Approach to the Menopausal Woman

Shana L. Birnbaum

Annekathryn Goodman

Despite its inevitability, menopause can be difficult in a society that celebrates youthfulness, causing many to view this normal life cycle stage in almost illness-like terms as something that must be treated. The understandable desire for treatment to avoid the potentially disruptive emotional and physical changes that may accompany menopause is exacerbated by the view that it is good to stay “forever young.” The strong demand for treatment has been tempered somewhat in recent years by accumulating data on the risks as well as the benefits of pharmacologic measures and other remedies. The primary care clinician can do a great deal to help the woman entering menopause cope and make informed choices regarding options for symptom relief and disease prevention.

PHYSIOLOGY, CLINICAL PRESENTATION, AND COURSE (1, 2, 3, 4, 5, 6, 7, 8, 9 and 10)

The essential cause of menopause is decreased estrogen due to decreased responsiveness to follicular stimulating hormone (FSH) in aging ovaries. This results in the cessation of menses and an increase in gonadotropins. Some estrogen production continues, but its source is primarily the peripheral conversion of androstenedione. There is an accompanying marked increase in gonadotropins; maximum levels of FSH and luteinizing hormone (LH) occur within 1 to 2 years of onset and remain high for 10 to 15 years.

Based on the generally accepted definition of menopause as a full year without menstrual flow in a previously menstruating woman, the incidence of menopause is 10% by age 38 years, 20% by age 43 years, 50% by age 48 years, 90% by age 54 years, and 100% by age 58 years. The mean age of menopause is 51 years. About 1% of women experience menopause before age 40 years. In addition, the prevalence of surgically induced menopause is estimated to be 25% to 30% of women in their mid-50s. Mothers and daughters seem to experience menopause at the same age. Early menopause is seen in smokers, vegetarians, and women who are thinner or malnourished.

The physiologic events are similar in surgically induced menopause, but the time course is shorter, with FSH and LH increasing to high levels within 20 to 30 days. Approximately 25% of women do not experience any symptoms (10% of those undergoing surgical menopause), perhaps because of nonovarian sources of estrogen production or differences in the time frame of hormone shifts.

The earliest symptom of menopause is a decrease in cycle length, which may be interspersed with long anovulatory cycles. The perimenopause, with irregular cycles and menopausal symptoms, may go on for years before menses cease completely. Some women experience few if any changes other than a cessation in menses, but most note some symptoms, the most bothersome being hot flashes, vaginal atrophy, and disturbed sleep. Risks of atherosclerotic disease and osteoporosis are among other important concerns.

Hot Flashes

Hot flashes, which are associated with estrogen withdrawal and resultant vasomotor instability, are among the most specific and disruptive of menopausal symptoms and generally begin during perimenopause. As many as 75% to 80% of women experience hot flashes during the transition into menopause. The precise mechanism is complex and incompletely understood, but it involves a generalized activation of the hypothalamic thermoregulatory center in response to the significant decline in circulating estrogen levels. This leads to transient increases in sympathetic activity producing what is commonly referred to as a “hot flash,” which is manifested by both flushing (from small-vessel vasodilation in the skin) and sweating. An intense warm sensation radiates upward from the chest to the neck and face, lasting 2 to 6 minutes before subsiding. The skin is visibly flushed, and skin temperature rises due to vasodilation, with a resultant decrease in core temperature. A reflex tachycardia may ensue and produce noticeable palpitations.

Eating, exertion, emotional upset, and alcohol are known precipitants. As many as 20 episodes per day may occur; in most patients, the condition lasts for 2 to 3 years, but it may continue for 6 years or more. Hot flashes are usually most problematic at night, when they cause arousal and sleep disruption, which may lead to considerable morbidity, including chronic fatigue, depression and irritability, and, potentially, memory and cognition problems.

