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It was bound to happen sooner or later. I recently saw an ad on television soliciting patients by a law firm. “If you have been taking testosterone and recently suffered a heart attack, then you may be entitled to a large compensation from the pharmaceutical company that caused your heart attack. A recent study showed that testosterone therapy can cause heart attacks. Contact the experts in pharmaceutical claims to get you the compensation that you deserve.” Perfect!
Oddly enough only a few of my patients have contacted me out of the large population of men that I treat with testosterone, and I have heard from no one that stopped their testosterone. Patients seem to somehow understand that the recent media hype is just that, hype. On the other hand I have received emails (again) from several hundred physicians asking my take on the latest study and what advice I have for them. My advice is the same that I gave in November for the last negative article on testosterone: one (or two) negative observational studies of questionable power do not negate many other prior RCT’s that show benefit and lack of harm. Over 50 years of well designed controlled trials, as well as laboratory research, should not be ignored based on several observational studies of questionable design. All be it, clinical decision making should be the summation of all available data and not reflexive rejection of all past studies based on one recent observation. Had this study, or review, occurred 40 years ago it probably would be very much ignored today due to the succeeding 40 years of data after the study that supports safety and efficacy of testosterone administration. However since it is of recent publication, it catches the public eye as well as all the naysayer physicians (and legal zealots) that will jump on the bandwagon to condemn all the physicians (and patients) that take or prescribe testosterone. (Sounds just like the WHI all over again). The true challenge that we will face is to convince our peers that an MI that occurs in a man that has been on testosterone for years is probably not due to testosterone but rather the natural course of the disease. Nevertheless, there have now been several recent negative reviews (I have difficulty referring to them as studies) that should be addressed and not completely ignored. Forty years of positive studies of women’s hormones were suddenly challenged by the WHI and HERS trials that proved undiscovered harm of cardiac events in some older women (30 per 10,000) with pre-established heart disease. These recent reviews certainly require careful scrutiny but also concern if there is truly an early iatrogenic, thrombotic effect of testosterone that to date has not been evident. I therefore do not change my therapy based on several studies of weak data that is the opposite of the plethora of data showing safety and benefit. Rather, I base my therapy on a composite of many studies over several decades of research. As stated recently in Family Practice News, February 15, 2014: “The FDA has not concluded that approved testosterone formulations increase cardiovascular risk. Final recommendations are pending.” Hopefully the FDA will access all prior studies in addition to the recent study before coming to any conclusion.
The gist of the PLOS study was that researchers encountered an unexpected increased incidence of MI shortly after initiating testosterone therapy. The risk was seen in older men, both with and without a prior history of heart disease, and in younger men with prior CVD. This same phenomenon was also observed in older women that started HRT in both the HERS and WHI trials, whereas we had 40 years of prior study demonstrating a protective effect of estrogen on CVD. Is there a pro-thrombotic effect of testosterone in men similar to the pro-thrombotic effect of menopausal hormones in older women many years out from menopause? Several recent studies seem to suggest this and therefore this phenomenon should not be ignored. There was also a similar pro-thrombotic effect in younger men with pre-existing CVD, whereas there was no pro-thrombotic effect seen in younger men who were healthy. This begs the question as to whether there is a pro-thrombotic effect of testosterone on diseased arteries similar to the pro-thrombotic effect that estrogen has on diseased vessels in women that start estrogen for the first time and are beyond the 10 year protective window since menopause as seen in the WHI. Oddly enough, and similar to that seen in the WHI study, after 3 months of TT the incidence of MI seemed to resolve once the men (and women) with the diseased vessels get weeded out. We then experience a protective effect on the vasculature due to the many positive effects demonstrated on lipids, lipoproteins, inflammatory cytokines, endothelium, visceral fat, and BMI. So far this phenomenon in men seems to be identical to that in women in the HERS and WHI trials with older men (and women) suffering an MI (plaque rupture) after initiation of HRT. However now we see an early and unexpected inflammatory effect seen in men with significant pre-existing disease that occurred late in the course of their vascular disease process causing rupture in plaque, destabilization and thrombosis. This effect in men, similar to women, shows that heart disease ≠ heart disease. One type of heart disease is slow deposition of plaque over years (protection against which has been clearly demonstrated for both estrogen and testosterone in multiple studies). A completely different type of heart disease that involves plaque rupture occurs only in mature plaque with a necrotic core that ruptures due to some inflammatory factor (as in matrix metalloproteinase or MMP-9) and occurs in older women with pre-established severely diseased vessels. As in the HERS and WHI, younger women that did not have diseased vessels did not suffer plaque destabilization and rupture as did older women, and these women derived CVD protection by prevention of plaque build-up. In other words, it requires healthy vessels to achieve benefit (prevention of plaque build-up) whereas diseased vessels may thrombose secondary to some undiscovered inflammatory effect similar to that caused by increased MMP from first pass effect of oral estrogen that ruptures plaque in severely diseased coronary arteries. If this truly is the same process, let us not repeat history and ignore these observed pro-thrombotic effects of HRT which can lead to an increase in CAD (plaque rupture but not plaque deposition) and CVD in women, just as we observed in the WHI and HERS trials. As we learned from the WHI, early administration of estrogen is protective and should be started early, long before some vessel becomes seriously diseased. On the other hand we really need to further investigate any possible thrombotic effect on diseased vessels so that we can avoid an increase in MI, just as we witnessed in the WHI and HERS studies. In women, avoiding first pass effect of oral estrogen by using transdermal estrogen eliminated that plaque rupture from oral estrogen as there is not any pro-thrombotic effect from transdermal estrogen as it does not raise MMP.
I have read many different posts from physicians, all criticizing the study design and rejecting the outcomes. In fact I don’t think that I have read one physician rebuttal that did not reject the design and/or findings of this study. And I agree that we should not extrapolate a poorly designed and weak study to include all men on testosterone, i.e. don’t repeat the WHI fiasco. However, rather than rejecting and ignoring this study for its flaws, perhaps we should carefully reconsider our denigration of this study, and other recent studies, so that we don’t make the same mistakes that we did by rejecting the WHI and HERS analysis. As of right now, my take on this study is that there truly might be an early pro-thrombotic effect from testosterone administration as evidenced by 3 most recent studies demonstrating such risk. There is a pattern here that should not be ignored, yet should be further studied and evaluated. This would then allow us to be most cautious in our prescribing to older men with pre-established CVD so that we don’t cause any increase in morbidity or mortality. On the other hand, we should still continue to prescribe testosterone to all younger men (and healthy older men) just as we have been doing in order to prevent the plaque from forming in the first place. Prevention of ASVD thereby would prevent any future plaque rupture as there would not be any plaque present to rupture. However, once an older man develops this unstable vulnerable plaque, it could rupture upon starting testosterone for the first time. I will still continue to do what I have been doing by prescribing testosterone to most men, but I might be more cautious in prescribing testosterone for the first time to older men that have pre-existing disease or significant risk factors for such. In women the solution is simple by avoiding oral HRT that can cause plaque rupture through first pass effect that increases MMP that is responsible for the plaque rupture. Transdermal estrogen is the simple solution/prevention in older women that have diseased vessels as later studies demonstrate excellent safety of transdermal estrogen. Therefore we avoid oral estrogen in any women that may be at risk. The answer, however, is not as easy in men as we don’t know/understand the mechanism that is responsible for the plaque rupture and I’m not sure what the solution will be. However, according to the most recent study, if you believe it, there is no risk in younger men and TRT may certainly be of benefit, according to the last 50 years of studies. And the apparent risk was seen only in the first 90 days which should provide confidence in continuing TT in current users. We should use our medical literature to guide our therapy and learn to decipher and analyze these studies, keeping in mind that one or two studies do not negate 4 decades of study and our course of therapy should be based on the summation of all the data and studies, not on just one or two contradictory studies to dictate our therapy. Years of studies prove the effect of testosterone in preventing plaque deposition which should be our goal. Preventing the plaque from forming in the first place would thereby render any future pro-thrombotic effect of testosterone improbable. However lack of that beneficial effect of testosterone in protecting the vasculature, i.e. not utilizing testosterone for its anti-atherogenic effect, may eventually lead to this pro-thrombotic effect on already established mature plaque as seen in older women in the HERS and WHI trials. Knowledge of all the studies on women’s hormones, as presented in Parts III & IV of the WorldLink Medical courses, is tantamount to understanding the mechanism by which testosterone may do the same.
In addition to the PLOS study which demonstrated harm in the first 90 days of initiation of therapy, which is the most recent published and criticized study, there was also a recent separate retrospective analysis of 8,000 men that also showed an increase in MI and CVA within the first year of therapy. In contrast to the PLOS study, this study is more similar to the WHI and HERS trials that demonstrated harm within the first year of initiating therapy. This early pro-thrombotic effect of testosterone then diminishes with time, resulting in less relative risk as time progresses which can also provide security to practitioners in not needing to terminate long-term administration. Again, as per recent FDA recommendations, men should continue their current course of treatment until final analysis is made by the FDA.
