Menopause

Hot flushes (hot flashes) and/or night sweats due to vasomotor instability affect 75 to 85% of women and usually begin before menses stop. Vasomotor symptoms last an average of 7.4 years and can persist for > 10 years in some groups of women (1 Symptoms and signs reference Menopause is physiologic or iatrogenic cessation of menses (amenorrhea) due to decreased ovarian function. Manifestations may include hot flushes, night sweats, sleep disruption, and genitourinary... read more ).

Women feel warm or hot and may perspire, sometimes profusely; core temperature increases. The skin, especially of the face, head, and neck, may become red and warm. The episodic flush, which may last from 30 seconds to 5 minutes, may be followed by chills. Flushes may manifest during the night as night sweats.

The mechanism of hot flushes is unknown, but they are thought to result from changes in the thermoregulatory center located in the hypothalamus. The range of core body temperatures that is comfortable to the woman decreases; as a result, a very small increase in core body temperature can trigger heat release as a hot flush.

Vaginal symptoms include dryness, dyspareunia, and occasionally irritation and itching. As estrogen production decreases, vulvar and vaginal mucosae become thinner, drier, more friable, and less elastic, and vaginal rugae are lost.

Genitourinary syndrome of menopause includes symptoms and signs due to estrogen and androgen deficiency such as

Neuropsychiatric changes (eg, poor concentration, memory loss, depressive symptoms, anxiety) may transiently accompany menopause. Many women experience these symptoms during perimenopause and assume that menopause is the cause. However, evidence supporting a connection between menopause and these symptoms is mixed. Also, these symptoms are not directly related to the decreases in estrogen levels that occur with menopause.

Recurrent night sweats can contribute to insomnia, fatigue, irritability, and poor concentration by disrupting sleep. However, during menopause, sleep disturbances are common even among women who do not have hot flushes.

After menopause, levels of low-density lipoprotein (LDL) cholesterol increase in women. Levels of high-density lipoprotein (HDL) cholesterol remain about the same as before menopause. The change in LDL levels may partly explain why atherosclerosis and thus coronary artery disease become more common among women after menopause. However, whether these changes result from aging or from the decrease in estrogen levels after menopause is unclear. Until menopause, the high estrogen levels may protect against coronary artery disease.

Up to 20% of bone density loss occurs during the first 5 years after menopause. After this period of rapid bone loss, the age-related rate of bone loss in women is similar to that in men.

Menopause is a normal, healthy phase in a woman's life, but each woman has a unique experience.

Quality of life may decrease if symptoms are severe or if less common symptoms of menopause, such as joint aches and pains, develop. For some women (eg, those with a history of endometriosis, dysmenorrhea, menorrhagia, premenstrual syndrome, or menstrual migraine), quality of life improves after menopause.

For hot flushes, the following may help:

Devices that cool skin receptors may help some women; they can be worn as wristbands or necklaces or placed on the back of the neck.

Over-the-counter vaginal lubricants and moisturizers help relieve vaginal dryness. Regular sexual intercourse or other vaginal stimulation helps preserve vaginal function.

A wide variety of complementary and alternative therapies have been used (4) to relieve symptoms. Black cohosh, other herbal preparations, and over-the-counter products do not appear helpful. Also, some herbal preparations interact with other drugs. Soy protein, which can have estrogenic effects, has been studied with mixed results; however, one soy product, S-equol, has been reported to relieve hot flushes.

Use of regular exercise, paced respirations (a type of slow, deep breathing), mindfulness, or relaxation techniques to reduce hot flushes have had mixed results, although exercise, yoga, and relaxation techniques may improve sleep and reduce stress. Acupuncture has also had mixed results.

Because not all complementary and alternative medicine therapies are efficacious and safe, clinicians should discuss the risks and benefits of these therapies to make sure that women are well-informed (4 Treatment references Menopause is physiologic or iatrogenic cessation of menses (amenorrhea) due to decreased ovarian function. Manifestations may include hot flushes, night sweats, sleep disruption, and genitourinary... read more ).

In well-designed, randomized, controlled trials, selective serotonin reuptake inhibitors (SSRIs), serotonin-norepinephrine reuptake inhibitors (SNRIs), and gabapentin have been shown to be moderately effective in reducing hot flushes. A low dose (7.5 mg once a day) of paroxetine (an SSRI) is the only approved nonhormone therapy used specifically for hot flushes. However, all of these drugs are less effective than hormone therapy.

