The Hopkins Health Watch - Vol 1, Issue 4
& Nutrition News,
Drug Watch and More...
One of the issues up on the radar screen in natural hormone replacement therapy is whether taking estrogen in the oral (pill form) or transdermal (skin cream or patches) works best. (It's already very clear that progesterone cream works better than progesterone pills.) A few studies have been published showing that oral estrogen increases levels of C-reactive protein (CRP), a marker of inflammation that is associated with heart disease.
The Voices of Experience
Jane Murray M.D., who specializes in natural hormone replacement therapy in her medical practice in Kansas City, decided to test this for herself after she noticed that her patients who used estradiol patches seemed to be doing better than those taking pills. She first tested an elderly patient who had been on a small dose of Premarin for many years. When her blood tests showed high CRP levels, Dr. Murray suggested she switch to a patch. After three months on the patch, the patient was tested again, and her CRP levels were normal. According to Dr. Murray, That was my index case that woke me up to the fact that this is a real and clinically relevant phenomenon. Since then I've had other patients with the same result, so I now routinely recommend patches or cream over pills. I have noticed that my overweight patients who are insulin resistant are more sensitive to the CRP-elevating effects of oral estrogen. This may be why we've gotten such conflicting reports over the years about estrogen's effects on heart disease.
Oral Estrogens Associated with Low Sex Drive
Dr. Murray continues, I also found that patients on oral hormones tended to have more problems with low libido or sex drive. When I researched this I found that oral hormones stimulate the liver to make proteins, including SBHG [serum binding hormone globulin], which binds to hormones and makes them inactive. When I tested hormone levels in my patients I found that when they were put on oral hormones their SBHG went way up and their free testosterone went way down, which accounts for the low libido. I found this to be true with oral hormone replacement hormones and with birth control pills. When I switched these women to the birth control patches their libido came back.
Dr. Randolph Weighs In on Oral Estrogens
C.W. (Randy) Randolph, M.D. of Jacksonville Beach, Florida has had similar results in his busy natural hormone therapy practice, and adds that compared to transdermal estrogens, oral estrogens increase the risk of thromboembolic events [strokes and blood clots]. He points out that the liver proteins created by oral estrogens also raise blood pressure, raise triglyceride levels, and suppress thyroid function. Because he is a pharmacist as well as a physician, Dr. Randolph makes his own transdermal hormone gels. He usually recommends that women begin with a combination of 0.75 mg of estradiol and 1.5 mg of estriol daily, and then adjust according to salivary hormone level tests and symptoms.
Ylikorkala O, Evio S, Effects of hormone therapy and alendronate on C-reactive protein, E-selectin, and sex hormone-binding globulin in osteoporotic women, Fertil Steril. 2003 Sep;80(3):541-5. Kawano H, Yasue H, Effects of transdermal and oral estrogen supplementation on endothelial function, inflammation and cellular redox state, Int J Clin Pharmacol Ther. 2003 Aug;41(8):346-53.
Frohlich M, Muhlberger N, Markers of inflammation in women on different hormone replacement therapies, Ann Med. 2003;35(5):353-61.
Atrazine is the most heavily used agricultural pesticide in the U.S., and it’s estimated that 60 percent of the U.S. population is exposed to it daily. It is used to control grasses and broadleaf weeds in everything from woodlands and orchards to lawns and cornfields. It doesn't break down easily in the environment, and thus is the most widely found pesticide in surface and ground water. Atrazine contamination of wells and city water supplies is widespread in the U.S.
Atrazine is a known endocrine disrupter. Endocrine disrupters are substances that can affect hormone balance in both males and females.
Animals and Atrazine
Rats exposed to atrazine while pregnant—in doses below the levels considered safe in the U.S.—had female offspring with abnormal mammary gland (breast) development, making them more susceptible to the effects of carcinogens. The implication of this research is that humans exposed to atrazine while still in the womb may have abnormal breast development that makes them more susceptible to breast cancer.
Frogs exposed to atrazine have a much higher rate of hermaphroditism (both male and female sexual characteristics), and the males have significantly lower levels of testosterone.
Humans and Atrazine
Male workers in a Louisiana factory making atrazine are reported to have more than triple the risk of prostate cancer compared to other men in the state of Louisiana, although subsequent studies that tweaked the data did not find a correlation. Atrazine exposure has also been linked to leukemia in migrant farm workers in California.
Atrazine has been banned in a number of European countries, including France, Denmark, Germany, Norway and Sweden because of its endocrine-disrupting properties. In spite of the evidence against atrazine use, the U.S. Environmental Protection Agency (EPA) chose not to limit atrazine use in 2003.