Some others have posted criticism as to the type of study (pick and choose from a data bank without any control or randomization). Picking from a data bank sure can be fraught with error, slanted, and biased which detracts from the credibility of the study as opposed to having a randomized, controlled trial. Others have presented excellent rebuttals and criticisms. I have a very geriatric practice in Palm Springs and have an excellent patient population that provides a similar age range as did the article by Finkle et. al. In my population of older men that I have placed on testosterone, I have not encountered one patient that developed an MI while on testosterone or upon initiating it in over 15 years. It is true that some have moved or been lost in follow up, however during this time of initiation the patients are seen on a monthly basis and not one patient reported to us on follow up that an MI occurred. I had taken over a practice of 5,000 established patients. Out of this population, I have treated approximately 2,000 men and with an average age of 60-70 (that certainly would have included by chance many men with pre-existing heart disease). I feel confident that the population that I have scanned is quite similar to the one published in PLOS. When I took over my current practice, I solicited all male patients with the intent of initiating testosterone for purely preventive medicine reasons and cardiovascular protection, compatible with so much of the literature in the past 15 years. I thought that I was providing an excellent preventive service and treatment that which most physicians were unaware. The current search of my patient population also included new patients that were of varying age groups, some of which included older men similar to the age range of my pre-existing patient population. Just from natural selection, I would have imagined that at least one man would have ruptured plaque and had an MI, yet I did not find that in my records. More importantly, however, not one patient had suffered an MI after initiation of testosterone in my 15 years of treating men. The PLOS study demonstrated that in older men, as well as in younger men with pre-existing CVD, the risk of MI following initiation of TT is substantially increased. In my cohort of approximately 2,000 patients, which I feel is an excellent older cohort of men to search and evaluate, I did not find one patient that experienced an MI, either immediately after initiation of TT or thereafter. My patient population was quite small (2,000) in comparison to the large number (55,000) studied in the PLOS. Nevertheless I did not encounter any adverse event in the last 15 years. Of course my study is not a study, rather it is an anecdotal observation of “my” patient population which I feel is fairly well representative of an older population that might be prone to plaque rupture, but they didn’t! My study shows no increased risk of MI and prolonged safety of therapy. However it is an observation, not a RCT, and that’s all that should be surmised from my study population. Maybe it was the clean desert air that was protective and not the testosterone? Perhaps my caring staff was the protective effect? Regardless of whatever association I might claim, it does not prove that anything that I did, including administering testosterone, resulted in any protection or benefit and any claim by me is only speculation.
The same critique of my study applies to the PLOS: small sample, subject to selection bias, so on and so forth. Everyone in every post has their own take or criticism of the PLOS article by which they reject the results or conclusions (and extrapolations) of the study. Nevertheless, three recent studies have raised some concerns about possible adverse cardiovascular outcomes from TT, especially myocardial infarction, and we should not ignore this. A meta-analysis of smaller studies also suggests an increase in cardiovascular risk. The recent VA study also reported an excess of events, however an identical study in a similar VA cohort 2 years ago did not. We should keep in mind though that these are observational studies in design, and other recent more powerful controlled trials did not show cardiovascular harm which has supported the long term safety seen in 40 years of study. I cannot emphasize the importance of realizing that one or two negative studies, that are weak studies in contrast to RCT’s, do not negate all of the past 40 years of positive studies that demonstrated the opposite of this study and that are RCT’s with more power and predictive value. A recent statement from the AACE is right on when they suggest that physicians and patients not jump to conclusions and stop the testosterone prescription, rather patients should continue taking testosterone until further evaluation and review by the FDA is complete. The PLOS study creates more questions than answers, but we should not change 40 years of practice and positive studies based on several observational studies. However we should not ignore them either.
The issue and concern with several of the recent studies, though, is the increase in events that appear very soon within 3 months of initiation of TT. This is similar to the harm seen in the first year of initiation of HRT in older women with pre-existing CVD. For decades the medical literature supported a protective effect of estrogen against cardiovascular disease. The medical establishment was shaken when 2 studies (HERS & WHI) demonstrated increased cardiovascular harm in older women with pre-existing disease that was felt to be due to plaque rupture from the enzymatic degradation of the inner necrotic core by MMP production through first pass liver effect that occurred within the first year of initiating HRT. Utilizing transdermal estrogen, and avoiding the first pass effect of oral HRT, has resulted in no further risk (plaque rupture) by HRT in older women that initiate HRT more than 10 years after menopause which is the time frame for them to develop mature vulnerable plaque that can rupture by enzymatic degradation by MMP-9. The current studies on TT have the same pattern of risk enhancement soon after initiation of therapy which is consistent with an effect of the drug on thrombosis. This underscores the concerns of initiating TT in men with pre-established disease as evidenced in these recent studies, and particularly in older men as well as younger men with more extensive coronary vascular disease. On a good note, and similar to the results seen in the HERS and WHI trials, this early pro-thrombotic risk diminishes with time such that after 90 days of therapy the risk decreases and TT (and HRT) become protective. This appears to be same with TT and it makes no sense to stop TT if there is a long-term protective effect once men pass that 3 month window of harm. This bodes well for both patients and practitioners in that once they have been on the therapy for 90 days, any risk subsides and therapy thereafter does not appear to be harmful. As the result, stopping TT does not appear to be indicated in men once they have been on TT for a period of time, and TT is protective once the patient is past that critical window of plaque rupture, and this applies to both men and women.
On the other hand, a plethora of data and studies supports that low endogenous levels of testosterone may be positively associated with cardiovascular disease. Many RCT’s have demonstrated the protective effect of testosterone replacement, both on symptomatic improvement as well as CVD progression. I refer you to my prior post from November 2013 where I listed many of those trials providing evidence and confidence for those of us that continue to prescribe TT for health and wellness. However I urge caution in prescribing TT to any man with pre-existing CVD or to one that may have the undiagnosed disease with many risk factors. On the other hand it does not make sense to prematurely stop TT once a patient has passed the critical window of plaque rupture which seems to be 90 days, as per the recent studies. Utilize extreme caution when initiating TT and perhaps do further work up and evaluation to discover any undiagnosed CVD and thereby use caution in initiating therapy as well as thoroughly discussing the issues and concerns with the patient. Given the popularity of TT, the current study emphasizes the urgency for further study of this early pro-thrombotic effect and the need for addressing the potential risk of TT in men with pre-existing CVD.
Lastly, and beyond the scope of this review, I found the comments from the many posts amazing, entertaining, fascinating, and troubling as to the proposed mechanism of harm of testosterone. These will be addressed in a separate post but briefly mentioned here. Similar points/concerns/causes for the increase in risk of CAD were also addressed by the authors of the PLOS study. However, most physicians do not understand the effects of testosterone on erythrocytosis or aromatization into estrogen, both of which are incorrectly claimed to result in thrombosis and clotting. Testosterone does not cause polycythemia, RBC clumping, hyperviscosity, or platelet aggregation as they surmised. Polycythemia (PV or polycythemia vera) does cause the foregoing, however testosterone does not cause polycythemia, rather testosterone produces physiologic erythrocytosis via increase in erythropoietin produced in the kidneys. Unfortunately everyone mistakenly makes claim that testosterone causes PV but it does not. See the this article on polycythemia vera and my article on polycythemia vs. erythrocytosis. If erythrocytosis truly caused thrombosis and “RBC clumping”, then we would witness a later and persistent effect on clotting as erythrocytosis (increase in RBC’s) occurs after several months of therapy and not much during the first three months of therapy which is the time frame of harm in the recent study. Therefore if erythrocytosis were the culprit, then we would continue to see the thrombosis escalate as time progresses but we don’t, either in this study or other long-term studies. The effect on thrombosis should escalate as the erythrocytosis progresses but it doesn’t. More importantly, if erythrocytosis truly caused clotting and RBC clumping, then everyone that lived at altitude (above 5,000 feet) would experience an increase in CAD, CVD, and RBC clumping and clotting. If this did occur, then everyone would run to the beach and not live at altitude. In addition, every patient with COPD with physiologically high RBC counts due to hypoxemia (which I see in the ER daily) would have significant increases in MI and CVA yet we don’t see that either. If we phlebotomized every COPD patient with erythrocytosis, they would all die from hypoxia. Physiologic erythrocytosis is never harmful, only beneficial, otherwise we would phlebotomize everyone that lives at altitude but we don’t. Testosterone causes the same physiologic effect as living at altitude and the effect is only on RBS’s, not platelets. Polycythemia is different and PV is not physiologic erythrocytosis. Polycythemia vera is an increase in multiple (poly) cells including white cells, red cells, and platelets with the resultant splenomegaly, not seen with testosterone use. It is the platelet count of over a million that causes clotting, not high RBC’s. Unfortunately we monitor phlebotomy by hemoglobin counts, and not by platelet counts, which makes us intuitively think that it is the RBC that is the important factor to lower whereas it is the high platelet count that is the culprit and not the high hemoglobin. Just because we monitor RBC counts and adjust phlebotomy based on H & H does not mean or prove that high hemoglobin causes any morbidity or mortality, as does PV. Phlebotomizing lowers platelets and that is the beneficial effect in protecting against thrombosis. The meta-analysis from the NEJM demonstrated that in over 40 years of studies on testosterone therapy, not one study showed any thromboembolic event to date. Polycythemia is a blood cell dyscrasia that causes increased clotting, DVT’s, cancer, myelofibrosis, myelodysplasia, and progression to leukemia. Does any study show that testosterone causes any of this? Absolutely not and therefore testosterone does not cause polycythemia, or an increase in WBC’s or platelets or splenomegaly, in spite of the literature incorrectly stating testosterone causes PV. Multiple published papers mistakenly claim that testosterone causes polycythemia whereas testosterone only causes erythrocytosis and patients should receive the same therapy as those with erythrocytosis that live at altitude-nothing. I recently treated a prominent physician who was overly phlebotomized by a prominent clinic which resulted in extreme fatigue, with a serum iron level of 5 and a ferritin level of 2! IV iron (Venofer) completely resolved the year long fatigue and the physician swore never to phlebotomize again. I’m still searching for that study that demonstrates high H & H with normal platelet count causes harm. Erythrocytosis is not PV and testosterone does not cause PV, regardless of the incorrect claims. My hemoglobin has been above 19 since I was 20 because I have worked and trained at a ski resort since I was 20. My platelet and white counts are normal. I once saw a Sherpa that had a hemoglobin of 23 as he frequently traveled between 20,000 to 30,000 feet. Phlebotomizing patients with PV saves lives as evidenced in the attached article. No study has ever shown benefit to phlebotomizing anyone with physiologic erythrocytosis and normal platelet counts.