Other therapies that may be useful include the anticholinergic drug oxybutynin, stellate ganglion blockade, and neurokinin B antagonists (5 Treatment references Menopause is physiologic or iatrogenic cessation of menses (amenorrhea) due to decreased ovarian function. Manifestations may include hot flushes, night sweats, sleep disruption, and genitourinary... read more , 6 Treatment references Menopause is physiologic or iatrogenic cessation of menses (amenorrhea) due to decreased ovarian function. Manifestations may include hot flushes, night sweats, sleep disruption, and genitourinary... read more ). Kisspeptin and neurokinin B (NKB) antagonists are nonhormone treatments that appear to reduce vasomotor symptoms and thus reduce the need for estrogen therapies (7 Treatment references Menopause is physiologic or iatrogenic cessation of menses (amenorrhea) due to decreased ovarian function. Manifestations may include hot flushes, night sweats, sleep disruption, and genitourinary... read more ).

For women who have had a hysterectomy, estrogen is used alone. Oral, transdermal (patch, lotion, spray, or gel), or vaginal forms may be used. Treatment should start with the lowest dose; the dose is increased every 2 to 4 weeks as needed. Doses vary by preparation. Low doses include

Women who have a uterus should be given a progestogen in addition to estrogen because unopposed estrogen increases risk of endometrial cancer. The progestogen is taken with estrogen continuously (ie, daily) or sequentially (12 to 14 consecutive days of every 4 week). The dose is

Bleeding due to progestogen withdrawal is less likely with continuous therapy, although irregular bleeding can occur during the first 6 months of therapy.

Combination products of estrogen and a progestogen are available as

Combination conjugated estrogen/bazedoxifene (a selective estrogen receptor modulator [ SERM Selective estrogen receptor modulators (SERMS) Menopause is physiologic or iatrogenic cessation of menses (amenorrhea) due to decreased ovarian function. Manifestations may include hot flushes, night sweats, sleep disruption, and genitourinary... read more ]) is an alternative. Bazedoxifene protects the uterus; thus, a progestogen is not needed. Benefits of conjugated estrogen/bazedoxifene include a lower incidence of breast tenderness and bleeding than with other forms of hormone therapy; incidence is similar to that with placebo. Breast density and incidence of breast cancer did not increase in women who were followed for 2 years (2 Hormone therapy references Menopause is physiologic or iatrogenic cessation of menses (amenorrhea) due to decreased ovarian function. Manifestations may include hot flushes, night sweats, sleep disruption, and genitourinary... read more ). Conjugated estrogen/bazedoxifene can relieve hot flushes, improve sleep, prevent bone loss, and lessen symptoms of vaginal atrophy. Risk of venous thromboembolism is similar to that with estrogen, but conjugated estrogen/bazedoxifene appears to protect the endometrium and potentially the breast. Bazedoxifene as a single drug is not available in the US.

When the only symptoms are vaginal, low-dose vaginal estrogen therapy is preferred. Topical forms (eg, creams; vaginal tablets, suppositories, or rings) may be more effective for vaginal symptoms than oral forms. Vaginal tablets, suppositories, or rings that contain estradiol in low doses (eg, 10 mcg for tablets, 7.5 mcg for rings, 4 mcg and 10 mcg for vaginal suppositories) deliver less estrogen to the systemic circulation. When vaginal estrogen is used at the lowest recommended doses, a progestogen is not needed. Higher doses of vaginal estrogen can deliver as much estrogen as oral or transdermal therapy and, if given to women who still have a uterus, require the addition of a progestogen. Any vaginal bleeding in women taking hormone therapy should be immediately evaluated to rule out endometrial cancer.

If symptoms are mild, nonhormone over-the-counter treatments (eg, vaginal lubricants, moisturizers) may be sufficient (3 Hormone therapy references Menopause is physiologic or iatrogenic cessation of menses (amenorrhea) due to decreased ovarian function. Manifestations may include hot flushes, night sweats, sleep disruption, and genitourinary... read more ). For women at high risk of breast cancer,small amounts of topical estradiol may be used after consultation with their oncologist (4 Hormone therapy references Menopause is physiologic or iatrogenic cessation of menses (amenorrhea) due to decreased ovarian function. Manifestations may include hot flushes, night sweats, sleep disruption, and genitourinary... read more ).

For moderate to severe symptoms, treatments include

When low-dose vaginal estrogen or DHEA or ospemifene is used, a progestogen is not needed; however, there are no long-term endometrial safety data for these drugs (3 Hormone therapy references Menopause is physiologic or iatrogenic cessation of menses (amenorrhea) due to decreased ovarian function. Manifestations may include hot flushes, night sweats, sleep disruption, and genitourinary... read more ).

