Natural Hormone Replacement Update

Exclusive Interview with Jonathan V. Wright, M.D.

Natural Hormone Replacement Update

onathan V. Wright, M.D., is well known to readers of Life Enhancement by virtue of his medical and nutritional expertise. He is celebrated as one of the leading alternative and life extension physicians practicing in the United States today. As medical director of the Tahoma Clinic in Renton, Washington, Dr. Wright has overseen and administered treatment to tens of thousands of patients over 31 years, using innovative natural therapies, including diet, vitamins, minerals, other nutritional supplements, botanicals, glandular extracts, and bioidentical hormones, as well as natural energies.

Among his most recent books are the bestsellers Natural Hormone Replacement for Women Over 45, Maximize Your Vitality and Potency for Men Over 40, and Why Stomach Acid Is Good for You. Dr. Wright has also written 20 years of monthly columns for Prevention and Let’s Live magazines. His Nutrition & Healing Newsletter has been published monthly since 1994. Since 1982, along with Dr. Alan Gaby, he has taught health care practitioners at his annual four-day intensive seminar, entitled “Nutritional Therapy in Medical Practice.”

Despite his innovative and outstanding accomplishments in natural medicine, Dr. Wright was made infamous to those outside the natural medicine field by the FDA, which in 1992 raided his clinic at gunpoint and arrested his B-vitamins! Not surprisingly, one of his favorite sayings is, “Let’s outlive the FDA!” In this exclusive interview with Life Enhancement’s publisher, Will Block, he discusses bioidentical hormones and a unique liposomal delivery system for hormones that has previously not been available to the public without a prescription; it can also be used for more readily attaining higher levels of vitamin B12 and folic acid.

LE: Throughout Western history, women have been considered second-class citizens, with far less attention being paid to their medical needs than to those of men. So we eagerly await the new edition of your extremely informative and readable book Natural Hormone Replacement for Women Over 45, which we understand is due out in 2005. What are your reasons for revising the book at this time?

DR. WRIGHT: When the book first came out in 1997, its purpose was to let women know that there were preferable alternatives to the horse hormones (conjugated estrogens, such as Premarin®) and synthetic progesterone analogs (progestins, such as Provera®) that were in current use. Apparently there was great interest, and the book sold almost 200,000 copies. In fact, it was #1 on’s Natural Medicine list. But the purpose of the updated edition is a bit different. Everyone, it seems, is now aware of the so-called Women’s Health Initiative debacle, which finally exposed, after some 40 years, what we in natural medicine have known all along, namely, that taking horse hormones and synthetic progestins puts women’s health at risk while not actually improving it that much.

That knowledge is now widespread, particularly since the publication this year of Suzanne Somers’ latest book, The Sexy Years—Discover the Hormone Connection: The Secret to Fabulous Sex, Great Health, and Vitality, for Women and Men, which has drawn much attention (with sales of over a million copies) to bioidentical hormones. That term means hormones that are chemically, and therefore biologically, identical to human hormones. By and large, it’s no longer necessary to let people know that bioidentical hormones exist, and what they do. Instead, we need to inform them of the many studies that have used bioidentical hormones, showing that they are safe—which is a vital point—and effective. Finally, we need to discuss doses and timing.

We did cover much of this in the first book, but unfortunately, as a result of the Women’s Health Initiative, some conventional medical doctors are adopting the use of bioidentical hormones without understanding the scientific literature, and as a result some are prescribing overdoses. For example, Ms. Somers is using 1 mg or more of estradiol daily, even though studies show that this level is putting her at unnecessary risk. She can achieve the same effect—and so can all other women—with smaller doses and by including estriol, which offsets the slightly carcinogenic tendencies of estradiol.

Not only are mainstream physicians slow in utilizing bioidentical hormones and often using too much, but they are also not following nature’s timing. In my book, I will emphasize all the hormones of the menstrual cycle, not just bioidentical estrogen.

LE: Nature’s timing does tend to vary in different women.

DR. WRIGHT: Absolutely. We ask women to use bioidentical hormones in such a way that they mimic, as closely as possible, the timing of their full menstrual cycles in their earlier years. However, research so far shows that having menstrual bleeding each month is not necessary for a woman to be perfectly healthy as she ages and is affected by menopause.

