It is estimated that by the year 2030, the number of women over age 50 will exceed 1.2 billion. The life expectancy for women is 81 years of age or greater, and today, women can expect to live nearly 1/3 of their lives after the menopause. While for some women, menopause signals the beginning of an era of aging, it should and can, mark the beginning of a new and promising period of life, free from previous obligations with the possibility of new career choices, more education and new ventures. buy prometrium The menopause is that point in time when permanent cessation of menstruation occurs, following the loss of ovarian activity. The perimenopause is the period immediately before and after the menopause. The climacteric  is a more encompassing word, indicating the period of time when a women passes through a transition from the reproductive stage of life to the post menopausal years, a period marked by decreasing ovarian function (decreasing estrogen production).
The median age of menopause has been estimated to be somewhere between 50 and 52. The median age for the onset of the perimenopause is 47.5 years. Only 10% of women cease menstruating abruptly with no period of prolonged irregularity. The perimenopausal transition for most women is approximately 4 years in duration. The range, however, for the age of menopause, is approximately age 48 to age 55. It is not necessarily true that mothers and daughters tend to experience menopause at the same age. Undernourished women may experience an earlier menopause, and women that smoke will experience menopause 1.5 years earlier. Thinner women may also experience a slightly earlier menopause. Living at high altitudes may hasten the onset of menopause and also previous hysterectomy may cause premature ovarian failure in a small percentage of women. Approximately 1% of women will experience menopause before the age of 40.
Some women equate menopause with old age and/or the end of sexuality. Actually, sexuality is a lifelong behavior with evolving change and development. There are two main sexual changes in the aging woman. There is a reduction in the rate of production in volume of vaginal lubricating fluid and some loss of vaginal elasticity. There may be a feeling of dryness and tightness, vaginal irritation and burning with intercourse, and spotting and soreness after intercourse. Less vaginal atrophy (thinning) is noted in sexually active women compared to inactive women; presumably, the activity maintains the vaginal blood supply and elasticity of the tissue. Estrogen therapy, as will be discussed later, prevents vaginal dryness and atrophy.
The decline in sexual activity with aging may be influenced more by culture and attitudes than by nature or hormones. The two most important influences on older sexual interaction are the strength of a relationship and the physical condition of each partner.
When women are in their 40’s, ovulation is inconsistent and therefore, the menstrual cycle length increases beginning two to eight years before menopause. We know that Estradiol (Estrogen) levels do not gradually decrease in the years before menopause, but remain in the normal range until the growth of ovarian follicles (eggs) ceases. An FSH and LH level may be measured and if there is a 10 to 20-fold increase in FSH and a three-fold increase in LH, this may likely signify the onset of the menopause. At this point, the estrogen secretion by the ovary has decreased. However, total estrogen levels in the body may still be in the normal range due to conversion of adrenal hormones to estrogen-like substances (Estrone) in peripheral tissues (ie., fat, muscle, liver, etc.). Obese women have higher estrogen levels due to increased conversion and decreased sex hormone binding globulin (SHBG). This contributes to the well known association between obesity and the development of uterine cancer.
The most frequent symptoms in the perimenopause are:
  1. Disturbances in menstrual pattern, including irregular periods, heavy periods, or decreased flow.
  2. Hot flushes and sweats.
  3. Psychological symptoms including anxiety, increased tension, mood depression, irritability, although a direct cause and effect relationship between these symptoms and estrogen is hard to establish.
  4. Atrophic conditions: atrophy of vaginal tissue, painful intercourse, vulvar itching and burning, general skin atrophy, urinary difficulties such as urgency and irritation of the urethra and bladder.
  5. Health problems secondary to long term deprivation of estrogen: the consequences of osteoporosis and cardiovascular disease and possibly dementia and macular degeneration.
