Potential interventions

Intervention for high-risk populations

PPD; hepatitis A vaccine; amantadine

Institutionalized persons

PPD

Chronic medical conditions; TB contacts low income; immigrants; alcoholics

Fall prevention intervention

Persons ≥75 years; or ≥70 years with risk factors for falls

Consider cholesterol screening

Cardiovascular disease risk factors

Avoid excess/midday sun, use protective clothing

Family h/o skin cancer, nevi, fair skin, eyes, hair

PPD; hepatitis A vaccine

Native Americans/Alaska natives

Hepatitis A vaccine; hepatitis B vaccine

Travelers to developing countries

HIV screen; hepatitis B vaccine

Blood product recipients

Hepatitis A vaccine; HIV screen; hepatitis B vaccine

High-risk sexual behavior

RPR/VDRL

Injection or street drug use

PPD; hepatitis A vaccine; HIV screen; hepatitis B vaccine

Health care/lab workers

RPR/VDRL; advice to reduce infection risk

Persons susceptible to varicella, amantadine/rimantadine; hepatitis B vaccine

PPD; hepatitis A vaccine

Injury prevention

Varicella vaccine

Lap/shoulder belts

 


CPR, cardiopulmonary resuscitation; STD, sexually transmitted diseases; TB, tuberculosis; PPD, purified protein derivative; HIV, human immunodeficiency virus; RPR, rapid plasma reagin test; VDRL, Veneral Disease Research Laboratory test.
*Leading causes of death: heart disease, malignant neoplasms (e.g., lung, colorectal, breast), cerebrovascular disease, chronic obstructive pulmonary disease, and pneumonia and influenza.
†Annually.
§All women who are or have been sexually active and who have a cervix. Consider discontinuation of testing after age 65 years if previous regular screening showed consistently normal results.
Adapted from the US Preventative Services Task Force: Guide to Clinical Preventative Services. 2nd edn. Baltimore: Williams & Wilkins, 1966.

In addition to the evaluations listed in the guidelines, special attention should be paid to issues that the gynecologist is uniquely qualified to address. The Department of Health and Human Services Clinical Practice Guidelines stress that all patients be screened and offered treatment for urinary incontinence.13 It is important to routinely ask about this condition. Other problems such as atrophic and infectious vaginal urinary frequency and sexual dysfunction can follow from the urogenital effects of menopause.

PREOPERATIVE AND POSTOPERATIVE MEDICAL CARE

About 190 surgical procedures per 100,000 persons older than 65 are performed annually. The medical problems of the elderly affect surgical treatment of their gynecologic problems. A trend toward higher surgical mortality in the elderly observed during the 1960s and 1970s has been attributed to more older and sicker patients being taken to the operating room than ever before.14, 15, 16 Sikes and Detmer reported 10.8% mortality rate for patients between the ages of 90 and 94.15 Weighing the risk versus the benefit is critical,16 especially for elective surgery. Eighty percent of those older than 65 have a chronic illness, and 35% of these have more than three problems; general health is an important area for the gynecologist to assess before surgery.

There is no specific risk assessment for gynecologic and urogynecologic surgery. Few data exist on the risks of these procedures compared with general surgical procedures. The overall mortality rate for gynecologic surgery in the aged is 0.6%, according to an older study.17 Sultana and colleagues18 found incontinence procedures to have a mortality rate of only 0.33% for patients older than 64 years of age. Most deaths and complications were related to coronary artery disease and embolism. Death rates increased after age 80. Elderly patients undergoing surgery for gynecologic malignancy are at no greater risk than their younger counterparts.19 In general, the physician should evaluate medical and surgical history, assess all medications, and conduct a thorough review of systems. Prophylaxis for venous thrombosis should be planned.

Two rating scales are in common use in preoperative evaluation. The Goldman Multifactorial Cardiac Risk Index was developed after a study of 1001 patients older than 40 on general surgical services.20 Nine factors were associated with life-threatening or fatal complications (Table 2). A point score greater than 26 carries a 22% chance of life-threatening complications and a 56% chance of death. The American Society of Anesthesiologists (ASA) scale is a clinical measure that correlates with arterial blood gas, pulmonary capillary wedge pressures, and right heart catheterization in predicting mortality21 (Table 3). Cardiac complications peak 3 to 5 days postoperatively.

Table 2. Goldman Multifactorial Index of Cardiac Risk in noncardiac surgical procedures


 

Points

1. Hx: (a) Age >70 years

5

 (b) MI <6 months ago

10

2. PE: (a) S3 gallop or JVD

11

 (b) Valvular aortic stenosis

3

3. EKG: (a) Rhythm other than sinus or PACs

7

 (b) >5 PVCs/min any time before surgery

7

4. General status: PO2 <60 mmHg

3

 PCO2 >50 mmHg

 

 K <3 or HCO3 <20 mEq/L

 

 BUN >50 or creatinine >3 g/dl

 

 Abnormal SGOT

 

 Chronic liver disease

 

 Bedridden patient

3

5. Type of surgery: (a) Intraperitoneal, intrathoracic, aortic, (b) Emergency

4

 

53 points


Hx, history; MI, myocardial infarction; PE, physical examination; JVD, jugular venous distention; PAC, premature atrial contraction; PVC, premature ventricular contraction; BUN, blood urea nitrogen; SGOT, serum glutamic oxaloacetic transaminase.

 

Table 3. American Society of Anesthesiologists Physical Status Scale20

  Class 1: A normal, healthy person
  Class 2: A patient with mild systemic disease
  Class 3: A patient with severe systemic disease that is not incapacitating
  Class 4: A patient with incapacitating systemic disease that is a constant threat to life
  Class 5: A moribund patient who is not expected to survive 24 hours with or without operation

General nutritional status can be assessed by albumin level and total lymphocyte count. This is important for wound healing and in planning postoperative nutrition when patients must depend on parenteral feeding for prolonged periods. Discharge planning to the patient's home, that of a family member, or to a nursing home or extended care facility needs to be discussed preoperatively. A team approach that takes into account the effect of surgery on the patient's ADLs works best.