One important research study done over a 5–7-year period found that with the use of bioidentical hormones, it’s not necessary to have a regular bleeding period every month to keep a woman safe from endometrial problems. That study even involved endometrial biopsies and other measures to examine the safety of bioidentical hormones. Compared with controls, the researchers found no excess of endometrial proliferation with the use of bioidentical estrogen and bioidentical progesterone. However, the bioidentical hormones provided clear beneficial effects, such as better mood and less irritability, even though the bleeding cycles were not necessarily regular—there were just pauses in menstruation, i.e., skipped months.

LE: How does a woman establish the true length of her period?

DR. WRIGHT: We ask each woman to think back to her thirties, to whatever a normal cycle was for her at that time—a time that was not perimenopausal or “wobbly,” as it’s sometimes called.

LE: Are there other uses for natural hormones that go beyond replacing what’s lost with aging, such as special applications?

DR. WRIGHT: Certainly. In addition to hormone replacement after menopause, there is the large area of hormone supplementation for women who are approaching menopause. As every woman knows, the approach can start as little as a year or two before menopause actually begins. For some women, however, the ovaries will slow down on progesterone production as much as ten years before menopause—well before estrogen production slows down.

In rare cases, estrogen production can collapse while progesterone is still going strong, but usually, progesterone goes into decline before estrogen does. The result is the well-known premenstrual syndrome (PMS), which also occurs in women in their twenties and thirties. As menopause approaches, of course, PMS occurs more and more. One way to deal with it is with supplemental progesterone—but that’s not the only way. For example, we find that some women actually need to be desensitized to their own progesterone—it’s because of a sensitivity problem that they’re having PMS.

However, desensitization is needed much more often in younger women—those in their twenties and thirties. Women in their late thirties and forties with PMS are more likely to experience the slow, gradual decline of progesterone, and supplementation will almost always alleviate their problem. Note that this is supplementation, not full-scale replacement, because the ovaries are still making some.

LE: How does one determine how much progesterone is appropriate?

DR. WRIGHT: Before menopause, it’s a matter of observing the symptoms. The doses then can range from a low of 30 to 50 mg/day all the way up to a couple of hundred milligrams/day. And it really does vary from woman to woman. In fact, some doctors prescribe as much as 300 to 400 mg/day. I rarely do that, because that amount may represent full-scale replacement, and before menopause, supplementation instead of replacement is more appropriate.

LE: Do you recommend progesterone supplementation for women in their twenties or thirties experiencing PMS?

DR. WRIGHT: Yes, I do. But, as I said, the problem is more likely to be progesterone sensitivity at that age, and that requires help from a doctor. With younger women, the supplemental amounts are going to be higher—usually a minimum of about 100 mg/day, and one might go to 200 or 300 mg. Again, we don’t want to discourage the ovaries from making progesterone on their own, so I don’t like going as high as 400 mg.

LE: In a joint interview we did with Dr. John Lee and yourself a number of years ago, Dr. Lee opined that progesterone should never be used continuously. Do you agree?

DR. WRIGHT: Yes, with a modification. Our bodies don’t produce the same amount of progesterone continuously. There’s always a little being made, as it’s a precursor to cortisone, aldosterone, and other steroid hormones, but the big “surge” of progesterone occurs after ovulation, in the second phase of a normal menstrual cycle. This surge subsides before menstruation, during which a much smaller amount of progesterone is produced. So we want to copy Nature and give everyone a pause when the menstrual period occurs.

Further, the receptors are accustomed to the natural cycle of the hormones, so overriding the cycle with supplementation at the wrong time can cause undesirable effects. But estrogens cycle differently, so if a woman is replacing estrogens, I recommend that she copy the natural estrogen cycle with a monthly break. The pattern for progesterone can be more complicated, because progesterone is not just an ovarian hormone. The process by which steroids are made and used starts with cholesterol, which is turned into pregnenolone, and then something else, and so on. One of the first things that pregnenolone turns into is progesterone and, as mentioned, progesterone is also a precursor for cortisone and aldosterone, two end-product metabolites.

Thus if you use progesterone for ovary-mimicking alone, there may be times when there’s not enough from which to make cortisone, aldosterone, etc. So for some women who feel really bad without continuous progesterone, we can modify the amount on a monthly basis, by a small amount depending on whether a woman is premenopausal and having a bleeding cycle, or postmenopausal.

LE: What would a small amount be?

