Richard G. Petty, MD

Leg Length and Cognitive Reserve

I recently mentioned the "Barker Hypothesis" which says that fetal malnutrition is associated with many physical problems later in life.

Well the difficulties may not only be physical.

I would like to tell you about an important concept that we call "Cognitive reserve." This can be thought of as our cognitive resilience. This first came to light almost twenty years ago when a post-mortem study of 137 elderly people was published in the Annals of Neurology, and confirmed something that we had suspected for years: there was a large discrepancy between the degree of Alzheimer’s disease neuropathology and the clinical manifestations of the disease. Some people had extensive pathology but they  clinically had no or very little manifestations of the disease. The investigators also showed that these people had higher brain
weights and greater number of neurons compared with age-matched
controls. This lead to the idea that they had a greater "reserve." This is why building your brain throughout life is thought to reduce the ce of cognitive impaitrment later on.

Studies have shown that childhood cognition, educational attainment and adult occupation all independently contribute to cognitive reserve, and more recently it has been confirmed that education and the complexity of a person’s occupation may both slow the rate of decline in people who already have Alzheimer’s disease.

Although height is in part genetically determined, shorter leg length has been found to be associated with an adverse environment in early childhood. In a recent study of older Afro-Caribbean people living in London, shorter leg length was significantly associated with cognitive impairment, leading to the suggestion that shorter leg length may be a marker of early life stressors that then result in reduced cognitive reserve.

It is also worth recalling our discussion about the association between growth hormone and intelligence in children and between intelligence and head size.

And nutrition is one of the determinants of growth hormone synthesis and release.

Naturally this does not mean that less tall people will all get Alzheimer’s disease. But these observations have a number of practical consequences. They re-emphasize the importance of good nutrition during pregnancy: something that is simply not available to over a third of the world’s population. They also help us to identify some of the people who would most benefit from strategies to increase their cognitive reserve and to avoid some of the things that can strip it away from them.

Hormonal Disturbances and Bulimia

Bulimia, more accurately called bulimia nervosa, is an eating disorder that was first described by  Professor Gerald Russell in 1977 whilst he worked at the Royal Free Hospital,in London in 1977.

There are five criteria that have to be met for someone to be diagnosed with bulimia nervosa:

  1. Recurrent episodes of binge eating. An episode of binge eating is characterized by both of the following:
    • Eating, in a discrete period of time (e.g., within any two-hour period), an amount of food that is definitely larger than most people would eat during a similar period of time and under similar circumstances.
    • A sense of lack of control over eating during the episode (e.g., a feeling that one cannot stop eating or control what or how much one is eating).
  2. Recurrent inappropriate compensatory behavior in order to prevent weight gain, such as self-induced vomiting; misuse of laxatives, diuretics or other medications; fasting; or excessive exercise.
  3. The binge eating and inappropriate compensatory behaviors both occur, on average, at least twice a week for three months.
  4. Self-evaluation is unduly influenced by body shape and weight.
  5. The disturbance does not occur exclusively during episodes of anorexia nervosa.

It has long been known that there can be a number of hormonal disturbances in people with both anorexia nervosa and bulimia, but it has never been clear whether they are a result of malnutrition, vomiting and/or the use of laxatives and diuretics. When we were both at the Maudsley Hospital in London, Gerald and I once spent several hours talking through the possibilities of doing some collaborative work on the hormonal problems in people with eating disorders. The list of disturbances was so long that we decided that we had other priorities.

So I am fascinated to see some new research from the Karolinska Hospital in Stockholm.

Amongst the most prominent problems in people with bulimia are menstrual irregularities and increased rates of polycystic ovarian syndrome (PCOS). A Dr Sabine Naessén studied 77 women with bulimia and 59 healthy volunteers.

As expected the women with bulimia had higher rates of menstrual disturbances, hirsutism and PCOS. And in line with previous research, levels of testosterone correlated with amounts of hirsutism.

The women with bulimia also had lower bone density, particularly if their menstrual cycles had stopped or if they had ever had anorexia nervosa.

