MALCOLM KENDRICK, MbChB, MRCGP (email - malcolm@llp.org.uk )

November 28, 2002

Part 1, Part 2, Part 3, Part 4, Part 5

Women, Heart Disease And Sex Hormones


Women don't suffer as much CHD as men - of the same age - despite having slightly higher LDL levels. I'm talking here about women under the age of about seventy. After that the statistics become horribly inaccurate and, in the end, we all have to die of something.

For years and years it was suggested that women were protected against LDL by their sex hormones. In fact the ‘‘sex hormones protect women against CHD'' hypothesis became an accepted fact, a given.

Like most people, I accepted it too, in "a kind of, I can't be bothered checking out every fact that I hear," sort of a way. Anyway, superficially, it made sense. Women have similar risk factors (usually higher LDL levels), they suffer about one third the rate of CHD, and they have hormones. Ergo, it is the hormones that protect women. Nice and simple: To quote H.L. Mencken on simple solutions.

‘‘For every complicated problem there is a solution that is simple, direct, understandable, and wrong.''

However, as with almost every other known ‘‘fact'' about CHD, if you do choose to look for the evidence, it doesn't exist. For years I assumed that someone had carried out a massive pivotal trial proving that female sex hormones really were protective. But when I went to look for it, I found that the cupboard was bare. This fact, quoted endlessly, with utter conviction, is based on absolutely nothing at all.

It is true that oestrogen and progesterone (as we call them in the UK), have some beneficial impact on lipids and blood coagulability, but in fact, if you look hard enough you can find effects on almost everything in the cardiovascular system. Any of these effects could, theoretically, have some protective benefit. And lo it was decided that these ''test-tube'' benefits really were important.

Perhaps the most important of these effects was an increase in High Density Lipoproteins (HDLs), otherwise known as ‘‘Good Cholesterol.'' I love the idea of good and bad cholesterol; it's like something out of Star Wars. ‘‘This cholesterol has gone over to the dark side……"

Give us a break ‘‘Good'' and ‘‘Bad'' cholesterol. How scientific is that? And HDL isn't cholesterol anyway. It's a lipoprotein. But the very fact that such emotive words as good and bad have slipped into this area is a powerful indication that the cholesterol/diet-heart hypothesis is not driven by reason, but by emotion. Frankly, that is the only reason why a hypothesis that makes absolutely no sense whatsoever has survived this long.

Anyway, to return to sex hormones, HDL, and female protection against heart disease. It is true that a high HDL level is associated with a lower rate of CHD. I don't think that anyone could argue with this, not even me, and I can pick a fight in an empty room. For this reason, it was decided that HDL protects against CHD. Quite how, is lost in the mists of time.

Again, it is true that HDL ‘‘picks-up'' loose cholesterol from dead cells and transports it back to the liver, using the ‘‘reverse cholesterol transport system.'' But if you want to explain how it manages to suck cholesterol out of an atherosclerotic plaque, then you are going to have to travel well past the realms of the improbable, and into the zone of the completely impossible.

HDL is travelling through an artery when, suddenly, it spots a cholesterol laden plaque. It stops at that exact point and transports itself through the endothelium. Bravely, battling against a concentration gradient, our plucky HDL locks onto the plaque, sucks cholesterol out, changes direction, reverses back through the endothelium and into the bloodstream. From there to the liver where it heroically unloads its package of ‘‘Bad cholesterol.'' File under: Great Myths of the Western World.

Despite this, it has become another established truth that HDL is not just associated with a reduced rate of CHD; it is, in fact, an active protective factor. Oh, would someone please set up a university dedicated to teaching the difference between an association, a cause, and an effect. All researchers into CHD will be forced to attend, and beaten with large clubs until they finally understand that when you find factor X is raised in condition Y, it does not mean that factor X causes condition Y. Other explanations are possible - thwack! ‘‘Repeat after me, other explanations are possible.'' Thwack! ‘‘And have another Thwack for good measure - you dolt.''

From this, you may be able to gather that I am not a great supporter of the hypothesis that HDL protects against CHD. So it came as no great surprise to me to find that, although HRT raises HDL levels and thus, according to accepted wisdom, should protect against CHD, when this was finally studied, guess what?

The rate of CHD in women on HRT went up. Despite the increase in HDL, (and a decrease in LDL). To quote from the conclusion of the heart and estrogen/progestin study.

Conclusion

‘‘Although many mechanistic and observational studies suggest that estrogen or estrogen plus progestin reduces the risk of morbidity and mortality from CHD in postmenopausal women, the HERS (The heart and estrogen/progestin study), the only large, randomised, controlled study of this question to date, failed to confirm this. Until data from ongoing studies are available, health care providers must reconsider prescribing ERT or HRT for the secondary prevention of CHD.''

This study was completely negative. Actually it was worse than negative; death rates from CHD rose in the first year of treatment. And these results were confirmed by a further study called ‘‘The effects of estrogen replacement on the progression of coronary-artery atherosclerosis.'' This too showed no benefit of HRT on CHD. These results have been so negative that the American Heart Association was forced to re-write their guidelines in 2001, and now recommends strongly against using HRT to protect against CHD.

Not only, it would appear, do female sex hormones fail to protect against CHD. They actually make it worse.

In reality, what has happened with women, and CHD, is something that I consider to be quite extraordinary. Over the years it gradually became a ‘‘known fact'' that a high cholesterol/LDL level causes CHD, yet it was also discovered that women had high cholesterol levels and low rates of CHD, so an ad-hoc hypothesis was developed, which is that women are protected by their sex hormones. This in itself is not extraordinary; it's what happened next.

And what happened is that the sex hormone theory became so popular that it, in turn, become a ‘‘known fact,'' despite a complete and utter lack of evidence. In fact, whenever anyone has studied female sex hormones in relation to CHD they have only found results that completely contradict the ‘‘protection'' hypothesis. Yet, this is just completely ignored. Swept blithely under the carpet.

When I have discussed this issue with researchers in the area they merely shrug and state words to the effect, ‘‘Oh well, they must be protected by something else then.'' No attempt to state what the amazing protective ‘‘factor'' may be? But, of course, we are now into the ‘‘Neptune is angry'' form of circular argument.

‘‘Why do women, who have LDL/cholesterol levels just as high as men, if not higher, have a low rate of CHD?''

‘‘Because they are protected.''

‘‘How do you know that?''

‘‘Because they have high LDL/cholesterol levels and a low rate of CHD, and a high LDL/cholesterol level is the cause of CHD, so they must be protected.''

Strip away all of the scientific jargon and this is all that is left of the cholesterol hypothesis when you look at women and CHD. In reality, the rate of CHD in women should be another fatal wound in the cholesterol hypothesis. But, as I have pointed out before, fatal wounds have no effect on the cholesterol hypothesis, or the LDL hypothesis, or the diet-heart hypothesis, or the Omega 3 fatty acid hypothesis - or whatever it has currently mutated into. For this hypothesis is now an article of faith, and you can't kill faith with facts. For faith, to quote from the Bible:

‘‘Faith is the substance of things hoped for; the evidence of things not seen.''

Just try arguing against that.