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DHEA, and degenerative disorders of ageing
Can replacing DHEA
through oral, sublingual or transdermal route help prevent the degenerative
disorders of ageing? Is it safe?
Research keeps answering these questions in the affirmative. At the same time,
the picture is complex. DHEA appears to be metabolized differently in men than
in women, and consequently have somewhat different effects. It may be more
crucial to men for cardiovascular protection, yet the antidepressant effect may
be stronger for women, who are also more likely to report an increase in
libido, and show improvement in skin thickness and bone mass. Interestingly,
the rise in serum estradiol and testosterone is more commonly seen in women
(Legrain 2000; Baulieu 2000). At this point, the majority of studies point to
anti-ageing benefits of DHEA replacement that simply cannot be ignored.
Note: Women diagnosed with breast cancer and men with prostate cancer should
not take DHEA, unless under strict medical supervision.
Hormone Replacement For Older Men And Postmenopausal Women
"Andropause," also referred to as "partial androgen deficiency
in the ageing male," is characterized by symptoms such as decline in
muscle mass and strength, increase in body fat, especially around the abdomen,
dry skin, reduction in libido, fatigue, loss of bone mass and mood disorders
such as depression and apathy. The simple answer seems to be testosterone and
DHEA replacement. Mainstream physicians are slowly beginning to accept the need
for testosterone replacement, but most are still unaware of the need to replace
DHEA as well.
One of the most exciting studies on the importance of DHEA for older men was
published by Morley (1997). Morley found that bioavailable testosterone (also
known as "free testosterone," meaning testosterone not bound to sex
hormone binding-globulin [SHBG]), correlated best with various markers of
physical and cognitive function. DHEA, in turn, correlated well with the levels
of bioavailable testosterone. It is well known that both free testosterone and
DHEA dramatically decline with ageing. It is also known that DHEA can be easily
converted to testosterone, and in that sense DHEA and its sulfated form serve
as precursors for testosterone. But the values obtained in this study indicated
a larger involvement of DHEA in the regulation of the levels of free
testosterone. As Morley puts it, "The rate of decrease in bioavailable
testosterone paralleled almost exactly that of DHEA." Free testosterone
travels in the bloodstream bound to albumin, a protein in the serum that can
serve as a carrier for various substances needed by the tissues. Morley
suggests that DHEA facilitates the binding of testosterone to albumin. If this
hypothesis is correct, then DHEA would be a very welcome addition to
testosterone replacement. Total testosterone does not decline as rapidly with
ageing in men; it is the loss of free testosterone that is crucial. The right
dose of DHEA would presumably increase both DHEA and the delivery of free
testosterone to tissue receptors.
Several other studies have confirmed the benefits of DHEA replacement. For
instance, a Czech study investigated the effects of transdermal DHEA (50 mg in
gel) on men of various ages (mean age 52). The authors found that dermal DHEA
was well absorbed and quickly converted to DHEA-S, androstenedione, and then
the estrogenic and androgenic metabolites, including estradiol and
testosterone. Negative correlations were found between DHEA and lipoprotein
(a), DHEA-S and cholesterol, and DHEA, DHEA-S, testosterone and triglycerides.
In other words, as DHEA levels rose, the levels of various serum lipids went
down in a way that indicated cardioprotective benefits. There was, however, a
decrease in endogenous DHEA. Because of the brief duration of the study, the
main conclusion that can be drawn is that the transdermal route of DHEA
application (gel) does significantly increase the levels of those steroids that
are the metabolites of DHEA.
DHEA supplementation may be of most help to both men and women over 70, since
their natural production has usually suffered a profound decline by that age. A
recent study investigated the effects of 50 mg oral DHEA per day for six months
on men and women between the ages of 72 and 74. In response to DHEA
replacement, both sexes showed an increase in bone mineral density, both total
and in lumbar spine, and an overall increase in lean body mass combined with a
decrease in fat mass. DHEA replacement also resulted in increased IGF-1 and
total testosterone. At the same time, a small placebo-controlled pilot study at
a University of Vienna impotence clinic found that supplementation with 50 mg
DHEA resulted in an improvement in erectile function without an increase in PSA
or prostate volume. Such findings indicate that DHEA replacement can at least
partly reverse ageing-related changes in the elderly, increasing the sense of
well-being and sexual function.
Speaking of the prostate, the fear that is often raised when it comes to any
androgen replacement is the possibility of increased risk of prostate cancer.
Some unexpected findings in animal studies suggest that starting DHEA treatment
early may in fact help prevent prostate cancer. In a study by McCormick and Rao
(1999), rats treated with DHEA prior to exposure to carcinogen appeared to be
resistant to developing prostate cancer. As the authors state, "DHEA
inhibits prostate cancer induction both when chronic administration is begun
prior to carcinogen exposure, and when administration is delayed until
preneoplastic prostate lesions are present." While retinoic acid turned
out to be the most potent inhibitor of prostate cancer induction, DHEA produced
sufficiently dramatic results to make the authors name both retinoic acid and
DHEA as "the most active agents" for the chemoprevention of prostate
cancer.
Another study by Rao confirmed that, "nontoxic doses of DHEA confer
significant protection against prostate carcinogenesis in rats."
Furthermore, the findings indicate that DHEA is effective also in later stages
of induction and can inhibit the progression of precancerous lesions to
invasive cancer. We do know that DHEA may help prevent certain kinds of cancer.