Last year I presented this lecture at AMMG on estrogen in men. It is commonly accepted that estrogen should be lowered in men due to the cardiovascular complications of high estrogen in men. Nothing could be further from the truth. You may view the lecture at WLM.com. Understanding that observation does not prove causation is paramount to understanding that estrogen does not cause harm in men. Every interventional trial (except for high dose DES) where estrogen has been administered to men has prevented heart disease, both for oral as well as transdermal estradiol. Every long-term study whereby estrogen is elevated through aromatization of testosterone into estrogen has resulted in cardiovascular benefit. Every study where estrogen is blocked or lowered has resulted in harm. Lowering estrogen in men has shown to increase the risk of cardiovascular disease, DM, lipid abnormalities, memory loss, Alzheimer’s disease, bone loss and osteoporosis, and loss of libido and EF. Raising estrogen in men, either via testosterone administration or estrogen administration, has shown protection against the foregoing. I was once tickled by an attendee’s comments that we only want to lower estrogen a little bit. Translation: you only want to increase the risk of CAD, CVD, osteoporosis, DM, and ED a little bit? The estradiol level of a young is 75-90 pg/ml. Should we start blocking estrogen in young men? View the lecture on the harm of using aromatase inhibitors in men.
The authors of the PLOS study site the same observational studies, as does Life Extension and everyone else, where high estrogen levels in men are associated with increase in CVD. (Remember association does not prove causation). However, it is the increase in visceral fat that increases the production of estrone, and concomitantly estradiol, which only proves an association and not causation. In order to prove causation, one must intervene and administer estrogen. The results of the interventional, randomized trials prove the opposite of the observation that high estrogen is harmful. It is the increase in visceral fat, insulin resistance, inflammatory cytokines, and lipid abnormalities that cause the increase CVD risk, not the claimed estrogen elevation. And how do we then prove that? The answer is simply to intervene and administer estrogen in an interventional trial and observe if the increase in estrogen proves causative or protective. Every study (except the high dose DES) proves a protective effect of raising estrogen, and that applies to both oral and transdermal estrogen. It has been shown that the cardioprotective effects of testosterone are related to aromatization to estrogen. Block the testosterone and the cardioprotective effect of estrogen persists. Raise testosterone and block estrogen and the cardioprotective effect will thereby be eliminated as well as all the beneficial effects on lipids and lipoproteins. Every study whereby estrogen is raised by testosterone administration has resulted in long-term cardiovascular protection. The randomized trials whereby estrogen was administered to men resulted in cardiovascular protection. (View the lecture on line). The randomized trials whereby aromatization is blocked by anastrozole result in loss of CVD protection when estrogen is lowered. So then why is everyone promoting blocking estrogen when studies show harm to lowering estrogen and other studies show benefit when we intervene and raise estrogen? The reason is simply because they don’t understand the literature, the difference between observational vs. randomized trials, or the concept that observation does not prove causation, and the fact that multiple RCT’s prove estrogen’s cardiovascular protective effects, and that observing high baseline levels of estradiol in obese men with heart disease does not prove anything.
Finally one should not extrapolate the first pass effect of oral estrogen on clotting factors to be the same as raising estrogen via aromatization from testosterone or by transdermal administration. The effect on clotting and clotting factors from oral estrogen is through the first pass liver effect. Transdermal estrogen has never been shown to have the thrombotic effects of oral estrogen, and neither has testosterone. The PLOS authors do make this mistake as testosterone, with the aromatization into estrogen, has never been shown to raise clotting factors, lower clotting inhibitors, or increase clotting as does oral estrogen, yet these authors make claim that raising estrogen via aromatization is the mechanism for the increase in thrombosis. Their extrapolation to testosterone causing the harm of oral estrogen and polycythemia is without any basis in fact.
Although many articles have many postulated theories as to the cause of this newly discovered plaque rupture in recently treated men, we do not understand the mechanism as of yet. Perhaps some form of testosterone has a similar effect in raising matrix metalloproteinase as seen with oral estrogen thereby causing plaque rupture? Until that research is conclusive, speculation should be careful and cautious. In the interim we must be careful in administering testosterone to older men that may have significant cardiovascular disease. However don’t throw out 40 years of studies that demonstrate long-term cardiovascular protection by testosterone therapy. Treatment should be prevention in the first place by early administration of testosterone and continued indefinitely as per 40 years of study, and then we would never have to worry about that plaque rupture in the first place. Evidence, not conjecture, should guide clinical practice and policies. And don’t extrapolate evidence or conjecture.
The Institute for Continuing Healthcare Education
A Panel Discussion on the Importance of Early Diagnosis for Myeloproliferative Neoplasms
As the popularity of bioidentical hormones continues to spread, more men and women are finding that balancing hormones improves vitality, health and well-being. But what does the research demonstrate? We’ve hand-selected nine articles with summaries and responses from Dr. Neal Rouzier’s library. The article reviewed in this post comes from the March 2012 issue of The Journal of Clinical Endocrinology and Metabolism.
(Bhavnani BR, Stancyzk FZ. J Clin Endocrinol Metab. 2012 Mar;97(3):756-759)
Article Summary: As a review of BHRT dosage, forms, and claims are outlined in this article, the authors explain there is concern that the unregulated BHRT may be overdosed, treated with ineffective products, or contain unknown risks. The authors’ objective was to explain how BHRT may not be identical to hormones naturally produced in the body and that the lack of regulation could cause adverse effects in postmenopausal women.
Neal’s Response: I absolutely agree with the conclusions of these authors and that is the main criticism of the bioidentical industry. The main risk that I perceive of compounded BHRT is failure to achieve therapeutic levels of HRT to guarantee therapeutic endpoints. Symptoms may improve for patients on BHRT; however, the doses used and the levels achieved may not provide cardiovascular, musculoskeletal, breast or uterine protection, which defeats the purpose of HRT replacement.
Most patients that come to me from other BHRT practitioners are taking subtherapeutic amounts. Their prescriptions provide very low serum levels of HRT that will not be protective at all, and that pertains to hormones E2, P4, testosterone, DHEA and thyroid. (The author’s comments about overdosing and unknown risks are over-hyped, as I haven’t seen any overdoses of estriol in the ER lately. If saliva testing shows overdose, it does not correlate with an overdose when testing serum levels, which are more meaningful for hormone therapy.)
My main criticism of the bioidentical industry is the lack of emphasis to maintaining scientific standards that have demonstrated scientific efficacy of HRT as carried out in the studies. When I prescribe compounded BHRT, I copy and maintain the same standards and levels as seen in the scientific literature that utilizes pharmaceutical BHRT, something that this author probably does not understand. I also have experienced many patients that come to me on conventional bioidentical therapy that do not have efficacious or therapeutic levels of conventional bioidentical hormones, and that does not provide much health benefit either.