A useful approach to evaluating medical concerns before surgery is by organ system. Neurologic functioning, especially in terms of ADLs, is important, because most patients lose ground with prolonged hospitalizations. Many studies22, 23 have looked at whether Acute Care of the Elderly units can avoid this complication. Functioning is related to the patient's baseline cognitive state. Dementia is a symptom complex that affects 5% of those older than 65 and 20% of those older than 80. It is defined as a deterioration of cognitive functions sufficient to interfere with the activities of daily living. Fifteen percent of cases have reversible causes. Dementia is an independent risk factor for surgical mortality, which is as high as 45% in some studies.24 Dementia must be distinguished from postoperative delirium, which occurs in 10–15% of cases and can be caused by infection, drug toxicity, intensive care unit psychosis, and metabolic derangement.

The elderly are vulnerable to cardiac death because of age-associated decreases in myocardial contractility and inotropic response. A decrease in the maximum achievable heart rate and an increase in vascular resistance result in a decreased maximum cardiac output. Cardiac status has been extensively studied for prediction of mortality and postoperative complications. Simple tests such as chest radiographs can predict left ventricular dysfunction by identifying cardiomegaly and pulmonary edema.25, 26 An electrocardiogram with asymptomatic sinus bradycardia or bundle branch block requires no further evaluation, but evidence of premature ventricular contractions, atrial fibrillation, or T-wave inversion does. The treadmill test has not been well defined as a predictor of postoperative complications,27 although some investigators recommend it.28 For patients with a recent history of infarction, the rate of reinfarction decreases to 5% after 6 months, and surgery therefore should be delayed. Patients with coronary artery disease who undergo cardiac bypass before elective surgery have decreased mortality compared with those who do not (0.9% vs. 2.4%).29 Asymptomatic carotid bruits do not need evaluation before surgery, and most systolic murmurs are insignificant. However, any findings that suggest aortic stenosis mandate investigation, because stenotic or regurgitant lesions of the mitral or aortic valves are associated with a 20% risk of heart failure postoperatively. Hypertension in and of itself is not associated with increased surgical risk. Goldman found no correlation between preoperative blood pressures less than 170/110 mmHg and the incidence of postoperative arrhythmias, ischemia, heart failure, or renal failure.30 There appears to be no association between hypertension and complications in patients having incontinence procedures.18

With aging, there is a linear increase in functional residual capacity and decreased vital capacity. Sensitive indicators of potential pulmonary problems are a maximum breathing capacity less than 50% predicted and a forced expiratory volume in 1 second (FEV1) of less than 2 L. Hypercapnia is a better predictor than hypoxia, but in general the age-adjusted PaO2 should equal 100 – (1/3 age in years). The risk of postoperative pneumonia in elderly patients may be as high as 17%.31 Underlying asthma, chronic obstructive pulmonary disease, and cigarette smoking increase the chance of pulmonary complication, as does upper abdominal surgery. Lower abdominal surgery has less impact on ventilation, and vaginal surgery has the least. The most common time for pulmonary edema is 36–48 hours postoperatively, when fluid mobilization begins. The kidneys undergo a decrease in renal mass and glomeruli with aging. Concentrating ability is lessened. The decrease in glomerular filtration rate can be masked by decreased muscle mass and a corresponding drop in serum creatinine. Creatinine clearance remains the best indicator of renal function in the elderly, but a blood urea nitrogen level over 50 mg/dl and a serum creatinine level over 3 mg/dl are also signs of poor renal function.

Patients with diabetes suffer from poor tissue repair and compromised leukocyte function. For type I insulin-dependent diabetic patients, the intraoperative blood glucose level should be kept at 250 mg/dl, and a continuous insulin infusion should be used if needed to keep levels in the postoperative period between 70 and 140 mg/dl. Type II diabetics should be closely observed but may not need their oral agents restarted until they are ready for discharge and back on their usual diets.

UROGENITAL ATROPHY AND VULVOVAGINITIS

The types of problems that women in this age group develop depend to some degree on whether they are using hormone therapy (HT). When postmenopausal patients complain of increased vaginal discharge without itching, physicians should be aware that this may represent improved vaginal lubrication that some women interpret as infection. However, estrogen replacement can also cause some women to be susceptible to yeast infections again. Older women can still contract sexually associated vaginitis; a thorough sexual history can help identify a woman at risk. Vulvar dystrophy and dysplasia can present with itching, as can malignancies of the vulva. Physicians should have a low threshold for performing a biopsy of any red, white, or ulcerated lesion on the vulva. If these causes have been excluded, older women with vulvovaginal discomfort or dyspareunia should be evaluated for vulvodynia, vulvar vestibulitis, simple atrophic vaginitis that responds to HT, and desquamative vaginitis. The latter is a painful condition whose cause is unknown. It is characterized by a severely reddened mucosa with alkaline pH and seems to respond to clindamycin creams.

Pain and bleeding around the urethra can be the result of a urethral caruncle, which is treatable with estrogen creams. Caruncles that do not resolve need a biopsy to exclude transitional cell carcinomas. Other vulvar problems that increase with age are seborrheic keratoses, senile hemangiomas, papillary hidradenoma, and Bartholin's cysts.

