Pharmaceutical Hormones for Women

Date: 03/21/2011 Written by: Jon Barron

In case you missed it mid-February, the popular contraceptive YAZ®/Yasmin® was briefly in the news. Stories surfaced that indicated that numerous severe and life-threatening side effects caused by YAZ® (a formula built from two synthetic hormones -- ethinyl estradiol and drospirenone) were downplayed to the extreme in Bayer's high-end-production-value ads for the product. Even the FDA mandated "cleaned-up" versions of the ads managed to make the side effects sound incidental.

In the early 2000s, YAZ® hit the American market in a huge advertising blitz claiming that YAZ® was not only the primo, number-one birth control pill in the world (backed by studies), but also offered the additional benefits of eliminating acne and reducing the effects of PMS/PMDD. And in fact, YAZ® is still promoted that way on its website. Unfortunately, YAZ® comes with a host of side effects -- all blithely laughed off at the end of the ads by young women admiring the wisdom of their friend, the "doctor." And women responded (to the buy part, not the warning part) so much so that YAZ® quickly became the top selling birth control pill in America and Canada.

It's now a few years down the road, and many of those women wished they had paid more attention to those laughed-off warnings. Users of YAZ® have reported everything from gallbladder disease to blood clots, not to mention liver damage, stroke, paralysis, nerve damage, heart attacks, cervical cancer, and the always exciting anaphylactic shock. And then the stories quickly faded from the news -- pushed aside by events in the Middle East, and now Japan.

But out of sight, does not necessarily mean out of mind; lawyers have busily been working in the background. Sensing blood, they are now aggressively trolling the net for victims/clients -- even setting up "YAZ Injury Legal Center" websites. Some estimates suggest that the total number of lawsuits filed may eventually exceed 25,000. In the meantime, Bayer acknowledges the problems on their website where they post the warning:

"BeYAZ™ [a variation of the original YAZ® formula] and YAZ® are associated with increased risks of several serious side effects, including blood clots, stroke, and heart attack. Women, especially those 35 and over, are strongly advised not to smoke because it increases these risks. In addition, BeYAZ™ and YAZ® contain drospirenone, a different kind of hormone that for some may increase potassium too much."

And yet despite the lawsuits and dangers, Bayer continues with business as usual and even recently released a new birth control product called "Natazia™" based on the same concept, but using different synthetic hormones. To me, the stunning part of this story is not that it happened in the first place, or that Bayer is continuing with business as usual, but that people actually seem surprised.

How can you be surprised by synthetic hormones?

The dangers associated with HRT (hormone replacement therapy) for older women involving the administration of synthetic estrogen and synthetic progesterone (aka progestin) to relieve the symptoms of menopause, prevent osteoporosis, and reduce the risk of heart disease are now certainly widely known. And the medical community has even responded -- somewhat -- with the use of HRT dropping by 50% since the dangers were first publicized in the medical community. Coincidentally (and surprising no one in the alternative health community where the dangers of HRT have been gospel for several decades), there has been a measurable drop in the incidence of breast cancer directly correlating with the drop in HRT prescriptions.  Amusingly (well, maybe that's not the best word), the medical community takes credit for the drop in breast cancer as opposed to issuing a mea culpa for giving breast cancer to women by prescribing HRT in the first place. But that's HRT, and we're not talking about HRT today.

Birth control pills use essentially the same type of synthetic estrogen and progesterone hormones to prevent pregnancy and to treat PMDD (premenstrual dysphoric disorder) as are found in HRT treatments. And specifically, we're talking about YAZ®, YAZmin®, BeYAZ™, and the newly released Natazia™ (who comes up with these names?) from your friendly people at Bayer. Incidentally, the term PMDD was not coined by gynecologists or obstetricians. It was, in fact, coined by psychiatrists and first appeared in the last major update of the Diagnostic and Statistical Manual of Mental Disorders, published in 1994. Then again, it's probably no surprise to most women that severe PMS was actually considered a mental disorder for years, at least until the medical community figured out how to make money from it. In any case, the FDA finally sanctioned the term in 1999. The question one is compelled to ask, of course, is: "Why should anyone be surprised that using essentially the same synthetic hormones for PMDD and birth control that were known to cause problems when used for HRT turns out to be just as dangerous?"

Oh, and let's not forget, as I mentioned earlier, that the people at Bayer who make YAZ® also recommend using it for the treatment of acne in young girls and for BeYAZ® as a folate supplement for pregnant woman to lower the risk of having rare neural tube birth defects in their children. (When you actually think about that marketing position for a moment, it hardly qualifies as a ringing endorsement for the effectiveness of YAZ® as a birth control pill.)

Steroid hormone pathways

In order to understand why the problems with YAZ® were so predictable from the beginning, it's necessary to understand where hormones come from and the difference between natural hormones and synthetic hormones.