She also found an association between two common polymorphisms in the estrogen receptor (ER) β gene and bulimia. She has speculated that this genetic variation might predispose women to the development of bulimia.

Her results suggest that some women with the condition may have too much of the male hormone testosterone. Half of the people treated for this imbalance reported less hunger, and fewer cravings for fatty and sugary foods.

This is important work. It is highly unlikely that eating disorders could ever be reduced to biochemical disturbances in the brain. There are so many environmental factors, for instance sexual abuse or other types of trauma, and even social pressure, that have been implicated in the etiology of the illness.

But the key point is this: why do some people develop an eating disorder after trauma while other do not? And why do some people develop eating disorders, even when they have never been traumatized in their lives?

The answer as always lies in the ways in which genes and the environment interact. If confirmed, this research may point the way toward some new ways of helping some people with this group of illnesses.

Hormone Replacement Therapy, Breast Cancer and Causality

It seems a remarkable "coincidence" that they very day after writing about breast cancer screening, we should hear the news about a sudden fall in the rates of breast cancer amongst a certain proportion of the population.

Researchers from the M.D. Anderson Cancer center in Houston presented their data at a meeting of the San Antonio Breast Cancer Symposium. They recorded a 7% drop in new breast cancer cases in the US in 2003, ad an even bigger fall – 12% – in cases of hormone-dependent breast cancer among women aged 50-69. This is the first time that breast can cancer rates have fallen since 1945.

The decrease was most striking for women with so-called estrogen-positive tumors, which account for 70% of all breast cancers. It is the growth of these tumors that may be fueled by estrogen.

The scientists believe that the fall could be linked to the fact that millions of women gave up hormone replacement therapy (HRT) following reports questioning its safety. Around 14,000 fewer US women were diagnosed with breast cancer in 2003, compared with the previous year. The number of American women on HRT had halved by the end of 2002 in the wake of a large study was halted in 2002 after evidence emerged indicating that the therapy was associated with an increased risk of developing breast cancer.

The data are striking, but they need to be confirmed. That being said, there was a different type of study in last month’s issue of the Journal of Clinical Oncology. Researchers found an even larger drop in breast cancers in some parts of the State of California where there had been some of the highest rates of HRT use in the nation.

If the figures are correct – and they will have to confirmed – they could be explained by existing tumors stopping growing, shrinking or disappearing so that they could not be detected.

When I was a full time endocrinologist I saw a great many women who suffered terribly with menopausal symptoms, but I always declined to use HRT because of my take on the research data. I used dozens of alternatives, and if they failed, I had plenty of colleagues who were happy to use HRT, but I was always uneasy about using it.

There is also another important point: epidemiology can never prove causality. We have a plausible link, but no direct proof that a fall in the use of HRT is responsible for the fall in breast cancer.

Let me give you another example. Few people doubt the link between cigarette smoking and lung cancer, but no causality has ever been proven. Typhoid can cause a horrible illness, but all that the epidemiologist can do is to suggest an association between the bug and the pattern of an outbreak. It requires a microbiologist to prove that the bacterium Salmonella Typhi is the cause of the symptoms.

A number of years ago I became involved with the Oxford Causality project. It was fascinating, because not only did we call into question the issue of uni-causality in medicine – one cause for one illness – but some scientists and philosophers – such as Roy Bhaskar and Rom Harre even went so far as to suggest that “laws” of nature are better thought of as “habits” of nature. Clearly there are laws and there is causality. I throw a stone into a pond and there should be a plopping noise and then the ripples spread out. If there were no laws, then atoms could disintegrate. But at the deepest levels of nature, it no longer appears that we live in a clockwork universe in which free will is an illusion.

This is not just of theoretical importance, I recently received some interesting correspondence after I mad some comments about how self-cutting, if ignored, could lead to the development of borderline personality disorder. One correspondent thought that this implied causality, but I do not think so. “Disorders” are best viewed as deviations from a norm and they usually appear in bits and pieces. For example, some people with bipolar disorder may have had problems years before the illness had declared itself. The first signs were there, but they could have evolved along a dozen different pathways. Some people with borderline personality disorder have had varying degrees of distress since childhood, but back then it was impossible to say for sure what was wrong.

