Menopause

Permanent cessation of menses due to loss of ovarian function.

In the USA, the average age at which menopause occurs is 51. Thus, on average, women are postmenopausal one third of their life. Despite an increase in the average life expectancy for women in the USA, the average age at menopause is probably unchanged. Prolonged hypothalamic amenorrhea, number of pregnancies, and oral contraceptive use do not influence the age of onset.

With age, ovarian follicles decrease in number, become less responsive to stimulation by gonadotropic hormones, and consequently produce progressively less estrogen. Typically, ovarian function waxes and wanes over several years. This transitional phase is termed perimenopause or the climacteric. Eventually, no estrogen is produced, resulting in menopause.

Symptoms and Signs

Early symptoms and signs of menopause include irregular menstrual cycles, hot flashes, changes in mood and cognition, insomnia, headache, and fatigue. Palpitations, tachycardia, and vertigo may occur. Later manifestations include dry skin, breast changes, genital atrophy with dyspareunia, loss of pelvic muscle tone, urinary incontinence, cystitis, and vaginitis. Osteoporosis and atherosclerosis may develop.

Irregular menstrual cycle: The first manifestation of menopause is often irregular periods. They vary in duration, frequency, and amount of flow but may be regular occasionally. However, unusual bleeding (eg, bleeding that is unusually heavy, that lasts for more than 10 days, or that occurs more frequently than every 3 weeks) should be evaluated to rule out neoplasms.

Hot flashes: Another early manifestation of menopause is hot flashes. About 80% of perimenopausal women report hot flashes. Of these women, 85% are symptomatic for > 1 year, and 25 to 50% are symptomatic for up to 5 years. During perimenopause, hot flashes occur when estrogen levels decrease and cease when estrogen levels increase. They become less frequent and less intense with age, in contrast to other sequelae of menopause (eg, genital atrophy, osteoporosis, atherosclerosis), which progress with age. Hot flashes also occur after surgical menopause or after discontinuation of exogenous estrogen.

Hot flashes are the subjective sensation of intense warmth in the upper body, typically lasting 4 minutes (range, 30 seconds to 5 minutes). A vasomotor flush, the objective counterpart of a hot flash, is a blush that ascends the thorax, neck, and face, followed by profuse sweating. Skin perfusion increases about 1.5 minutes before the sensation and 6 minutes before the peak increase in skin temperature. This increase in skin perfusion causes heat loss with a simultaneous decrease in core body temperature.

A hot flash may follow a prodrome of palpitations or a sensation of pressure in the head and can be accompanied by weakness, faintness, or vertigo.

Insomnia: Perimenopausal women may have difficulty falling asleep, wake often during the night, or wake early. Insomnia is commonly caused by hot flashes but occurs among perimenopausal women whether they have hot flashes or not.

Mood and cognitive changes: Changes in hormone levels during perimenopause may result in moodiness, anxiety, irritability, nervousness, or depression. Perimenopausal symptoms may resemble premenstrual symptoms. Women may become forgetful and less able to concentrate.

Skin changes: The skin may become thinner, less elastic, and drier because collagen production decreases as estrogen levels decrease. The subcutaneous layer of fat also thins. As a result, wrinkles are more likely, and the skin becomes more vulnerable to injury.

Breast changes: Breast tissue requires estrogen for growth. As estrogen levels decrease, the breasts change in size and shape. They become less firm and begin to sag. Fibrous bands may become more prominent.

Genitourinary atrophy: The tissues of the lower vagina, labia, urethra, and bladder trigone are estrogen dependent. As estrogen levels decrease during menopause, the vaginal walls become pale (because of diminished vascularity), thin (usually decreasing to a thickness of only three or four cells), and vulnerable to ulceration and infection. These changes usually occur within several years of the onset of menopause. The epithelial cells contain less glycogen, which, before menopause, was metabolized by lactobacilli to produce an acidic pH, thereby protecting the vagina from bacterial overgrowth. The vagina also loses its rugae, becoming shorter and inelastic. This condition is called atrophic vaginitis. Patients with atrophic vaginitis may report symptoms secondary to vaginal dryness (eg, dyspareunia, vaginismus) or secondary to vaginal ulceration and infection (eg, vaginal discharge, burning, itching, bleeding).