If you have abnormal bleeding, an endometrial biopsy may be necessary. This can be accomplished in the office with a small plastic aspiration device and is frequently a painless procedure. A D&C (Dilation and Curretage) may be suggested if it is difficult to do an office biopsy or the uterus is abnormal in size or contour or if you are at high risk for uterine cancer. A pap smear will indicate a problem with the cervix and less commonly a problem with the lining of the uterus. In the absence of significant uterine disease, a course of progesterone may be offered for irregular bleeding. This may be prescribed until all bleeding ceases. At this time, the symptoms of estrogen deprivation may appear (hot flashes) and estrogen therapy may also be indicated.
Please be aware that during the climacteric, it is still possible to achieve a pregnancy and contraception may be required. The use of low dose oral contraceptive pills (OCP’s) is particularly useful during this stage of life.
It is important to not use OCP’s if you are a smoker, as the incidence of complications such as heart attack and pulmonary embolism may be increased. If you are on OCP’s, your FSH level may be measured beginning at the age of 50 and on a yearly basis during day 5 to 7 of the last week of the pack (hormone-free week). If the FSH level is greater than 30, it may be time to switch to regular post menopausal hormone replacement (estrogen and progesterone).
There are some symptoms in the perimenopause that are seen frequently, but their relationship to estrogen is uncertain. These problems include fatigue, nervousness, headaches, insomnia, depression, irritability, joint and muscle pain, dizziness, and palpitations. Many of these symptoms may be due to ineffective sleep patterns as a result of being awakened by hot flashes. Treatment with estrogen may improve many of these symptoms once the hot flashes have abated. Estrogen therapy improves the quality of sleep, decreasing the time to onset of sleep, and increasing the Rapid Eye Movement (REM) sleep time, even in postmenopausal women without vasomotor symptoms (Amer. J. Obst/Gyn 1998; 178:1002-9).
Urogenital complaints are common in menopause – dryness, itching, painful intercourse, UTI’s (urinary tract infections), frequency and urgency of urination, and incontinence. Estrogen restores normal pH and bacterial flora and glycogen deposition. It reduces recurrent UTI’s, improves urethral function, and strengthens muscle contracting and tone. It improves vaginal blood flow and reduces incontinence.
Depression is a common finding in women; as many as 1/3 may experience a depression during their life. There is no evidence that menopause per se causes depression, yet estrogen has been used successfully to treat depression in some instances. There is evidence that estrogen helps alleviate depression (PostGrad Medicine, March 2001, “Treatment of Depression in Women”).
There are some early findings that indicate that Alzheimer’s Disease and related dementia occur less frequently in estrogen users. The administration of estrogen to patients with Alzheimer’s has improved their cognitive performance.
Estrogen treatment also retards osteoporosis (loss of bone mass) and can increase bone mass. This disease is epidemic in the United States, affecting more than 20 million individuals. The rise in osteoporotic fractures indicates that women lose more bone today, possibly due to less physical activities, dietary decrease in dairy products, and an earlier and greater loss of bone because of the impact of smoking cigarettes. Bone density peaks in the mid to late 20’s, and begins to decrease around age 30. Beyond age 40, reabsorption of bone exceeds the new formation of bone by about 0.5% per year. Bone loss accelerates after menopause and up to 5% of bone mass loss will occur per year after menopause, for 10 to 15 years after which the bone loss is diminished but continues as an age related loss. This process is slower in the black population. There is also a genetic influence, but the most important factor in menopausal bone loss is the loss of estrogen. There is an increased loss in white, Asian, thin, and sedentary women. The average non-treated post-menopausal white woman can expect to shrink 2.5 inches, due to vertebral fractures. By age 90, 20% of all white women will have developed hip fractures. One-sixth of these will be fatal within three months. Estrogen combined with calcium can give an 80% reduction in vertebral compression fractures and significant increases in bone mineral density in hips as well (PEPI Study JAMA 1996; 276:1389-96. Lancet 1976; 1:1038-41). There is a greater than 50% decrease in hip fractures in women who stay on HT (Marcus R., Osteoporosis, Academic Press).