It is usually a mistake to try to find one cause for a problem. It is equally a mistake to try and diagnose a problem prematurely. We sometimes need to wait and see how things will evolve.

Conflicts of Interest

Last week I made some comments about the claims made in the new book by Suzanne Somers.

As expected, I had a good many people who said, “About time somebody said something,” and a few others who just felt that her publisher should have arranged for more fact checking.

To the people who agreed with me, thank you.

To those who did not, I respect your various positions, and I think that we have to look at this problem in a bit more detail.

By “this problem,” it is not simply about whether Suzanne needs to have some facts checked. I think that there is a very real problem with someone who has no medical training giving medical advice.

The more so if that person or persons is unable to undertake a critical review of published research.

This is much the same as the monstrous comments made by Tom Cruise earlier this year. He abused his position to make comments that made no sense. I saw several people who were weeping and distressed by what he had said. Many were saying things along the lines of “These medicines have saved my life, how can he say something so terrible?”

This is similar to the recent problem with Kevin Trudeau, who has made a great deal of money out of peddling highly questionable advice. He can do so in the United States because of the First Amendment. Nobody would want to change a constitutional right, but I get very worried about people saying anything that they want about health, and if anyone gets harmed, they say that it’s not their fault.

Some don’t even seem to have the wit to understand that their recommendations may cause harm. Harm that can come not just from commission – taking something harmful or being given a harmful treatment – but also of omission: not getting a treatment with proven efficacy. Trudeau claims that he is fighting on behalf of the American public. In which case, why has he not contributed the entire proceeds from the sales of his books to an independent central fund to educate the public about health?

I certainly do not think that people with an MD, DO or ND have all the answers: none of us does. But when we are talking about people’s health, I think that we all have to be extremely careful about dishing out advice.

I am also very aware that there are millions of people – mainly, but not exclusively women – who have severe problems with hormonal imbalances, and that they have not always been well-served by the medical professions. Giving unsubstantiated advice to people who are suffering is so unfair.

A number of people who are known for their work in hormone replacement have published an open letter that they have written to Suzanne Somers’ publisher, Crown House, expressing their dismay over some of the claims in her book. The signatories include Christiane Northrup and Diana Schwarzbein. Neither of whom would be called pillars of the establishment.

The Endocrine Society has just published a position paper about bioidentical hormones that I would urge you to read if you want further clarification about the whole issue of hormone replacement.

The front cover of the magazine Life Extension gleefully proclaims “Suzanne Somers Versus the Medical Establishment.” Life Extension is a fine looking glossy publication that looks like a peer reviewed Journal. It seems, though, to be a medium for disseminating information about supplements. Some of the articles are really quite good, but there is always the subtext that they are written in order to promote products.

The Journal uses a familiar tactic in some of these magazines that are selling products. This tactic is that they are letting you in on A Secret. A secret that is being kept from you by those terrible doctors or, shock horror, pharmaceutical companies that are trying to keep you sick. I’ve worked with countless pharmaceutical companies, and I’m well known for speaking my mind. But I have to tell you that in every company that I’ve worked with on five continents, the vast majority of the people involved have had a genuine concern for human welfare. Yes, they have a business to run, but pretty much all the people that I’ve known in the industry have been in that particular industry because it meshes with their own life goals of helping humanity. And as I pointed out a moment ago, the open letter to the publishers was not penned by pharmaceutical company lackeys.

Is Suzanne Somers making money out of her claims? Well, of course she is. She is using her celebrity and her extravagant claims to sell books. I’m quite sure that far fewer people would be interested in reading her material ff she just stuck to the facts.

That in itself presents some important ethical issues. Clearly, if she stuck to the data and gave a clear account of the pros and cons of what she is suggesting, she’s not likely to sell so many books.

