The use of hormone replacement therapy has increased enormously in recent decades, both for men and women at least until the recent warning provided by the large Women's Health Initiative study. In this extract from his book "AgeLess", Dean Schneider discusses the pros and cons for hormone therapy, and lays out four basic rules to guide readers. Robert Griffith, Editor.

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Lately, Maria has been having trouble sleeping through the night. During the day, her mood is all over the map. She can't go into a meeting without fear of a hot flash. And, at 47, she has a lackluster love life. Maria is perimenopausal, and she has some important decisions to make. Maria had always figured that she'd go the hormone replacement therapy (HRT) route when the time came, but new revelations about the increased risk of breast and ovarian cancer associated with estrogen and progestin replacement have made her reconsider. What's a smart woman to do?

David recently celebrated his 65th birthday but is feeling less than jubilant. He sees flab where once he saw firm muscle. His energy level is low. His belly has grown. His sex drive seems to be slipping away. David's father would have simply accepted these changes and found a hobby. But an onslaught of advertisements in David's daily e-mail trumpets new options. Modern pharmacology can manufacture any hormone you like, and the supplement makers claim that their pills can restore youth. Should David take the bait?

I meet people like David and Maria all the time. They come up to me at lectures, often holding a bestseller touting the latest miracle cure for aging and wanting to if it's true. Can you really restart your sex life with testosterone? Or stay forever young with DHEA? Melatonin?

What happens?

The production and secretion of most hormones decrease with age. At menopause, women experience a dramatic drop in estrogen levels and a host of unpleasant symptoms from night sweats and hot flashes to an increased risk of heart disease and osteoporosis. Most men experience a decrease in testosterone, the male sex hormone that spurs sex drive and preserves lean body mass, energy, and cognitive function, but it's far less marked. Secretions of human growth hormone (HGH) and DHEA (dihydroepiandrosterone) decrease with age for both men and women.
This leads to the million-dollar question: Can replacing these hormones as they decline forestall Father Time - and if so, at what cost or risk?

There's no question that hormone replacement therapy relieves menopausal symptoms and helps preserve bone mass. However, four decades after these benefits made hormone replacement therapy commonplace, many women felt blindsided when the news broke in 2002 that the Women's Health Initiative (WHI) study was stopped 3 years earlier than planned because the results clearly showed that the risks of taking estrogen and progestin outweighed their benefits. Findings of increased risks of heart attack, stroke, breast cancer, pulmonary embolism, and gallbladder disease lead the researchers to issue warnings about the safety of HRT.

New Hormone Rule #1: Women - Don't Take Hormone Replacement Unless Severe Menopausal Symptoms Warrant It . . .

If Maria had faced her decision about hormone replacement back in the 1990s, the answer would probably have been an easy "Yes, I'll take it". But today, results from better-controlled clinical trials are calling into question the findings of earlier observational studies. Study participants who take HRT tend to exercise more, smoke less, watch their weight, and eat better. These healthy lifestyle habits may well be what protect women on HRT from heart attacks, strokes, and Alzheimer's disease - not the hormones themselves. Only the data on estrogen's effect on menopausal symptoms such as hot flashes and protection against bone loss and colon cancer still look solid and unquestionable. Meanwhile, evidence for the risks of estrogen and progestin replacement continues to mount. In addition to the WHI's findings of increases in heart disease, stroke, pulmonary embolism, and breast cancer in the women who took HRT, other studies indicate an increased risk of ovarian cancer related to HRT. However, only one relatively high-dose combination of 0.625 milligrams conjugated equine estrogen (CEE), and 2.5 milligrams medroxyprogesterone acetate (MPA) were used in the WHI study and the Heart and Estrogen Replacement Study (HERS). It's possible that other estrogen and progestin combinations at lower dosage might not have these increased risks.

New Hormone Rule #2: Women, Consider Estrogen Alternatives, But Wisely

The risks of hormone replacement therapy are leading scientists to search for alternatives. At the forefront of these investigations are a new class of medications known as selective estrogen receptor modulators (SERMs) and estrogen-like compounds found in plants, called phytoestrogens.

SERMs
The recent discovery of SERMs may offer many women a significant edge on successful aging. SERMs are drugs that bind to cell receptors for estrogen to act like proestrogens in bones and blood, but block estrogen receptors in breast tissue to have an anti-estrogen effect. This means that SERMs can protect bone density without increasing cancer risk. In fact the first SERM to take the spotlight, tamoxifen, is now used as a highly effective treatment for breast cancer.