SEXUAL DYSFUNCTION

Sexuality in the woman older than 65 deserves to be part of a routine review of systems. Sexual dysfunction is commonly attributed to physical changes associated with the climacteric and emotional issues associated with this life event. The negative psychosocial connotations of aging and emphasis on youth as a prerequisite for sexuality in our society can also exert effects on patient's self-perceptions and beliefs about what is “normal” and expected at this time in the life cycle. The current generation of elderly women does seem to lose some interest in sex or to be less distressed than their male counterparts about medical problems that interfere with sexuality.32 In a study done at Duke in the 1960s,33 50% of the women older than 65 surveyed had no interest in sexual activity. However, the elderly are not a homogenous group when it comes to sexual functioning, and the physician must be aware of cohort bias in this type of survey study. The most important predictors of motivation for sexual activity are the importance of and enjoyment of sex in the person's earlier years.34 Those who report satisfying relations before menopause are likely to continue afterward. Problems can be divided into difficulty with interest, with arousal, with achieving orgasm, and with pain during coitus.

Androgen levels can play a role in problems with decreased libido.35 It is difficult to sort out the effects of changing estrogen and testosterone levels on libido from problems caused by stress and changes in the patient's social situation and relationships with partners. The frequency of intercourse may reflect male sexual dysfunction and not indicate the female partner's libido levels.36 In general, studies have shown no correlation between hormone levels and reported sexual activity. Vaginal atrophy scores, however, do correlate with decreased frequency of sexual activity. Traupmann37 found that 106 of 240 women surveyed between the ages of 50 and 82 were still having intercourse. There may exist an “interest-activity gap” because many patients cite lack of a partner as the reason for cessation of sexual activity. Because 70% of women older than 75 are widows, this is an issue for thousands of women. Newman found that 54% of married versus 7% of single, widowed, or divorced subjects were still sexually active.38 Many complaints are signs of relationship difficulties or changes in the nature of the relationship between two partners, whose passage through midlife is taking them in different directions. Even advances in therapy can alter the balance. The introduction of Viagra, which has allowed many formerly impotent men to again participate in coitus, may cause other issues as the status quo of the relationship changes. Aging in and of itself is associated with decreased pelvic blood flow and an increased length of time needed to reach orgasm with stimulation. This can occur in women who previously experienced no difficulties climaxing. Dyspareunia is common, affecting 13% of older women surveyed.39 HT can help with pain due to atrophy.

In summary, the physician should inquire about sexual activity, satisfaction, and problems. In addition to taking a history, prescribing HT (preferably if this is the only indication, as local vaginal estrogen) or lubricants, and encouraging regular intercourse to maintain vaginal function, physicians can also help patients by helping them alter behaviors and attitudes that are contributing to problems. Referral to a specialist or sex therapist may be helpful.

PELVIC FLOOR PROLAPSE

Pelvic floor prolapse refers to relaxation of any or all parts of the pelvic floor, including cystocele, urethrocele, rectocele, uterine prolapse, and in posthysterectomy patients, eversion of the vaginal vault and enterocele. Treatment should address the degree of discomfort and function limitation the patient is experiencing and any associated urinary or fecal incontinence. Asymptomatic patients do not require treatment unless ulceration becomes a problem. No studies address prophylactic treatment of prolapse to slow its progression. Patients who have sufficient levator muscle tone to retain a pessary can be treated indefinitely in this way. Sexually active patients can use certain types of pessary or learn to insert and remove them on their own. Pessary use is addressed in detail in the chapter "Conservative Therapy for Stress Incontinence".

Surgery for prolapse should be reserved for those who can tolerate these elective procedures without excessive risk and whose life expectancy justifies it. The procedure selected depends on the patient's activity levels and sexual functioning. LeFort colpocleisis should be reserved for patients who are not sexually active and have been counseled on the loss of a functional vagina. Other procedures include vaginal hysterectomy and anterior and posterior repair with suspension of the vaginal cuff by McCall's cul-de-plasty or uterosacral shortening. Sacrospinous fixation and abdominal sacral colpopexy are also used for prolapse, especially for treatment of vaginal vault prolapse. Paravaginal and other repairs that involve the pubococcygeal muscles or fascia have also been described.

URINARY INCONTINENCE AND URINARY TRACT INFECTION

The International Continence Society defines incontinence as urinary leaking that is “objectively demonstrable and a social and hygienic problem.”11, 40 The National Institutes of Health consensus conference on this topic, whose guidelines have been recently updated, estimated that 15% to 30% of community-dwelling women age 65 and older and 50% of nursing home residents experience some degree of urinary incontinence.13 The prevalence in women is twice that in men. Elderly women are more likely to experience detrusor instability than their younger counterparts, in whom stress incontinence is most common. They are also more likely to develop interstitial cystitis and urinary tract infections. Age-related changes such as declining estrogen levels, detrusor muscle degeneration, lower urethral closure pressure, and neurotransmitter dysfunction41 may play a role. As with other conditions in the geriatric population, continence can be the result of a fragile state of balance that is easily disrupted. Transient causes of incontinence should be sought before undertaking an extensive workup. These causes include infection, medications, constipation, delirium, and mobility problems.

The most common source of bacteremia in the elderly population is urinary tract infection (UTI). UTIs are addressed elsewhere in detail (chapter: "Acute Pelvic Inflammatory Disease"). In some postmenopausal patients, incontinence is the presenting complaint. The prevalence of bacturia in the elderly increases with age and debility,42 and this may contribute to higher infection rates. Atrophic vulvovaginitis is also a risk factor for UTI, and use of estrogen creams has been shown to decrease infection rates in patients with recurrent UTIs.43 The most common organisms are Escherichia coli, enterobacteriaceae, and enterococci.44 About one half of UTIs in the older population are nosocomial.