As a spin off, she is also getting large numbers of people to visit her website, where they may buy products that may not contain bioidentical hormones, but ARE touted as being “anti-aging.” In other words the products on sale make some of the same claims that are associated with the hormones. This is a well-known marketing tactic. She claims to have one million people in her database, though we have not been able to confirm those numbers.

People all over the Internet are trying to find out if she is receiving any payments for endorsing products. I know that because several have contacted me. Of course she can do any kind of business deals that she wants, but there are ever-evolving rules about conflict of interest. Some new rules have just been proposed in the medical literature, and it would be excellent if the same standards were applied in all publications, whether print, online, in infomercials, interviews or any other kinds of medium of communication.

An important article on conflict of interest and full disclosure has just been published in the American Journal of Psychiatry.

Most major scientific journals now require that authors fully disclose ALL sources of funding. There are also strong, and I believe welcome moves to ensure that when patients receive medications, that they are fully informed if the prescriber has any relationships with drug companies. I have seen some people suggest that there should be a complete separation of pharmaceutical industry and the medical professions. A moment’s thought shows that would not be an answer to anything. If we can do this in conventional medicine, why not in every area of healthcare?

(As I’ve said before, my own list of disclosures is available to anyone who wants them, and they get updated every time that I do any work for which I get compensated. And not just me, any members of our staff. We are determined to remain squeaky clean.)

So what to do about the people who make wild claims about health, without disclosing their conflicts of interest?

Since we’ve just been through an election we’ve all seen how the squeaky wheel gets the grease!

People who say things loudly and repeatedly and appear to be saying something novel, do get attention. There’s no question about it, and there’s a good reason: Our brains are hard wired to notice and respond to loud noises and novelty. But when we are dealing with outrageous medical claims, the soft whispers of good data will ultimately drown the foghorns of dogma and opinion, however loudly they are blasted from the rooftops.

Some of the claim makers retire behind the fig leaf of saying, “Well there isn’t any data but if there were any, it would prove what I’m saying.”

Believe it or not, I’ve had that said to me on several occasions by several different people.

All of whom managed to keep a straight face…

Hidden Harbingers of Weight: Salt Intake and Obesity

In Healing, Meaning and Purpose, I discuss some of the evidence for four previously little recognized causes of obesity:

  1. Stress
  2. Salt intake
  3. Pesticides
  4. Viruses

Each of these has been widely discussed in the professional literature, but little has percolated out into the general population except in advertisements for agents like Cortislim. I remain skeptical about these products. Tinkering with just one of the 260 hormones and neurotransmitters implicated in the control of weight is unlikely to be crowned with success. And their ingredients may also have the potential for causing problems. Recent advertisements have also mentioned that one of these products may elevate mood. Sad to say, in the last year we have seen two people who developed manic symptoms after taking one of the supplements. We are urging colleagues to see if there are any other cases, or whether these two were just coincidental.

I recently mentioned some of the evidence for viruses as a cause of weight gain.

Now a new publication from the Universities of Helsinki and Kuopio is out in this month’s journal Progress in Cardiovascular Diseases, that provides powerful support for the salt hypothesis.

The researchers report that an average 30-35 % reduction in salt intake during 30 years in Finland was associated with an extraordinary 75 % to 80 % decrease in both stroke and coronary heart disease mortality in the population under 65 years. During the same period the life expectancy of both male and female Finns increased by 6 to 7 years.

As expected, reducing salt intake has a beneficial effect on blood pressure.

But in my view the most interesting finding of the study is the close link between salt intake and obesity.

As bartenders, pub landlords and tavern owners have known since the beginning of time, increasing a person’s intake of sodium produces a progressive increase in thirst. (You didn’t think that those peanuts on the bar were put there out of the goodness of the establishment’s heart did you??!)

The progressive increase in the average intake of salt explains the observed increase in the intake of sugar-containing beverages which, in turn, has caused a marked net increase in the intake of calories during the same period in the United States.