Atrophy of the Urogenital Epithelium

Atrophy of the urogenital epithelium is due to a decrease in skin collagen and causes sexual dysfunction and urinary complaints. The vagina becomes smaller and less compliant; lubrication decreases. Women may present with complaints of itching, irritation, discharge, bleeding, or painful intercourse. Sexually active women often complain of vaginal dryness with intercourse, but they show less vaginal atrophy; regular intercourse and arousal appears to maintain vaginal blood flow and compliance. Lack of estrogen also affects urinary sphincter tone, with a resultant increase in urinary incontinence; urinary tract infections and urinary frequency are also more common.

Sleep Disturbances

Sleep disturbances occur in many menopausal women and can be of considerable consequence. Most are associated with nocturnal hot flashes, but abnormalities in the sleep pattern, including a decrease in rapid eye movement sleep, have been documented independent of hot flashes.

Cardiovascular Disease

Cardiovascular disease is the leading cause of mortality among postmenopausal women but is seen at fairly low rates among premenopausal women. Loss of estrogen is associated with an unfavorable change in lipoprotein profile, with a decrease in high-density lipoprotein cholesterol and an increase in lowdensity lipoprotein cholesterol, providing a plausible biologic mechanism for the theory that hormone replacement therapy might reduce cardiovascular risk (see later discussion).

Osteoporosis

Osteoporosis, an important consequence of estrogen decline, occurs when the micro architecture of bone tissue deteriorates. The rapid decrease in bone density occurs after menopause. Decreased activity, inadequate nutrition, and the aging process may also contribute. Risk factors for postmenopausal osteoporotic fractures include thin body build, premature surgical menopause, cigarette smoking, and heavy alcohol use. Prolonged bed rest is a potent stimulus of osteoporosis. Longacting benzodiazepines, anticonvulsants, caffeine, and impaired visual function are other risk factors for hip fracture.

Other Problems Attributed to Menopause

Other symptoms, such as headache, nervousness, and depression, which frequently occur during the climacteric, are more a reflection of the emotional stress that may be associated with this stage of life than a result of a change in hormonal milieu. Some women report feeling better emotionally on estrogen therapy, but large randomized trials have not shown a benefit in terms of quality of life. Younger, symptomatic women did report an improvement in vasomotor symptoms and sleep quality with no other quality-of-life improvements in the WHI trial, but there was a small improvement in depressive symptoms in the Heart and Estrogen/Progestin Replacement Study (HERS trial). Women who experience a prolonged symptomatic perimenopausal phase may exhibit some depressive symptoms, but depression is not a consequence of the menopause itself.

Cosmetic changes associated with aging have been attributed by some to a decrease in estrogens, but clinical evidence is to the contrary. Breast atrophy, loss of skin turgor, and redistribution of fat to the abdomen and thighs have not been shown to be influenced by estrogen therapy and most likely are part of the more general process of aging.

Concerns about an increased risk of cognitive impairment and Alzheimer disease derived from observations that Alzheimer disease is three times more common in women than in men and early reports of a beneficial effect of estrogen replacement on short-term memory. WHI memory study reported a slight increase risk of cognitive decline and dementia in women aged 65 years and older who took estrogen.

DIAGNOSIS (11)

The definitional criterion is a full year without menstrual flow in a previously menstruating woman. The diagnosis is confirmed by documenting a marked increase in levels of the gonadotropins FSH and LH; levels peak within 1 to 2 years of onset and remain high for 10 to 15 years. When the onset of hot flashes precedes full cessation of periods, other causes of flashing and flushing need to be considered, especially when the presentation is atypical (see Appendix 166.1).

PRINCIPLES OF MANAGEMENT (4,6,7,9,12, 13, 14, 15, 16, 17, 18, 19, 20, 21, 22, 23, 24, 25, 26, 27, 28, 29, 30, 31, 32, 33, 34, 35, 36, 37, 38, 39, 40, 41, 42, 43, 44, 45, 46, 47, 48, 49, 50, 51, 52 and 53)

Short-term objectives are to alleviate problematic symptoms that result from estrogen deficiency and to provide support for any emotional and functional problems that may accompany this phase of life. Estrogen therapy remains the standard for the relief of vasomotor symptoms and urogenital atrophy and is accepted for short-term therapy at the lowest possible dose adequate for symptom relief. Nonhormonal approaches also exist and provide women with a choice of options for dealing with menopausal symptoms, as well as with long-term disease prevention. Given an unfavorable risk-benefit ratio, hormone therapy is no longer recommended for prevention of chronic disease, being found ineffective in preventing cardiovascular disease, at least for older women and those with established disease, and safer alternatives exist for osteoporosis prevention and treatment.