The positive impact of hormone therapy on bone has been demonstrated to take place even in women over age 65. The equivalent of 0.625 mg of conjugated estrogens or 1mg Estradiol is necessary to preserve bone density. A lower dose of 0.3mg daily, or 0.5mg of Estradiol prevent the loss of vertebral bone, when combined with calcium supplementation to achieve a total intake of 1500 mg daily. Calcium absorption decreases with age and becomes significantly impaired after menopause. A positive calcium balance is necessary to achieve adequate prevention against osteoporosis. Estrogen improves calcium absorption and makes it possible to utilize effective supplemental calcium in lower doses. The average woman receives only 500 mg calcium in her diet, therefore, the minimal daily supplement equals an additional 500 mg in women on estrogen. Women not on estrogen require a daily supplement of at least 1000 mg of calcium. Vitamin D which enhances calcium absorption may be used in elderly patients in nursing homes, or women who have minimal sun exposure. The recommended dose is 400 units daily. Calcitonin may be used in patients for whom hormone therapy is contraindicated (i.e., breast cancer).
Biphosphonates are compounds which are known to reduce bone reabsorption. These may also be indicated in some patients who are not candidates for estrogen. However, unlike estrogen, these compounds have no effect in preventing cardiovascular disease, hot flushes, or the atrophic changes seen in the menopause.
Lifestyle can have a beneficial effect on bone density. Physical activity as little as 30 minutes a day for three days a week will increase the mineral content of bone in older women. Walking 1.5 miles and ordinary calisthenics may suffice.
Adverse habits such as cigarette smoking or excessive alcohol consumption are also associated with increased risk of osteoporosis. Exposure to excessive thyroid or glucocorticoid hormones (Prednisone) is also associated with osteoporosis. Hyperparathyroidism and renal disease and other less common diseases such as multiple myeloma, leukemia, lymphoma, or Cushing’s disease or metastatic cancer may also lead to bone loss.
Measuring bone density may be accomplished by a Dual Energy X-Ray Absorptiometry (DEXA). This test measures bone density and may be done in the radius of the arm, the hip or the spine. You may want a baseline at around age 50, or have the test if you’re not currently using estrogen.
One of the most beneficial reasons to take estrogen is to prevent cardiovascular disease; the most common cause of death amongst post-menopausal women in the United States. It includes coronary heart disease, cerebral vascular disease, hypertension, and peripheral vascular disease. Diseases of the heart are the leading cause of death for women in the United States followed by malignant cancers, strokes and motor vehicle accidents. Most cardiovascular disease results from atherosclerosis in major blood vessels (hardening of the arteries). Risk factors are the same for men and women: high blood pressure, smoking, diabetes, or obesity. After menopause, the risk of coronary heart disease doubles for women as the cholesterol and LDL cholesterol levels rise. The higher HDL (good cholesterol) levels in women compared to men represent the effect of estrogen in women and androgens in men. Estrogen decreases LDL levels and increases HDL. There are other beneficial effects of estrogen in inhibiting development of atherosclerosis. Please note that estrogen therapy does not cause high blood pressure. As a matter of fact, it may decrease blood pressure. Estrogen also has a direct effect on the walls of arteries, independent of its effects on circulating cholesterol. This may lead to dilating of the blood vessels, an anti-oxidant effect, anti-platelet action (anti-clotting activity), and decreased plaque formation. Women on estrogen therapy also have lower fasting insulin levels, which may also have a protective effect against cardiovascular disease. Estrogen is not indicated for treatment of existing heart disease and, while it may not improve heart disease initially, there is a time trend benefit (HERS Study Circulation 2001; 103:638-642, Grodstein & Stampfer, New England J of Medicine 1997; 336:1769-75, PEPI Study JAMA 1995; 273:199-208, Gerhard Circulation 1998; 98:1158-63).
