DHEA Helps Banish Midlife Depression

DHEA Helps Banish Midlife Depression
Attacking depression is a backdoor way to
combating its unwelcome partner, obesity
By Will Block

popular notion among some geopolitical conspiracy buffs is that, someday, the Chinese government could arrange for all of its billion or so able-bodied citizens simultaneously to climb up on something a few feet off the ground. Then, by means of a countdown that was broadcast nationwide, everyone would jump to the ground at the same instant. The mammoth THUD would generate a shock wave that would propagate through the globe and cause earthquakes on the other side of the world—like here in the USA.

The idea is nonsense—even a billion jumping Chinese are but a pipsqueak in terms of geophysical forces (not to mention that if an earthquake were produced, it would occur right there in China, not over here)—but let’s give credit for its imaginativeness. And let’s try to imagine how obese the Chinese would have to become before the idea did have a chance of being successful. The answer is … inconceivable.

In terms of weight gain, that’s the direction that we in America, at least, seem to be taking (just look around you!), despite our obsession with dieting and health foods. Even though there are only about 300 million of us, maybe we could turn the tables on China through sheer fatpower …

Depression and Obesity—A Vicious Cycle

But seriously, we are way too fat, and it’s killing us—literally. Obesity is increasing in all age, racial, and ethnic groups, and at all educational levels in the United States, where over 300,000 deaths are attributed to it each year.1 While all those extra pounds, which are so easy to put on and so hard to take off (it’s not fair!), are apparently causing our clothes to shrink, they’re also reducing our life expectancy. They increase our risk for type 2 diabetes, cardiovascular and cerebrovascular disease, cancer, Alzheimer’s disease, and arthritis, among other chronic conditions. That’s a depressing thought, especially to those who already are overweight or obese.

It’s hardly surprising, then, that some studies show that obese people are more prone to depression than their thinner counterparts.2* All else being equal, they have more to be depressed about—not just the reduced life expectancy, but also the loss of self-esteem, the impaired mobility, the curtailed occupational and recreational options, the difficulty in attracting the opposite sex, the worry about social stigma, and even the outright discrimination that is sometimes visited upon the heftier members of society. It’s not easy being gravitationally challenged.

*This conclusion seems almost self-evident, but it should be noted that the literature on this subject is contradictory: some studies show the opposite effect, and yet others show no statistical correlation at all between obesity and depression. Thus, despite what common sense tells us, the question remains open.

But if obesity tends to produce depression, is the opposite also true? It can be—many depressed people turn to food for comfort and solace. Without intending to, perhaps, they overindulge in their favorite treats, and the pounds accumulate. It can’t help, of course, when they begin to realize what’s happening to their bodies and find that too to be depressing. Hello, vicious cycle.

A Lucky Discovery Turns Profitable

If depression and obesity are linked in a behavioral sense, as seems to be true, could there be a common physiological mechanism underlying these two conditions? Perhaps so, in the view of scientists who have noted that both disorders are commonly linked with brain deficiencies of the neurotransmitter serotonin, as well as with excessive secretion of the stress hormone cortisol (there are many other factors involved in depression and obesity as well). Consider the story of sibutramine, a prescription drug that acts as a serotonin reuptake inhibitor, i.e., an agent that prevents serotonin levels in neural synapses from being unduly depleted (it does this for two other monoamine neurotransmitters, dopamine and norepinephrine, as well).3

In the 1980s, sibutramine was being evaluated for the treatment of depression, but when it was finally released (as Meridia®) in 1998, it was marketed not as an antidepressant but rather as an anorexic, or weight-loss agent. That’s because the researchers who had been studying its effects in depressed individuals noticed that the patients tended to lose weight and to keep it off for up to 2 years. The focus of testing on sibutramine was switched to this more lucrative market, and lo, a new drug was born.

Are Depression and Obesity Two Sides of the Same Coin?

Because of the apparent neurophysiological link between depression and obesity (both of which often run in families), some scientists have speculated that these two disorders may be, in effect, the same condition—two sides of the same coin—at least in some cases.3 (Bear in mind, however, that any such generalization invites a certain skepticism, and one can easily think of counterexamples, such as depressed people who undereat rather than overeat, and obese people who are well-adjusted and happy.) The reasoning goes like this: if there is already a genetic predisposition for depression and obesity, then environmental factors such as emotional stress or physical illness might trigger an imbalance in the brain’s serotonin metabolism, leading to both depression and obesity.

This theory provides a rationale for treating obesity with antidepressants.4 Conversely, it suggests that depression may be treatable with anorexics. Basically, what it implies is that there ought to be agents, such as sibutramine, that can successfully treat both conditions—not in all cases, probably, but perhaps in many.

