HORMONE REPLACEMENT THERAPY: QUESTIONS AND ANSWERS

March 1998

Media Contacts: Sarah Goodwin, 404/727-3366 - sgoodwi@emory.edu
Kathi Ovnic, 404/727-9371 - covnic@emory.edu
http://www.emory.edu/WHSC/

A petering out of sex hormones as we age coincides with a number of the less desirable aspects of growing older, namely brittle bones, loss of the ol' sex drive and sagging muscles.

So why not replace the lost hormones -- and be done with all this decrepitness?

Answers to this simple solution are as complex as hormones themselves. Nonetheless, scientists are eagerly trying to put this theory to work -- particularly to prevent frailty in later life.

"Hormones are not merely vitamins or minerals or herbs," says Penny Castellano, M.D., a gynecologist and researcher who treats women for menopause at The Emory Clinic North in Alpharetta. "Hormones are potent biochemical messengers that trigger all sorts of bodily mechanisms. And while we know that hormone replacement can work wonders to prevent osteoporosis and heart disease after women undergo menopause, we also know that sex hormones must be used appropriately. Under certain circumstances, for instance, they can stimulate abnormal growth in some tissues."

Doctors learned all about the risk/benefits of hormone supplementation in the early days of estrogen replacement therapy. Alarming increases in rates of endometrial cancer among women prescribed the early does of estrogen replacement led to the addition of a synthetic progestogen called progestin to the formulation.

"This also spurred a name change from estrogen replacement therapy to hormone replacement therapy (HRT)," says Emory University's Nanette Wenger, M.D., named one of the Top Ten Women in Medicine (Ladies Home Journal, 1994.

Dr. Wenger is a lead researcher in the national Heart Estrogen-Progestin Replacement Study (HERS) in which hundreds of postmenopausal women with heart disease from Atlanta and throughout Georgia have enrolled and are helping to clarify the role HRT plays in preventing recurrent coronary events.

MORE ABOUT ESTROGEN

Between puberty and menopause, the female sex hormone estrogen (really a set of related hormones) is produced in abundance in the ovaries to mediate a number of important aspects of reproductive health, including breast development. Estrogens are also produced by the placenta during pregnancy and in small amounts -- in both women and men -- in the adrenal glands. Scientists have identified no known function for estrogen in men. Certain estrogen drugs are used in younger women for birth control or to treat menstrual disorders, some types of infertility and certain breast cancers.

The near cessation of estrogen production at menopause causes a number of short-term and long-term physical changes. Hot flashes and night sweats occur in about 70 percent of menopausal women and vaginal dryness occurs in about 20 percent.

Tissue in the vagina and urethra becomes thinner and dryer, thus predisposing women to more frequent minor infections and the need to urinate more frequently. Administering HRT locally via an Estrogen Ring to alleviate these problems is being evaluated by Joseph Ouslander, M.D., who directs Emory's Division of Geriatric Medicine.

He currently is enrolling older women into a study of estrogen releasing vaginal ring for atrophic vaginitis and related lower urinary symptoms (call 404/321-6111, ext. 7350).

Metabolic changes due to menopause can have long-term consequences. Bones lose calcium so quickly in the first few years after cessation of the menses that women can become dangerously prone to the bone fractures associated with osteoporosis. Women are at much lower risk for heart disease prior to menopause but at much greater risk once the protection derived from estrogen is lost at menopause. At that time, blood pressure rises along with levels of circulating blood fat, putting women at risk for coronary artery disease, including heart attack and stroke.

Estrogen drugs administered after menopause have been shown to reduce all the above-mentioned symptoms. Drugs are made from natural and synthetic estrogens and include 17B estradiol, conjugated equine estrogen, estrone and dienestrol, among others. Some 60 million prescriptions are written each year to help women through "the change," yet experts estimate that only about 20 percent of postmenopausal women are on HRT.

Estradiol is an important estrogen hormone, yet it is somewhat difficult to "replace." In pill form, it is not absorbed nearly as well by the bloodstream as some other forms of estrogen. But new and effective transdermal estradiol skin patches are now available.

Recent reports suggest HRT with estrogen is associated with reduced risk for colon cancer and studies at Emory and elsewhere are evaluating links between estrogen replacement and delaying Alzheimer's disease.

"Very few women are not candidates for HRT," Dr. Castellano says. "There still exists some controversy over the use of HRT in women with previous history of breast or endometrial cancer. There have been some reports of very small increases in the risk of blood clots in new users. But overall, most women can choose to use HRT."

TESTOSTERONE -- AND OTHER HORMONES -- FOR WOMEN

Researchers are looking at other non-estrogen hormones for HRT.