DR. WRIGHT: For premenopausal women, it might be around 25 to 50 mg/day. For postmenopausal women, it will be more like 10 to 15 mg/day. If you recall Dr. Lee’s recommendation and mine, the most progesterone to be used during the so-called luteal phase, the second half of the cycle (and, of course, if one is not having periods at all) is around 25 to 30 mg. If one needs to use it the rest of the month, the step-down dose would be about 10 mg.

LE: What are your thoughts about Pluronic lecithin organogel (PLO) as a method of transdermal application?

DR. WRIGHT: That gel, PLO, is one of my favorites. In fact, the majority of compounding pharmacists who fill prescriptions for doctors use PLO. But one does not have to be a pharmacist to use it. It’s an innocuous material made, as the name implies, from lecithin, and the gel won’t hurt anyone—although I should note that every year we run into one or two women who are allergic to PLO, so we have to switch to a different delivery form.

But we’ve moved away from transdermal application in any case. As you know, our clinic has been prescribing hormones since the early 1980s. That has given us over 20 years of experience, and what we’ve observed is that, although transdermal application is usually effective at first, it becomes less effective with time, even with rotating skin sites. So we’ve asked our patients to switch from transdermal to transmucosal application, which means across a mucous membrane—in this case, the mucous membrane of the vaginal area.

That is really the best area for delivery of the hormone. We can include the inner surfaces of the labia or, for women having problems with incontinence (mostly women in their seventies and eighties), the area around the urethra. Interestingly, rubbing it inside a cheek, which is another mucous membrane, also works, although the volunteers who did that for experimental purposes said it tasted weird. Women who have had problems with transdermal applications becoming less and less effective have found that when they switched to these mucous membrane sites—bingo!—it started working again, just about universally. Testing showed the hormones back at the levels we wanted. So we are discouraging transdermal application in favor of transmucosal.

LE: What are some of the symptoms that women might be expected to alleviate, and are there other benefits that accompany the transition?

DR. WRIGHT: The initial relievable symptoms are those of PMS: mood swings, irritability, and the like. These are so well known that PMS has spawned its own genre of jokes. After menopause, one can still get those PMS symptoms, but the focus shifts to such things as improvement in bone health, which Dr. Lee was first to tell us about. But remember that these results are with bioidentical progesterone and not that artificial medroxyprogesterone.

A recent study from the University of South Florida found no disruption to the inner lining of arteries of experimental animals given bioidentical estrogen or bioidentical progesterone. But the medroxyprogesterone caused all the changes that one sees in incipient atherosclerosis. It’s scandalous that for some 35 to 40 years, the concept of progestins instead of natural progesterone has been sold to the women of this country.

Bone health is one of the first things we want to think about after menopause, using progesterone and, of course, estrogen, because the two work together. Dr. Lee, however, did many of his studies with just progesterone—we have to admit that.

Also, there is the impact of hormone production on mental health. Progesterone receptors exist on every brain cell, as do estrogen receptors. While there has been more publicity about the use of bioidentical estrogens for slowing cognitive decline, I strongly suspect that when we get around to doing the same sort of studies with bioidentical progesterone, we’ll find that it plays a role too—perhaps not as strongly as estrogen does, but the two of them cycle together in women’s brains from the time their periods start to the time they stop. They’ve got to have some function up there in the brain. We also now know that there are progesterone receptors nearly everywhere in the body. They’re found on white cells—we find them here, we find them there, we find them everywhere. Progesterone is one of those basic hormones, for men and women alike. In order to keep a woman’s body as healthy as it can be, a somewhat larger amount of progesterone is needed than for men.

LE: What are some of the other problems women might be expected to encounter without supplemental use of hormones such as bioidentical estrogen or progesterone?

DR. WRIGHT: One of the big ones is cardiovascular trouble. The studies that use physiological doses—the amounts that produce the levels found in young adulthood—have shown improved blood lipid patterns. The PEPI (Postmenopausal Estrogen/Progestin Interventions) study, which came out in 1995, before the Women’s Health Initiative, showed that the use of horse estrogens and bioidentical estrogens (albeit to a smaller extent in the latter case) produced improvements in blood lipids. When the researchers added medroxyprogesterone, the cardiovascular improvements disappeared. Yet when they used bioidentical progesterone, a large majority of those improvements were preserved. So the combination of bioidentical progesterone and bioidentical estrogen helps women achieve enhanced blood lipid patterns, thus improving their heart health.