The similar atrophic changes that occur in the urethral epithelium are called atrophic urethritis. Patients with atrophic urethritis may develop dysuria, urgency, frequency, and stress incontinence (partly because thick, well-vascularized urethral mucosa, which is lost during perimenopause, is necessary to provide resistance to urinary flow). Loss of estrogens may also affect the muscles that help maintain continence. Suprapubic pain can occur, even without infection, possibly because the markedly thin urethral mucosa may allow urine to come in close contact with sensory nerves.

Osteoporosis: For about 10 years after menopause, bone loss accelerates by as much as tenfold. Because of this accelerated bone loss, type I (menopausal) osteoporosis (bone density > 2.5 SD below the young adult mean) occurs mainly in women > 60. It is six times more common among women than among men. Osteoporosis leads to fractures.

Atherosclerosis: At menopause, the risk of atherosclerosis increases, although the incidence of atherosclerosis is lower in women than in men at all ages. The increased risk is probably due to decreased estrogen levels, which result in a 6% decrease in high-density lipoprotein (HDL) cholesterol levels and a 5% increase in low-density lipoprotein (LDL) cholesterol levels. Unopposed estrogen replacement therapy significantly reduces the incidence of atherosclerosis in postmenopausal women (and increases the survival rate of those with coronary artery disease), possibly in part because it increases HDL cholesterol levels by 16 to 18% and decreases LDL cholesterol levels by 15 to 19%.

Diagnosis

Menopause can usually be diagnosed clinically. The diagnosis may be confirmed by an elevated level of serum follicle-stimulating hormone. A low level of serum estradiol is not diagnostic, because levels are often low during menses.

A history and physical examination should be sufficient to diagnose hot flashes and exclude other disorders, such as thyrotoxicosis, carcinoid, and pheochromocytoma, that produce similar symptoms.

Atrophic vaginitis may be diagnosed by visual examination of the vaginal tissue, but any atypical lesions should be biopsied. If vaginal discharge is present, cultures for such pathogens as Neisseria gonorrhoeae, Chlamydia sp, Trichomonas sp, and Gardnerella sp (formerly, Haemophilus vaginalis) should be obtained. If Candida sp is found, the patient should be screened for diabetes, because the low glycogen content of unestrogenized vaginal epithelial cells ordinarily does not support this organism's growth. The diagnosis of atrophic vaginitis may be confirmed by a vaginal cell maturation index, using scrapings from the lateral vaginal wall at the level of the cervix. The exfoliated cells are classified by degree of maturation; a small proportion of superficial cells indicates severe atrophic vaginitis.

Urethroscopy, although rarely needed, shows a pale, atrophic urethra. Cystoscopy may detect the local inflammation of trigonitis.

Treatment

Nondrug treatment such as aerobic exercise, relaxation techniques, meditation, massage, and yoga may help control the effects of hot flashes (eg, fatigue, irritability, depression). However, estrogen replacement therapy is the optimal treatment for all symptoms. (see below) Topical (vaginal) estrogen or low-dose oral estrogen replacement therapy may be adequate for managing genital atrophy, but other symptoms of menopause require systemic therapy at standard doses.

An alternative to estrogen replacement therapy is clonidine, a centrally acting -adrenergic agonist-antagonist, which reduces hot flashes in 30 to 40% of menopausal women. The initial dose of 0.1 mg bid may be increased to 0.2 mg bid if no adverse effects occur and hot flashes persist. Clonidine has a high incidence of adverse effects (eg, postural dizziness, blurred vision), but it is better tolerated by hypertensive patients. If estrogens are inappropriate, synthetic mucopolysaccharides or water-soluble lubricants may relieve dyspareunia associated with genital atrophy.