A thorough medication history can identify incontinence caused by or aggravated by diuretics, α-adrenergic blockers, and cholinergic drugs. Many over the counter remedies can affect continence. The other reversible causes of incontinence such as constipation or excessive consumption of caffeine, alcohol, and cigarette smoking (all of which can worsen or cause detrusor instability) do not require extensive evaluation other than a history to initially address. Delirium and dementia can cause incontinence by interfering with volition to reach a restroom. Functional incontinence can result when restricted mobility, difficulty undressing because of arthritis, and or other conditions make toileting without assistance difficult for the patient. Patients who do not respond to simple measures of treatment are candidates for urodynamics, especially if surgical repair of stress incontinence is a consideration. Behavioral measures for detrusor instability are preferred over medications because of the lack of side effects.45

The elderly are more susceptible to incontinence that has a neurologic basis at the cerebral, pontine, or spinal cord levels. Screening for lower extremity abnormalities on examination is indicated for every patient.46 Older women have a higher baseline rate of intrinsic sphincter deficiency. This is a type of stress incontinence that requires different therapy from that for genuine stress incontinence with normal urethral closure pressure. A tenuous equilibrium exists between the storage and micturition functions of the bladder in many older patients. A patient may have simultaneous incontinence and inability to adequately empty the bladder because of detrusor muscle dysfunction. This condition is called detrusor hyperactivity with impaired contractility. As many as one half of nursing home residents may have this problem, and it can be difficult to manage.47 Urge incontinence with an abnormally elevated postvoid residual is a sign, but definitive diagnosis requires urodynamics. Treatment options include anticholinergic drugs along with straining, frequent voiding, or intermittent self-catheterization.

Another important issue is identifying occult incontinence in patients who are undergoing surgery to correct pelvic floor prolapse. It is thought that without prophylactive urethropexy, 36% to 80% of these patients may become incontinent after they undergo reduction of the occluding procidentia, cystocele, or enterocele.48 Testing for this problem has not been standardized, although many investigators advocate urodynamic testing with the prolapse reduced by a speculum or pessary.49 If stress incontinence is demonstrated, some type of urethropexy should be done along with the primary procedure.

Because the incidence of incontinence that is caused by detrusor instability rises and that caused by genuine stress incontinence falls as the population being studied ages, it is useful to consider empiric treatment for detrusor instability in patients with normal postvoid residuals who complain of urgency. Infection should be excluded, and those at risk for bladder carcinoma (i.e. smokers) should be assessed with urine cytology and cystoscopy.

Incontinence in the nursing home setting is a large problem. The Omnibus Reconciliation Act of 1989 requires that all patients entering nursing homes be screened as to their continence status, using the parameters in Table 4. Prompted or timed voiding means actively checking patients for wetness and encouraging them to void every 2 hours. This technique, as well as assistance with toileting and the use of adult diapers when incontinence cannot be controlled, is preferable to the use of indwelling Foley catheters in female patients. Prolonged urethral catheterization is associated with infection, urethral sphincter damage, and vesicovaginal and urethrovaginal fistulas. The nursing home environment should be carefully evaluated and designed for toilet access, commodes, lighting, need for grab bars, and mobility aids such as self-rising chairs. Garments should be easy to take on and off (e.g. with Velcro fasteners).50

Table 4. Omnibus Reconciliation Act: Recommended Evaluations for All Nursing Home Admissions

  Assessment of bowel and bladder function
  Review of medications
  Observation of voiding behavior
  Identification of antecedent of incontinence
  Evaluation of responsiveness to timed voiding
  Fecal impaction treatment
  Pelvic examination
  Urinalysis
  Estimation of postvoid residual volume

SCREENING AND TREATMENT OF GYNECOLOGIC MALIGNANCIES

Gynecologic cancers deserve particular attention in the elderly because their incidence increases with age. Screening for cervical, vulvovaginal, endometrial, and ovarian cancer should be done at annual visits. There is no upper age limit for Pap smear testing. The group older than 65 years of age accounts for 25% of the incidence and 40% of the deaths from cervical cancer.51, 52 The normally slow progression of disease from dysplasia to invasion allows effective therapy to prevent cancer. The American College of Obstetrics and Gynecology recommends annual screening for at least 3 years, with the option to perform smears less frequently at the discretion of the physician after three normal results. Hysterectomy does not eliminate the need for cytologic assessment, because vaginal cancers and dysplasia can occur at the cuff margin. If the patient has no history of dysplasia, the frequency of Pap smears after removal of the uterus can be decreased. Vaginal cancers make up less than 1% of all gynecologic malignancies, but they peak in incidence between the ages of 60 and 70. More than 75% of all invasive vulvar carcinomas are diagnosed in women older than 60. Risk factors include smoking, immunosuppression, and other lower genital tract cancer or dysplasia.

Endometrial cancer is diagnosed at a median age of 61. The best screening consists of aggressive evaluation of all postmenopausal bleeding or spotting, especially in patients not on hormone replacement or those who use tamoxifen for treatment of breast cancer. Patients should be routinely asked about bleeding. The most common cause is endometrial atrophy, but the entire genital tract should be carefully examined. Cervical polyps as a cause of postmenopausal bleeding decrease in incidence after the sixth decade. Other sources of spotting are myomas, polyps, endometritis, and endometrial hyperplasia. Obesity, nulliparity, early menarche, late menopause, hypertension, and diabetes are all risk factors for this type of cancer. Office endometrial biopsy is the initial procedure of choice, but may be more difficult because of cervical stenosis. If the office biopsy indicates atypia with hyperplasia or is inadequate, a full dilatation and curettage (D&C) should be done. Uterine ultrasound with saline introduced into the cavity can measure endometrial thickness and delineate polyps or masses in the endometrial cavity. Hysteroscopy has improved the diagnostic rate of D&C because focal biopsy of small polyps can be done. Advanced age is a poor prognostic variable in 5-year survival rates for endometrial cancer. If uterine sarcoma or other müllerian tumors are the cause of bleeding, they may not be sampled during D&C. Patients on hormone replacement therapy whose withdrawal bleeding deviates from the usual pattern deserve full evaluation.

