Menopause continued
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Forms of Hormone Replacement Therapy

Estrogen can be given alone (unopposed estrogen; or, ERT) or in combination with progestins (combined hormone therapy; or, HRT). Each regimen and form of administration has specific benefits and risks. Due to the uncertainties surrounding HRT, some doctors counsel taking the lowest dose that still averts menopausal symptoms.

*Estrogens. The oldest form of supplemental hormones is estrogen alone, called unopposed estrogen, which does not contain a progestin. Since unopposed estrogen increases the risk for uterine cancer, it is only recommended for women who have had the uterus removed (hysterectomy). Estrogen comes in several pharmacologic formulations:

*Conjugated estrogen is most commonly marketed as Premarin, which contains a mixture of natural estrogens derived from the urine of pregnant mares.
Cenestin is a more recent synthetic form of conjugated estrogen and is derived from compounds found in yams and soy.
Other plant-derived estrogens, called esterified estrogens, are usually made from modified soy (Estratab, Menest).
Estradiol, the most potent estrogen, is available as tablets (Estrace), in skin patch form (Estraderm, Alora, Climara, Vivelle, FemPatch, Evorel), as a vaginal ring (Estring), through injections, and as pellets inserted under the skin twice a year.
Estropipate (Ogen, Ortho-Est) is a version of estrone, a weaker form of estrogen.
A vaginal tablet (Vagifem) has been developed, and estrogen nasal sprays are being investigated. Very small (nickel-sized), water-resistant skin patches are now available. Using skin patches, vaginal devices, or gels to deliver hormones may avoid problems, such as gallstones and blood clots, that can occur with the use of oral estrogen.

*Progesterone and Combined Hormone Replacement Therapy. To avoid the risk of endometrial (uterine) cancer physicians have generally prescribed estrogen along with a progestin (either natural progesterone or a synthetic form of progesterone), known as combined hormone replacement therapy. Progesterone is referred to by one of several names:

Progesterone is the name for the natural hormone.
Progestin is the term for any agent, natural or synthetic, that causes progesterone effects.
Progestogen is any agent that has effects similar to progesterone. Progestins are sometimes prescribed alone for the irregular bleeding that can be associated with perimenopause.

There are several progestins available:

Synthetic progestins include medroxyprogesterone (Provera, Amen, Curretab, Cycrin, Depo-Provera), norethindrone acetate (Aygestin, Norlutate), and norgestrel.
Natural forms of finely ground progesterone, made from wild yams, is available in an oral form (Prometrium) and in a cream (Crinone). It is unclear whether there are fewer long-term side effects with natural or synthetic progesterone.
When used in HRT progestins are combined with estrogen either in oral forms (Prempro, Premphase, and Activelle) or skin patch (CombiPatch). Under investigation are combinations (Ortho-Prefest, Femhrt) that use progestins that are usually only in oral contraceptives and may not have as many side effects. A typical combination HRT regimen simulates the natural menstrual cycle:


Estrogen is taken for the first 25 days of the month, and a progestin is added for days 13 through 25.
No hormones are taken for the next five or six days.
Since the body's premenopausal hormone balance is being mimicked, mild vaginal bleeding will usually occur at the end of the cycle. Such bleeding does not indicate any significant health problem, nor does it indicate a return of fertility, but some women find it unpleasant. An alternative oral regimen significantly reduces end-of-cycle bleeding by using both estrogen and a progestin together on a daily basis. This simultaneous approach, however, may not be as heart protective, and some studies indicate that it may still carry a small risk for uterine cancer. There is currently intensive debate over the optimal regimen.

Side Effects

HRT has a number of side effects, including bloating, nausea, breast tenderness, vaginal bleeding, fluid retention, irritability, mood swings, headaches, dizziness, fatigue and an increased risk for blood clots. Breast soreness usually subsides in three to four months and can be relieved with over-the-counter pain killers and possibly by decreasing caffeine intake and adding vitamin E. Vaginal bleeding is a primary reason why many women stop treatment. Side effects can often be reduced or relieved with lower dosages or a different type of regimen.

Complications of Hormone Replacement Therapy

Taking hormone replacement therapy for five years or less is generally acknowledged to pose little or no danger. Still, many women who are prescribed HRT do not go back to the pharmacy to refill their prescription. Studies are under way to conclusively define the risks that might occur in older women or those taking HRT for long periods.

Selective Estrogen-Receptor Modulators (SERMs)

Drugs known as selective estrogen-receptor modulators (SERMs) have been designed to produce the benefits of estrogen without its risks. They are thought to act like estrogen in some tissues but behave like estrogen blockers (antiestrogens) in others.

They include the following:

*Raloxifene (Evista) is actually the first SERM to be approved for preventing spinal fractures. In 2000, updated results of a major on-going study on raloxifene reported a reduced risk for breast cancer of 72% over a four-year period. This drug has actions similar to tamoxifen but does not increase the risk of uterine cancer. Raloxifene has some benefits on cholesterol levels but increases the risk for deep vein blood clots.

