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For no good reason, it took decades to medical doctors to find out that interfering with body's estrogen management, which gradually evolved into so called Hormone Replacement Therapy (HRT), can be pretty risky business. And it's no wonder, since they didn't really know what they were doing (not that much has changed in that respect since).

And, as you can read in the last issue of Neurology, that story isn't over yet.

After establishing that HRT risks do not justify its blanket use - opposite to what drug companies and medical establishment were advocating for long time (estrogen-alone has been widely prescribed since 1940s) - the Women's Health Initiative (WHI), a large 6-year government study, has come up with more disturbing news. Magnetic resonance imaging (MRI) of 1400 woman (65 and older) showed that those on HRT for 4-6 years had "small but significant" loss in volume of the frontal lobe and hippocampus, compared to placebo group.

Plainly put, the HRT made their brains shrink.

This is not a complete surprise, since it's already been known that HRT increases the risk of dementia and overall mental decline in older women. Since the frontal lobe and hippocampus have key role in memory function and thought process, it was to expect that they were affected in some way by HRT. But no one thought it was as drastic as to have them actually physically reduced.

This comes after the same study found evidence that estrogen-alone therapy (Premarin) significantly increases the risk of stroke and deep vain thrombosis in women over 50, and increased risk of dementia for women over 65. That comes on top of already known 5-10 times increased risk of endometrial cancer, which is why progestin has been added to the mix.

The study also found that the estrogen+progestin (PremPro) therapy caused significantly increased risk of myocardial infraction, stroke, invasive breast cancer, pulmonary emboli and DVT (deep vein thrombosis) in women over 50, and also increased risk of dementia in women over 65.

The FDA decided, back in 2003, that putting boxed warning on these drugs will do.

Yet, it doesn't take much of a thought to conclude that the possibility of serious adverse effects should have been anticipated, and why. The fact that no one thought about it only reaffirms that the long-practiced "medicate the symptom" approach of the official medicine which, conforming to the business priorities of pharmaceutical industry,

keeps ignoring and neglecting how the body actually works.

 And with it, of course, what is it that your body really needs in order to maintain, or regain health.

It is well known that ovarian steroid hormones have very complex and only partly understood effect on the brain. It expands to significant brain structures not involved in reproduction, which in addition to the forebrain, and hippocampus, include basal ganglia (voluntary movement), midbrain raphe and parts of brain stem (locus coeruleus, also involved in brain's cognitive function, and associated with various brain dysfunctions, including dementia).

Ovarian steroids act either by binding to the cellular membrane receptors, or to receptors in the cell nucleus (being lipid soluble, ovarian steroids freely enter brain cells trough their lipid-based cellular membranes). The former affects cellular communication and signaling, the later cell's internal functioning, including cellular DNA.

 What effects arbitrarily elevated levels of ovarian steroids can have in general, and on the brain in particular, is anyone's guess. More so in the longer term. A 2006 study (Ehlrich et al., Journal of Biological Chemistry by Yale School of Medicine) has found out that high levels of male steroid hormone, testosterone, kill nerve cells by triggering programmed cell death (apoptosis).

Earlier, in 2003, SARS (Severe Acute Respiratory Syndrome) virus patients in Hong Kong, treated with high doses - nearly 30 times the daily dose of estrogen-alone, and less than 10 times of estrogen+progestin HRT therapy - of another steroid, Prednisolone (corticosteroid), quickly showed early signs of irreversible brain damage.

Can anyone guarantee that female steroids taken orally won't have similar effect? Not really. Women undergoing HRT can also have abnormally high blood level of steroids which, by the way, no one finds necessary to pay attention to.

One would think that an active substance with direct access to the DNA would be used more carefully. But it doesn't have to get to the DNA. Among the host of other processes, steroids also are very likely to be affecting so called heat shock proteins inside the cell. Being in charge of "protein folding" (proper structuring of protein molecules), these proteins have their fingers in everything in the cell that relates to, or depends on proteins. 

