DHEA: Hype, Hope and Disappointment

Dehydroepiandrosterone (DHEA) is a hormone that has attracted a lot of attention. It’s launched hundreds of websites, product lines and a few books and magazine articles. So what’s all the fuss about, and should we all be chomping down on DHEA tablets?

DHEA is manufactured at several sites in the body, but by far the most important is in one of the outer layers of the adrenal gland. Like all the steroid hormones it is made from cholesterol. It has various protective effects in the body, regulates some enzyme systems, can be converted to estrogen and under certain circumstances to testosterone. It has very weak androgen (male hormone) activity.

In cell culture it has a lot of other actions too, but it is always difficult to jump from effects seen using large doses in isolated cells, to giving advice on what supplements people should be taking.

There has been a lot of talk about the possibility that some people may, as a result of stress or toxins, suffer from exhaustion of the adrenal glands. There is a great long list of symptoms that may be caused by this so-called adrenal fatigue, deficiency or insufficiency: the terms are often – and incorrectly – used interchangeably. And therein lies the problem. It is such a long list that it is non-specific. It’s always a bit of a worry when someone tells me that dozens of different symptoms are all caused by one single biochemical problem. That just isn’t the way that the human body works.

I have seen and treated countless people with a condition known as Addison’s disease: true chronic adrenal insufficiency. It can be a very serious illness and it is quite different from the “adrenal fatigue” that people talk about in some popular books. People with chronic fatigue syndrome do have lower levels of activity in what is known as the hypothalamic-pituitary-adrenal axis, but it is not because the adrenal glands are not working properly, but because the hypothalamus in the brain is not doing it’s job properly. There’s also no proven link between “burnout” and adrenal function.

During my years as an endocrinologist and holistic physician, I’ve spent a great deal of time looking for adrenal fatigue in sick people and I’ve never found it. I’ve done all the tests recommended by proponents of adrenal fatigue and adrenal insufficiency and when we’ve done the tests properly, we’ve drawn a blank. There are a great many parallels between the adrenal insufficiency story, and the old – and discredited – myth about people becoming unwell because of a thyroid deficiency that cannot be picked up on standard thyroid function tests.

So can DHEA do you any good? Or can it be harmful? What exactly is the evidence?

1. There is a comprehensive study, called The Dehydroepiandrosterone And WellNess (DAWN) study that should give us some solid answers as to the risks and benefits of DHEA. I shall post details of the findings as they become available. But some things we know already:
2. DHEA has been touted as an anti-aging supplement. But in a two-year prospective study done in older people attending the Mayo Clinic in Rochester, Minnesota, neither DHEA nor low-dose testosterone replacement had physiologically relevant beneficial effects on body composition, physical performance, insulin sensitivity, or quality of life. Perhaps the people in the study didn’t get enough DHEA, but it doesn’t look that way. Instead it seems that just giving the supplement doesn’t seem to do very much. But there is increasing evidence that 50-100mg of DHEA each day will improve muscle strength and muscle mass in older people who are doing strength training. Once again, it does nothing in people who are not exercising. Sorry!
3. According to the results of a small placebo-controlled, randomized trial published in the Archives of General Psychiatry, DHEA can be effective for midlife-onset minor and major depression. The study was conducted the National Institute of Mental Health Midlife Outpatient Clinic. In the trial, 23 men and 23 women aged 45 to 65 years with midlife-onset major or minor depression were randomized to six weeks of DHEA therapy, 90 mg/day, for three weeks and 450 mg/day for three weeks or to six weeks of placebo followed by six weeks of the other treatment. The subjects did not receive any other antidepressant medications during the study. Both of the doses of DHEA helped improve depression: there was no advantage in going to a higher dose, and there was no difference in the treatment response of men and women. The trouble with this study was not just the small size and the short duration, but the DHEA was not compared against a standard antidepressant. So we are still in the dark as to how effective it really is. It’s nice that it’s better than placebo, but this is just the first step in a larger research program.
4. A study from Taiwan indicated that people with higher levels of DHEA sulfate had a lower overall mortality over a three-year period. That is interesting, but absolutely does NOT mean that artificially increasing our levels of DHEA with supplements will make us live forever: we don’t yet have that kind of magic bullet.
5. In mice, quite large amounts of DHEA have the effect of slightly reducing the normal increase in stiffness of the left ventricle that can happen as animals get older. We have no idea whether something similar might help in humans, and the amounts of DHEA involved may rule it out as a viable treatment in people.
6. 50mg/day improves subjective wellness in people who have no active pituitary gland. A rare condition, and we cannot use this evidence to advise healthy people about what to take.
7. Because DHEA is converted into estrogen and/or testosterone, it may have the potential to exacerbate or initiate hormone-responsive tumors. The evidence is not strong one way or the other, but it remains a worry. I don’t think that anyone recommends DHEA to people who have a personal or family history of breast or prostate cancer.

There is a BIG literature on DHEA. But my current conclusions from all this?

1. 50-100mg of DHEA is probably worth trying if you are over 50 years of age and doing regular exercise.
2. It may help a bit with mild depression.
3. It should not be used in people with a personal or family history of breast, prostate or any other type of hormone-sensitive cancer.