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Menopause is diagnosed by the presence of amenorrhea for six to twelve months, together with the occurrence of symptoms such as hot flashes. If the diagnosis is uncertain, a high serum concentration of follicle-stimulating hormone (FSH) can confirm the diagnosis. 1.Perimenopausal transition1). Perimenopause is defined as the two to eight years preceding menopause and the one year after the last menstrual period. It is characterized by a normal ovulatory cycle interspersed with anovulatory cycles. Menses become irregular, and heavy breakthrough bleeding can occur. Some women complain of hot flashes and vaginal dryness. 2). Chronic anovulation and progesterone deficiency in this transition period may lead to long periods of unopposed estrogen exposure and endometrial hyperplasia. Oligomenorrhea (irregular cycles) for six or more months or an episode of heavy dysfunctional bleeding is an indication for endometrial surveillance. Endometrial biopsy is the standard to rule out endometrial hyperplasia, but screening with vaginal ultrasonography is acceptable. Biopsy can be deferred if endometrial thickness is 4 mm orless. 3). Irregular bleeding and menopausal symptoms during this perimenopausal transition may be treated by estrogen-progestin replacement therapy. However, some women still require contraception. In this case, menopausal symptoms may be effectively treated with a low-dose oral contraceptive if the woman does not smoke and has no other contraindications to oral contraceptive therapy. 4). The oral contraceptive can be continued until the onset of menopause, determined by a high serum FSH concentration after six days off the pill. Estrogen replacement therapy can be started at this point. 5). In women with no symptoms of estrogen deficiency but with dysfunctional uterine bleeding who smoke or have other reasons to avoid an oral contraceptive, monthly withdrawal bleeding can be induced with medroxyprogesterone acetate (5 to 10 mg daily for 10 to 14 days per month).
2. Menopause occurs at a mean age of 51 years in normal women. Menopause occurring after age 55 is defined as late menopause. The age of menopause is reduced by about two years in women who smoke. 3. Short-term effects of estrogen deficiencyA. Hot flashes. The most common symptom of menopause is the hot flash, which occurs in 75 percent of women. Flashes are self-limited, with 50 to 75 percent of women having cessation of hot flashes within five years. B. Hot flashes typically begin as the sudden sensation of heat centered on the face and upper chest, which rapidly becomes generalized. The sensation of heat lasts from two to four minutes, is often associated with profuse perspiration and occasionally palpitations, and is often followed by chills and shivering. Hot flashes usually occur several times per day. 4. Treatment of menopausal symptoms with estrogen1). Data from the WHI and the HERS trials has determined that continuous estrogen-progestin therapy increases the risk of breast cancer, coronary heart disease, stroke, and venous thromboembolism over an average follow-up of 5.2 years. As a result, the primary indication for estrogen therapy is for control of menopausal symptoms, such as hot flashes. 2). Estrogen therapy remains the gold standard for relief of menopausal symptoms, and is a reasonable option for most postmenopausal women, with the exception of those with a history of breast cancer, CHD, a previous venous thromboembolic event or stroke, or those at high risk for these complications. Estrogen therapy should be used for shortest duration possible (eg, 6 months to 5 years). 3). Dose. A low-dose estrogen is recommended when possible (eg, 0.3 mg conjugated estrogens or 0.5 mg estradiol). 4). Adding a progestin. Endometrial hyperplasia and cancer can occur with unopposed estrogen therapy; therefore, a progestin should be added in women who have not had a hysterectomy. Medroxyprogesterone (Provera), 1.5 mg, is usually given every day of the month. Prempro 0.3/1.5 (0.3 mg of conjugated estrogens and 1.5 mg of medroxyprogesterone) or Prempro 0.45/1.5 (0.45 mg of conjugated estrogens and 1.5 mg of medroxyprogesterone), taken daily. 5). Low-dose oral contraceptives. A low-estrogen oral contraceptive (20 µg of ethinyl estradiol) remains an appropriate treatment for perimenopausal women who seek relief of menopausal symptoms. Most of these women are between the ages of 40 and 50 years and are still candidates for oral contraception. For them, an oral contraceptive pill containing 20 µg of ethinyl estradiol provides symptomatic relief while providing better bleeding control than conventional estrogen-progestin therapy because the oral contraceptive contains higher doses of both estrogen and progestin. 6). Treatment of vasomotor instability in women not taking estrogen: Venlafaxine (Effexor), at doses of 75 mg daily, reduces hot flashes by 61
percent. Mouth dryness, anorexia, nausea, and constipation are common. 5.Urogenital changes. Menopause has been associated with decreased sexual function and an increased incidence of urinary incontinence and urinary tract infection.a. Sexual function - Estrogen deficiency leads to a decrease in blood flow to the vagina and vulva, causing decreased vaginal lubrication and sexual function.
