DHEA Is Back in the Spotlight

Stopping the Biological Clock
in Postmenopausal Women

Hormone replacement with DHEA helps prevent bone loss

e've all OD'd on bad news lately, so let's hear some good news. In the field of nutritional supplements, there is always good news, because Mother Nature's treasure chest of biological secrets is far from exhausted, and medical researchers, like the greedy pirates of old, have an insatiable lust for more "booty." With scientists, it's partly the unquenchable drive to learn the Truth, partly the desire to help people lead healthier lives, partly the need to feed their egos, and partly the need to feed their families. Who cares, as long as they keep getting paid to find things out?

DHEA AS HORMONE REPLACEMENT THERAPY?
One interesting thing found out recently by Italian researchers at the University of Modena and the University of Pisa is that our old friend DHEA (dehydroepiandrosterone) can be helpful in enhancing the postmenopausal years in women.1 (Well, of course in women - men don't undergo menopause, the silly term "male menopause" notwithstanding. But men, there are aspects of this article that you should find interesting too, apart from merely wanting to understand more about women.)

DHEA, you may recall, is a steroid hormone found in both men and women. It is by far the most prevalent one in the blood, and it is a precursor to a variety of other hormones, including the male and female sex hormones. In women, according to the Italian researchers, DHEA appears to offer some of the same benefits as those of hormone replacement therapy, a regimen that millions of women undergo to maintain the health and vigor of their youth by making the aging clock run a little more slowly.

OUR HORMONES DECLINE WITH AGE
The reason why hormones need to be replaced - especially in women but also, to a lesser extent, in men - is that after the age of about 40, there is a marked decrease in hormone production, and with it a broad spectrum of age-related decline that slowly robs us of our youthful vitality. Many researchers believe, for example, that some of the notable signs of aging, such as shrinking muscle mass and decreasing bone density, are related to this age-associated decline in hormone production.

In men, the decline in sex-hormone output is relatively steady, but in women it can be a roller-coaster ride. Menopause is a wrenching readjustment of body chemistry arising from dramatic changes in hormone levels during just a few years. The aftermath, called postmenopause, leaves women with special kinds of health problems that can affect many organs and their functions, such as the urogenital, skin, cardiovascular, and skeletal systems. Among the potential problems are those associated with a woman's diminished desire for sex and her ability to enjoy it. Not surprisingly, such problems are often accompanied by a general decline in a woman's sense of well-being.

HORMONE REPLACEMENT THERAPY WORKS
Readers of this magazine know that conventional hormone replacement therapy (HRT) for women, although very successful by and large, is a mixed blessing, with side effects that tend to offset the benefits to some degree. In part this is because HRT entails the use of synthetic hormones, such as the progestins in Provera®, or natural ones that are natural for horses, not humans. The well-known drug Premarin® is called that because some of its components are extracted from the urine of pregnant mares.

An attractive alternative to conventional HRT is the use of natural progesterone, a female sex hormone that is found in men as well. (Remember that all men have some female sex hormones in their systems, just as all women have some male sex hormones in theirs.) Progesterone is a precursor to the estrogens, of which there are three primary ones: estrone, estradiol, and estriol, known collectively as "estrogen." It is also a precursor to testosterone. (For more on the many benefits of progesterone versus conventional HRT, see "What Women Want to Know About Natural Progesterone," Life Enhancement, November 2000.)

WHAT THE ITALIANS SAY ABOUT DHEA
But what about DHEA, a hormone whose decline begins, rather steeply, in our twenties and keeps on dropping? The levels are down to about 50% of their peak value when we are in our forties, and to less than 20% when we are in our seventies. DHEA is a precursor to the male sex hormone androstenedione, which in turn is a precursor to both testosterone and estrogen.

It is known that many (but not all) users of DHEA - particularly women - notice an increase in libido when they take the supplement. This may be due to a significant increase in testosterone, which has a prosexual effect. The effect is dramatically evident in older women, especially those over 70, who have been reported to experience not only increased desire but also increased sexual activity and satisfaction.2 (See "DHEA Improves Sex and Helps Keep Women in Love," Life Enhancement, June 2000.)


According to the researchers,
DHEA offers some of the same
benefits as those of hormone
replacement therapy.