And that amounts to the cellular respiration itself.

One of those functions seems to be loading another class of proteins, MHC (major histocompatibility complex) molecules with intracellular peptide fragments, which then take the load out to the membrane. These peptide fragments are telling to the immune cells patrolling around whether the cell is O.K. or not (infected, cancerous, or abnormal in some other way). If the cell doesn't look O.K.,

it gets destroyed.

These are only two random examples of how ovarian steroids could affect cells. There is much more to it, and no one can tell for sure what should be a typical effect of their long-term use, much less how an individual could be affected. And less so for synthetic steroids, like progestin, which is used to "counterbalance" estrogen's side effects. And the least about possible synergistic effects and interactions between the two.

Put simply,

no sufficiently long controlled clinical study before the WHI
was ever conducted.

If that's true - and it is - how could pharmaceutical companies and medical profession market/condone HRT as a blanket long-term hormonal therapy?

They gamble. Not with their money, mind you, but with your health, because they hardly can lose. All they need to show is that treatment's "benefits outweigh the risks", which is rather easy with medical professionals conditioned to follow lead of pharmaceutical companies (not seldom benefiting from it as well), and the FDA that effectively became their business partner. In the worst case scenario, when lots of people get hurt, and it can't be covered up, they are still likely to pay in compensations less than what they have made marketing the product.

In short, everything's taken care of... except you. When establishing what the risks of therapy are, drug-makers are only required to show that their product is effective in relieving particular symptoms, while not making people having their healthy liver damaged, or suffer other obvious and significant adverse effects in a short to moderately prolonged time period.

That "safety net", as corrupted as it is, doesn't protect you from harm - there are plenty of examples.

And good part of the reason for this happening is the second part of the problem: medical professionals neglecting - or often simply being ignorant of -

what is it that your body needs to maintain, or regain health.

Most every drug interferes, to a lesser or greater degree, not only directly with body functions, but also with body's nutritional status. You have only so much of vital nutrients available - which in many are imbalanced or insufficient to begin with - and what is left after detoxifying the drug, or being used or destroyed by it, may not be enough to optimally support your vital functions.

In this particular example, it is known that ovarian steroids interfere with carbohydrate and fat metabolism, as well as suppress or destroy several vital nutrients, which include vitamin B6, C and E. They also tend to increase copper and iron, and decrease zinc levels. How all this will affect you much depends of what your nutritional status is.

Unless you are low in copper and iron, their higher level will likely expose you to more oxidative damage, by stimulating production of the most reactive free radical of all, hydroxyl radical. If you are at the same time low on vital antioxidants like vitamin C and, particularly, E, which is needed for protection of lipid structures, more than anywhere else important in your brain cells, you'll suffer damage. Low zinc, needed for the principal internal cellular antioxidant, superoxidase dismutase, will only make things worse.

In addition, it can seriously compromise your ability of efficiently using another important antioxidant, vitamin A, regardless of its body level. And it will also impair efficiency of pyridoxal kinase, the enzyme needed to convert vitamin B6 in its usable form.

All this spells low B6 - and some other B-vitamins - level. That, in turn, makes aldehyde detox pathway less efficient, and resulting toxic metabolites (from, for instance, alcohol, VOC like formaldehyde, or acetaldehyde produced by Candida albicans)

more damaging to the brain.

More so if it lacks adequate antioxidant protection. B6 is also actively involved in the functioning of the nervous system - in short, you need it for healthy brain.

These typical effects of taking oral steroids like estrogen and/or progestin on your nutritional status and, with it, your vital body functions, show that one can't afford the luxury of taking hormonally - and, for that matter, biologically - active substances while ignoring their complex and potentially significant effect on the body and overall health.

The fact that your average medical doctor does ignore it, doesn't make it neither good, nor safe.

The good part of this latest news about adverse effects of the Hormone Replacement Therapy, as bad as it is, is that it may, hopefully, turn a few more medical minds around and make them see more clearly the shortcomings of their professional training and practice.