Sex Hormones

The perfect hormonal balance in each sex requires complementary levels of androgens from the opposite sex: women need a bit of testosterone and men, a bit of estrogen. Additionally, pregnenolone, as a precursor hormone from which many of the sex steroids are produced, is critical to both sexes. A HRT plan customized for your health needs restores this integral and intricate balance.

One of the most startling clinical studies ever conducted was a 1996 survey examining the benefits of ERT on 454 women born between the years of 1900 and 1915 who were members of the Kaiser Permanente Medical Care Program in Oakland, California. About half the group, 232 women, used ERT for a least a year, starting in 1969, while the rest, 222 age-matched women did not. This is what Dr. Bruce Ettinger and his colleagues found when they compared the estrogen users versus the nonusers:

• Overall mortality from all causes were reduced 46% (53 deaths for estrogen takers versus 87 for nonusers)
• Coronary heart disease deaths were reduced 60%
• Stroke deaths were reduced 70%
• Cancer deaths were approximately the same in both groups, with the estrogen users having a slightly higher death rate from breast cancer and a slightly lower death rate from lung cancer

"The overall benefit of long-term estrogen use is large and positive," the study concluded, noting that women who use this "relatively inexpensive drug can substantially reduce their overall risk of dying prematurely." Ultimately, the risk of death in women from heart disease is almost 10 times greater than premature death from breast cancer. Given the fantastic improvements in the early detection and prevention of breast cancer, with modern detection such as mammography, ERT should be viewed as a big net win in the life extension equation.

Estrogen is a heart saver. In studies involving thousands of women, ERT has been shown to protect against coronary heart disease and improve blood lipids, raising the good HDL cholesterol and lowering the bad LDL cholesterol. But the opposite happens when you remove estrogen by the taking out the ovaries. The LDL cholesterol and total cholesterol jumps up, escalating the risk of heart disease, although the disease may not appear for 20 years.

Today, many doctors prescribe HRT, a combination of estrogen plus progesterone or its synthetic equivalent, progestin. Although the hormonal combination more closely mimics the body prior to menopause, it greatly reduces the risk of endometrial cancer associated with using estrogen alone, but it may also reduce some of the benefits of estrogen on the heart. But taking estrogen in combination with progesterone is still more favorable for the heart than not taking any hormones.

There is evidence that estrogen may prevent Alzheimer's disease and benefit those who are afflicted. Two studies show that women on estrogen are far less likely to develop Alzheimer's. The first, a study of a group of 143 women with Alzheimer's by Victor Henderson and his associates, found only 7% were on ERT, while 18% of a non-demented control group of 92 matched for age and education used estrogen post-menopausally.

The second study on estrogen and Alzheimer's, conducted on 9,000 women living in a retirement community in southern California, found that those on ERT had a 30 to 40% lowered risk of developing Alzheimer's compared with those not receiving ERT. Henderson and his colleagues also found that women who had Alzheimer's and were receiving estrogen did better on a test for mental function than the women who had Alzheimer's and were not on estrogen. One way in which estrogen may help the Alzheimer patient is by stimulating the production of acetylcholine, a neurotransmitter involved in memory. Dr. Howard Fillit, a geriatrician at Mount Sinai Medical Center in New York City, found that after only three weeks of daily treatment with estrogen, women with mild to moderate Alzheimer's symptoms were suddenly able to recall the day and month of the year, even though they were previously unable to do this. The women were also more alert, ate and slept better and were more sociable. And a recent study found that estrogen reduced the levels of beta-amyloid, a toxic protein now considered to be a marker of Alzheimer's.

These studies have compelled the National Institutes of Health (NIH) to fund an unprecedented comprehensive study of the effects of HRT on Alzheimer's. The five-year study will examine 4,500 women age 75 and older who belong to the Kaiser Permanante medical group in southern California. It includes women who are on long-term HRT, short-term HRT, and those who have never had HRT. "This will be the first large-scale study of whether HRT can prevent Alzheimer's in women genetically predisposed to the disease," says Diana Petitti, M.D., one of the lead researchers.

The foremost concern about using estrogen is whether it increases the risk of cancer, particularly endometrial cancer. When progesterone is given along with estrogen for ten or more days per cycle, it not only eliminates the risk of this cancer but may actually reduce it beyond that which occurs spontaneously.