DHEA Reduces Fat and the Blues

In the February 2005 issue of Life Enhancement (see “DHEA Wins the Battle of the Bulge”), we saw how a nutritional supplement—the natural steroid hormone DHEA (dehydroepiandrosterone)—can reduce abdominal fat (and improve insulin sensitivity to boot) in elderly men and women. The study was done by the same researchers who had previously demonstrated DHEA’s ability to reduce total body fat in humans. These studies confirmed, at long last, that DHEA induces fat loss not just in rats and mice, but also in humans.*

*For more information on this remarkable hormone, see “DHEA—The Most Versatile Hormone” (February 2001), “Stopping the Biological Clock in Postmenopausal Women” (December 2001), “DHEA—The Hormone of Youth?” (December 2002), “DHEA Protects Against Heart Disease and Diabetes” (October 2003), and “DHEA Helps Restore Hormonal Balance” (March 2004).

Now there is new evidence, from a study published by researchers at the National Institute of Mental Health and the National Institutes of Health in Maryland, that DHEA is effective in treating depression as well.5 The literature on this subject has been somewhat confusing. For example, some studies have shown a decreased secretion of DHEA in depressed patients (compared with control subjects) at midlife and at other ages, whereas other studies have shown an increased secretion. Furthermore, some studies have shown a mood-elevating effect of DHEA in normal (nondepressed) adults, whereas others have not.

In patients suffering from depression, the findings are also inconsistent, but some studies have shown significant positive effects from DHEA treatment. For example, improved mood due to DHEA has been reported in people suffering from severe depression6 or from dysthymia, a mood disorder associated with mild depression.7 The new study adds to that body of evidence, but without answering a key question: Is DHEA’s antidepressant effect due to the correction of a supposed DHEA deficiency in depressed individuals compared with people of similar age who are not depressed? The evidence suggests that the answer may be no—a different mechanism may be involved—but whether or not this relative DHEA deficiency even exists in the first place is controversial, because different studies have shown contradictory results.

Not controversial, however, is the fact that in all normal men and women, DHEA levels peak in the 20s and drop sharply thereafter, so all older people are highly DHEA-deficient relative to their younger selves.

DHEA Improves Patients’ Depressive Symptoms …

The NIMH/NIH researchers conducted a randomized, double-blind, placebo-controlled study with 46 men and women (23 of each), aged 41 to 63. All the patients suffered from major or minor depression that had begun in midlife within the past 5 years, but they were otherwise healthy. The study was of the “crossover” design, meaning that the patients served as their own controls: on a random basis, they were first treated with DHEA for 6 weeks, then given placebo for 6 weeks—or vice versa. These two periods were separated by a “washout” interval of 1 to 2 weeks. The 6-week treatment period was divided into two segments: for the first 3 weeks, the patients received 90 mg/day of DHEA (30 mg thrice daily), and for the second 3 weeks, they received 450 mg/day (150 mg thrice daily).

The results showed substantial
improvements in the patients’ scores
for mood and other factors related to
depression: on six of the tests,
the scores improved, on average,
by 36% to 51%.

With neither the patients nor the physicians knowing who had received what treatment, the patients were evaluated for symptoms of depression at baseline (the beginning of the study) and after 3 weeks and 6 weeks of treatment, using seven standardized tests. At baseline, 19 women and 9 men met the criteria for major depression (although the severity in all cases was judged to be “at most moderate”), and the remaining patients were classified as having minor depression.

Depression in Adolescence—A Bad Omen

It has long been known that both depression and obesity are more common in women than in men, and there is no shortage of theories, both physiological and psychological, to account for this. Adolescents are also vulnerable to these conditions, of course, and obesity in adolescence is a strong predictor of obesity later in life—a life that will almost certainly be made less healthy and happy as a result (not to mention shorter, in all probability). Curiously, obesity seems to be more prevalent among boys than among girls—a trend that obviously gets reversed as the years go by.1

Although obesity is on the rise in all age groups, the greatest rate of increase is among young adults aged 18 to 29.2 This suggests that there may be factors that predispose young adults to obesity, beyond the epidemic of adolescent (and even childhood) obesity itself. One such factor may be depression. Certainly obesity can cause depression in adolescents, who are especially vulnerable to problems with self-image and self-esteem as they struggle to find their identity in a perplexing world.

But can depression cause obesity in this age group? That question was the focus of a recently published study in which researchers in Cincinnati analyzed existing health data (both physical and emotional) for a nationally representative sample of 9374 adolescents in grades 7 through 12.3 Data pertaining to obesity and depression were compared over a 1-year period to see whether teenagers who were depressed but not obese at the outset were significantly more likely, a year later, to be obese than their initially happier counterparts. The answer was yes. After controlling for many potentially confounding factors, the researchers found that the risk for obesity in this group was doubled. They also found that teens who were both depressed and obese at the outset were likely to be even more obese a year later.