DHEA Dehydroepiandrosterone (DHEA) Dehydroepiandrosterone (DHEA) is a steroid produced by the adrenal gland and is a precursor of estrogens and androgens. Effects on the body are similar to those of testosterone. DHEA can also... read more may relieve vaginal dryness and other symptoms of vaginal atrophy; it is available and effective for relief of dyspareunia due to menopause and is under study as treatment for sexual dysfunction in women Overview of Female Sexual Function and Dysfunction Men and women initiate or agree to sexual activity for many reasons, including sharing sexual excitement and physical pleasure and experiencing affection, love, romance, or intimacy. However... read more (5 Hormone therapy references Menopause is physiologic or iatrogenic cessation of menses (amenorrhea) due to decreased ovarian function. Manifestations may include hot flushes, night sweats, sleep disruption, and genitourinary... read more ).

Progestogens (eg, medroxyprogesterone acetate 10 mg orally once a day or depot 150 mg IM once a month, megestrol acetate 10 to 20 mg orally once a day, progesterone 300 mg nightly) are sometimes used alone to relieve hot flushes when estrogen is contraindicated, but they are not as effective as estrogen for hot flushes and do not relieve vaginal dryness. Micronized progesterone can be taken in doses of 100 to 300 mg at bedtime. Drowsiness may occur. Micronized progesterone in peanut oil is contraindicated in women who are allergic to peanuts. Newer combination products do not contain peanut oil.

Estrogen therapy has beneficial effects on bone density and reduces the incidence of fractures in postmenopausal women (not particularly those with osteoporosis). In one large study, hormone therapy reduced the incidence of fractures by 24% (6 Hormone therapy references Menopause is physiologic or iatrogenic cessation of menses (amenorrhea) due to decreased ovarian function. Manifestations may include hot flushes, night sweats, sleep disruption, and genitourinary... read more ). Nonetheless, estrogen therapy (with or without a progestogen) is usually not recommended as first-line treatment or as prophylaxis for osteoporosis. When osteoporosis or prevention of osteoporosis is the only concern, clinicians should consider starting hormone therapy if the following apply:

Risks with estrogen therapy or combined estrogen/progestogen therapy include

The risk of endometrial cancer is higher in women who have a uterus and are given unopposed estrogen therapy. Nevertheless, any vaginal bleeding in a woman on hormone therapy should immediately be evaluated to rule out endometrial cancer.

The risk of breast cancer begins to increase after 3 to 5 years of combination therapy when the standard dose (eg, conjugated estrogen 0.625 mg and medroxyprogesterone acetate at 2.5 mg once/day) is used. When estrogen is used alone, risk of breast cancer was slightly lower at 7 years in the Women's Health Initiative study, but this benefit appears to disappear after 10 to 15 years of use. The risk of venous thromboembolism and stroke may be lower when low-dose transdermal estrogen is used. Older postmenopausal women (> 10 years past menopause or > 60 years old when they start hormone therapy) are at higher risk of coronary artery disease and dementia when they are given combination therapy. Incidence of gallbladder disease and urinary incontinence may be increased with combination therapy or estrogen alone. Risk of all these disorders is very low in healthy women who take hormone therapy for a short time after menopause.

Estrogen therapy may be contraindicated in women who have had or are at high risk of breast cancer, stroke, coronary artery disease, or thrombosis.

Progestogens may have adverse effects (eg, abdominal bloating, breast tenderness, increased breast density, headache, increased LDL); micronized progesterone appears to have fewer adverse effects. Progestogens may increase the risk of thrombosis. There are no long-term safety data for progestogens.

Before prescribing hormone therapy and periodically as therapy continues, clinicians should discuss its risks and benefits with women.

The SERMs tamoxifen and raloxifene have been used primarily for their antiestrogenic properties and not to relieve menopausal symptoms. However, ospemifene, a SERM, can be used to treat dyspareunia due to vaginal atrophy if women cannot use estrogen or a vaginal drug (eg, if they have severe arthritis) or if they prefer to use an oral drug other than estrogen; dose is 60 mg orally once a day (7 Hormone therapy references Menopause is physiologic or iatrogenic cessation of menses (amenorrhea) due to decreased ovarian function. Manifestations may include hot flushes, night sweats, sleep disruption, and genitourinary... read more ). In women who have recently been taking hormone therapy, hot flushes may temporarily increase, but in most women, hot flushes resolve after about 6 weeks.

Bazedoxifene Choice of hormone therapy is given with conjugated estrogens; it can relieve hot flushes, improve sleep, prevent bone loss, and lessen symptoms of vaginal atrophy.