Here is an extraordinary statistic: Between 1977 and 2001, energy intake from sweetened beverages increased on the average by 135 % in the United States. During the same period, the energy intake from milk was reduced by 38 %. The net effect on energy intake was a 278 kcal increase per person a day. The American Heart Association has estimated that, to burn the average increase of 278 kcal a day and avoid the development or worsening of obesity, each American should now walk or vacuum 1 hour 10 minutes more every day than in 1977. As we all know, that has not happened.

In the decade from 1976-1980 to 1988-1994 the overall prevalence of obesity increased 61 % among men and 52 % among women. During 1999 to 2002, the prevalence of obesity was 120 % higher among men and 99 % higher among women as compared with the 1976 to 1980 figures. The increased intake of salt, through induction of thirst with increased intake of high-energy beverages has clearly made a significant contribution to the increase of obesity in the United States.

It is also of note that until 1983 the use of salt did not change or even showed a continuous decreasing trend in the United States. The prevalence of obesity was relatively low and remained essentially unchanged from early 1960s to early 1980s.

This new study suggests that a comprehensive reduction in salt intake, which would reduce the intake of high-energy beverages, would be a potentially powerful means in the so far failed attempts to combat obesity in industrialized societies.

There is now conclusive population-wide evidence that indicates that we could achieve powerful beneficial health effects simply by reducing our overall salt intake. These benefits include a decrease in obesity.

As an aside, the population-wide long-term experience from Finland indicated that a remarkable decrease in the salt intake has not caused any adverse effects.

A number of years ago we were engaged in some experiments in which we replaced regular table salt – sodium chloride – with potassium chloride. For the first three weeks food seemed rather tasteless. But then we all suddenly discovered a new universe of flavors that had previously been hidden under a thick coating of salt. So a dietary change does have a temporary effect on your taste buds.

Although the paper doesn’t say so, there is also some data that salt may itself increase cortisol release.

The bottom line?

We now have clear, empirical data to support three out of the four points that I made in Healing, Meaning and Purpose, and there is some less robust data for the fourth.

I urge you to try gradually to reduce your personal intake or salt, and to encourage your family and friends to do the same. I mentioned that food may initially seem a little less flavorful, but then things change rapidly and for the better.

And your body will love you for the change!

Hormones, Pseudoscience and Self-Deception

A few months ago I saw a letter in Time magazine from the actress Suzanne Somers. She roundly and quite unfairly criticized Andrew Weil for not talking about hormone replacement therapy using what are known as “bio-identical hormones.”

I didn’t say anything at the time. Andrew Weil is well able to take care of himself and treated the letter quite correctly: by not responding. Suzanne did not reveal in the letter that she has a commercial interest in the bio-identical hormones. I assume that she did tell the editors of Time magazine, to have not done so would obviously have been unethical.

Her comments were a bit silly. But why respond to her now? After all the world’s full of silly things, and most of the time we can just move on. But now she’s promoting a new book and I am afraid misleading people. It may be that these bio-identical hormones are the answer to a maiden’s prayer and maybe they are not. My worry is that she does not discuss the pros and cons of using these products. Just lots of pros, implying that almost every woman of a certain age should be taking them. She claims that there is some research to back her up. In fact there are some very big holes in the research.

Now we see the recommendation to measure sex hormone binding globulin (SHBG), because “if that number’s not right, it doesn’t matter how high your testosterone is.”

I am an endocrinologist, but this advice is so mind bogglingly absurd that I still thought that I might perhaps have missed something. SHBG is not a single entity carrying sex hormones like some molecular equivalent of the number 9 bus.

It is a complex of proteins and glycoproteins that has many jobs, only one of which is the transport of some sex hormones to tissues that need them. Measuring the SHBG is complex: there are many genetic variations in SHBG and each has a different capacity for carrying estrogen and testosterone. You, your brother, sister, and spouse may all have different types of SHBG, with varying numbers of recognition sites geared toward testosterone or estrogen transport. Some vary if you have inflammation or liver trouble, and the amount of abdominal fat impacts SHBG but subcutaneous fat does not. You see that is it quite a complex topic!