What’s Your Take?
Tell us what you think of this research on bioidentical hormone therapy. Remember to check back regularly for more of these reviews from Neal’s library, and feel free to share additional articles or links to studies on bioidentical hormones.
On the first day the JAMA article was released I received 500 emails from physicians and patients requesting my opinion of the article that demonstrated an increase in heart attacks and strokes in men treated with testosterone. Today is the second day and I’m afraid to turn on the computer. First of all this was an observational study that was retrospective in nature and this type of study is fraught with compounding biases that are difficult to control as expressed in the discussion section of this study. A randomized controlled trial (RCT) would have much more power than this type of study. Also the problem with an observation study is that it does not prove causation as would an interventional study in a blinded fashion. Therefore observational studies can’t prove causation as well as RCTs and what we should take away from the study is that which the researchers state in the last paragraph, that more studies are necessary before definitive conclusions can be made as to cause and effect. Also, treatment decisions should not be based solely on one study but rather on a trend of studies. Unfortunately the editorial comment section did not express this clearly.
The discussion section of this article mentions that this is the only study that showed this adverse outcome and it was in a select group of individuals. All other studies have shown the opposite outcome, either no effect or protection against heart attacks. Since all other studies show the opposite, and one study does not negate all the other studies, and there were some biases in this study, I would suggest that we do not change anything that we do based on one study with flaws and biases when all other studies demonstrate protection against heart disease and stroke (see attached articles). And this was an observational study which has weaker power than a randomized controlled trial. I'm sure that other experts will voice the same opinion once they review the discussion section of this article as there were many biases and flaws in this study. A review of the index lists the studies that demonstrate protection against heart disease and strokes. In the “Longevity Section” that I present in the Part II course, all of the articles demonstrate improved longevity in those treated with testosterone, but increased morbidity and mortality in those men not treated with testosterone. The WHI study showed that Prempro increased heart attacks and strokes in certain individuals. Subsequent studies have proven that estradiol and progesterone, particularly in younger women, don't. Perhaps there is a confounding problem in older Veterans with cardiovascular disease that is different from other studies. However, as presented in the Part II course, every study that I review (and there are many) demonstrated a significant improvement in longevity and decreased morbidity and mortality in addition to improvement in all cardiovascular risk factors in men treated with testosterone as opposed to control groups treated with placebo (see attached studies).
Had this study been published years ago, and all subsequent studies since then showed protection against cardiovascular disease, then this study would have probably been ignored and forgotten. However, since it is recent, then we tend to believe it and reject all the past studies that showed the exact opposite outcome. Nevertheless, one study does not negate many other studies that show opposite results and benefits. So I will log this study on the negative side for testosterone results but it is the only such study on this side. This is in contrast to all the other studies that show benefit of testosterone administration. It is interesting that this study appears now, just after I gave 2 lectures to a medical academy this past weekend in Las Vegas. The two one hour lectures were on all the studies of both estrogen and testosterone protecting against heart attacks and strokes. These reviews of the world's literature demonstrate all the various mechanisms of benefits of hormones in protecting the heart and brain against heart disease, stroke, dementia, and plaque deposition. The data and literature is overwhelming in favor of a protective effect of estrogen in women and testosterone in men. This recent study, although interesting and intriguing, does not change any of the evidence that I presented in these lectures nor does it change my treatment strategies. Until more studies demonstrate the same, I will continue to follow the scientific literature that demonstrates benefit. As per the suggestion from the authors, they state that more study is needed to evaluate these results. I recommend to patients and physicians that they continue the same treatment with both estrogen in women and testosterone in men based on all prior studies that show benefit in spite of this one negative study.
Certain statements in the discussion section of the study deserve comment. The authors do note that other trials and meta-analyses do not demonstrate adverse cardiovascular outcomes. The trend so far in the literature has been a protective effect as trials demonstrated that testosterone therapy improves a number of intermediate outcomes and cardiac risk factors. This new JAMA study is the first and only study to demonstrate harm and should therefore be interpreted carefully in light of all the other studies demonstrating opposite results. In addition, the results of this study differ from a similar retrospective VA study by Shores et al that demonstrated a 39% reduction in mortality risk among patients treated with testosterone which again suggests caution in coming to conclusions only based on the present study. Different confounders and biases might account for the discrepancy. Multiple limitations of this study are noted by the authors that certainly can affect outcomes. All in all, it is an interesting study with unexpected results that are in discordance with all other studies and should not influence current therapy, but one that begs for more study.
For those patients and physicians that are unfamiliar with the current literature on testosterone therapy, I have included 3 attachments that review various categories of hormone replacement. First are studies that review mortality in men treated with testosterone compared to control groups. Studies show improved survival in treated men versus untreated men. There are fewer heart attacks, cancer, and reduced mortality in men treated with testosterone (in contrast to the current study). Other studies go on to prove that low levels of testosterone increase morbidity and mortality in contrast to men with testosterone levels in the higher quartiles. Low levels of testosterone are predictive of an increase in all-cause mortality (CAD, CVD, cancer). So where would you like your levels to be? Other studies show that there was no increased risk of cardiac events in men treated with testosterone (in contrast to the current study).
The second attachment lists all the articles that demonstrate all the physiologic benefits of testosterone administration on cholesterol, lipoproteins, insulin sensitivity, diabetes, inflammatory cytokines, endothelial dysfunction, atherosclerosis, blood pressure, memory loss, Alzheimer’s disease, mood, strength, energy, muscle mass, fat mass, osteoporosis, ED, sexual function, and all-cause mortality. Do you really want to stop the testosterone based on only one negative study? I’m not! What are the consequences of stopping or not taking it? Read the foregoing.
The third attachment reviews beneficial effects on quality of life as well as disease protection. It is amazing the data on reduction of body fat, insulin levels, diabetes, inflammation, and vascular disease. “Testosterone serves to maintain health in every system of the body.” Levels of testosterone in the low to mid-normal range are associated with an increase in illness as listed above.” And don’t forget (pun intended) the protection against Alzheimer’s disease.
Respectfully submitted, Neal Rouzier
Read Dr. Josh Trutt's response to the JAMA article here.
Read Dr. Mike Clark's response to the JAMA article here.
Find out more about Dr. Rouzier here.
When Dr. Rouzier walked into the meeting room for his Lifetime Achievement Award on October 18th, he was confronted with 110 people yelling, “Surprise!” It was no easy task keeping this event a secret from Neal during the 8 months of planning and emails to thousands of doctors, but it was truly a surprise that made an impact. As the lights came on, he was overwhelmed with a standing ovation for his achievements.It was an incredible evening of video clips, stories and what seemed like endless speeches by attendees about how their lives changed because of Dr. Rouzier. Both Neal and Carolyn received achievement and appreciation awards along with a book of letters and an array of gifts. Neal later commented it was without a doubt the happiest day of his life. A big thank you goes out to all those involved in making this an experience that will not be easily forgotten by those who attended.
The event was held at the Green Valley Resort and Spa in Las Vegas, Nevada where hundreds of medical professionals, including doctors, nurses, pharmacists and students were able to attend as well as contribute to the fundraiser for MRSA research, a cause that is important to Dr. Rouzier.
We appreciate those who were able to attend this event and contribute to the fundraiser for MRSA research, a cause that is important to Dr. Rouzier. We’d like to once again congratulate him on his Lifetime Achievement Award and thank him for his contributions to evidence-based medicine in the specialty of hormone replacement therapy and preventive care. For those of you unable to attend, we encourage you to watch the video shown at the event, which contains testimonials from a few of the many people that Dr. Rouzier has impacted. You can also view photos of the event, or go a step further and show your thanks by donating to MRSA Research.
Catch a glimpse of what it was like to be there:Watch the Video
See the PhotosSay thanks once more—Donate to the cause important to Dr. Rouzier:Donate to MRSA Research
Helping patients successfully modify their dietary habits is often highly effective for preventing and treating a wide variety of illnesses and symptoms, especially when paired with appropriate supplements and other natural substances. This basic yet intricate knowledge is supported by scientific research and clinical experience that is reinforced by new studies every year. As described in Nutritional Medicine by Alan R. Gaby, M.D., unlike drug-based medical therapies that often trade negative side effects for symptom relief (e.g., osteoporosis in exchange for pain relief), nutritional medicine almost never causes serious adverse effects. To the contrary, nutritional therapies often produce positive side effects, such as “more energy, better mood, fewer cravings, better mental concentration, and less aches and pains.” To begin unraveling the intricacies of nutritional medicine, read on for an excerpt directly from Dr. Gaby’s book that provides an introduction to the practice of nutritional medicine and the synergistic effects of nutritional treatments. You can also attend CME accredited lectures on Nutritional Medicine taught by Dr. Gaby himself at the Part II and Part III Courses.
