Menopause

Elizabeth K. Stanford, MD

The average age of menopause is 51 years, with a range of 41-55. Menopause occurs before age 40 in about 5% of women. An elevated follicle-stimulating hormone (FSH) level greater than 40 mlU/mL.
Pharmacologic therapy for symptoms of menopause
Vasomotor instability. A hot flush is a flushed or blushed feeling of the face, neck and upper chest. The most severe hot flushes usually occur at night. Estrogen therapy can reduce hot flushes.
Psychologic symptoms. Mood swings, depression and concentration difficulties are associated with menopause. Estrogen improves mood or dysphoria associated with menopause.
Urogenital symptoms. Declining estrogen levels lead to atrophy of the urogenital tissues and vaginal thinning and shortening, resulting in dyspareunia and urethral irritation. Urinary tract infections and urinary incontinence may develop. Estrogen treatment (oral or intravaginal) reduces these problems
Pharmacologic management of long-term risks
Coronary artery disease. Physiologic effects of estrogen, such as arterial vasodilatation, increased high-density lipoprotein (HDL) cholesterol levels and decreased low-density lipoprotein (LDL) cholesterol levels, are likely to reduce cardiovascular risk.
Osteoporosis. More than 250,000 hip fractures occur annually. Estrogen deficiency is the primary cause of osteoporosis, although many other secondary causes for osteoporosis exist (eg, poor diet, glucocorticoid excess). Thus, women at risk for osteoporosis should be considered candidates for HRT.
Minimum Effective Dosages of Estrogens for Prevention of Osteoporosis
Formulation
Minimum effective dosage
Conjugated estrogen
Premarin (0.3, 0.625, 0.9, 1.25, 2.5 mg)
0.625 mg
Micronized estradiol
Estrace (0.5, 1.0, 2.0 mg)
1.0 mg
Esterified e strogen
Estratab (0.3, 0.625, 2.5 mg) Menest (0.3, 0.625, 1.25, 2.5 mg)
0.625 mg
Estropipate
Ogen (0.625, 1.25, 2.5 mg) Ortho-Est (0.625, 1.25 mg)
1.25 mg
Transdermal estradiol
Climara (0.05, 0.1 mg) Estraderm (0.05, 0.1 mg)
0.05 mg
Combination preparations
Combipatch
0.05 mg estradiol/0.14 mg norethindrone
Estratest
1.25 mg esterified estrogen/2.5 mg methyltestosterone
Estratest HS
0.625 mg esterified estrogen/1.25 mg methyltestosterone
Premphase
0.625 mg conjugated estrogen (14 tablets) and 0.625 mg conjugated estrogen/5 mg medroxyprogesterone (14 tablets in sequence)
Prempro
0.625 mg conjugated estrogen/2.5 mg or 5.0 mg medroxyprogesterone. Take one tab daily.
Vaginal preparations
Micronized estradiol cream ( Estrace)
0.01% or 0.1 mg per g (42.5 g/tube)
Estropipate cream ( Ogen)
1.5 mg per g (42.5 g/tube)
Conjugated estrogen cream ( Premarin)
0.625 mg per g (42.5 g/tube)
Estradiol vaginal ring ( Estring)
7.5 :g per 24 hours every 90 days
Hormone replacement therapy administration and regimens
The benefits of HRT in reducing the risks of hip fracture outweigh the risk of breast cancer in nearly all women. However, long-term HRT is not recommended for women at high risk for breast cancer.
Effective doses of estrogen for the prevention of osteoporosis are: 0.625 mg of conjugated estrogen, 0.5 mg of micronized estradiol, and 0.3 mg of esterified estrogen.
In those women with a uterus, a progestin should be given continuously (2.5 mg of medroxyprogesterone per day) or in a sequential fashion (5-10 mg of medroxyprogesterone ( Provera) for 12-14 days each month). The most common HRT regimen consists of estrogen with or without progestin. The oral route of administration is preferable because of the hepatic effect on HDL cholesterol levels.
Estrogen cream. 1/4 of an applicator(0.6 mg) daily for 1-2 weeks, then 2-3 times/week will usually relieve urogenital symptoms. This regimen is used concomitantly with oral estrogen.
Relative and Absolute Contraindications for Hormone Replacement Therapy
Absolute contraindications Estrogen-responsive breast cancer Endometrial cancer Undiagnosed abnormal vaginal bleeding
Active thromboembolic disease History of malignant melanoma
Relative contraindications Chronic liver disease Severe hypertriglyceridemia Endometriosis Previous thromboembolic disease Gallbladder disease
Adverse effects attributed to HRT include breast tenderness, breakthrough bleeding and thromboembolic disorders.
Bisphosphonates inhibit osteoclast activity. Alendronate (Fosamax) is effective in increasing BMD and reducing fractures by 40 percent. To prevent esophagitis, alendronate should be taken in an upright position with a full glass of water 30 minutes before eating. Alendronate is indicated for osteoporosis in women who have a contraindication to estrogen.
Raloxifene (Evista), a selective estrogen receptor modulator has been FDA-labeled for prophylactic treatment of osteoporosis. This agent offers an alternative to traditional HRT. The modulator increases bone density (although only one-half as effectively as estrogen) and reduces total and LDL cholesterol levels.
Complementary therapies
Adequate dietary calcium intake is essential, and supplementation is helpful if dietary sources are inadequate. Total calcium intake should approximate 1,500 mg per day, which usually requires supplementation.
Vitamin D supplementation (400 to 800 IU per day) is recommended for women who do not spend 30 minutes per day in the sun.
Treatment of low libido consists of micronized testosterone cream (1 mg/mL) applied to the inner surface of both forearms daily. Start with 1 mg/day and increase to 2.5 mg/day if necessary. Androgens are known to increase libido and protect bone mass.