In a study that used only estrogen, reported on just this year, researchers found that estrogen induced an enzyme that improved respiration, and thus lung health, in experimental animals.1–3 Another study found that, among nonsmokers who were beyond the age of menopause, close to 80% of those with chronic lung disease were women. Taking these two results together, it makes sense that replacing hormones will help the lungs.

LE: Absolutely. What about cancer?

DR. WRIGHT: Well, progesterone mitigates cancers. In fact, even a synthetic progesterone analog, such as medroxyprogesterone—as bad as it was with regard to its cardiovascular hazards—mitigates cancer associated with estrogens. Now, if we take away the bad old medroxyprogesterone and replace it with real, bioidentical progesterone, we’ll be doing an even better job in mitigating cancer. Certainly, no one can say it will protect everyone against all cancers—not at all!—but it will help with risk reduction.

LE: Let’s move to some of the other supplements that you think are important for a woman to take along with natural hormones.

DR. WRIGHT: Bioidentical estrogens carry more risks than bioidentical progesterone, which is one reason why they’re available only by prescription. With bioidentical estrogens, we should be sure to use omega-3 fish oils, because even natural estrogens promote blood clotting. The low doses used in hormone replacement therapy, however, are unlikely to cause that problem—it usually arises much more during pregnancy, when estrogen levels are very high. Even so, omega-3 fish oils do help reduce blood clotting—they’re natural inhibitors of platelet aggregation, meaning that they make platelets more slippery, so they don’t stick together as much. Thus fish oil is an important supplement.

Of course, whenever we use any fatty acids, including the ones in fish oil, we should also use vitamin E and the vitamin B complex. That’s because bioidentical estrogens put pressure on some of the enzyme systems, particularly those that depend on vitamin B6 or folic acid. This can result in depression, irritability, etc., which can easily be alleviated with the vitamin B complex. So for women using bioidentical estrogens, I always recommend the omega-3 fish oils, vitamin E, and the vitamin B complex.

With progesterone, we don’t really need much additional supplementation, because bioidentical progesterone doesn’t cause much trouble. But it is possible to take too much, and overdosing with anything can cause trouble. Unlike Dr. Lee, I always recommend a little bioidentical estrogen for bone health. Vitamins K and D can also help rebuild bone, however, so I recommend them for anyone using progesterone.

LE: I understand that vitamin K2, of all the K forms, is especially beneficial for another application: as an anticancer nutrient.

DR. WRIGHT: Yes, there is quite a lot of research on K2 as an anticancer agent, and although no one is saying that it can cure cancer, much experimental animal and basic scientific research, especially in Japan, has shown that vitamin K2 can really slow the growth of cancer cells. This research has also shown that the K2 form is probably more effective at bone building than the others. I recommend a minimum of 2 mg/day, with a preference for higher levels, up to 5 or 6 mg or more. It’s very safe.

LE: Are there other supplements that would be valuable to use adjunctively for promoting bone health?

DR. WRIGHT: Well, we can’t build bones without calcium—there’s no question about that, and it’s useful to take magnesium along with calcium to enhance absorption. One of the most exciting aspects of osteoporosis research over the last five years has been the addition of strontium to that mix. In fact, the research shows that calcium, strontium, and vitamin D can be powerful bone-rebuilding agents. It’s also useful to take boron, vitamin B12, folic acid, manganese, and copper.

LE: Can you say more about vitamin B12?

DR. WRIGHT: Well, as we get on in years, we’re increasingly worried about osteoporosis—especially the ladies. At the same time, vitamin B12 and folic acid levels are starting to fall off owing to poor absorption. Health experts, and particularly people in sports and athletics, point out that both sexes, but especially women, should be concerned about osteoporosis well before the age of menopause for women. Let’s not wait around, ladies. Let’s eat right, get our exercise, take our calcium and other nutrients, and not suffer bone loss. Prevention is always the way to go.

Unfortunately, I see many women at our clinic who first become aware that they have a problem in their 40s, when they go in for a regular examination, perhaps with a Pap smear and a bone-density test. Much to their dismay, they find that they’re already starting to lose a little bone mass. Worse still, some women don’t discover this until they have a fracture. After menopause—and roughly at a similar age in men—the absorption of vitamin B12, in particular, falls off. It drops rapidly for some, and more slowly for others, and the drop in folic acid tracks right along with it.