"Older women," of course, are well into postmenopause, a stage of life that can be both liberating and oppressive in various ways, including aspects of a woman's sexuality and the pleasure she can derive from it. Optimizing women's capacity for a healthy, satisfying sex life is one of the objectives - although not necessarily the most important one - of hormone replacement therapy.

With regard to DHEA, it is intriguing to hear the Italian researchers say,1

Our data support the hypothesis that DHEA treatment acts similarly to estrogen-progestin replacement therapy . . . This suggests that DHEA is more than a simple "diet integrator" or "antiaging" product, but rather should be considered an effective hormone replacement treatment.

FOUR GROUPS OF WOMEN ON DHEA GET TWELVE BLOOD TESTS
Let us see what drew the researchers (who are affiliated with the departments of obstetrics and gynecology at their universities) to that conclusion. They set out to determine the effects of chronic DHEA administration (50 mg per day orally for six months) on the function of certain endocrine systems - those responsible for the release of growth hormone and of insulin - like growth factor-1 (described below).


Many users of DHEA -
particularly women - notice an
increase in libido when they
take the supplement.

The 31 subjects in this trial were healthy postmenopausal women who were not receiving any kind of treatment related to that physiological state. They were selected to be either "early postmenopausal" (aged 50 to 55) or "late postmenopausal" (60 to 65). Within those categories, they were selected to have a body mass index in either the 20 to 24 range (ideal to slightly overweight) or the 25 to 30 range (significantly overweight to obese). Thus there were four categories of subjects in all, and part of the objective was to see whether these groups would respond differently to the DHEA regimen.

The "Good" News About DHEA

At the beginning of the article, we mentioned that there is always good news in the nutritional supplement arena, and that is true. Good news can take different forms, however. Sometimes it's about something brand new and unexpected, such as the important role of NAD (a derivative of niacin) in the function of antiaging genes. Sometimes it supplements existing knowledge by adding something new to it - as in the research described in the article - or by providing new confirmation of that knowledge, thereby increasing our confidence in its validity.

Sometimes, however, good news comes disguised as bad news, as when it contradicts something good that we thought we knew, showing it not to be true after all - or apparently not true, anyway, according to the latest and best effort to understand what the truth really is. What makes such news "good," of course, is that it represents an advance in our knowledge, allowing us to abandon a discredited idea and embrace the new truth. That is genuine progress, which always trumps the status quo.

ARE YOU SURPRISED TOO?
Obviously, we're leading up to something regarding DHEA, so let's get right to it. It has been claimed that DHEA improves memory, mood, and a sense of well-being in older people; the study generally cited in this regard was published in 1994.1 A new, more rigorous study, however, conducted on a group of 46 normal older men (aged 62-76) at the University of Cambridge in England, has found no evidence to support these claims - at least not in normal (i.e., not depressed or otherwise afflicted) older men.2

The British researchers conducted a randomized, double-blind, placebo-controlled, crossover study of 26 weeks' duration, using an arsenal of eight validated tests of cognition and well-being. The treatment consisted of 50 mg per day orally for 13 weeks, followed by placebo for 13 weeks, or the reverse. The authors stated, "When treatment effects were analyzed, no significant effects of DHEA were observed on any of the trial outcomes, providing no support for benefits of DHEA supplementation for cognition or well-being in normal older men in the shorter term."

This conclusion appears to have surprised the researchers, who discuss the theoretical reasons why DHEA could be expected to demonstrate benefits for mood and cognitive function. The reasons hinge on the fact that DHEA could act as a "buffer" against the memory- and mood-impairing effects of the stress hormone cortisol. Because cortisol levels do not generally decline with age (in fact, they sometimes increase with age), while DHEA levels do decline, the ratio of cortisol to DHEA increases with age - an undesirable condition. Supplementing with DHEA tends to reduce this ratio to more benign levels and might therefore be expected to have beneficial effects on mood and cognition, among other aspects of health.

ARE YOU DEPRESSED? TRY DHEA!
But facts are facts - at least until even more solid ones are discovered.The positive findings of the 1994 study (which was apparently not very well designed, according to the British scientists) have also not been confirmed by other studies done on normal older people. On people with problems, however, it's a different story. For example, improved mood due to DHEA has been reported in people suffering from severe depression3 or from dysthymia, a mood disorder associated with mild depression.4 (For more on this subject, see "DHEA: A Better Antidepressant," Life Enhancement, July 1999.)