The first surprise, for most people, since they have been programmed to believe that cholesterol is bad for them, is to learn that all of the steroid hormones -- every single one of them -- come from cholesterol. As you can see in the chart below, cholesterol is the precursor to pregnenolone and, thus, to all the other steroid hormones. Pregnenolone is converted into progesterone and DHEA (dehydroepiandrosterone). DHEA is then converted in the ovaries and testes into the corresponding female and male hormones. In women, DHEA is converted in the ovaries into the estrogens: estrone, estradiol, and estriol. In men, DHEA is converted into testosterone. Note that men produce a small amount of estrogen in their testes and women produce a small amount of testosterone in their ovaries.

Now that we understand how the different hormones actually all derive from the same source, it should be no surprise to learn that their molecular structures are very, very similar.

However, similar is not the same as identical. When it comes to hormones, small differences have huge consequences. So even though the structures of the above molecules are very similar, their functions could not be more different. Cholesterol repairs arterial walls and builds the brain; estrogen makes women; and testosterone makes men. These are huge differences. So, to repeat one more time, when it comes to hormones, small differences can profoundly change the impact on the body.

Which now brings us to the key point of this discussion: how similar are the synthetic versions of the hormones used in pharmaceutical products such as YAZ® to their natural counterparts?

And the answer is not very.

First let's compare drospirenone, the progestin (synthetic progesterone) used in YAZ®, to natural progesterone.

As we can see, the visual differences in molecular structure are significant -- more significant, in fact, than the differences we saw when comparing estrogen to testosterone -- the hormone that makes women VS the hormone that makes men. From this we can conclude that the synthetic drospirenone used in YAZ® is likely to behave quite differently in the human body than natural progesterone. But that's not the only problem with YAZ®. As we've already discussed, YAZ® uses a synthetic estrogen (estradiol) hormone. So now let's compare the synthetic ethinyl estradiol found in YAZ® to natural estradiol.

Again, the differences are significant -- as is their performance in the human body, with severe health consequences. And as we view the evidence above, we are forced to ask, why would Bayer use synthetic progesterone and synthetic estrogen if they are so much more dangerous and no more effective than easily manufactured bio-identical hormones?

And one major part of the answer is money. A drug company cannot patent a bioidentical hormone since it is an exact copy of what nature produces. Only synthetic hormones can be patented. No synthetic hormone means no patent. And no patent means no huge profits since only with a patent can a drug company protect its market share.

But it gets even worse. There are a couple of problems when you put estradiol in a pill. First, it's not very stable. It tends to oxidize easily, which means it tends to have a short shelf life -- not very good for the bottom line. And when you try to take estradiol orally, it tends to degrade in the digestive tract before it is absorbed. So you need to find a way to "protect" the estradiol molecule from the digestive process. Not to worry, the pharmaceutical companies have developed a neat workaround (unnatural though it may be) for such problems. In YAZ®, the ethinyl estradiol is enclosed within a beta-cyclodextrin (betadex) clathrate. A clathrate is a molecule that forms a "cage" around another molecule or molecules. The betadex clathrate in YAZ® is a Bayer-patented technology that protects the enclosed ethinyl estradiol molecule and stabilizes the product against oxidation. This patented technology enhances the product's shelf life and allows more of it to come through the digestive process in good order.

Visually, the final presentation of the synthetic estrogen "protected" inside its clathrate is a far, far cry from natural estradiol indeed.

The consequences of using synthetic hormones

Of course, a key piece of this equation is the assumption that the synthetic hormones used in pharmaceutical drugs are more dangerous than natural or bioidentical hormones. And, in fact, it's not an assumption; it's a fact. So let's talk about the differences between synthetic and natural when it comes to progesterone and estrogen.

Progesterone

I've covered this issue in detail in Lessons from the Miracle Doctors, so I'll just give just a quick summary here.

Most HRT programs, birth control pills, and PMDD hormone treatments include a progestin component along with estrogen compounds. Progestins -- sometimes called progestogens -- are synthetic forms of progesterone that are given to reduce the possibility that the estrogen by itself will cause cancer of the uterus.  Progestins are "modeled" after natural progesterone, but are "modified" to make them patentable. Natural progesterone cannot be patented, which means it is not useful to the pharmaceutical companies. Progestins are commonly prescribed under the brand names Provera and Depo-Provera. Other common brand names are Norlutate, Norlutin, and Aygestin. In YAZ®, the progestin is known as drospirenone. The bottom line is that it is this "slightly" modified, synthetic progesterone that your doctor is most likely prescribing for you when she tells you she's giving you progesterone. This synthetic form of progesterone carries a whole range of serious side effects, including depression, birth defects, increased body hair, acne, risk of embolism, decreased glucose tolerance, and allergic reactions. In exchange for these significant side effects, progestins do offer some protection against endometrial cancer and a very modest, short-term increase in bone formation.