Because of declining stomach function, among other things, in women in their late 40s and beyond, I have routinely had to ask them to give themselves injections of vitamin B12 and folic acid to ensure that they got enough of these vitamins in their bodies. The food supply is not all that high in B12 anyway, and folic acid is a problem as well. So we have both intake and absorption problems, and the latter get worse as we get older.

One reason why B12 and folic acid are so important for bone health is that they keep our homocysteine levels down. We’ve all heard the homocysteine story in regard to heart trouble: high levels of homocysteine can contribute to atherosclerosis. We should thank Dr. Kilmer McCully for postulating this in 1969, even though it took some of us 30-odd years to hear it. But elevated homocysteine levels also contribute to osteoporosis, and that information hasn’t gotten out as well as the word about atherosclerosis. They also contribute to Alzheimer’s disease. I know you’ve been getting that word out, but it still hasn’t reached the mass media as much as it should. So taking extra B12 and folic acid, along with vitamin B6 and a substance called betaine can lower homocysteine levels and cut our risk for bone disease.

But there are many other reasons for taking extra B12 and folic acid, particularly when we get past our late 40s. One reason is their importance in cell division. We must have B12, folic acid, and zinc in order to activate the enzymes that help our DNA replicate itself when making new cells. And then there are the DNA repair enzymes. Without sufficient B12 or folic acid, those enzymes may not do their job as effectively as they should, in which case the cell might become cancerous. It’s well known that folic acid, in particular, reduces the risk of a variety of cancers—for example, breast cancer, colon cancer, and esophageal cancer. Folic acid (it’s also called folate, by the way) is known to lower the risk of more different cancers than any other single nutrient, and even though the studies with B12 haven’t been done, we know that B12 goes hand in hand with folic acid in its metabolic functions. We’ll probably find out sooner or later that B12 helps to reduce the risk of all those cancers too.

LE: Provided that we can get it into our bodies efficiently.

DR. WRIGHT: Indeed—that is so important.

LE: Is there an alternative to injecting these vitamins?

DR. WRIGHT: Yes, there is. My patients don’t like sticking themselves with a needle even once or twice a week, but we haven’t had any good alternatives until recently. That includes the B12 lozenges that you put under your tongue and the large B12 capsules. The idea is that if we take enough of it, some of it will be absorbed.

I asked the manufacturer of one of those sublingual lozenges a few years back to give me any data they might have on how much B12 was absorbed from the lozenge. The data showed that for some people, the blood levels of B12 did go up, but for others they didn’t change much at all. The problem is, how do we know which group we belong to? Although the sublingual lozenges and the large capsules were worthwhile efforts, Life Enhancement Products is now introducing something better, and I’m happy to work with you on that, because most people I know would like to avoid sticking themselves with needles if they can. What makes that possible are these microscopic spheres called liposomes.

LE: Liposomes encapsulate the vitamins with a lipid bilayer, thus enabling them to penetrate readily into the system through the mucous membranes in the mouth. It’s called buccal absorption (from the Latin word for cheek), because you put the substance between your cheek and your gum. The data are pretty clear on how much more efficient absorption can be than via the stomach. That route entails a great deal of loss, because with age comes a deficiency in intrinsic factor, a substance secreted by the gastric mucosa that is essential for absorption of vitamin B12 in the intestines. There are other problems as well. However, delivering B12 in liposomal form turns out to be one of the best ways to increase your levels of this vitamin. This is likely to be true for folic acid as well, enabling it to enter readily into your system.

DR. WRIGHT: I’m sure that many people will want to switch from needles to the liposomal form of delivery—permanently!


  1. Massaro DJ, Massaro GD. Estrogen receptor (ER) alpha regulates pulmonary alveolus formation, ER beta regulates lung tissue function. Experimental Biology 2004 meeting, April 17–21, 2004, Washington, DC.
  2. Massaro D, Massaro GD. Estrogen receptors regulate pulmonary alveolus formation and estrogen is required for alveolar architectural stability, and induces alveolar regeneration in mice. Am J Physiol Lung Cell Mol Physiol 2004 Aug 6 (in press).
  3. Massaro DJ, Clerch LB, Massaro GD. Ovariectomy in adult mice causes alveolar loss, estrogen replacement after alveolar loss induces alveolar formation. Experimental Biology 2004 meeting, April 17–21, 2004, Washington, DC.

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