*Tamoxifen (Nolvadex) is the best-studied SERM. In a major study, tamoxifen (a drug used to treat breast cancer) reduced the risk for breast cancer by half in high-risk women. It was particularly protective in women over 60. Two other European studies have reported no protection, but they were smaller trials that differed in eligibility requirements and in the use of supplemental estrogen. Tamoxifen poses other health hazards, including a risk for blood clots and uterine cancer.
SERMs under investigation include lasofoxifene and droloxifene. They are also promising in producing increased bone density and improvement in cholesterol levels.

Common Side Effects.
Most SERMs do not relieve menopausal symptoms, and some exacerbate them. Raloxifene appears to have fewer side effects than hormone replacement therapy and women tend to stay on it longer. Because of the common risks for blood clots, anyone taking these agents should stop three days before any prolonged immobilization, such as long air flights or surgery.

Other Hormones or Hormone-Like Agents

*Tibolone. Tibolone (Livial) is showing promise in improving bone mineral density, most effectively in the lower spine. It is not yet available in the US. Tibolone is a synthetic hormone that acts more like a progestin; it also has properties similar to estrogen and androgens (male sex hormones, such as testosterone), depending on the tissue in the body to which it binds. Tibolone protects against bone loss; its effects on other diseases are not yet clear.

*Dehydroepiandrosterone (DHEA). Dehydroepiandrosterone (DHEA) is a weak male hormone secreted by the adrenal gland, and is available over the counter. There are some claims that it increases psychological well being and improves bone density. The hormone may, however, reduce HDL (the so-called good cholesterol) in doses higher than 50 mg and its effect on cancer-cell growth is unknown, with some evidence indicating that high levels may increase the risk. In any case, DHEA is not regulated and brands vary widely in their content. No one should take any so-called "natural hormone" without consulting a physician.

*Combinations with Male Hormones. Some doctors are now prescribing combinations of estrogen and small amounts of the male hormone, testosterone. Estratest, for example, adds small doses of testosterone to estrogen therapy and appears to increase bone mass, improve sexual drive (when taken in higher doses), and improve mental alertness. Side effects of testosterone include increased body hair, acne, fluid retention, anxiety, and depression. Many experts have not historically recommended taking male hormones for postmenopausal problems, although this may change as more studies are performed.

Women:
Tend to Your Heart Now, Not LaterMaking Changes Before Menopause
 

Latest News

March 7, 2003 -- A woman's risk of heart disease will increase once she reaches menopause, and making healthy lifestyle changes in the years before menopause may be a woman's best defense. A new study shows women may be less likely to require treatment for heart disease after menopause if they incorporate lifestyle changes such as quitting smoking, improving their diet, and increasing physical activity before they reach age 55. Regardless of their health, women are bumped into a higher risk category for heart disease once they reach menopause. But by targeting risk factors for heart disease in the years preceding menopause, a time known as perimenopause, researchers say women can lower their risk and reduce the need for later treatment. "The idea was to look at where the women are now, in terms of risk factors, and then try to predict where they will be when they reach age 55," says researcher Carol Derby, PhD, assistant professor of neurology and epidemiology and social medicine at Albert Einstein College of Medicine in New York City, in a news release. At this age, women may need cholesterol-lowering therapy or lifestyle modifications to lower their risks of heart disease based on the number of risk factors they have. Other risks factors include smoking, high blood pressure, poor cholesterol levels, body mass index (BMI, a measure of weight in relation to height used to determine obesity) and having a family history of early heart disease. "Even if everything else were constant and there were no age-related changes in heart disease risk factors, just crossing the age threshold will make a lot more people eligible for treatment, according to the latest guidelines," says Derby. Derby presented the findings of the study this week at the American Heart Association's 43rd Annual Conference on Cardiovascular Disease Epidemiology and Prevention in Miami. Researchers evaluated risk factors for heart disease in a group of 1,349 women between the ages of 42 and 52. Overall, they found that these risk factors made 9.5% and 5% of the women eligible for lifestyle modification alone or in combination with drug treatment, respectively, in order to reduce cholesterol levels, according to current treatment guidelines. Researchers then applied the age-related risks and found that the number of women who would require some type of intervention to lower "bad" LDL cholesterol increased by 19%. Lifestyle modification would increase by 5% and the number of women who would need cholesterol-lowering medications would increased by 2%. Those increases suggest that almost 20% of these women would become eligible for some sort of cholesterol-lowering therapy after age 55. The magnitude of the shift in risk associated with age was greatest among Hispanics and blacks. The study estimated that 27% of Hispanic women and 23% of black women would require treatment after age 55, compared with 19% of whites, 11% of Japanese, and 8% of Chinese women. "If efforts to modify risk factors are not successful during the pre- and perimenopausal years, large numbers of women, particularly Black and Hispanic women, will rather abruptly require more aggressive treatment during their postmenopausal years," write the researchers.

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