Unfortunately, no test other than the annual pelvic examination has proved to be adequately sensitive or specific for ovarian cancer screening. This disease increases at an age-specific rate until age 81, but it peaks at age 60. It is estimated that 45% of ovarian tumors in older women are benign, and 42% are malignant epithelial tumors.53 All adnexal masses should be considered potentially malignant until proved otherwise by pathologic examination. Endometriosis accounts for only 3% of masses in women 40 years old or older. Postmenopausal women can still develop benign ovarian cysts, such as germinal inclusion cysts, despite the fact that they are not ovulating. Assessment of pelvic masses in this age group should include screening for breast and colon cancers because of the high rate of metastases to the ovaries. Fallopian tube carcinoma also peaks in this age group. It classically manifests with pain, watery vaginal discharge, and a pelvic mass. It is a rare condition, and the diagnosis is usually made intraoperatively. The standard management of adnexal masses in the elderly has been laparotomy through a midline incision for all cases.

The feasibility of serial ultrasound and CA 125 testing has been addressed by several studies. Creasman and Soper first noticed that malignancy in an enlarged postmenopausal ovary was unusual.54 Size was found to be a prognostic sign; in one study, only 1 of 32 tumors smaller than 5 cm were malignant,55 whereas another found a 15% rate of malignancy in cysts smaller than 5 cm.56 Parker found that 25 masses with reassuring ultrasonic characteristics and a normal CA 125 level were all benign, and they were successfully treated through the laparoscope.57 As more studies are done on this issue, perhaps more patients with incidental ultrasonic findings of ovarian cysts can avoid laparotomy.58 Aspiration of cysts for cytology with computed tomography or ultrasound guidance is another option in patients too ill to tolerate laparotomy. This practice is not generally recommended for diagnosis because of the risk of spilling and seeding tumor cells and because of the high rate of false-negative cytologic results. As for all gynecologic malignancies, age should not deter aggressive surgical management in patients who are otherwise candidates for laparotomy.

DISEASE PREVENTION IN OLDER WOMEN

The three leading causes of death for patients 55 years old or older are cancer, cardiac disease, and cerebrovascular accident. Cigarette smoking, hypertension, hypercholesterolemia, diabetes, obesity, and a sedentary lifestyle are risk factors for these conditions that can be addressed in screening visits. Many of these risk factors can be favorably affected by appropriate use of certain pharmacotherapy such as statins, antihypertensives, and antidiabetic agents.

HT (estrogen/progestogen use) is no longer recomended for disease prevention or risk reduction in older women.59 The major advantages of its use in younger women are in prevention of  osteoporosis, urogenital atrophy, and possibly colon cancer and cognitive decline. The favorable risk-benefit profiles are less clear for women older than 65 than for those in their fifties, but almost certainly become negative in favor of risk.

Prevention and treatment of osteoporosis is the second major  prevention issue in women older than 65. Physicians should assess bone density status, calcium and vitamin D intake, and use of prophylactic medications at health maintenance visits. It is known that bisphosphonates and HT  can arrest bone loss no matter how late it is begun, and it can increase bone density60 and decrease the risk of femoral neck and vertebral fractures. This in not a trivial issue, because one fourth of all women have spinal compression by age 60, 20% of white females have a hip fracture by age 90, and 15,000 women die annually as a result of the consequences of osteoporotic fracture. Unfortunately, if HT is not prescribed for women who have or are at risk for osteoporosis early, the risks of starting such therapy after 65 will outweigh the potential benefits.59, 61 At the least, calcium supplementation to a level of 1500 mg per day and vitamin D should be routinely advised, along with weight-bearing exercise.  Dual-energy x-ray absorptiometry (DEXA) scanning is recommended for all women older than 60. DEXA scanning can also be used to follow response to treatment. Prevention of falls in the elderly is also important in preventing fractures.62, 63

Cardiovascular disease causes 46% of deaths in women in the United States, compared with 4% of deaths from breast cancer.64, 65, 66, 67 Observational and preclinical tudies of HT tended to show a consistent 50% reduction of coronary artery disease in estrogen-treated women in their fifties compared with untreated controls.6, 11, 68, 69, 70, 71, 72, 73, 74, 75, 76, 77, 78, 79, 80, 81, 82, 83, 84, 85, 86, 87, 88, 89, 90, 91, 92, 93, 94, 95, 96, 97, 98, 99, 100, 101, 102 Some studies demonstrate that estrogen replacement therapy decreases the risk of cardiac death in women with angiographically proved coronary stenosis.87, 88, 91, 103 The HERS trial,104 although controversial, showed an initial increase in death in a similar population treated with HRT. The possible mechanisms for these effects include regulation of plasma lipids; autonomic and neuroendocrine regulation of systemic vascular resistance and blood pressure, modulation of vascular endothelial and smooth muscle cells, decreasing thromboembolic risk through fibrinogen and factor VII, and modulation of the activity of cardiac myocytes. An extensive discussion of this topic is beyond the scope of this chapter. The Womens Health Initiative data has definitely confirmed that in older women there is no justification in starting HT with the sole indication of risk reduction for cardiovascular disease.59

 

Gynecologists can have a significant impact on the health of the elderly female patient as specialists and primary care physicians. They can have a leadership role in this important area of women's health care.