PROGESTERONE, another important female sex hormone, comes into play in its natural form after the ovulation stage of the monthly menses by inducing the uterine lining to shed. Synthetic progestin derivatives have become standard compliments to estrogen in HRT for their role in reducing risk of uterine endometrial cancer. Natural progesterone drugs may, in fact, be used alone solely to treat uterine cancer. Research is ongoing.

TESTOSTERONE, which is produced naturally in the ovaries, is reduced by about one half during menopause. It currently is used in some estrogen formulations to treat acne, and is being evaluated for the long-term consequences of its use in HRT.

AGE-DEFYING DRUGS FOR WOMEN AND MEN

GROWTH HORMONE, produced by the pituitary gland, assures proper musculoskeletal growth in children. Why can't it help maintain proper musculoskeletal form if administered to older adults? That is exactly what research teams across the country to trying to determine. Growth hormone, growth hormone releasing hormone (GHRG) and insulin-like growth factor 1 (IGF-1) are probably the most scrutinized antiaging drugs of all. Preliminary research suggests growth hormone does appear to be among the most promising of compounds for reducing frailty in older adults, but it is not without side effects. Exacerbation of diabetes, fluid retention and carpal tunnel syndrome in the wrist are associated with its use in human study subjects.

DHEA (dehydroepiandrosterone), is an adrenal hormone used by the body to make estrogen and testosterone. In fact, the body makes more DHEA than any other hormone by far. DHEA has recently been touted to prevent cancer and heart disease, improve memory and reduce fat. It is considered a food additive and therefore is not regulated by the Food and Drug Administration. Health food stores have been selling cytosterol, a precursor of DHEA derived from yams that has not been proven to benefit humans. Studies of DHEA supplementation in aging animals are the basis for its health claims. But the first two controlled studies to date of DHEA in humans, conducted by Arlene Morales, M.D., who has recently joined the faculty of the Emory University School of Medicine, found that there may be effects in humans with replacement doses of DHEA, but the findings are preliminary and warrant large-scale clinical trials, which are on-going.

"At this point, there is not nearly enough data to recommend DHEA supplementation," Dr. Morales says. "DHEA is a potent pre-hormone that definitely creates estrogen and testosterone."

MELATONIN is a hormone produced in the brain's tiny pineal gland that anecdotal evidence suggests may help induce sleep, prevent cancer and boost the immune system. It has been approved to treat jet lag. As with DHEA, it has not been proven either safe or effective in humans, though animals studies are promising. SERMS (selective estrogen receptor modulators) such as raloxifene have different effects on different estrogen receptors found in various cells. SERMS appear to mimic estrogen benefit in bone, but have an anti-estrogen effect on reproductive tissues. Investigators believe SERMS may help reduce some of the serious effects of menopause such as osteoporosis and may help prevent breast cancer and uterine cancer, but they appear to increase hot flashes and have little effect on vaginal dryness. Preliminary data suggest some cardiovascular benefit.

"We still need a lot more research before these compounds become commonly used," Dr. Castellano says.

MANAGING MENOPAUSE WITHOUT HORMONES

Although the cardiovascular benefits of HRT are fairly well established -- and heart disease is bar none the greatest health threat to older women -- women and even their doctors fear the breast cancer and uterine cancer associated with older forms of estrogen replacement. More than ever, people are looking to non-hormonal means to stave off the frailties of aging.

SOY PROTEIN has estrogen-like components called phytoestrogens (a type of isoflavone) that bind to estrogen receptors. Many investigators are assessing the ability of soy isoflavones in preventing heart disease, breast cancer and bone loss. Results are promising but preliminary. Researchers suggest taking 30-50 mg of isoflavones per day.

FLAXSEED is a source of lignans that may help control cholesterol and symptoms of menopause. Studies are numerous and ongoing but data is unclear at present. Most of the lignans have been removed from flaxseed oil, therefore it is not considered an optimal source of flaxseed. Interested persons take about four tablespoons of flaxseed per day.

VITAMIN D is a hormone that helps bone absorb calcium -- and calcium is essential to keeping osteoporosis at bay. But whether vitamin D is best consumed by food or pill is not known.

Clarifying this is one of the questions being addressed by thousands of Atlanta women in the Emory component of the Women's Health Initiative -- the largest women's health study ever. National health agencies recommend that women over 50 take 1,500 mg of calcium a day (men over 50 should take 1,200 mg) along with 400 IU of vitamin D.

"Keep in mind that nonpharmaceutical compounds have by and large not been tested for safety and efficacy," Dr. Castellano says. "Before deciding to turn to these compounds, check with your physician."

ALENDRONATE (Fosamax) and CALCITONIN (a nasal spray) are new drugs for preventing and treating osteoporosis.

STATINS and other new cholesterol-lowing agents appear on the market regularly -- and many more are expected.

Dr. Morales says the importance of maintaining a healthy lifestyle cannot be overemphasized during menopause management. ###

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