Likewise, some holistic physicians believe that if androgen replacement is
started early enough, both DHEA and testosterone actually help prevent prostate
cancer (although as a precaution, holistic physicians also recommend
supplements such as zinc, saw-palmetto, omega-3 fatty acids, lycopene and
flavonoids [green tea, soy], as well as regular exercise). More research is
obviously needed. For now, we have the findings of one in-vitro study using
culture prostate cancer cells, showing that while the so-called "strong
form" of testosterone, dehydroepiandrosterone (DHT) stimulated cell
growth, DHEA had no effect. Likewise, patients with prostate cancer do not
appear to have higher DHEA levels than healthy controls, as confirmed by a
recent study done at the University of Vienna (Schatzl 2000). Nevertheless, it
is too early to make any firm statements about DHEA and the risk of prostate
cancer. (Note of caution: Our knowledge is incomplete, and it is better to err
on the side of caution. Men diagnosed with prostate cancer should not take
DHEA.)
Because of the risks involved in the mainstream hormone replacement therapy for
postmenopausal women, scientists have turned their attention to DHEA as a
possible alternative. Several studies have explored the effects of short-term
treatment with DHEA on postmenopausal women. It is worth noting that while in
men the levels of DHEA decline in a linear fashion, in women there is a
dramatic 40% fall during the sixth decade, reflecting menopause. This is due to
the fact that a portion of women's DHEA is produced by the ovaries. After
menopause the ovarian production of androgens normally diminishes or even
ceases with ovarian atrophy. Recent findings from the Rancho Bernardo Study
indicate that women in the 50 to 89 age range have lower levels of DHEA than
men and, what is potentially more worrisome, a higher cortisol/DHEA-S ratio.
The latter may be related to women's higher risk for osteoporosis and decline
in brain function, including greater susceptibility to depression and
Alzheimer's disease.
There is a special interest in the ability of DHEA to improve the sense of
well-being in postmenopausal women. This effect appears to correlate with the
rise in the levels of circulating beta endorphins, known to decline with
menopause. One recent Italian study compared women taking 50 mg of DHEA sulfate
with women using the low-dose (50 micrograms) estradiol patch, and women taking
both DHEA sulfate and using the low-dose estradiol patch. All three groups
showed a similar improvement in the levels of beta endorphins and a decrease in
menopausal symptoms. The group receiving DHEA or DHEA plus the estradiol patch
also showed higher levels of DHEA, DHEA-S, androstenedione and testosterone. In
addition, the group receiving either estradiol alone or the combined therapy
also showed increased levels of estradiol, estrone and growth hormone. The
ability of DHEA supplementation to increase the levels of androgens argues for
the desirability of the combined therapy, since it restores a more balanced
endocrine profile.
Another Italian study investigated the effects of 50 mg DHEA on postmenopausal
women according to their age (50 to 55 for early postmenopause versus 60 to 65
for late postmenopause) and weight (normal versus overweight, BMI 26 to 30).
The study found an increase in DHEA, DHEA-S, androstenedione, testosterone and
dehydroepiandrosterone in all women. The levels of sex hormone-binding globulin
decreased only in women who were older and overweight. All groups showed a
three-fold rise in beta endorphins, together with an increase in
allopregnanolone (a neurosteroid with a calming effect). In addition, all
groups showed a drop in cortisol and gonadotropins. Younger women experienced
an improvement in menopausal symptoms. There was no effect on uterine
endometrium, which is good news for those women who are bothered by
breakthrough bleeding when using mainstream-type hormone replacement therapy.
The antidepressant effect may be the best news of all. A separate study by the
same team of investigators found a significant increase in plasma
beta-endorphin levels in women using 100 mg of oral DHEA. The authors
hypothesize that DHEA could enhance the sense of well-being by restoring
neuroendocrine control of beta-endorphin secretion by the pituitary.
A German study, likewise using 50 mg oral DHEA, found similar effects in women
with initial DHEA deficiency due to adrenal hypofunction. The serum levels of
DHEA, androstenedione and testosterone rose into the normal range; sex
hormone-binding globulin decreased. The women reported improved overall sense
of well-being, less anxiety and depression, less obsessive-compulsive behavior,
stronger libido and more sexual satisfaction. One negative effect was a
lowering of HDL cholesterol. Minor side effects included increased oiliness of
the skin and scalp hair, acne, more sweating, and increased growth of facial
and body hair (on the forearms, for instance), the coarsening and darkening of
facial and body hair, and deepening of the voice. These side effects are
androgenic in nature, that is, related to male hormones, especially
dehydroepiandrosterone (DHT). The most prevalent side effect of DHEA
replacement in women is simply acne, which some women find mild enough to
control with a topical lotion.
Unfortunately, it is very difficult to control the way the body chooses to
convert DHEA. In women (but not in men), both testosterone and its stronger
form, DHT, usually go up considerably when DHEA is taken; in fact, DHT levels
can triple. One solution is to lower the dose. Women naturally produce less
DHEA than men, and their replacement dose should be lower than for men. Some
holistic physicians recommend no more than 25 mg of DHEA every other day. Men
do not seem to have any side effects when taking even large doses of DHEA,
although there have been some anecdotal reports of elderly,
testosterone-deficient men developing acne. One theory is that in women (i.e.
in predominantly estrogenic milieu), the conversion of DHEA is mainly
androgenic, while in men (i.e. in predominantly androgenic milieu), it's mainly
estrogenic. More research on the metabolism of DHEA is needed before the
question of sex differences can be settled.
The repeated finding of improved well-being in women on DHEA replacement is
especially interesting in light of the Rancho Bernardo Study findings that low
DHEA, but not the deficiency of other sex hormones, correlates with depression
in older women. A Japanese study similarly found a significant inverse
correlation between mood and DHEA levels, but not between mood and other
steroids.
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