To put this in perspective, it’s unlikely that typical atrazine exposure is going to directly or immediately harm a healthy human adult. However, it’s important to take cumulative exposure into account. For example, if you're using pesticides in your house, garden and lawns; exposing yourself to paint fumes, solvents, glues and other endocrine-disrupting toxins; and have high levels of estrogen in your system because you're overweight or using high doses of supplemental estrogen, then there might be some cause for concern.
Most Risk to the Unborn
Those most at risk from exposure to pollutants such as atrazine are in utero—in the womb—where even small exposures to endocrine disrupters can affect later development of the reproductive organs, including the breasts, ovaries and uterus in women, and the testes in men.
Removing Atrazine from Your Water
The good news is that atrazine is fairly easy to remove from water with home water filtering systems, including the simple and inexpensive charcoal water filters. If you're interested in knowing whether your water supply contains measurable levels of atrazine, try the Pesticides in Water test kit.
Birnbaum LS, Fenton SE, Cancer and Developmental Exposure to Endocrine Disruptors, Environ Health Perspectives 2003 April; Vol 111(4):389-394.
Feminized Frogs: Herbicide disrupts sexual groups, Science News Online, April 20, 2002, Vol. 161, No. 16, http://www.sciencenews.org/20020420/fob1.asp; Hayes, T.B., et al. 2002.
Hessel PA, Kalmes R et al, A nested case-control study of prostate cancer and atrazine exposure, J Occup Environ Med. 2004 Apr;46(4):379-85.
The good news is that finally an excellent study has been done which shows that when we use progesterone cream, the progesterone is very well absorbed into the blood and from there into the cells. This should effectively put any further doubts or debates about this matter to rest. The bad news is that the conclusions drawn from the study are based on an incomplete understanding about the difference between progestins and progesterone.
The headline on a press release for the study reads:
NEW RESEARCH PROVES PROGESTERONE CREAM AS POTENT AS PILLS
-- PUTTING MILLIONS OF WOMEN AT RISK -
The second part of the headline should read, "Protecting Millions of Women from Estrogen Dominance!"
The first paragraph of the press release about the study reads as follows:
(Washington, DC)....A new study shows that a popular, over-the-counter progesterone cream (Pro-Gest) is absorbed into the blood to the same extent as FDA approved progesterone capsules, meaning that progesterone cream is as strong as the pills.
This press release was put out by Bassett Healthcare, a network of three hospitals and 21 health centers, offering the finest in medical care to the residents of rural, central New York, to introduce an excellent study done by Anne Hermann, M.D., of the Clinical Pharmacology Research Center at Bassett Healthcare.
Here’s a partial description of Hermann’s study from the press release:
The Bassett study measured whole blood with red blood cells and other cells in it. Many progesterone studies measure serum, which is blood that has had the cells in the blood filtered out. This gives inaccurate results because progesterone circulates in the blood bound to cell membranes. When progesterone reaches receptors in the organs of influence, the breast, uterus or placenta, it detaches from cell membranes and attaches to the receptors. Therefore, in order to be accurate, whole blood must be measured."
It's fantastic that Hermann realized that when progesterone creams are used, the progesterone does not show up in the serum (the watery part of the blood), making conventional blood tests inaccurate. Now let's try to convey this message to those doctors who insist on giving their patients super high doses of progesterone in pill or cream form in order to force it to show up on conventional blood tests.
the press release continues: The study also measured the steady state levels of whole blood by using a very sensitive instrument to measure progesterone levels. Steady state means it takes about a week of use for progesterone to reach maximum daily concentrations in the blood. Prior to five to seven days, average progesterone levels in the blood are still building up. After about a week, a dose of progesterone will yield blood concentrations that are the same every day, whether on day 10 or day 100. Levels were measured on day 12 to ensure that the concentration was steady and no longer "building up." Many prior studies measured blood levels of progesterone after one dose, which will give much lower concentrations. In addition, older studies often used instruments that gave incorrect data on blood progesterone levels.
The Conclusions of the Study Are:
Our data show that one brand of progesterone cream (Pro-gest®) results in equal steady state exposure compared to an FDA-approved oral progesterone preparation (Prometrium®) at daily doses recommended by the product labels.
The results of this study are more accurate than most previous progesterone pharmacokinetic studies because more extensive blood sampling, sampling of whole blood to measure total progesterone and progesterone specific assay techniques.
The use of topical progesterone without medical supervision is concerning because of the possibility of increased risk of coronary artery disease, stroke, thrombosis and breast cancer.
Because the efficacy of oral micronized progesterone is partially due to its metabolites, further studies comparing active metabolites from oral micronized progesterone and topical progesterone are recommended.
Over-the-counter progesterone cream yields the same exposure to progesterone as the prescription oral micronized capsules. Women who use the non-prescription form of this drug do not have the benefits of physician counseling, screening and supervision.