REFERENCES

1

US Senate Subcommittee on Aging, American Association of Retired Persons, Federal Council on Aging, and US Administration on Aging: Aging America: Trends and Projections. DHHS publication no. (FCOA) 91–98001. Washington, DC: US Department of Health and Human Services, 1991

2

Last JD (ed): A Dictionary of Epidemiology, p 103. 2nd ed. New York: Oxford University Press, 1988

3

Byyny RL, Speroff L: A Clinical Guide for the Care of Older Women, p 49. Baltimore: Williams & Wilkins, 1990

4

Morgan K, Adllosso H, Ebrahim S et al: Prevalence, frequency and duration of hypnotic drug use among the elderly living at home. BMJ 296: 601, 1988

5

Vestal RE, Jue SG, Cusack BJ: Increased risk of adverse drug reactions in the elderly: Fact or myth? In O'Malley K, Waddington JL (eds): Therapeutics in the Elderly, p 97. Amsterdam: Elsevier Science Publishers, 1985

6

Elward K, Larson EB: Benefits of exercise for older adults. Clin Geriatr Med 8: 35, 1992

7

Swabo PA: Substance abuse in older women. Clin Geriatr Med 9: 197, 1993

8

La Croix AZ, Long J, Scherr P et al: Smoking and mortality among older men and women in three communities. N Engl J Med 324: 1619, 1991

9

Goldstein NZ, Perkins CA: Mental health and the aging woman. Clin Geriatr Med 9: 191, 1993

10

Baranovsky A, Myers MH: Cancer incidence and survival in patients age 65 and older. Cancer 36: 27, 1986

11

Boring CC, Squires TS, Tong T: Cancer statistics 1991. Cancer 41: 1, 1991

12

Oddone EZ, Feussner JR, Cohen HJ: Can screening older patients for cancer save lives? Clin Geriatr Med 8: 51, 1992

13

Clinical practice guideline: Urinary incontinence in adults. AHCPR publication no. 902–0038. Rockville, MD: Agency for Health Care Policy & Research, 1992

14

Keating HB, Lubin MF: Perioperative responsibilities of the physician/geriatrician. Clin Geriatr Med 6: 459, 1990

15

Sikes ED, Detmer DE: Aging and surgical risk in older citizens of Wisconsin. Wis Med J 78: 27, 1979

16

Linn BS, Linn MW, Wallen N: Evaluation of results of surgical procedures in the elderly. Ann Surg 195: 90, 1982

17

Panayiottis G, Ellenbogen A, Grunstein S et al: Major gyn surgery in the aged. J Am Geriatr Soc 26: 459, 1978

18

Sultana CJ, Campbell JW, Pisanelli WS et al: Morbidity and mortality of incontinence surgery in elderly women: An analysis of Medicare data. Am J Obstet Gynecol 176: 345, 1997

19

Pierson RL, Rigge PK, Buschsbain HJ: Surgery for gyn malignancies in the aged. Obstet Gynecol 46: 523, 1975

20

Goldman L, Caldera DB, Nussbaum SR et al: Multifactorial index of cardiac risk in noncardiac surgical procedures. N Engl J Med 297: 845, 1977

21

Owens WD, Felts JA, Spitznagel EL Jr: ASA physical status classifications: A study of consistency of ratings. Anesthesiology 49: 239, 1978

22

Landefeld CS, Palmer RM, Kresevic DM et al: A randomized trial of care in a hospital medial unit especially designed to improve the functional outcomes of acutely ill older patients. N Engl J Med 332: 1338, 1995

23

Campion EW: The value of geriatric interventions. N Engl J Med 332: 1376, 1995

24

Palmberg S, Hirsjarvi E: Mortality in geriatric surgery. Gerontology 25: 103, 1979

25

Mangano DT, Hedgcock MW, Wisneski JA: Non-invasive prediction of ventricular dysfunction: Coronary artery disease. Anesthesiology 57: A21, 1982

26

Seymour DG, Pringle R, Shaw JW: The role of the routine preoperative chest x-ray in the elderly general surgical patient. Postgrad Med J 58: 741, 1982

27

Gage AA, Bhayana JN, Hook N et al: Assessment of cardiac risk in surgical patients. Arch Surg 112: 1488, 1977

28

Nolan TE: Surgery in the elderly: Lowering risks by understanding special needs. Postgrad Med 91: 199, 1992

29

Foster E, Davis KB, Carpenter JA et al: Risk of noncardiac operation in patients with defined coronary artery disease: The Coronary Artery Surgery Study (CASS) Registry experience. Ann Thorac Surg 41: 42, 1986

30

Goldman L, Caldera DL: Risks of general anesthesia and elective operation in the hypertensive patient. Anesthesiology 50: 285, 1979

31

Burnett W, McCaffrey J: Surgical procedures in the elderly. Surg Gynecol Obstet 134: 221, 1972

32

Goldstein MK, Teng NNH: Gynecologic factors in sexual dysfunction of the older woman. Clin Geriatr Med 7: 41, 1991

33

Pfeiffer E, Verwoerdt A, Wang H: The natural history of sexual behavior in a biologically advantaged group of aged individuals. J Gerontol 24: 93, 1969

34

Pfeiffer E, Davis GC: Determinants of sexual behavior in middle and old age. J Am Geriatr Soc 20: 151, 1972

35

Appelt H, Strauss B: Effects of antiandrogen treatment on the sexuality of women with hyperandrogenism. Psychother Psychosom 42: 177, 1984

36

Applegate WB: Sexuality and the elderly. In Calkins E, Davis PJ, Ford AB (eds): The Practice of Geriatrics, p 281. Philadelphia: WB Saunders, 1986

37

Traupmann J, Eckels E, Hatfield E: Intimacy in older women's lives. Gerontologist 22: 493, 1982

38

Newman G, Nichols CR: Sexual activities and attitudes in older persons. In Palmore E (ed): Normal Aging, p 277. Durham, NC: Duke University Press, 1970

39

Diokno AC, Brown MB, Herzog AR: Sexual function in the elderly. Arch Intern Med 150: 197, 1990