We're now working on the second generation of SERMs, and the leading drug, raloxifene (trade name Evista), may rewrite old rules to end up in the New Rules canon. Not only does raloxifene increase bone mineral density and reduce the risk of breast cancer, but for some women it could also cut the risk of cardiovascular events.

Phytoestrogens
In the search for estrogen alternatives, many women look to Mother Earth. Estrogen-like compounds occur naturally in a number of plants, including isoflavones in soybeans, coumestans in clover and alfalfa sprouts, and lignans in flaxseed. These phytoestrogens (phyto- means "plant") are held up as a beacon of hope by those who prefer not to take pharmaceutical estrogen or SERMs. Do these natural chemicals have the same protective benefits of estrogen without the risks, or are phytoestrogens a product of wishful thinking?

At the moment, we don't know. The phytoestrogens in soy, called isoflavones, are similar in structure and function to estrogen, but like SERMs, they pick and choose which estrogen receptors to connect with or block, and they seem to make smart choices. Isoflavones act as antiestrogens in breast and uterine tissue but proestrogens in blood and bones. Theoretically, isoflavones could provide health benefits to women during and after menopause without increasing cancer risk.

The effects of phytoestrogens are weak compared to estrogen or SERM therapy, and the limited data that we have suggests that, at best, eating a lot of soy may:

• Moderately attenuate bone loss
• Lower total and LDL cholesterol, though the effect on heart disease risk is not known
• Slightly relieve the symptoms of menopause, but far less effectively than estrogen

Until we have long-term research on the effects of phytoestrogen exposure, it's not time to take isoflavone supplements. Isoflavones isolates may not contain the natural compounds found in soy foods and could even turn out to be harmful. For now, feel free to enjoy moderate amounts of whole soy foods in your healthy diet. But don't overdo it, hoping to replace lost estrogen. There's not enough evidence in favor of phytoestrogens, and we know little about the risks of high consumption.

Here's a table that summarizes the facts for estrogen, raloxifene, and phytoestrogens.

Benefit/Risk	Estrogen	SERM	Phytoestrogens	Other Alternatives
Bone Mineral Density	Very good increase	Good increase	Little to no effect	Bisphosphonates (Fosamax), strength exercises
Cardiovascular Disease Risk	Slightly increased	May reduce	May reduce	Diet, exercise, weight management
Total & LDL (bad) cholesterol levels	Lowered	Lowered	Lowered somewhat	Diet, exercise, weight management
Thromboembolism risk	Increased	Increased	None
Breast cancer risk	Increased	Decreased	Not clear
Ovarian cancer risk	Increased	Not clear	Not clear
Uterine cancer risk	Increased if given without progesterone	None	Not clear	Not clear
Hot flashes & other menopause symptoms	Relieves	Can make worse	Little to no effect	Clonidine, Paxil, black cohosh, vitamin E, vaginal estrogen creams

New Hormone Rule #3: Men, Don't Take Testosterone Unless Your Doctor Recommends It

Testosterone, the male counterpart to estrogen, fuels sex drive and helps to maintain muscle mass and bone strength. Unlike estrogen, however, testosterone doesn't decline abruptly with age. In their thirties, many men begin to experience a gradual, progressive decline in testosterone levels at an average rate of about 1% per year. By age 60, about 20% of men are below normal testosterone levels for healthy young men, and the number has grown to 50% of us by age 80. This represents a much less dramatic and more variable change than that faced by the female population; in some men, testosterone levels don't diminish at all. Though we don't know precisely what factors cause testosterone loss, possible ones include genes, excess weight, poor diet, alcohol or tobacco use, stress, and medical conditions. AgeLess living can help you avoid all of these factors except for genetics.

In young men who are genetically deficient in the hormone, testosterone replacement is very effective in boosting libido, increasing muscle mass, and lowering cholesterol. For men middle-aged and above whose testosterone levels have declined below the youthful range of normal, it can be tempting to get a quick injection in hopes of recovering your firm biceps and sexual fire - but you probably shouldn't. Taking supplementary testosterone increases your risk of a heart attack, the biggest threat to your health span. Testosterone replacement can also enlarge the prostate and may increase your prostate cancer risk. In fact, one of the ways doctors treat advanced prostate cancer is with (brace yourself) castration to remove testosterone from your bloodstream or with chemicals that block the hormone's effects (indelicately known as chemical castration). Do you really want to take a hormone that feeds prostate cancer cells?

