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Welcome alexdrandia,
Please read this post.
[quote='chrishoney' pid='87767' dateline='1383254379']Post: #7RE: PM and blood clot risk
As far as any of us has been able to determine, there are no studies regarding use of PM by human males. However, there are a few studies with post-menopausal human females as well as a fair number of studies using animal models, ie animals as test subjects, including trying to establish an LD50 for PM.
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Since the procedure for determining the LD50 involves megadosing of the substance or drug in question, it seems reasonable to assume that any deaths resulting from cardiovascular complications would form part of the 50% of the test subjects that succumbed when given excessive PM. Since the studies specifically designed to determine the LD50 actually failed in their purpose (NO LD50 has been established for PM because 50% of test subjects did NOT die, despite being given extremely high doses of PM to the point they could not practically give the animals any more PM), it is safe to assume that even extremely high doses pose little if any cardiovascular risk, at least to those animals. (To head off the spurious argument that just because something didn't happen in a study, doesn't mean it can't happen, this is simple set theory. The subset of deaths due to cardiovascular events is part of the larger set of all deaths due to ingesting PM. If the set of all deaths is so low, NO LD50 could be established, then the subset of deaths due to cardiovascular events is equally low if not lower.)
Add to that the prolonged use (spanning several generations at least and without reported cardiovascular complications) of PM in areas of Thailand and the far east, and the risks from taking PM seem low indeed.
I do understand all the vagaries of experimental design and the danger of inferring or generalizing results for a specific subset of test subjects, to the population at large as well as extrapolating results using animal models to humans, but we have to base a judgement call on something. In my opinion, based on the research I have been able to read, PM is as safe, if not safer than current formulations of bio-identical estradiol.
And just to set the record straight, the danger inherent in Premarin and ethinyl-estradiol are NOT because serum estradiol levels cannot be measured accurately. Please read the research if you don't believe me. Part of the problem with Premarin is that it unnaturally elevates serum estrone and estriol levels which throws things severely out of wack. The other part of the problem is the large number of unknown substances in Premarin that throw off dangerous metabolites as it is being metabolized by the liver in combination with the relatively high doses necessary to be effective since Premarin has relatively low amounts of estradiol, the most effective naturally occurring estrogen.
Premarin was used with and without synthetic progestins (formulated as depot medroxyprogesterone acetate and marketed as Depot Provera) in a longitudinal study of post-menopausal women. The study was called the Women's Health Initiative, so please google it and see why it was HALTED prematurely because of the relatively high number of women who experienced severe health complications, including death! Realize, in a study like this, the goal is NOT to elevate serum estradiol levels to that of pre-menopausal women, but just enough to alleviate the undesirable effects of menopause. The test subjects (over 160,000, so sample size ISN'T an issue) were taking Premarin at levels to sustain serum estradiol BELOW normal levels for pre-menopausal women, and they STILL had severe health complications. Premarin is INHERENTLY dangerous and in combination with medroxyprogesterone, actually, really and truly lethal. It has nothing to do with measuring serum estradiol, estrone and estriol levels.
Ethinyl-estradiol is an extremely potent estradiol analogue (more estrogenic than 17-beta estradiol) that unfortunately forms deadly metabolites as it is slowly being processed by the liver. Again, do the research. The deadly nature of ethinyl-estradiol has nothing to do with how serum estradiol is measured.
Accurate monitoring of serum estradiol levels is possible even if prohibitively expensive for for all but a few. But this begs the question of whether there actually is a link between bio-identical estradiol administration and blood clots. None has been established by any studies I have been able to find. As Abi pointed out, the (flawed) assumption of the medical establishment and big pharma is that all estrogen replacement drugs are equal, in effect as well as risks. This is just false on many many levels.
Finally, all of this is complicated by the fact that PM is NOT an estrogen, it is NOT estradiol, nor estrone nor estriol, the three naturally occurring estrogens found in biological females. The purported active ingredients in PM (deoxymiroestrol and miroestrol) are estradiol MIMICS. That is, they mimic many of the effects of estradiol. This does NOT mean they mimic ALL of the effects of estradiol as evidenced by the studies (using animal models or in vitro cell cultures) showing PM has a PROTECTIVE effect with regard to certain types of cancer, including estrogen sensitive cancer cell lines. This is seemingly illogical if we assume PM has ALL the properties of estradiol since certain cancers are known to be estrogen sensitive, that is estrogen accelerates their growth and development. It is NOT illogical if we remember that just because PM mimics some of the effects of estradiol, it is NOT estradiol, and therefore does NOT necessarily have the same risks.
I do agree that everyone considering taking PM should be very cautious when they start in order to determine how it affects their particular system. Everyone reacts somewhat differently to every drug or herb. That is part of the reason there are numerous drugs in any class of medications, such as NSAIDs, statins, diuretics, antianxiolytics and so on. It is entirely conceivable that PM precipitated the event of the 20 year old that threw a clot to the lungs. But then there are folks that develop deadly clots which are ideopathic. He may be genetically prone to excessive arterial plaque build-up too. Estradiol has a heart protective function, but it is NOT a given that PM has the same effect, and even if it does, it would not eliminate the occurrence of clots. Some folks form clots easily, and some don't. It is equally conceivable that his taking PM and throwing a clot are completely unrelated except for their proximity in time.
Taking PM is NOT risk free and each person has to assess the level of risk tolerance they are comfortable with. In order to do that, we need to consider facts, not just what we read on some forum (YES! including this polemic--DO THE RESEARCH FOR YOURSELF.) However, in my opinion the preponderance of evidence indicates that PM is as safe, if not safer than most if not all of the common drugs many of my patients currently take, including ibuprofen (if you're the type to stay up at night worrying, DON'T read the possible side effects and complications from this common OTC drug), celebrex, coumarin, oxycodone, and even nicotine (check out the LD50 of nicotine, which is more toxic than pure cocaine!)
(This post was last modified: 09-08-2013 12:04 PM by chrishoney.)
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