NOTE: The information in this post has been excerpted from Part 1 of the textbook:
Gaby AR. Nutritional Medicine, 2011 (www.doctorgaby.com).
Scientific research and clinical experience have shown that dietary modifications and administration of nutrients and other natural substances are frequently effective for preventing and treating a wide range of symptoms and illnesses. Moreover, when properly administered, nutritional therapy has an excellent safety profile and almost never causes serious side effects. The nutritional approach to preventing and treating disease rarely subjects patients to the unpleasant trade-offs inherent in many drug treatments, such as statin-induced myalgia in exchange for a lower risk of having a heart attack; beta blocker-induced loss of joie de vivre in exchange for better control of heart failure; or glucocorticoid-induced osteoporosis in exchange for relief of arthritic pain. To the contrary, many of the “side effects” reported by patients who follow a nutritional program are positive, such as more energy, better mood, fewer cravings, better mental concentration, and less aches and pains.
The practice of nutritional medicine includes several main components, the relative importance of which varies from one patient to another. For most patients, nutritional therapy starts with “cleaning up the diet” by emphasizing a wide variety of whole, unprocessed foods and minimizing intake of refined sugars, other refined carbohydrates, trans fatty acids, food additives, and other undesirable constituents of a typical Western diet. Restricting the use of salt, caffeine, and alcohol is also important for some individuals. In addition, emphasizing cooking methods that minimize the formation of potentially toxic compounds (such as cholesterol oxides, lipid peroxides, and advanced glycation end products) may be beneficial. Nutritional therapy also includes the use of a wide array of vitamins, minerals, amino acids, herbs, and other naturally occurring compounds, individualized according to the patient’s needs. This “natural pharmacopoeia” stands alongside the conventional pharmacopoeia of prescription and over-the-counter drugs. Depending on the clinical situation, these natural substances can be used as an adjunct or alternative to conventional medicine.
In my experience, four distinct but overlapping metabolic/endocrine/immunological disorders frequently play a role in the pathogenesis of a number of chronic health conditions. Identification and appropriate treatment of these disorders is important for the successful practice of nutritional medicine. The first disorder, reactive hypoglycemia, is characterized by abnormalities of blood glucose regulation, as well as other accompanying metabolic and endocrine disturbances. Treatment of reactive hypoglycemia includes avoiding refined sugar, other carbohydrates, caffeine, and alcohol; eating small, frequent meals; and supplementing with vitamins, minerals, and other natural substances that aid in blood glucose regulation. The second common disorder is hidden food allergy. In many cases, identifying and avoiding allergenic foods can play a key role in restoring health. In many cases, identifying and avoiding allergenic foods can play a key role in restoring health. Third, a substantial minority of patients appears to have subtle hypothyroidism, despite the presence of normal laboratory tests for thyroid function. These patients benefit from treatment with low doses of thyroid hormone. Fourth is a clinical syndrome that has been called candidiasis or Candida-related complex. This syndrome is characterized by an overgrowth of, or hypersensitivity to Candida albicans. Symptoms overlap with those caused by reactive hypoglycemia, food allergy, and hypothyroidism. Treatment includes antifungal medication and dietary modifications similar to those used for reactive hypoglycemia and food allergy. Hypothyroidism and Candida-related complex are beyond the scope of this chapter.
Nutritional medicine is highly individualized, and effective treatment varies from one patient to another. For example, some patients with chronic fatigue respond best to dietary modifications such as avoiding refined sugar and eating 6 small meals per day, or identifying and avoiding allergenic foods. In other cases, the most effective treatment for fatigue is a low dose of thyroid hormone or a specific nutritional supplement, such as potassium magnesium aspartate, iron (to correct iron deficiency), or intramuscular vitamin B12 (even in the absence of vitamin B12 deficiency). Frequently, the best results are achieved with a combination of interventions.
Determining which treatments are most likely to be effective for a particular patient requires a proper medical and dietary history, a good physical examination, and a working knowledge of the nutritional-medicine literature. Laboratory tests are essential in some circumstances (as in diagnosing iron deficiency), but may be of questionable validity or even misleading in other situations (as in identifying hidden food allergies or subtle nutritional deficiencies). In practicing nutritional medicine, I have rarely ordered laboratory tests other than those that might be ordered by a conventional medical doctor.
A recurring theme in nutritional medicine is that combinations of interventions often have additive or synergistic effects, in that they are more effective than single interventions. For example, combinations of nutrients may be more effective than individual nutrients; the beneficial effects of dietary modifications are often more pronounced when combined with appropriate nutrients, hormones, and other natural substances; and the benefits of nutrients, hormones, and other natural substances are often more pronounced when patients also adhere to appropriate dietary recommendations. A corollary to these observations is that nutrients, hormones, and other natural substances are sometimes effective at lower doses when they are used in combination with other interventions than when they are given singly.
Clinical observations regarding the existence of additive and synergistic effects are supported by both clinical and basic-science research. For example, anemia has been found in some studies to respond better to multiple nutrients than to a single nutrient. The combination of B6 and magnesium was reported to be more effective than either of these treatments alone in the treatment of autism. In addition, the homocysteine-lowering effect of folic acid was enhanced by the addition of vitamin B12.1 In dermatology, vitamin E has been used to increase the therapeutic effect of vitamin A. In healthy volunteers, the combination of vitamin C and vitamin E enhanced parameters of immune function to a greater extent than did either of these nutrients individually.2
In mice with experimentally induced atherosclerosis, combined supplementation with vitamin E and coenzyme Q10 was more anti-atherogenic than was either supplement alone.3 In isolated rat hearts subjected to ischemia and reperfusion, various hemodynamic and metabolic abnormalities were prevented by simultaneous administration of carnitine and coenzyme Q10, but not by administration by either of these nutrients individually.4
There are a number of possible mechanisms by which dietary modifications and treatment with natural substances could have additive or synergistic effects. For example, dietary improvements might decrease inflammation and oxidative stress, thereby allowing nutritional supplements to be used for processes other than mounting an inflammatory response and quenching free radicals. In addition, certain nutrients enhance the absorption of tissue uptake of other nutrients. For example, vitamin C increases iron absorption and magnesium promotes the uptake of potassium from serum into cells. Some nutrients inhibit the degradation of other nutrients (e.g., flavonoids decrease vitamin C requirements by preventing the oxidation of vitamin C).5 6 Furthermore, certain nutrients may relieve biochemical “bottlenecks” by activating parallel pathways. For example, the conversion of homocysteine to methionine proceeds largely through a folate-dependent pathway, but it may also proceed through a separate pathway that requires betaine. Similarly, multiple biochemical pathways exist to detoxify xenobiotic chemicals, bacterial toxins, and endogenous metabolites.
Because multiple nutritional interventions are often more effective than a single treatment, practitioners may be tempted to “throw everything but the kitchen sink” at various medical problems. However, nutritional “polypharmacy” is not without potential drawbacks, including high cost to the patient, increased time and effort involved in following the complex treatment regimens, and the possibility that ingesting numerous tablets and capsules will cause gastrointestinal or other side effects.
The art of nutritional medicine includes being able to identify which dietary modifications and supplements are most likely to be beneficial for a particular patient, and which interventions are more likely to be ineffective or unnecessary. As with other healthcare disciplines, mastering the art of nutritional medicine requires education, contemplation, and practice. According to one of my mentors in medical school, Dr. Theodore Woodward, the better trained you are, the fewer tests you will need to perform and the fewer medications you will need to prescribe. That principle also applies to nutritional medicine.
Dear Part I Attendees,
WorldLink Medical has worked with me to rebuild the 2013 courses by replacing old articles with new content and updated articles, and placing them all on PowerPoint slides to make the overhead slides a thing of the past. In fact, those of you who attended the last Part I course in Salt Lake City have already experienced many of those changes. Anyone attending the Part II course in September will also have the opportunity to see these improvements.
The Part II course goes beyond the basics of Part I to explore advanced protocols that are critical to mastering complex cases not taught in my Part I course. In addition, since the field of age management medicine continues to grow at a rapid rate, the redesigned Part II course will help you stay ahead of the changes by covering a remarkable amount of material (over 1,300 slides), including highlights of new and important therapies, clinical pearls, tricks of the trade, recent controversies and every crucial element that I could not fit into Part I.
My favorite part of this course is the Saturday night informal discussion, which involves a question and answer session with me. This discussion explores difficult cases, controversies, legal issues and tribulations from seasoned attendees. It also expands your clinical knowledge through sharing experiences and feedback in round table discussions. There is no other place where you can participate in such a gathering of the minds.
For this year's nutrition lectures, WorldLink has teamed up with Dr. Alan Gaby. He has extensively researched and written on this topic, and in my opinion there is no greater authority on vitamins and nutrition. Dr. Gaby will lecture Friday morning before I take over in the afternoon.