Could the new British study itself be fallible? Of course - any study can be, and with admirable candor, the researchers discuss at length the potential flaws in their work. They freely admit that their word is not the final one. Nonetheless, it appears that their study has raised the bar of quality in this field and has established - for now - that DHEA has little or no value for improving mood or cognition in normal older men, even though it clearly has value for both men and women suffering from depression.

As for normal older women, we just don't know. But since it is known that men and women metabolize DHEA very differently, it is quite possible that, in the areas of mood and cognition, women benefit from DHEA in ways that men do not. (For more on the gender differences of DHEA's actions, see "DHEA: The Most Versatile Hormone," Life Enhancement, February 2001.)

References

  1. Morales AJ, Nolan JJ, Nelson JC, Yen SS. Effects of replacement dose of dehydroepiandrosterone in men and women of advancing age. J Clin Endocrinol Metab 1994 Jun;78(6):1360-7. Erratum: J Clin Endocrinol Metab 1995 Sep;80(9):2799.
  2. van Niekerk JK, Huppert FA, Herbert J. Salivary cortisol and DHEA: association with measures of cognition and well-being in normal older men,and effects of three months of DHEA supplementation. Psychoneuroendocrinology 2001;26:591-612.
  3. Wolkowitz OM, Reus VI, Keebler A, Nelson N, Friedland M, Brizendine L, Roberts E. Double-blind treatment of major depression with dehydroepiandrosterone. Am J Psychiatry 1999 Apr;156(4):646-9.
  4. Bloch M, Schmidt PJ, Danaceau MA, Adams LP, Rubinow DR. Dehydroepiandrosterone treatment of midlife dysthymia. Biol Psychiatry 1999;45:1533-41.

At the outset of the study and again at three months and six months, the women's blood was tested for the following 12 substances:

  • Luteinizing hormone (LH) and follicle-stimulating hormone (FSH) - These are pituitary hormones that jointly stimulate the process of ovulation in women and the production of testosterone in men.
  • DHEA and DHEA sulfate - The latter compound is formed by metabolism of DHEA in the liver. About 90% of the DHEA in our bloodstream actually exists in the form of DHEA sulfate.
  • Progesterone - This hormone, a chemical derivative of pregnenolone (the "mother of all sex hormones") is a precursor not only to DHEA, estrogen, and testosterone, but to many other steroid hormones as well, including cortisol and cortisone.
  • Estrone and estradiol - These are the two most biologically active of the three primary estrogens, although they represent only about 20-40% of the total; estriol represents about 60-80%. All three estrogens are derived from progesterone and DHEA.
  • Androstenedione and testosterone - Androstenedione is derived from both progesterone and DHEA (via different pathways) and leads to testosterone and estrogen (via different pathways).
  • Growth hormone (GH) and insulin-like growth factor-1 (IGF-1) - These are hormones that, as their names suggest, are involved in growth processes, but they also play key roles in various aspects of the metabolism of proteins, carbohydrates, and lipids.
  • Osteocalcin - This is a protein whose level in the blood is a good indicator of the rate of formation of new bone tissue. It is produced in bone by osteoblasts, or bone-forming cells, and some of it escapes into the bloodstream, where it can be easily measured.

OLDER WOMEN "CATCH UP" TO YOUNGER ONES
At the outset of the study, the older women, in both the normal and overweight groups, showed substantially lower levels of DHEA, DHEA sulfate, and androstenedione than their younger counterparts (levels of the other nine substances were, for the most part, similar). Over the course of the study, there were major increases in the blood levels of all three of these hormones in all four groups of women, but the older women showed greater gains than the younger ones, and the disparities between the older and younger groups were largely eliminated.


The older women showed
greater gains than the younger
ones, and the disparities between
the older and younger groups
were largely eliminated.

Also showing substantial - often dramatic - increases were estrone, estradiol, testosterone, the two growth-related hormones, and osteocalcin. Progesterone levels increased only slightly, and the levels of LH and FSH, as expected, decreased significantly.

BONE LOSS IS HALTED
To evaluate the progress of age-related bone loss (osteoporosis) in these women, the researchers made additional measurements of bone-mass density in the lumbar spine and the femur (thigh bone). Over the six-month course of the study, there were no statistically significant changes in the density values in any of the four groups of women.