New Hormone Rule #4: Just Say "No" to Human Growth Hormone, DHEA, Androstenedione, and Melatonin

These days, you can't open your mail, read the paper, or surf the Web without finding a spate of claims for hormones purported to make you age less. As lovely as the prospect sounds, don't believe the hype. We don't have the hormone of eternal youth - at least not yet. Here's the truth about some of the fake contenders.

HGH
Back in 1990, the news media broadcast far and wide the findings from a small study of 21 elderly men in Wisconsin. These participants increased muscle and bone strength, lost fat, and regained the skin of 50-year-olds with a mere 6 months of HGH treatment. The HGH craze was on.

Sounds too good to be true? It is. Unfortunately, the facts don't support the fantasy; not even close. Since that 1990 study, countless controlled clinical trials have failed to confirm the miraculous results of HGH replacement. This was not for lack of trying. Researchers have hunted for the supposed benefits of HGH in men and women alike and found little evidence that growth hormone supplements do anything to slow down the aging process or that a decline in growth hormone levels is a major contributor to age-related bone and muscle loss. Meanwhile, there are clear risks to taking HGH: diabetes and carpal tunnel syndrome.

For now, no one should take growth hormone supplements simply to combat the effects of age. The best ways we know to optimize your natural HGH secretions are to stay active, watch your weight if you're gaining abdominal fat, and get plenty of sleep.

DHEA
Another common acronym in the anti-aging trade is DHEA, or dehydro-epiandrosterone. (You see why the nickname caught on.) A steroid formed in the production of male and female sex hormones, DHEA seems to have gained its sexy reputation by association. However, there's no evidence to support claims that taking DHEA restores amour, melts away love handles, bolsters lagging energy, or lengthens lives.

A number of well-designed clinical studies have administered DHEA to older people with low levels of the hormone and found no discernible effect on body fat, strength, sense of well-being, sexual function, or anything else you might want to improve with age. Other studies have found no consistent relationship between DHEA levels and heart disease or overall mortality. The evidence that taking DHEA can prevent age-related complaints simply doesn't exist.

Androstenedione
Androstenedione is a precursor steroid, which means that the compound can be converted in the body to both testosterone and estrogen, and some believe 'andro' can serve as a natural alternative to chemical steroids to build muscle size and strength. However, the few controlled studies that have been conducted show no such benefit. The list of potential risks, however, is long: heart attack, prostate cancer, decreased good (HDL) cholesterol, acne, and male pattern baldness. Women on andro may experience a new crop of body hair and a deeper voice. I recommend that you say "No" to andro.

Melatonin
Your pineal gland secretes melatonin in response to signals from your eyes about exposure to light and dark. Melatonin secretion peaks at night to signal the brain and body that it's time to go to sleep. This has led to some speculation that low melatonin levels might account for age-related sleep loss as well as other "unspecified" signs of aging. Might it then follow that melatonin supplements can restore healthy sleep and other youthful attributes? Probably not. Age-related sleep loss doesn't appear to be due to any drop in melatonin levels. Older people make plenty of the stuff. Furthermore, melatonin has proven to be a poor sleep medication, and people who take it show no other signs of aging less.

Still, you might not want to throw your melatonin stash away. A supplement can be helpful for resetting your body clock to compensate for jet lag, early weekday mornings after late-night weekends, night shift work, or for blind individuals who don't respond to cycles of light and dark with appropriate melatonin secretion.

Have an AgeLess Day

Still thinking about hormones? Think again. These AgeLess sleep, exercise and diet activities give hormones a natural boost.

• Get up at the same time each morning to regularize secretion of melatonin.
• Toss out your HGH, DHEA, androstenedione, and isoflavone supplements.
• Don't beg your doctor for testosterone.
• Work out. An aerobic workout followed by a weight-lifting session can provide many of the benefits of estrogen, testosterone, and growth hormone without the risks.
• Enjoy soy. Sure, have some tofu in that stir-fry! Moderate amounts of soy are part of a longevity diet for men and women alike - but don't expect anti-aging miracles.
• Re-assess. If you'e taking HRT, now is the time to re-assess the need and duration of its use and consider possible alternatives. Sit down and write your list of pros, cons, questions, and concerns. Make an appointment to discuss them with your doctor.
• Sleep tight! Get a good night's sleep to maximize secretion of HGH and boost your energy in the world's most natural way.

In the next, and final, extract from "AgeLess", Dean Schneider gives advice on "shopping for longevity" and a few concluding thoughts.