It is simply absurd to make pronouncements based on “Levels” of this group of proteins and glycoproteins. There is no such thing as a “normal” level: when we measure hormones or their carriers, we use “reference ranges,” because the levels “refer” to numbers obtained from large panels of apparently healthy people.

I’ve carefully examined all the papers that she cites in support of her line of bio-identical hormones, and they certainly do not say the things claimed. This worries me: pulling bits of half-understood studies does not help us to advance health care or quality of life. Suzanne can tell us about as many cases as she likes, but she is using pseudoscience to buttress her position.

Yes, it is possible that she is correct, but why oh why isn’t there some proper research to say so?

Hormones, whether naturally occurring or bio-identical, are powerful chemical mediators. Used judiciously they have a role in the care and treatment of some women, whose lives would otherwise be miserable. But you also need to remember that some tumors may be promoted by bioactive hormones, whether they are synthesized or derived from plants or animals. And there are other potential health risks.

Caveat emptor!

Medical Correspondents

When I am at home, I have a regular Sunday morning ritual: I watch the Fox News medical correspondent while working out. It’s a fair bet that every week he will make at least one major howler that is guaranteed to increase the amount that I can bench press by 50%!

I don’t personally know the Sunday Fox medical correspondent, and he seems a nice fellow. But why oh why doesn’t he do his research before going on the air?

A few weeks ago he was endorsing “Wilson’s syndrome” that was created by E. Denis Wilson, M.D., who practiced in Florida in the early 1990s. The syndrome’s supposed manifestations include a rag bag of fatigue, headaches, PMS, hair loss, irritability, fluid retention, depression, decreased memory, low sex drive, unhealthy nails, easy and excessive weight gain, and about 60 other symptoms. Wilson claimed to have discovered a type of abnormally low thyroid function in which routine blood tests of thyroid are often normal. He claimed that the main diagnostic sign is a low body temperature that is on average below 98.6° F and that the diagnosis could be confirmed if the patient responds to treatment with a "special thyroid hormone treatment." The American Thyroid Association published a position paper about this syndrome, saying that it probably does not exist. People have paid good money to be tested and treated, and though some may have benefited, most probably have not.

It is very easy to check these facts. So why didn’t the Fox medical correspondent do so?

Then a couple of weeks ago he talked about an herbal preparation without once mentioning that the FDA had just issued a warning about potential liver toxicity.

Then today he starts discussing a preparation called Airborne, that is purported to help prevent colds. It may or may not do so. The FDA has not evaluated the claims. The problem was that the correspondent then said that it could do no harm. Yet that is quite wrong. Though I could find no published cases of harm, the possibility most certainly exist, and the public needs to be made aware of the reasons to be a bit cautious:

  1. It contains 5,000 IUs of vitamin A. If you take it every three hours as recommended, some people could overdose on it.
  2. The same with vitamin C. If you take a lot, most is quickly passed out in the urine. But some people can get bladder irritation and could conceivably get kidney stones from taking that amount over a period of time.
  3. The remedy also contains seven herbs: Lonicera, Forsythia, Schizonepeta, Ginger, Chinese Vitex, Isatis Root, Echinacea. In a couple of hours I did a literature review looking at potential toxicity of these compounds. They all look fairly benign, but there are scattered reports of side effects with a couple of them.
  4. The difficulty is that side effects can be cumulative if several herbs and supplements are taken at the same time.

I have nothing at all against the Sunday Fox Medical Correspondent: he seems an affable and quite knowledgeable fellow. Neither do I have anything against Airborne. If it helps people, all well and good.

The trouble is that we have had at least three occasions in the last couple of months where advice has been given that had clearly not been checked. I think that unfortunate. Before I post any article I spend hours checking and re-checking. Even with all that checking, I’m quite sure that something could slip through, and if an error occurs, I shall be delighted if someone picks it up, so that I can correct it.

I only wish that everyone who writes or speaks about things medical would do the same kind of obsessive checking.