The relationship between HRT and breast cancer is much less clear cut. Studies go both ways. One 1995 New England Journal of Medicine study by researchers at Harvard Medical School found that women who currently used ERT were 32% more likely to develop breast cancer, and women who used both estrogen and progestin were 41% more likely to develop breast cancer, when compared to women who never used HRT. Long-term users were 46% more like to develop breast cancer than nonusers. Age was even a bigger risk factor, with older women between 60 and 64 who had been on HRT for more than five years having 71% higher risk of developing breast cancer than women who had never taken estrogen.

But other studies found just the opposite. In a Journal of the American Medical Association study, which looked at a group of 537 patients with breast cancer compared with 492 randomly selected control women without a history of breast cancer, there was no statistical difference between the use of HRT in those who breast cancer and those who did not. If anything, the researchers concluded, those who used the combination HRT for eight years or more had a reduced risk of breast cancer.

And, according to an Australian study, HRT may actually have a protective effect against breast cancer recurrence. Dr. Jennifer Dew and her associates at the Royal Hospital for Women in Paddington, compared a group of 167 women who used HRT to relieve severe menopausal symptoms after they were treated for breast cancer with an equal number of women with a history of breast cancer who had not taken the hormone.

After a follow-up period of seven years, those on HRT had a recurrence rate that was nearly half that of the control group, 9.6%, compared with 18.5%, respectively. 90% of the hormone users took continuous progestin along with estrogen, while only 10% used estrogen alone. The researchers suggest that a combined continuous regimen of estrogen and progestin could counteract the cell division needed to produce a cancer.

In addition, an American Cancer Society study, which followed more than 422,000 postmenopausal women for nine years, showed that women on ERT had a 16% lower risk of dying from breast cancer than those who did not take the hormone. Dr. Dawn Willis, the lead researcher, suggests that the lower death rate among estrogen users may be that they are more likely to get mammograms on a regular basis and be treated earlier.

A study published in the June 1999 issue of JAMA found that ERT may slightly increase the risk of developing tumors, but they tend to be less aggressive and easier to kill. With no hormone replacement therapy, you have more aggressive tumors and no benefits from estrogen.

Until recently, high testosterone levels were assumed the cause of why men developed heart disease at a younger age than women did. But a recent study at Columbia University College of Physicians and Surgeons indicates that it is far from being the culprit. The male sex hormone may actually help protect the heart. When the researchers looked at 55 men undergoing x-ray exams of their coronary arteries, they found that the men with higher levels of testosterone had higher levels of protective HDL cholesterol, while those with low testosterone had higher degrees of heart disease as shown by their coronary clogging. Testosterone supplementation may also lower the bad LDL cholesterol and total cholesterol. And low testosterone is also correlated with hypertension, obesity, and increased waist-to-hip ratio -- all heart attack risk factors.

Testosterone replacement therapy (TRT) in men who are deficient in male hormones appears to be as potent in its anti-aging effect as the counterpart, estrogen and progesterone replacement, for women. It renewed strength, improved balance, raised red blood cell count, increased libido, and lowered LDL cholesterol. In one double-blind study, 12 of 13 men who were receiving testosterone rather than placebo could tell they were on the active drug because they felt more aggressive and energetic at work, and had better sex, including an increased ability to maintain an erection.

Bone loss and osteoporosis is not only a female problem. Men after age 60 have a dramatic rise in hip fractures, with the rate doubling every decade. Hypogonadal males (men with abnormally low levels of testosterone) are six times more likely to break a hip during a fall than are those with normal testosterone levels. According to studies of TRT in both young hypogonadal men and older men with low testosterone levels, TRT increased bone density, bone formation, and bone minerals, such as osteocalcin.

Testosterone benefits age-related autoimmune disease. Giving male hormones to men with autoimmune conditions, such as rheumatoid arthritis or systemic lupus erythematosus, improved their condition. Testosterone, like estrogen, also heightens mood and sense of well being and increases some mental functions, particularly visual spatial ability.

UCLA Endocrinologist Stanley Korenman, M.D., professor of endocrinology, finds that when he gives TRT to older men who are deficient in testosterone, it improves their activity level, mood, libido and sexual function, although it doesn't help impotence. The two side effects to watch out for, he says, are a rise in PSA levels, and a rise in hematocrit, a measure of blood volume.

A concern with testosterone replacement therapy is increased risk of prostate cancer. This is the second most diagnosed malignancy in men and the second leading killer of men after heart disease. The prostate gland is a small, chestnut-sized organ that sits just below the urinary bladder. Among its functions are the production of semen and storage of sperm. Signs of prostate abnormality -- which can occur after age 40 -- include frequent daytime and night time urination, slight pain or burning sensation during urination, dribbling or stopping urine flow, and leakage of urine.