40

The standardisation of terminology of lower urinary tract function: International Continence Society Committee on Standardization of Terminology. Scand J Urol Nephrol Suppl 114:5, 1988

41

Ouslander JG: Aging and the lower urinary tract. Am J Med Sci 314: 214, 1997

42

Boscia JA, Kobasa WD, Knight KA et al: Therapy vs no therapy for bacteria in elderly ambulatory nonhospitalized women. JAMA 257: 1067, 1987

43

Raz R, Stamm WE: A controlled trial of intravaginal estriol in postmenopausal women with recurrent urinary tract infection. N Engl J Med 329: 753, 1993

44

Barnett BJ, Stephens DS: Urinary tract infection: an overview. Am J Med Sci 314: 245, 1997

45

Burgio KL, Goode PS: Behavioral intervention for incontinence in ambulatory geriatric patients. Am J Med Sci 314: 257, 1997

46

Karram MM, Bhatia NN: Importance of a neurologic evaluation in women with lower urinary tract dysfunction. J Reprod Med 35: 799, 1990

47

Resnick NM, Yalla SV, Laurino E: The pathophysiology of urinary incontinence among institutionalized elderly person. N Engl J Med 320: 1, 1989

48

Bump RC, Fantl JA, Hurt WG: The mechanism of urinary incontinence in women with severe uterovaginal prolapse: Results of barrier studies. Obstet Gynecol 72: 291, 1988

49

Richardson DA, Bent AE, Ostergard DR: The effect of uterovaginal prolapse on urethrovesical pressure dynamics. Am J Obstet Gynecol 146: 901, 1983

50

Ouslander JG, Schnelle JF: Incontinence in the nursing home. Ann Intern Med 122: 438, 1995

51

Mortality in Vital Statistics of the United States, 1976, part A, vol 2. Washington, DC: National Center for Health Statistics, 1976

52

Celentano DD, Shapiro S, Weisman CS: Cancer prevention screening behavior among elderly women. Prev Med 11: 454, 1982

53

Katsube Y, Beng JW, Silverberg SG: Epidemiologic pathology of ovarian tumors age >60 years old. Int J Gynecol Pathol 1: 3, 1982

54

Creasman WT, Soper JT: The undiagnosed adnexal mass after the menopause. Clin Obstet Gynecol 29: 446, 1986

55

Rulin MC, Preston AL: Adnexal masses in postmenopausal women. Obstet Gynecol 70: 578, 1987

56

Miller RC, Nash JD, Weiser EB, Hoskins WJ: The postmenopausal palpable ovary syndrome: A retrospective review with histopathologic correlates. J Reprod Med 36: 568, 1991

57

Parker WH, Berek JS: Management of selected cystic adnexal masses in postmenopausal women by operative laparoscopy: A pilot study. Am J Obstet Gynecol 163: 1574, 1990

58

Goldstein SR, Subramanyam B, Snyder JR et al: The postmenopausal cystic adnexal mass: The potential role of ultrasound in conservative management. Obstet Gynecol 73: 8, 1989

59

Steinberg KK, Thacker SB, Smith SJ et al: A meta-analysis of the effect of estrogen replacement therapy on the risk of breast cancer. JAMA 265: 1985, 1991

60

Recker RR, Davies KM, Doud R et al: The effect of low-dose continued estrogen and progesterone therapy with calcium and vitamin D in elderly women. Ann Intern Med 130: 897, 1999

61

Cauley JA, Cummings SR, Black DM: Prevalence and determinants of estrogen replacement therapy in elderly women. Am J Obstet Gynecol 163: 1438, 1990

62

Tideiksaar R: Preventing falls: How to identify risk factors, reduce complications. Geriatrics 51: 43, 1996

63

Greenspan SL, Myers ER, Maitland LA: Fall severity and bone mineral density as risk factors for hip fracture in ambulatory elderly. JAMA 271: 128, 1994

64

Anderson RN, Kochanek KD, Murphy SL: Report of final mortality statistics, 1995. Monthly Vital Statistics Report, vol 45, no 11, suppl 3, table 7, pp 23–33. Hyattsville, MD: National Center for Health Statistics, 1997

65

Advance report of final mortality statistics, 1989: Monthly Vital Statistics Report, vol 40, suppl 2, pp 1–47. Hyattsville, MD: National Center for Health Statistics, 1992

66

Manson JE, Tosteson H, Ridker PM et al: The primary prevention of myocardial infarction. N Engl J Med 326: 1406, 1992

67

Cummings SR. Black DM, Rubin SM: Lifetime risks of hip, Colles' or vertebral fracture and coronary heart disease among white postmenopausal women. Arch Intern Med 149: 2445, 1989

68

Beard CM, Kottke TE, Annegers JF, Ballard DJ: The Rochester Coronary Heart Disease Project: Effect of cigarette smoking, hypertension, diabetes and steroidal estrogen use on coronary heart disease among 40- to 59-year-old women, 1960 through 1982. Mayo Clin Proc 64: 1471, 1989

69

Stampfer MJ, Colditz GA: Estrogen replacement therapy and coronary heart disease: a quantitative assessment of the epidemiologic evidence. Prev Med 20: 47, 1991

70

Potocki J: Wplyw leczenia estrogenami na niewydolnose wiencowa u kobiet po menopauzie. Pol Tyg Lek 26: 1812, 1971

71

Burch JC, Byrd BF Jr, Vaughn WK: The effects of long-term estrogen on hysterectomized women. Am J Obstet Gynecol 188: 788, 1974

72

Talbott E, Kuller LH, Detre K, Perper J: Biologic and psychosocial risk factors of sudden death from coronary disease in white women. Am J Cardiol 39: 858, 1977