I really do believe that readers, listeners and watchers deserve nothing less.

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.

Testosterone and the Death of Brain Cells

I’m sure that you’ve heard the Robin Williams joke, “See, the problem is that God gives men a brain and a penis, and only enough blood to run one at a time.”

Well it may turn out that Robin was right for the wrong reason.

Typically thought of as the “male hormone,” testosterone plays key roles in maintaining health and wellness in both men and women. It is true that most men produce about twenty ties as much testosterone as women, but in both sexes, it is involved in energy, libido, and immune function and helps protect against osteoporosis. It is also essential for the normal development, growth and functioning of the brain. In small amounts it may also be neuroprotective.

However, too much of a good thing can quickly turn bad. Researchers from the Departments of Pharmacology and Cellular and Molecular Physiology at Yale University in New Haven, Connecticut have just published an important study of apoptosis or programmed cell death in neurons exposed to excessive amounts of testosterone. Apoptosis is a process for disposing of un-needed or unwanted cells, but if it gets out of control, it can begin to remove cells that should have been left alone. Apoptosis is thought to pay a role in illnesses including Alzheimer’s disease and schizophrenia.

While too much testosterone destroyed nerve cells, estrogen appeared to be neuroprotective: there was less cell death in the presence of the hormone.

This new finding has a number of important practical implications.

Testosterone is one of the hormones abused by some athletes. It certainly can enable them to pump up their muscles, but it may also make them aggressive. Now we know that the practice may also kill neurons. And loss of brain cells is associated with a loss of brain function. This is yet another reason why people should think long and hard before they try to use testosterone supplements. The concentrations used in the experiments were very close to what we might expect to see in someone supplementing with the hormone.

These effects of testosterone on neurons will likely have long term effects on brain function. Though you do generate new connections and some new neurons throughout life, there is a limit to how many you can put back, once they’ve been tainted by testosterone.

And since this is election year here in the United States, I’m sure that we’re now going to have to have a string of off-color jokes about the esteemed Governor of California….

Insulin Resistance, Polycystic Ovarian Syndrome and Sleep Apnea

Polycystic ovarian syndrome (PCOS) is a common endocrine disorder that affects between 5-10% of women in the Western World. It is a leading cause of infertility, and although the underlying cause is still speculative, it is very heavily associated with insulin resistance.

There was an International Consensus Workshop sponsored by the European Society of Human Reproduction and Embryology and the American Society of Reproductive Medicine came up with this set of criteria. PCOS is present if a woman has at least two out of three of:

  1. Oligoovulation and/or anovulation (ovulating only occasionally or not  at all)
  2. Excess androgen (male sex hormone) activity
  3. Polycystic ovaries (which needs a gynecological ultrasonography) and other causes of PCOS are excluded

There is still a great deal of debate about the precise way to define the syndrome. We are currently preparing a scholarly article on the subject and our literature review has included over three thousand papers.

The combination of an excess of the male (androgenic) hormones and insulin resistance can cause an array of symptoms apart form the menstrual disturbances and infertility, including:
Central obesity
Hirsutism, while at the same time experiencing alopecia
Skin flaps and dark patches of skin, usually on the neck or in the armpit
Sleep apnea

It is the last of these that I would like to highlight today.

A new study by Dr. Esra Tasali and her colleagues from the University of Chicago has found that in women with PCOS, sleep apnea is, as expected, associated with high fasting insulin levels. Sleep apnea might worsen the metabolic consequences of insulin resistance.

Regular readers may recall that I highlighted the association between insomnia, insulin resistance, weight and diabetes a couple of months ago. Here we have yet more confirmation of this link.

Not getting enough sleep – for any reason – can play havoc with your metabolism. It seems that in women with PCOS, it’s really easy for a vicious circle to become established:
Insulin resistance -> weight gain -> sleep apnea -> insomnia -> more insulin resistance -> more weight gain and so on.

It is important for everyone to know about this association, because chances are that you know someone with PCOS and/or sleep apnea.

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