- Dyspareunia in postmenopausal women should be treated with estrogen. Systemic estrogen therapy is usually adequate in women who desire estrogen therapy for reasons in addition to genitourinary symptoms. Vaginal estrogens are a good choice for women who want to minimize systemic effects.
b. Urinary incontinence - Low estrogen production after the menopause results in atrophy of the urethral epithelium and irritation; these changes predispose to stress and urge urinary incontinence.
- Estrogen therapy should be attempted in women with stress or urge urinary incontinence. Urinary incontinence may be treated with systemic or vaginal estrogen.
c. Urinary tract infection. Recurrent urinary tract infections are a problem for many postmenopausal women. d. Treatment of urogenital atrophy in women not taking systemic estrogen a. Moisturizers and lubricants. Regular use of a vaginal moisturizing agent (Replens) and lubricants during intercourse are helpful. Water soluble lubricants such as Astroglide are more effective than lubricants that become more viscous after application such as K-Y jelly. A more effective treatment is vaginal estrogen therapy. b. Low-dose vaginal estrogen (1) Vaginal ring estradiol (Estring), a silastic ring impregnated with estradiol, is the preferred means of delivering estrogen to the vagina. The silastic ring delivers 6 to 9 µg of estradiol to the vagina daily for a period of three months. The rings are changed once every three months by the patient. Concomitant progestin therapy is not necessary. (2) Conjugated estrogens (Premarin), 0.5 gm of cream, or one-eighth of an applicatorful daily into the vagina for three weeks, followed by twice weekly
thereafter. Concomitant progestin therapy is not necessary. (3) Estrace cream (estradiol) can also by given by vaginal applicator at a dose of one-eighth of an applicator or 0.5 g(which contains 50 µg of estradiol) daily into the vagina for three weeks, followed by twice weekly thereafter. Concomitant progestin therapy is not necessary. (4) Estradiol (Vagifem). A tablet containing 25 micrograms of estradiol is available and is inserted into the vagina twice per week. Concomitant progestin therapy is not necessary. 6. Prevention and treatment of osteoporosisA. Screening for osteoporosis. Measurement of BMD is recommended for all women 65 years and older regardless of risk factors. BMD should also be measured in all women under the age of 65 years who have one or more risk factors for osteoporosis (in addition to menopause). B. Bisphosphonates - Alendronate (Fosamax) has effects comparable to those of estrogen for both the treatment of osteoporosis (10 mg/day or 70 mg once a week) and for its prevention (5 mg/day). Alendronate (in a dose of 5 mg/day or 35 mg/week) can also prevent osteoporosis in postmenopausal women.
- Risedronate (Actonel), a bisphosphonate, has been approved for prevention and treatment of osteoporosis at doses of 5 mg/day or 35 mg once per week. Its efficacy and side effect profile are similar to those of alendronate.
C. Raloxifene (Evista) is a selective estrogen receptor modulator. It is available for prevention and treatment of osteoporosis. At a dose of 60 mg/day, bone density increases by 2.4 percent in the lumbar spine and hip over a two year period. This effect is slightly less than with bisphosphonates. D. Calcium. Maintaining a positive calcium balance in postmenopausal women requires a daily intake of 1500 mg of elemental calcium; to meet this most
women require a supplement of 1000 mg daily. E. Vitamin D. All postmenopausal women should take a multivitamin containing at least 400 IU vitamin D daily. F. Exercise for at least 20 minutes daily reduces the rate of bone loss. Weight bearing exercises are preferable. 2011-07-26
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