Natural progesterone on the other hand, when used as directed in small amounts, has no known side effects. Incidentally, natural progesterone is best utilized by the body when administered transdermally with a skin cream that contains approximately 500 milligrams (mg) of natural progesterone per ounce and offers the following potential health benefits:

• Improves bone formation. According to Dr. John R. Lee, author of What Your Doctor May Not Tell You about Menopause, natural progesterone may significantly improve bone formation by as much as 15 to 35 percent. This is unique to natural progesterone -- estrogen supplementation does not increase bone formation but merely slows the rate of loss for a 5-year period around the time of menopause. And synthetic progestin only mildly increases bone formation.
• May help protect against endometrial and breast cancers.
• Relieves symptoms of PMS and menopause.
• Normalizes libido.
• Improves the body fat profile.
• Improves sleep patterns.
• Helps relieve migraine headaches.

The choice is clear: you want natural or bioidentical progesterone over synthetic progestins.

Estrogen

There are three types of estrogen in the human body.

• Estrone is the form of estrogen most often associated with women after menopause.
• Estradiol is the form of estrogen most often associated with perimenopausal women.
• Estriol is a weaker form of estrogen produced by the breakdown of other forms of estrogen in the body. This is the form of estrogen most commonly given in Europe. It is the only form that is thought not to cause cancer.

For the moment, let's set aside the fact that ethinyl estradiol, the estrogen used in YAZ® is a synthetic estrogen with a molecular structure not found in nature. We'll get back to that in a moment. And let's deal with an even more serious issue -- that, as we've already discussed, there are indeed three types of estrogen in the human body. This is significant because research has shown that the average ratio of serum estrogen in the female body is 90 percent estriol, 7 percent estradiol, and 3 percent estrone. (This includes the various estrogen metabolites, such as hydroxyestrogen and the 16a-hydroxylated estrogens.) The ratios are important once you understand that both estrone and estradiol are pro-carcinogenic, whereas estriol is cancer protective. So, why would you want to use an estrogen supplement that has only the pro-carcinogenic estrogens and not a single drop of the anti-carcinogenic estrogen that normally represents 90 percent of the body's total? And as its name indicates, ethinyl estradiol is a 100% pure estradiol supplement -- and not bio-identical at that. Side effects associated with the use of ethinyl estradiol (either alone or in combination with drospirenone) include:

• Uterine (endometrial) cancer
• Ovarian cancer
• Vaginal bleeding
• Stroke
• Dementia
• Blood clots
• DVT
• Heart disease
• Breast cancer

Incidentally, Premarin®, the pharmaceutical estrogen of choice a few years back, has similar problems -- although it does contain bioidentical estrone and estradiol. First, it contains no estriol, so it pushes the body into a cancer promotive, rather than a cancer protective, mode. Not good. But Premarin® also has another problem, unique unto itself. Premarin® is extracted from the urine of pregnant horses, which is why the estrone and estradiol in it are bioidentical to that found in the human body. Unfortunately, it also contains close to a dozen estrogens that are specific to horses such as equilin, 17 alpha-dihydroequilin, and equilenin. Another way of looking at this is that those "extra" estrogens are specifically designed to make you gallop and whinny. And that can't be good for you.

The bottom line when it comes to estrogen is that in those cases where estrogen supplementation is warranted, insist that your doctor give you either "true triple estrogen" (and insist that it be in a ratio similar to the 90-7-3 mentioned above) or use pure estriol cream. Studies have shown that the higher the ratio of estriol in the body versus the amount of estrone and estradiol combined, the lower the risk of breast cancer.

Conclusion

For years, I have been consistently cautious when recommending the use of formulas that modify the body's hormonal balance; and certainly the misuse of hormones by athletes and the medical community in the last decade has not helped change that point of view.

Nevertheless, once you throw out all of the preconceptions and look at the issue objectively (and look at the real results, both short and long term), the case for selectively correcting (or even altering in some cases) your hormonal balance becomes compelling -- with a few caveats:

• Only selected hormones should be "adjusted" without a doctor's guidance.
• Use only natural hormones (or hormones that are chemically identical to the natural hormone). Hormones are produced from many different sources: some are derived from animals, some from plants, some are created in laboratories, and some are created through changing the DNA of bacteria or single-celled plants so that they produce the desired hormone. As it turns out, for hormones, the source is not the real question. The real question happens to be: is the hormone a perfect match for the hormone found in our bodies? As we have learned, things are not always what they seem.
• Use only therapeutic or homeopathic doses. Therapeutic doses mimic the amount of hormone your body normally produces. Pharmacological (or medicinal doses) are substantially higher than therapeutic doses and are often accompanied by significant side effects. Never use pharmacological doses without a doctor's guidance.

And by all means, stop using birth control pills based on synthetic hormones. And don't be suckered by marketing ploys such as Bayer's Qlaira®.

Qlaira® was announced by Bayer after the furor surrounding YAZ® first surfaced. Qlaira® was designed to be marketed as a "natural" contraceptive, for those of you who get frightened after hearing bad things about YAZ®. But Bayer's claim to "naturalness" is deliberately misleading. Only the estrogen in it is bioidentical (or almost so), but the formula still relies on a synthetic progestin, with all its associated problems, for its progesterone component. And on top of that, because it still relies on pure estradiol for its estrogen content, it will throw off the body's natural balance of estriol, estradiol, and estrone -- once again putting you at risk.

Shameless!