Here is a summary of Part II topics:
Anti-aging (definitions and why we call it that). Reviewing articles that make us refer to BHRT as anti-aging and providing credibility for why we do what we do.
Longevity medicine and which hormones have a proven record for extending health, wellness and longevity.
Making sense out of the many HRT studies, the critiques and the rebuttals. Putting the pieces together will make you an expert on all of the if’s, and’s or but’s.
The positive and negative articles on BHRT. Laying to rest that estriol is a worthless metabolite, what the literature shows we should and shouldn’t use, and disproving what many are teaching without any facts.
“There are no studies that prove BHRT is different from synthetic HRT.” Baloney!
A literature review proving that HGH, testosterone, estrogen, progesterone, DHEA and melatonin protect against cancer. The perfect solution to Obamacare.
This includes optimization of progesterone and case examples, multiple studies that prove transdermal cream is worthless and harmful, and a discussion that saliva testing for monitoring therapy is worthless. Scientific studies prove where your levels should be for maximum protection and where they should not be in order to protect against cancer.
Beyond transdermal testosterone cream - New and different methods for raising testosterone in men and women: oral, SQ, IM, HCG, and Clomid.
Oral vs. transdermal estrogen - The relative risks of both and the safest versus the most beneficial.
A literature update on HGH, DHEA, and thyroid treatments for cardiovascular and osteoporosis protection.
What can you do to prevent and treat weight gain and bloating as far as hormones are concerned?
Cardiovascular disease protection, cardiac markers, eicosinoids, diet, EFA’s, insulin, and inflammation.
Cardiovascular case studies with management beyond statins.
Diagnosis and treatment of the most common premenopausal endocrinopathy that everyone fails to diagnosis, and its relation to cardiovascular disease, breast cancer, and uterine cancer.
Hair loss in men and women, TE, hirsutism, and the effects of hormones on skin.
Treatment of osteoporosis beyond biphosphonates: vitamin D3, vitamin K, strontium, and ipraflavone. Estrogen metabolites - do they or do they not predict breast cancer?
The importance of estrogen optimization in men and the harm of suppression. The harm in giving progesterone to men as it increases inflammatory cytokines.
Cortisol and fatigue - How and when to use it, how to monitor it, and how to test it with ACTH.
Complex cases, labs, adjustments, fun and interesting cases, and lots of WWND (What Would Neal Do?).
Hormones and cancer. The myths & controversies of the oncogenic effects of hormones. Literature review showing protection against cancer by optimization of hormones.
The last hour includes 100 pertinent questions and answers with discussion.
Dr. Gaby and I look forward to seeing everyone in Salt Lake City, Utah on September 27, 2013.
Why does a cup of coffee cost more at a trendy café like Starbucks than it does at the corner diner or when brewed at home? It’s the value that the experience holds for the individual that determines the worth of the offering and the work of the business. Marketers understand this principle and the market value of experiences to consumers. Automobile ads don’t sell cars; they sell the driving experience. Restaurants advertise the ‘fine dining experience.’ Travel agents no longer book vacations; they book ‘adventures’. And let’s not forget the granddaddy of experience sellers: Disneyland. The product they sell is ‘experiences’. You may not have given it much thought, but the same principle applies to your medical practice.
Just delivering great service to your patients is no longer a winning strategy. Aging baby boomers already expect great service. And if you’re still competing on the basis of price, then you are offering little or no true differentiation from the competition. What would your patients really value? Better yet, for what would they pay a premium? Experiences!
It’s not that we don’t give our patients experiences. In fact, the medical profession already has a long history of creating patient experiences. It’s just that these experiences are not particularly positive, more often than not. How many patients can honestly say they enjoy and look forward to going to the doctor? Not many. That’s because, in large part, the experiences patients have are mostly unintended, the result of not understanding the principles of experience design and execution. Yet, the kinds of experiences we could create for patients hold the potential to significantly improve clinical outcomes, patient compliance, patient satisfaction and loyalty, provider satisfaction, and, yes, even profit margins. Ideal patient experiences can give them hope and inspiration, and are powerful catalysts for them to take action. In essence, experiences are what change lives. With a little planning you can create meaningful and memorable experiences that improve the quality of your practice and your patient’s life.
The following steps will guide you through the processes of creating unique experiences in your practice:
What is the ultimate take-away experience you want your patient to have? Inspiration? Motivation? Transformation? Begin with the end in mind and engineer backwards, tweaking all of your practice processes in ways that contribute to the experience. Choosing a theme for your work is a helpful starting point for creating powerful experiences. How likely would you be to finish reading a novel if it had no theme? You would probably close the book before finishing the first chapter. A theme is essential, as it conveys the central idea of a story (or your work) and is necessary in order to fully and effectively engage an audience (i.e., your patients). Themes can be based on almost anything: people, places, events, times, ideas, messages, etc. Once you have your theme, build a story around it.
Give each patient the feeling that every interaction with him or her, and everything you do for him or her, is just for him or her. (-Or – Give your patients the feeling that every interaction with them, and everything you do for them, is just for them). You can personalize everything, such as phone calls, appointments, and patient handouts.
‘Mass customization’ is one way: Make small but personalized modifications and additions to standardized services, materials, or products that otherwise are the same for all patients. ‘Organizational memory’ is a way to give the patient the feeling that everyone in your organization knows and remembers the patient in a personal way. Your medical records already include the patient’s date of birth, so that information can help everyone in your organization to remember and celebrate the patient’s birthday. Similarly, you could collect personalized information in a new patient intake form that could be used in a variety of ways: favorite foods and music, who they admire and why, what kinds of things inspire them, where they go to ‘recharge their batteries’, what they list as personal strengths/weaknesses/fears, etc.?
Expand the patient experience to include the time and space before, during, and after the visit. Examples might include pre- and post-visit phone calls, newsletters, interactive web tools, and ‘homework’ assignments.
All work is theatre. Yes, even health care! Your office is the stage, the rooms in your office are different sets, stethoscopes and blood pressure cuffs are props, your white lab coat is your costume, you and your staff (nurse, receptionist, etc.) are the actors playing different roles, the things you say to patients (greetings, patient interview, advice for each medical condition, etc.) are the scripts. The reason for an appointment might be a ‘subplot’ in the patient’s life journey. Thinking of your theme and storyline (see above), imagine ways that your work processes can be applied or modified to fully and effectively engage your patient (the audience) in the story. How will you choreograph your ‘performance’, the sets, props, costumes, actors’ roles, scripts, etc.?
Become a storytelling organization. Medical practitioners have become so fixated on data as the focus of communication with patients that we have forgotten the most time-proven method in all of human history for passing along understanding and wisdom, for inspiring and motivating – storytelling. Data and information need stories to give them context. Stories add flesh and bone to the data and information. But the way stories are told is often as important as the story itself. Tell stories that are authentic to you and tell them with passion. Don’t be afraid to share your own story. Tap into timeless methods employed by every culture, religion, and organization to inspire: rituals, traditions, and ceremonies. Add them or incorporate them into your work and use them often.
Incorporate these design principles and the delivery of patient experiences into all of the organization’s operational systems. Make it a permanent and ongoing part of the overall organizational culture, and commit it to words in an organizational ‘manifesto’ (A manifesto is a published/public declaration of your principles, intentions, and objectives). Tie measures (e.g., patient experience surveys rather, than service satisfaction surveys) of the effectiveness of your designed experiences to financial rewards, or give them teeth that bite (e.g., financially), if we fail to fulfill.
More about Dr. Petersburg
In September 2012, a jury in Salt Lake City, Utah awarded a breast cancer survivor $5.1 million in a court case against the pharmaceutical company, Wyeth (also known as Pfizer), alleging that the use of Premarin-Provera (Prempro) was responsible for the development of her breast cancer.1 This is one of many lawsuits against Wyeth, since the Women’s Health Initiative trial (WHI) was published in 2002. The general matter for this case is whether Wyeth withheld data and failed to inform the public concerning the risk of breast cancer with the use of the synthetic hormones, Prempro. There have been over 10,000 cases filed against Wyeth, which has paid $896 million to resolve over 6,000 lawsuits. Furthermore, they have set aside an additional $330 million to resolve the remaining lawsuits.
Despite the knowledge Wyeth had of the increased risk, they made no effort to alert the public. For several years, Prempro was marketed without an advisory label or black box warning. This warning would discourage any woman from taking the drug, but it also resolves any future litigation for Wyeth, as they would not be blamed for a failure to warn the public.
While Prempro now contains a black box warning label, it is puzzling that millions of women still take it in spite of recognized harm. What is even more puzzling is that physicians continue to prescribe Prempro, even when safer alternatives are available. Wyeth downplays the harm of synthetic hormones by marketing against safer hormone alternatives. In this review, I will explain the literature and science demonstrating breast cancer, the chance of risk, and the process of how the jury came to award a plaintiff verdict in this and other cases filed against Wyeth.