Early detection of prostate cancer, which is lifesaving, includes doing a digital rectal exam (DRE) in which the physician palpates the back of the prostate and screening the blood levels of PSA (prostate specific antigen). Normal is 0 to 4, while men with cancer generally have PSA levels exceeding 10.

Testosterone can also potentially aggravate problems like benign prostatic hyperplasia (BPH), a noncancerous enlargement of the prostate, or promote an undetected cancer. For this reason, it is important to have regular prostate exams and PSA tests. As an added precaution, Dr. Michael Perring, medical director of the Optimal Health Clinic in London, who has treated over 800 patients with testosterone for symptoms of male menopause, recommends yearly ultrasound examinations of the prostate in addition to a PSA test.

Despite concerns of testosterone and malignancy studies have not proven any definitive link. In fact, this issue remains unclear as testosterone deficiency may be a risk factor for prostate malignancy, as optimal levels of this hormone appear to stimulate the immune system and its cancer fighting cells.

If you're over 40 and feeling old, like your life could use some zip, discuss the possibility of a hormone replacement program with your physician. Hormones can help you keep the bounce in your step and the mojo rising for those many more years ahead.

TESTOSTERONE

Between their late 40s and early 70s, men experience a gradual drop in testosterone of about 50%, with about 20% of men over age 60 have levels below normal. This hormone has been accused as being the trigger for over-aggression, overactive sex drive, coronary heart disease and heart attack: many of these notions are being overturned with new research studies.

• Studies show that testosterone levels rise in response to aggressive behavior, rather than the other way around. Rises in testosterone levels do not automatically lead to aggression, and violent behavior cannot be attributed testosterone alone.
• A study at Columbia University in New York has shown that men with higher levels of testosterone had less accumulation of fatty plaque in their coronary arteries, and had higher levels of HDL ("good") cholesterol.
• Muscle mass and strength increases, while abdominal fat decreases, in men receiving testosterone injections.
• Testosterone is important to neurobehavioral functions including sexual arousal, emotional state, and cognition. Evidence is mounting for a link between waning testosterone levels and major depression in men.
• Men lose about 25% of their bone mass by age 85 and experience a significant number of hip fractures. Men with osteoporosis may benefit from testosterone replacement therapy to increase the bone mineral density.
• Illnesses such as diabetes, kidney failure, and AIDS can lead to testosterone deficiency.
• Testosterone supplementation reverses the damage to skeletal and soft tissues caused by long-term use of the glucocorticosteroid class of asthma medications.
• In men seeking to have children, testosterone is important to production and viability of sperm.

Note: The role of testosterone in prostate cancer is not well understood, with some studies pointing to an excess, and others to a deficiency, as a contributing factor. Testosterone therapy can adversely affect liver function, and may increase red cells in the blood (elevating stroke risk).

Making the News:

In July 1999, the prestigious International Clinical Synthesis Panel on HRT issued its affirmation of the value of hormone replacement therapy for postmenopausal women. The panel found that:

• For the symptoms of menopause, HRT is "the treatment of choice" -- no other treatment is as effective
• For osteoporosis, benefits are "very well founded"
• In cardiovascular disease, the "overwhelming observational data" suggests cardioprotection
• In dementia, "there may be long-term beneficial effect"
• For colonrectal cancer, a possible 50% protective role

Here are some of the reasons for their glowing review:

• For life extension: Postmenopausal women face at least 15 times the risk of dying of heart disease than of an estrogen-dependent cancer. In 1993, Zubialde and colleagues found that women who began hormone replacement therapy at age 50 years showed benefits ranging from 0.3 years of additional life for those at low risk of developing coronary artery disease, to 2.3 years for those at high risk. Postmenopausal estrogen therapy reduces the risk of developing coronary artery disease, thereby increasing life expectancy.
• Estrogen is also beneficial for women who are at great risk for stroke or hypertension because it raises the HDL cholesterol level and lowers the LDL cholesterol, decreases the risk of heart attack, and does not elevate blood pressure.
• HRT can augment skeletal mass and reduce fracture incidence, offering an important prevention approach for osteoporosis.
• Several studies have suggested that estrogen replacement therapy in postmenopausal women improves cognition, prevents development of dementia, and improves the severity of dementia.

Note: Because estrogen has been linked to a slight increase in risk of cancers of breast, ovary, and uterus, it is generally not recommended for women with a family or personal history of those conditions.