73

Jick H, Dinan B, Herman R, Rothman KJ: Myocardial infarction and other vascular diseases in young women: Role of estrogens and other factors. JAMA 240: 2548, 1978

74

Pfeffer RI, Whipple GH, Kurosaki TT, Chapman JM: Coronary risk and estrogen use in postmenopausal women. Am J Epidemiol 107: 479, 1978

75

MacMahon B: Cardiovascular disease and noncontraceptive estrogen therapy. In Oliver MF (ed): Coronary Heart Disease in Young Women, p 197. New York, Churchill Livingstone, 1979

76

Hammond CB, Jelovsek FR, Lee LK et al: Effects of long-term estrogen replacement therapy. I. Metabolic effects. Am J Obstet Gynecol 133: 535, 1979

77

Nachtigall LE, Nachtigall RH, Nachtigall RD, Beckman EM: Estrogen replacement therapy II: A prospective study in the relationship to carcinoma and cardiovascular and metabolic problems. Obstet Gynecol 54: 74, 1979

78

Adam S, Williams V, Vessey MP: Cardiovascular disease and hormone replacement treatment: A pilot case-control study. BMJ 282: 1277, 1981

79

Bain C, Willett WC, Hennekens CH et al: Use of postmenopausal hormones and risk of myocardial infarction. Circulation 64: 42, 1981

80

Ross RK, Paganini-Hill A, Mack TM et al: Menopausal estrogen therapy and protection from death from ischaemic heart disease. Lancet 1: 858, 1981

81

Szklo M, Tonascia J, Gordia L et al: Estrogen use and myocardial infarction risk: A case-control study. Prev Med 13: 510, 1984

82

Lafferty FW, Helmuth DO: Postmenopausal estrogen replacement: The prevention of osteoporosis and systemic effects. Maturitas 7: 147, 1985

83

Bush TL, Barrett-Connor E, Cowan LD et al: Cardiovascular mortality and noncontraceptive use of estrogen in women: Results from the Lipid Research Clinics Program Follow-up Study. Circulation 75: 1102, 1987

84

Hunt K, Vessey M, McPherson K et al: Long-term surveillance of mortality and cancer incidence in women receiving hormone replacement therapy. Br J Obstet Gynecol 94: 620, 1987

85

Petitti DB, Perlman JA, Sidney S: Noncontraceptive estrogens and mortality: Long-term follow-up of women in the Walnut Creek Study. Obstet Gynecol 70: 289, 1987

86

Criqui MH, Suarez L, Barrett-Connor E et al: Postmenopausal estrogen use and mortality. Am J Epidemiol 128: 606, 1988

87

Gruchow HW, Anderson AJ, Barboriak JJ et al: Postmenopausal use of estrogen and occlusion of coronary arteries. Am Heart J 115: 954, 1988

88

MacFarland KF, Boniface ME, Hornung CA et al: Risk factors and noncontraceptive estrogen use in women with and without coronary disease. Am Heart J 117: 1209, 1989

89

Croft P, Hannaford PC: Risk factors for acute myocardial infarction in women: Evidence from the Royal College of General Practitioners' oral contraceptive study. BMJ 198: 165, 1989

90

Avila MH, Walker AM, Jick H: Use of replacement estrogens and the risk of myocardial infarction. Epidemiology 1: 128, 1990

91

Sullivan JM, Zwang RV, Hughes JP et al: Estrogen replacement and coronary artery disease: Effect on survival in postmenopausal women. Arch Intern Med 10: 2557, 1990

92

Henderson BE, Panagnin-Hill A, Ross RK: Decreased mortality in users of estrogen replacement therapy. Arch Intern Med 151: 75, 1991

93

Stampfer MJ, Colditz GA, Willett WC: Postmenopausal estrogen therapy and cardiovascular disease: Ten year follow-up from the Nurses' Health Study. N Engl J Med 325: 756, 1991

94

Wolf PH, Madans JH, Finucane FF et al: Reduction of cardiovascular disease-related mortality among postmenopausal women who use hormones: evidence from a national cohort. Am J Obstet Gynecol 164: 489, 1991

95

Falkeborn M, Persson I, Adami HO: The risk of acute myocardial infarction after oestrogen and oestrogenprogestogen therapy. Br J Obstet Gynecol 99: 821, 1992

96

Rosenberg L, Armstrong B, Jick H: Myocardial infarction and estrogen therapy in postmenopausal women. N Engl J Med 294: 1256, 1976

97

Thompson SG, Meade TW, Greenberg G: The use of hormonal replacement therapy and the risk of stroke and myocardial infarction in women. J Epidemiol Commun Health 43: 173, 1989

98

Jick H, Dinan B, Rothman KJ: Noncontraceptive estrogens and nonfatal myocardial infarction. JAMA 239: 1407, 1978

99

Rosenberg L, Stone D, Shapiro S et al: Noncontraceptive estrogens and myocardial infarction in young women. JAMA 244: 339, 1980

100

Wilson PW, Garrison RJ, Castelli WP: Postmenopausal estrogen use, cigarette smoking, and cardiovascular morbidity in women over 50: The Framingham Study. N Engl J Med 313: 1038, 1985

101

LaVecchia C, Franceschi S, Decarli A et al: Risk factors for myocardial infarction in young women. Am J Epidemiol 125: 832, 1987

102

Barrett-Connor E: Postmenopausal estrogen and prevention bias. Ann Intern Med 115: 455, 1991

103

Hong MK, Romm PA, Reagan K et al: Effects of estrogen replacement therapy on serum lipid values and angiographically defined coronary artery disease in postmenopausal women. Am J Cardiol 69: 176, 1992

104

Hulley S, Grady D, Bush T et al: Randomized trial of estrogen plus progestin for secondary prevention of coronary artery disease in postmenopausal women. JAMA 28: 605, 1998