By taking DHEA, the women
were able to more or less
"stop the clock" on bone loss.

But wait - the levels of osteocalcin had increased by anywhere from 112% to 171%, clearly indicating accelerated bone growth. So why did the bone density not increase? Presumably because the increased bone formation was offsetting what would otherwise have been an age-related decrease in bone density during the six-month period. Thus, by taking DHEA, the women were able to more or less "stop the clock" on bone loss. (For information on the beneficial role of natural progesterone in osteoporosis, see "Hip,Hip, Hooray for Progesterone," Life Enhancement, May 2001.)

ENDOMETRIUM IS OK
In another test of the women's health, the researchers used an ultrasound technique to measure the thickness of their uterine lining, called the endometrium. Changes in the endometrium would be a cause for concern, because endometrial cancer is one of the known risk factors in conventional hormone replacement therapy, and estrogen is believed to be the culprit. Although six months is a relatively short time in which to observe such an effect, it was nonetheless gratifying to note that there were no statistically significant changes in endometrial thickness in the women.

A STRONG ENDORSEMENT OF DHEA
All these results, and more, prompted the researchers to write, "Oral DHEA treatment annulled the differences observed between early and late postmenopause, including those strictly related to excess body weight." And the results led them to their final conclusion, quoted above, regarding the use of DHEA as an effective hormone replacement treatment. Altogether, it was a strong endorsement of the value of DHEA in helping to alleviate some of the problems faced by postmenopausal women.

DHEA HAS OTHER BENEFITS TOO
A growing body of research points to a variety of other potential roles for DHEA in human health. Supplementing with this hormone may result in some combination of benefits in the areas of libido (primarily in older women); immune function; weight loss; resistance to diseases, including autoimmune diseases, heart disease (primarily in men), diabetes, osteoporosis, and perhaps even cancer. Animal studies even indicate that there may be a life-extension effect. (For more on these topics, see "DHEA: The Most Versatile Hormone," Life Enhancement, February 2001.)

HOW MUCH SHOULD YOU TAKE?
Studies have shown that the lifelong decline in DHEA levels is due primarily, if not exclusively, to a decrease in output from the adrenal glands (the primary source of our DHEA), not to a change in metabolism.

With DHEA supplementation, the principal objective in most cases is to restore this hormone to the youthful levels of our twenties. It is generally accepted that this can be accomplished with about 50 mg per day, a dose that has been found to be safe for both men and women.3

Some people may benefit just as much from smaller doses - especially women, who typically need less DHEA than men for restoring youthful levels - and larger doses may also be considered, but only on the advice of a physician. Side effects are minor and uncommon, especially with low doses. The two that are reported most often are acne and unwanted facial hair in women. These can be eliminated by reducing the dosage or by stopping treatment altogether.

Whatever your focus, there's a good chance that DHEA can be good news for your health program.

References

  1. Genazzani AD, Stomati M, Strucchi C, Puccetti S, Luisi S, Genazzani AR. Oral dehydroepiandrosterone supplementation modulates spontaneous and growth hormone-releasing hormone-induced growth hormone and insulin-like growth factor-1 secretion in early and late postmenopausal women. Fertil Steril 2001;76(2):241-8.
  2. Baulieu ÉÉ, Thomas G, Legrain S, Lahlou N, Roger M, Debuire B, Faucounau V, Girard L, Hervy MP, Latour F, Leaud MC, Mokrane A, Pitti-Ferrandi H, Trivalle C, de Lacharrière O, Nouveau S, Rakoto-Arison B, Souberbielle JC, Raison J, Le Bouc Y, Raynaud A, Girerd X, Forette F. Dehydroepiandrosterone (DHEA), DHEA sulfate, and aging: contribution of the DHEAge Study to a sociobiomedical issue. Proc Natl Acad Sci 2000 Apr11;97(8):4279-84.
  3. Legrain S, Massien C, Lahlou N, Roger M, Debuire B, Diquet B, Chatellier G, Azizi M, Faucounau V, Porchet H, Forette F, Baulieu ÉÉ. Dehydroepiandrosterone replacement administration: pharmacokinetic and pharmacodynamic studies in healthy elderly subjects. J Clin Endocrinol Metab 2000;85(9):3208-17.

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