Any cigarette carton carries a warning that smoking tobacco will kill you. Yet for many years, the tobacco industry misled the public and hid the overwhelming amount of research that proved tobacco causes cancer and heart disease. Until the tobacco industry issued warning labels on their products, several lawsuits were filed against them for their failure to warn the public. These labels are meant to pardon the tobacco industry from future lawsuits. Similarly, the black box warning on the Prempro label prevents any future lawsuits against Wyeth and they can no longer be held accountable for failure to inform.
In spite of the scientifically-proven harm, the former president of the North American Menopause Society (NAMS), Dr. Wolfe Utian, at a recent NAMS meeting advised physicians to continue prescribing conventional hormones and avoid prescribing natural or bioidentical hormones. The continual promotion of Prempro and simultaneous marketing against the safer alternatives can be seen as points of contention against Wyeth. At first, many healthcare providers (myself included) may have felt sorry for the pharmaceutical company in being sued. However, once I heard firsthand the comments Dr. Utian made to denigrate bioidentical hormones and still recommend conventional HRT, I realized the promotion was instigated by Wyeth and therefore agreed with the jury.
I believe a jury of physicians most likely would not find judgment against Wyeth, due to the fact that breast cancer can be caused by factors other than synthetic hormones. Therefore, it is impossible to sort the blame. However, a jury that does not consist of physicians or medical experts, who understand the intricacies of cancer and hormones, can easily find fault based on the inappropriate actions taken by Wyeth.
Wyeth, ACOG, NAMS, and many of us well-read physicians know perfectly well that there is a safe alternative to Prempro. When the pharmaceutical industry markets against the safer alternatives, they are putting their profits ahead of women’s health. It is unsuitable to continually bash the bioidentical hormone industry and promote a scientifically-proven harmful, conventional hormone therapy. Regardless, the public knows of the harm and typically refuses to take harmful synthetic HRT, even if their doctor recommends it. Everyday more physicians are turning to safer alternatives, primarily based on patient demand. Physicians are certainly ignoring the promotion of Wyeth and the medical academies, as this is evidenced by the large number of doctors attending HRT training seminars. These physicians value the safety supported in the literature and want to be educated in the use of bioidentical hormones.
For physicians who have attended HRT training courses, it is quite obvious which hormones provide the best protection as is seen from the medical studies. However, the inexperienced physician and patient may not understand the reasoning behind preferred hormone therapies. I have included a review of the medical literature that supports why we do what we do. This will provide greater understanding of the risks and benefits of various hormones, and perhaps help us better comprehend the jury’s decision in this case.
A recent article that appeared in the Lancet Oncology journal demonstrated that women in the WHI trial who received estrogen-only (Premarin without Provera) experienced a 23% lower incidence of breast cancer when compared to the placebo group.2 This translates to suggest that there was a decrease in breast cancer risk in women who took just estrogen "Unless it was shown that Provera was only taken for a short period of time, blame should have been shared with the physician." without Provera. Research from the WHI also demonstrated that the use of estrogen-only did not result in an increased risk of breast cancer, but was actually associated with a decrease in breast cancer.3 These results are difficult to grasp seeing that everyone believes estrogen causes cancer. Estrogen may stimulate cancer to grow once cancer is established; however, estrogen does not cause it to occur in the first place. As is mentioned in the article published in Lancet Oncology, Premarin has become less popular in recent years, because many patients have switched to estradiol - a natural bioidentical estrogen that resembles estrogen naturally found in the body.
The addition of Provera to Premarin is what causes the harm of Prempro’s association with breast cancer. Provera is added to Premarin to protect against uterine cancer, but it has also resulted in an increase in stroke, heart attack, deep venous thrombosis, deep vein thrombosis, pulmonary embolism, breast cancer, and diabetes. Provera is generally prescribed to protect against uterine cancer, because the uterus is the only organ that seems to like it. All other organs – the heart, brain, blood vessels, and visceral fat – do not like Provera.
In the case of Mrs. Okuda versus Wyeth, it is most confusing that she took both Premarin and Provera after she had a hysterectomy at age 47. The only reason to use Provera is to protect the uterus against uterine cancer. The treatment is never indicated in women who have undergone a hysterectomy. The question remains as to the length of time Mrs. Okuda took Prempro, as opposed to just Premarin. Taking Prempro for a short period of time most likely would not influence the development of her breast cancer and it would be impossible to predict the effect Prempro would have for a short duration of time. This would make a vote in favor of Wyeth in this settlement. Yet, whose fault was it that she was taking Provera? Since she should not have been prescribed Provera in the first place, her increased risk could be blamed on the physician. What were they thinking? Unless it was shown that Provera was only taken for a short period of time, blame should have been shared with the physician. Unfortunately, we are not told the length of time that Mrs. Okuda took Provera.
Understanding the above complexities indicates how difficult it would be to render judgment in this case. In the post-commentary section of this article, I found the comment made by the “sanityinutah” reader most interesting, as they referred to the difficulty in having an uninformed jury that has no understanding of the medicine, science, literature, or pathophysiology of HRT. I believe the jury truly had no idea as to whether or not the hormones were responsible for the cause of breast cancer in Mrs. Okuda, nor should they have been able to comprehend all the aforementioned facts. I also believe that the jury voted against the drug company, not necessarily for the patient, Mrs. Okuda. I say that simply because 50% of the cases have been won by the pharmaceutical company and 50% have not. Once it can be shown that a drug company failed to warn of potential danger, particularly if they had good evidence ahead of time or hid data, then the jury would most likely vote in favor of the patient. Wyeth “failed to disclose, misstated, downplayed, and understated” the risks of Prempro, which lost the case for them.
So, now what? It is firmly proved in science and the courts that Prempro contributes to the increased risk of breast cancer. Do current warning labels pardon Wyeth from further wrongdoing? Apparently so, because this pharmaceutical company continues to manufacture and advertise Prempro. Why would a pharmaceutical company continue to manufacture Provera or Prempro with these inherent risks? Experts now recommend the HRT regimen should only be taken in the lowest dose and for the shortest period of time to control menopausal symptoms, after which time the HRT regimen should be stopped in hopes of avoiding any harm. Knowing the scientific facts, it seems unreasonable for a physician to continue prescribing Prempro. However without estrogen, women lose all of the tremendous health benefits and may suffer an increase in morbidity and mortality from estrogen deprivation.
What about estrogen-only? There is no evidence in recent medical literature that shows prescribing estrogen without a progestin increases the risk of developing breast cancer. The WHI trial and other recent studies amazingly prove a decrease incidence of breast cancer in women taking estrogen-only. In the CORA study, there were fewer cases of breast cancer in the estrogen (estradiol) group when compared to the placebo group.4 To date, a lawsuit has not been brought against any pharmaceutical company with the claim that taking estrogen-only caused breast cancer. All studies demonstrate a decrease in morbidity and mortality, which encourages physicians to recommend estrogen for all women. Preliminary "There is no evidence in recent medical literature that shows prescribing estrogen without a progestin increases the risk of developing breast cancer." Preliminary data from the recent completed KRONOS study of hormones found no increased risk of breast cancer in women taking estrogen and progesterone.5 The recently published DANISH study also demonstrated no increased risk of breast cancer in women taking estradiol for ten years.6 These results should be in the headlines of every newspaper. Yet, this research is not negative sensationalism and uninteresting to the media.
To this day, the most powerful scientific studies demonstrate that estrogen does not cause or stimulate the development of breast cancer. A recent study entitled “Aromatase Inhibitors: A Time For Reflection” critiqued the commonly prescribed estrogen-blockers termed aromatase inhibitors, which are commonly used in patients with breast cancer to block estrogen receptor sites on breast cancer cells.7 This renders the cancer cells to be insensitive to any stimulatory effect from estrogen. Estrogen does not cause cancer to occur; however, once breast cancer develops, estrogen can stimulate its growth as the tumor becomes estrogen-sensitive. In women with active cancer, this is an important treatment modality to prevent estrogen from stimulating breast cancer cells to grow.
These aromatase inhibitors have become standard care in women with breast cancer and are usually continued for five years after breast cancer is diagnosed. Pharmaceutical companies are pushing these drugs to be continued beyond the five-year recommendation with the hope and intent of preventing any further recurrence of breast cancer. So far, studies have demonstrated a very small decrease in the recurrence of breast cancer when these agents are used indefinitely. However, this article published in the journal Menopause refutes these suggestions and recommendations to continue the use of estrogen-blockers indefinitely. The study claims there is increased harm in blocking estrogen long-term, along with an increase of morbidity and mortality associated with loss of estrogen.