OTC PC [over-the-counter progesterone] at a dose of 40 mg twice daily gives equal exposure to oral P [Prometrium, an oral progesterone] at a dose of 200 mg daily.
It's unfortunate if the researchers consider 40 mg of progesterone cream twice daily to be a standard dose. It's double the dose normally recommended by Dr. Lee.
This was a beautifully done study that came to some erroneous conclusions, presumably due to an incomplete understanding of the differences between synthetic progestins (e.g. Provera) and natural progesterone. The conclusion about …increased risk of coronary artery disease, stroke, thrombosis and breast cancer, cites studies that used progestins and had nothing to do with natural progesterone.
Dr. Lee responded to this common and persistent misunderstanding among health care professionals with the following:
Progesterone and Progestins:
What's the Difference?
by John R. Lee, M.D.
I have clearly outlined the differences between progesterone and progestins in my books, but sometimes the Socratic method of questioning works better to illuminate an issue.
I suggest that those who still insist that progestins and progesterone are the same, or that progesterone is a generic term that also covers progestins, ponder the following questions. If progesterone and progestins are the same:
Why do fertility doctors always use progesterone and not progestins?
Why do progestins cause birth defects, while progesterone is essential for a viable and healthy pregnancy?
Why don't synthetic progestins show up in blood and saliva tests of progesterone levels? (In other words, why doesn't taking a progestin raise progesterone levels in the body?)
Pregnant women are making 300 mg of progesterone daily in the last trimester. Why don't they have higher rates of breast cancer, as women do who use progestins? [In fact, women who have never been pregnant have a significantly increased risk of breast cancer.]
Why doesn't natural progesterone cause the side effects listed for medroxyprogesterone acetate (Provera) the most commonly used synthetic progestin for HRT?
In Issue 3 of the Hopkins Health Watch I shared some research showing that dark chocolate has some health benefits. A few readers wrote to point out that the research was sponsored by the chocolate industry. Does that make it bad research?
At the risk of sounding cynical, all research is sponsored by someone, and most often by a biased party. After all, why would one put up substantial amounts of money for research if there wasn’t a benefit behind it? University research is almost always paid for directly or indirectly by commercial entities, and government research is heavily influenced by lobbyists, particularly those from the financially well-endowed pharmaceutical companies. Examples of true altruism in scientific research are extremely rare. This makes careful interpretation and analysis of research very important.
Examples abound of research that says one thing in a published article's title and abstract, while the research itself says something entirely different. Researchers who perform these sleight-of-pen tricks count on the fact that publishers rarely read and analyze the research carefully, and the media certainly doesn't read anything but abstracts and press releases.
I recently read a study published in a prestigious medical journal on the subject of oral contraceptives and breast cancer risk. The conclusion of the abstract was that there is no association between using contraceptive hormones and increased risk of breast cancer. Since this contradicts quite a bit of earlier research, I looked at the data more closely. Indeed, when the data was combined and averaged, there wasn't an increased risk. But when the data for different ethnic groups was pulled out from the rest of the data, some groups of Caucasian and African-American women who used oral contraceptives did have an increased risk of breast cancer. It's unlikely that the researchers missed this evidence.
I take research seriously and also with a grain of salt (or a piece of chocolate!). It should never be immediately taken at face value, one should never automatically assume it's true or meaningful, and it always bears a closer look if it's going to be used to prove a point.
As for the chocolate studies, there's no reason to dispute their findings--they weren't looking for earth-shattering revelations in medicine, just a couple more little justifications for chocolate lovers to indulge--in moderation of course!
Many horse lovers are waging the annual summer battle against flies and like me, don't want to use pesticide sprays (they're poisonous to flies… and horses… and humans). Even the so-called natural pyrethrums which are derived from chrysanthemums can be highly allergenic for horses and their human applicators. The more natural citronella, d-limonene, cedar wood oil and eucalyptus, for example, just don't seem to work very well.
I've also tried some of the expensive supplements containing garlic and biotin which are supposed to make the horse smell bad to flies, but haven't had much luck with them. But one day on an impulse I grabbed a bottle of garlic flakes from the spice rack at the supermarket and started sprinkling a small amount on my horses' dinner. Within a few days the flies didn't want much to do with them, except around the head, and fly masks take care of that area. Garlic has the added benefit of making the manure less desirable to flies laying eggs.
Another fly solution that can make a big difference is fly predators, which are tiny wasps that eat fly eggs. They're shipped to you each month during the summer in the immature stage, inside a cocoon. When they begin to emerge you sprinkle them in spots where flies like to lay their eggs—like manure piles and water troughs. They don't bite, sting or swarm around you and your critters—they're only interested in fly eggs. They occur naturally world-wide so they're not an environmental threat, and only cost $2 to $3 per horse per month. If you'd like to know more about them, go to http://www.spalding-labs.com.