It’s all very depressing, especially in light of the fact that obesity, once it develops at any age, is highly resistant to treatment. All the more reason, perhaps, to attack obesity indirectly by treating depression, if it coexists, because depression usually yields more readily to treatment than obesity does. This strategy may help to prevent further weight gain and perhaps even to reduce weight.

  1. Troiano RP, Flegal KM. Overweight children and adolescents: description, epidemiology, and demographics. Pediatrics 1998;101:497-505.
  2. Mokdad AH, Serdula MK, Dietz WH, Bowman BA, Marks JS, Koplan JP. The spread of the obesity epidemic in the United States, 1991–1998. JAMA 1999;282:1519-22.
  3. Goodman E, Whitaker, RC. A prospective study of the role of depression in the development and persistence of adolescent obesity. Pediatrics 2002;109:497-504.

After 6 weeks of treatment, the results showed substantial improvements, compared with the baseline and placebo conditions, in the patients’ scores for mood and other factors related to depression: on six of the tests, the scores improved, on average, by 36% to 51%.

. . . And Their Sexual Function Too

The seventh test, called the Derogatis Interview for Sexual Functioning (DISF), was a self-reported evaluation (with separate questionnaires for men and women). It consisted of five subscales measuring levels of sexual fantasy, sexual arousal, sexual activity, quality of orgasm, and sexual drive and the quality of the sexual relationship. In the study, both men and women showed significant improvement in their total DISF scores, as well as in all the individual subscales but one (quality of orgasm, where there was a trend toward improvement, but not a statistically significant one).

The lack of a significant difference between the results for men and women in any of the seven tests is surprising, because gender-specific differences in DHEA studies of various kinds are fairly common. DHEA is an androgen (a male sex hormone), and men and women metabolize it very differently. For example, it tends to increase testosterone levels markedly in women (who have small amounts of it to begin with), but not in men. In the new study, the free testosterone levels increased dramatically in the women (+513%), but only slightly (+17%) in the men. The changes in total testosterone levels, however, were much smaller and were judged by the authors not to be significant: +174% in the women and –10% in the men.

Half of the Patients Were Significantly Improved

In the study, 12 of the 28 patients (43%) with major depression were found to be significant responders to the DHEA treatment (meaning that their scores on a particular test improved by 50% or more from the baseline value), vs. 11 of the 18 patients (61%) with minor depression. Thus the total number of significant responders was 23, or exactly half of the patients in the study [by contrast, 13 of the patients (28%) were significant responders when they were on placebo].

Both men and women showed
significant improvement in their
sexual function scores, as well as in
all the individual subscales but one
(quality of orgasm).

Of the 23 DHEA responders, 13 elected to continue taking DHEA, at dosages of 25 to 50 mg/day, for up to 1 year after the 6-week study was concluded, and of those 13 patients, 10 (77%) remained free of depressive symptoms for as long as they took the supplement. The apparent efficacy of these relatively low dosages, at least in those 10 patients, seems to speak for itself, but the authors were unable to say that these—or any other—dosages are optimal for treating depression, because the results in different studies appear to depend on the medical condition of the patients involved. In the current study, the 450-mg/day dosage may or may not have been more effective than the 90-mg/day dosage, although the evidence suggested that it probably was not.

DHEA—The Supplement for You?

In conclusion, the authors stated, “We find DHEA to be an effective treatment for midlife-onset major and minor depression.” So there you have it—evidence that a supplement known to be of value for treating obesity is apparently also valuable for treating depression. Whether the dual effects are due to the possible neurophysiological link between these two disorders or to the psychological improvements resulting from either therapeutic approach … well, who cares? OK, scientists care, but most people surely don’t—they just want to feel better or lose weight, or both. Whatever category you may be in, it could be that DHEA is just the supplement for you.


  1. Allison DB, Fontaine KR, Manson JE, Stevens J, VanItallie TB. Annual deaths attributable to obesity in the United States. JAMA 1999;282: 1530-8.
  2. Dong C, Sanchez LE, Price RA. Relationship of obesity to depression: a family-based study. Int J Obesity 2004;28:790-5.
  3. Rosmond R. Obesity and depression: same disease, different names? Med Hypotheses 2004;62:976-9.
  4. Rosmond R, Björntorp P. The role of antidepressants in the treatment of abdominal obesity. Med Hypotheses 2000;54:990-4.
  5. Schmidt PJ, Daly RC, Bloch M, Smith MJ, Danaceau MA, Simpson St. Clair L, Murphy JH, Haq N, Rubinow DR. Dehydroepiandrosterone monotherapy in midlife-onset major and minor depression. Arch Gen Psychiatry 2005;62:154-62.
  6. 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.
  7. Bloch M, Schmidt PJ, Danaceau MA, Adams LP, Rubinow DR. Dehydroepiandrosterone treatment of midlife dysthymia. Biol Psychiatry 1999;45:1533-41.

Will Block is the publisher and editorial director of Life Enhancement magazine.

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