Remember that in the WHI trial the use of estrogen-only provided protection against breast cancer with an incidence of eight less breast cancer cases per 10,000 women treated with estrogen-only and that is the same protection against breast cancer as seen with aromatase inhibitors. Studies show that both medicines are equal for cancer protection. Estrogen-blockers increase the symptoms of menopause, whereas estrogen therapy eliminates those symptoms and improves quality of life. The aromatase inhibitor article goes on to say, "Estrogens play a critical role in multiple systems. The loss of estrogen is associated with an accelerated loss of bone, an accelerated progression of atherosclerosis and MI. If estrogen is started at menopause, there is a 60% reduction in coronary calcification, a 50% reductin in MI, and a 35% reduction in overall mortality. Estrogen deprivation causes decrease in cognition, mood, and memory. There is accelerated expression of neurodegenerative disease like Alzheimer's and Parkinson's disease. Evidence shows that neurodegenerative disease can be prevented by estrogen replacement."
Is there an alternative to Provera if the patient wants uterine protection without the risks and complications observed with Provera? By now, we should understand and appreciate all of the benefits of estrogen, but we cannot provide estrogen without some type of estrogen opposition to protect the uterus. This is provided by Provera and it is the sole purpose of this prescription. If Mrs. Okuda had taken Premarin (estrogen) with natural, micronized progesterone instead of Provera, would she have filed against Wyeth? Certain medical academies claim that there is no difference between synthetic and bioidentical hormones; yet, I’ve never heard of a breast cancer patient sue when taking Premarin with micronized progesterone.
Are we missing something here? A recent article demonstrated an increased relative risk of breast cancer with use of Provera, in comparison to progesterone with no increased risk.8 Interestingly, the new progestin, norethindrone, which is the recommended replacement for Provera, has a two-fold increased risk of breast cancer.9 This is even worse than Provera and makes it seem unreasonable that a physician would prescribe a medicine proven to increase breast cancer risk, when the data supports a safer alternative – micronized progesterone. Another study, the EPIC-E3N trial has found consistent results for over 10 years that demonstrate an increased risk of breast cancer with the addition of a progestin and a decreased risk in breast cancer with the use of progesterone.10 The implications of this study are enormous. Which hormone regimen would you rather take?
While ACOG and NAMS currently recommend that HRT only be taken in the lowest dose for the shortest period of time, it would be more appropriate to inform women on the many studies that demonstrate neither estradiol or progesterone have been associated with an increased risk of breast cancer. This combination is safe and effective. However, OB-GYN academies do not clarify these findings, which cause us to disdain pharmaceutical companies and the medical academies they support. I personally find the denigration of the bioidentical hormone industry by these medical academies to be erroneous. Micronized progesterone’s proven record of safety has worldwide implications for women’s health.
I personally do not believe that taking Provera for a short period of time had anything to do with Mrs. Okuda development of breast cancer. From my many years of research, writing, and teaching, I have gained a sound understanding of the published literature and science surrounding HRT. The very small increased risk of breast cancer that is associated with Provera, the short duration of Provera use (no statement was made as to how long it was taken), and the protective effect of Premarin-alone makes the increased risk of cancer in this case relatively small. Nevertheless, I can understand the jury’s reasoning to vote against Wyeth, based on the unsuitability of their prior actions, refusal to acknowledge the scientifically-proven risks, and disregard to advise the public of the risks. My personal dissatisfaction for Wyeth is based on their continual denial of a safe alternative, persistent marketing of harmful synthetic hormones, and continued production of a medicine shown to be harmful to women’s health. Fortunately, the public is becoming more aware of these deficiencies and is now refusing to accept synthetic hormone prescriptions.
The European studies demonstrate that the majority of physicians and patients avoid synthetic HRT, such as Prempro, in which the majority of women are taking the bioidentical hormones estradiol and progesterone. Interestingly, the pressure on drug companies that exists in Europe does not exist in the United States. For now, I expect Wyeth will continue to be reproved with large jury awards and front- page headlines. Perhaps the major harm in this controversy is that women may still refuse to take estrogen out of media induced fear; and thereby, suffer the consequences of estrogen depletion.
Which HRT would you prefer – conventional or bioidentical hormones? How would you have voted on the jury? In this article, I suggested that there should have been shared responsibility between the pharmaceutical company and the physician who prescribed Provera, when it was unnecessary for the patient to take it after a hysterectomy. This case would have never existed if Mrs. Okuda had not been prescribed Provera. Based on the foregoing paragraphs discussing the benefit of progesterone and lack of breast cancer risk, perhaps the third responsible party is the medical establishment that fails to acknowledge a scientifically-proven alternative. There is very adequate evidence to support a strong preference for micronized, natural progesterone over synthetic progestins. ACOG and NAMS may consider a safer alternative, instead of standing by the pharmaceutical industry to support the continued administration of problematic progestin. Until the OB-GYN academies acknowledge the alternatives, there will continue to be disapproval of the pharmaceutical industry and filed lawsuits.
During the last Part I course in Salt Lake City, Utah, I taught from a wheelchair in a snowstorm. For those of you who attended this conference, the content, format, and articles for my PowerPoint presentation were completely new and different from my past Part I course. Since then, Nancy Gardner and Dana Burnett from WorldLink Medical, as well as myself, have painstakingly reorganized Part II. We plan to redo and revamp all of the courses for 2013 by getting rid of old articles, replacing them with new, updated articles, and placing them all on PowerPoint slides to make the overhead slides a thing of the past. Part II has a new format, content, and articles.
Due to popular demand, Part II is being held on the east coast in Fort Lauderdale, Florida. While I prefer the powder of the Wasatch Mountains to a sandy beach, the surf is sounding pretty good since I can’t ski this year (recovering with crutches and IV antibiotics). For all of you on the east coast who are ready to dig out of the snow, come join us in Fort Lauderdale for a new Part II course and beautiful weekend in the sun.
You learned the basics in Part I, so Part II gives the experienced practitioner an opportunity to explore the advanced protocols that are important to mastering complex cases that are not taught in Part I. The field of age-management medicine continues to grow at a rapid rate making it difficult to stay ahead of the changes. Part II will serve as a short refresher and highlight new important therapies, clinical pearls, tricks of the trade, controversies, and every crucial element that I could not fit into Part I. Our update to Part II will condense an excessive amount of material into 2 ½ days. Dana has advised me that there are over 1300 slides (Yikes! I’ll talk fast).
My favorite part of this course is the Saturday night informal discussion, which involves a question and answer session on anything that you want to discuss. Expand your clinical knowledge by learning and sharing experiences, round table discussions, difficult cases, controversies, legal issues, suggestions, trials, and tribulations from seasoned attendees. There is no other place where you can participate in such a gathering and meeting of the minds.
The following is a summary of Part II topics:
Anti-aging (definitions of and why we call it that). This section reviews articles that make us refer to BHRT as anti-aging and provides credibility for why we do what we do.
Longevity medicine and which hormones have a proven record for extending health, wellness, and longevity.
Making sense out of the many HRT studies, the critiques, and the rebuttals. Putting the pieces together will make you an expert on all of the “ifs”, “ands”, or “buts”.
“There are no studies that prove BHRT is different from synthetic HRT.” Baloney!
A literature review proving that HGH, testosterone, estrogen, progesterone, DHEA, and melatonin protect against cancer. The perfect solution to Obamacare.
I have removed my section on vitamins and nutrition. What I know and teach is nothing in comparison to the knowledge and expertise of Dr. Gaby’s book on vitamins and nutrition. Dr. Gaby has extensively researched and written on this topic and in my opinion there is no greater authority on vitamins and nutrition. WorldLink has teamed up with Dr. Gaby to provide the health and nutrition lectures that are offered in the remaining courses. Dr. Gaby will lecture Friday morning before I take over in the afternoon.
Dr. Gaby and I look forward to seeing everyone in Fort Lauderdale, Florida on March 15, 2013.
Three years after the Women’s Health Initiative published that hormone replacement therapy (HRT) increased the incidence of certain health risks, clinical researchers at nine centers in the U.S. started the Kronos Early Estrogen Prevention Study (KEEPS). This study was anticipated to be a turning point to determine the benefits of HRT on cardiovascular health. Researchers posed the question, “Does HRT slow the progression of cardiovascular disease in post-menopausal women?” Results were finally released last week, in which the critical question was left unanswered and results seemed disappointing. Dr. Joseph Raffaele clearly explains the strengths, drawbacks, and overall conclusion of the KEEPS clinical investigation.
Read Dr. Raffaele's full article on the KEEPS Study
Joseph Raffaele, M.D., the co-founder of PhysioAge Medical Group, a clinical practice in New York City that is at the leading edge of the emerging field of medicine focused on scientifically sound approaches to staying younger longer. He has been a featured speaker at numerous events sponsored by WorldLink Medical.
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