 The recent Women’s Health Initiative Study that was in the papers 7/9/02 has shown a slight increase in non-fatal cardiac events, venous thromboembolism, stroke and breast cancer in women who received Prempro. This arm of the study was discontinued due to these adverse occurrences. It may be that the addition of Provera (medroxyprogesterone acetate) negates the beneficial effect of estrogen. They did not discontinue the part of the study including women who receive estrogen only, and in fact, this second “arm” of the study revealed less cardiovascular complications and less incidences of breast cancer. There are numerous progestogens available beyond Provera if there is a concern in a woman over 60 who may be at risk for those complications. Be aware, the increased risk involved only 8 extra cases per 10,000. This is not enough to say that women should be taken off HT. It simply indicates that some women at risk are better off not on Provera and that giving HT just to prevent heart disease is complex in women over 60 if they have risk factors**.
**NOTE: rarely a woman carries a hereditary factor that predisposes her to a blood clot that can lead to a DVT (deep vein thrombosis, usually in the leg), a PE (pulmonary embolism; clot in lung) strokes, or other serious complications.  If you have a history of any of these, you may NOT be able to take hormones. If you have a family history of any of these conditions, tell us at once so we may do blood tests to screen you for the presence of the factors. If you would like to be screened even without the presence any risk factors, please discuss it with your physician. Your insurance may or may not want to pay for the tests in this case, but we will try to help you. 
Estrogen has been shown to increase collagen levels in skin, preserving its elastic properties and thickness. It also maintains lean body mass (muscle) and this makes bodies stronger. It does not cause weight gain from increased fat.
There is a 50% decrease in risk of large-bowel cancer in HT users, and this risk reduction is maintained for 10 years after cessation of use (OB/Gyn 1999; 93:880-888).
Postmenopausal women on HT exhibit a markedly reduced risk of macular degeneration. Age-related macular degeneration is a major cause of painless bilateral antral visual loss in the elderly. Other risk reducers were lower cholesterol, absence of smoking, and higher carotenoid levels.
After fifty years of use of HT, over fifty case-control and cohort studies later, the evidence does NOT support an increased risk of breast cancer due to HT. The absence of convincing evidence is reassuring. If there is an increased risk, it must be too small, must occur in too limited a population to be observed in the studies performed to date. Your biggest risk factors for breast cancer are being female and a 3% increased risk every year you live. Longer life will also, unfortunately, give more cancers. Your most likely cause of death will be cardiovascular or complications of fractures due to osteoporosis, both of which can be lessened by use of HT. In addition, the latest article in OB/Gyn (98#3, 9/01) has revealed that HT users have a lower risk of death from breast cancer than never-users (see attached).
The increased risk of Endometrial Cancer (uterine cancer) can be prevented by adding a progestin in a dose and duration adequate to provide an atrophic (inactive) endometrium (J Nat’l Cancer Institute 1999; 91:1131-1137).
**The HERS study showed 1-2 extra cases of VTE (venous thromboembolism) per 10,000 women per year in women on HT. Women at risk for clots may not want to take HT.
In conclusion, there are a variety of reasons to consider HT. There are numerous types of estrogen and progestin products. Many failures of HT are due to not choosing the right product for an individual patient. Also, the medication you take at the onset of menopause may not be the medication you will need to stay on. Doses will change as you change. Also, the addition of testosterone may be helpful for some patients with decreased sex drive or hot flashes that don’t respond to HT. Ask your doctor for all the options including other treatments like Fosamax or SERMs.
Calcitonin, Fosamax, Boniva, or Actonel build bone mass and are non-hormonal. Side effects are mainly gastrointestinal. Selective Estrogen Receptor Modulators (SERMs), like EVISTA, are “designer estrogens,” meaning that they have selective positive properties of estrogen on bone and cardiovascular systems, but are not active in the uterus (no vaginal bleeding). They may be anti-estrogenic in breast tissue (STARR study underway). A well-known SERM is Tamoxifen. The newer SERM indicated for menopause is Raloxifene (Evista). Unfortunately, like HT, SERMs carry a risk of thromboembolism and may cause hot flashes. Patients with previous breast cancer or those with very high risk factors may be good candidates for SERMs. There is evidence SERMs prevent breast cancer.
Other References: Adapted from: Speroff, L. Clinical Gyn Endocrinology, 5th Edition, 1995 and Nachtigal, L. Hormone Replacement Therapy, OB/Gyn Special Report, 2000.

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