Hormone Therapy (HT)

Overview

Previously on the basis of observational data, HT was believed to confer significant chronic-disease-prevention benefits, particularly for prophylaxis of cardiovascular disease and osteoporosis. This led to a transiently marked increase in use. Subsequent outcomes from landmark randomized trials (Heart and Estrogen/Progestin Replacement Study [HERS] and the Women’s Health Initiative [WHI]) contradicted findings from the earlier observational studies and suggested potential harms of HT, including an increased risk of cardiovascular disease and stroke, as well as of breast cancer. This led many women and their physicians to reconsider use, since the risks now appeared to outweigh benefits for many women. Over a decade has passed since the resulting publicity of both WHI and HERS, and long-term follow-up data have become available, helping to better clarify risks and benefits and inform decisions regarding HT use.

Many women are reluctant to use any form of hormones, given the associated negative publicity in recent years. Because symptoms such as hot flashes and vaginal dryness can be sufficiently problematic to impair quality of life, and are most effectively treated with estrogen therapy, the clinician and patient are faced with the difficult decision of when and if to use HT. This necessitates careful consideration of benefits and risks. For the majority of women, the risks will outweigh the benefits for long-term therapy but may support short-term therapy for symptom relief.

Benefits of Hormone Therapy

Potential benefits include symptom relief, reduced risk of osteoporosis and related fractures, and reduced risk of colorectal cancer.

For Hot Flashes.

Hot flashes severe enough to be a serious bother to the patient are an important indication for estrogen replacement. Although in most instances the symptoms are self-limited, relief during the few years that symptoms are most severe can mean a great deal. HT is effective in relieving hot flashes in greater than 80% of women, although there is a placebo benefit of almost 30% in many trials. Sleep often improves due to a decrease in hot flashes or potentially another mechanism, although the WHI results indicate that improvement in sleep disturbance may be too small to be clinically meaningful.

For Atrophic Vaginitis.

Atrophic vaginitis responds well to both the topical and oral administration of estrogen. Vaginal estrogen creams used at low doses (0.3 mg of conjugated estrogens daily) and the estradiol-secreting vaginal ring (Estring) do not substantially increase serum estrogen levels and do not require the use of concurrent progestin in women with a uterus. Milder symptoms (e.g., mild dryness with intercourse) may respond well to use of a water-soluble vaginal lubricant such as Replens or Astroglide, obviating the need for estrogen in the woman
who wants to avoid its use. Urinary incontence worsens with systemic HT.

For Osteoporosis (see also Chapter 164).

Osteoporosis can be prevented by long-term prophylactic estrogen therapy. Controlled studies have shown that rates of vertebral, wrist, and hip fractures can be significantly reduced by estrogen replacement and that this protective effect is not impaired by the addition of progestin. The risk of hip fracture is reduced by 25% in women who have used estrogen in the past and to an even greater extent among current and recent users. In the WHI, estrogen plus progestin decreased the risk of hip fractures by one third and the risk of total fractures by 24%, whereas estrogen alone decreased the fracture rate by 30% to 39%. The combination of estrogen therapy in conjunction with exercise and dietary calcium and vitamin D₃ supplementation is an option for the prevention of postmenopausal osteoporosis.

In light of accumulating trial evidence cited earlier revealing serious risks associated with long-term hormone replacement therapy, many women and their clinicians consider the risks too great to warrant use for prevention or treatment of osteoporosis, especially in view of effective nonhormonal therapies. Menopausal women should be strongly encouraged to engage in efforts that slow reduction in bone density, including regular weight-bearing exercise and maintaining adequate calcium and vitamin D intake. Women at heightened risk for osteoporosis or with known low bone density should consider additional approaches to osteoporosis prevention, such as bisphosphonates or raloxifene (see Chapter 164).

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