The Lance Armstrong Mess-Up
One of the keys messages expressed through the political campaigns has been about regulation, with one side calling for more regulation and the other side calling for less – although as the debates unfolded in mid-October, both sides seemed to be calling for more. The argument for greater regulation has been that people don't do things according to the Golden Rule when there are no rules to control their behavior. The argument against more codes is the drag on the economy – and, of course, everything now is about boosting the economy. I think that the pro-regulation group has it right – there are lots of folks who will try anything if it will give them the edge. However, I am not sure if it's greater regulations that are needed. We probably need a stronger police force and inspectors. Regrettably, greed trumps all, and when people are capable of getting away with something, they will do it.
How else are we to explain the Lance Armstrong affair? Armstrong, the Tour de France champion for years, helped himself to illicit drugs, most notably EPO (erythropoietin; an agent used by physicians to counter the anemia caused by chemotherapy agents during cancer treatment). Did Armstrong use other agents also? The evidence is unclear, but there is no reason to believe that other drugs weren't used as well. Interviews with Armstrong's teammates talk about a "culture of drug use." I think that we can award Armstrong first-place achievement in laboratory science for being able to deceive drug detection technology. From the lab testing point of view, Armstrong's methods could conceivably be of benefit to many individuals who enjoy their jobs but are obligated to undergo periodic drug testing. Still it is disheartening to see one of our generation's outstanding athletes, revered as a demigod, brought to his knees, especially one who served as such an example by surviving cancer.
Despite the blame that we may have for Armstrong and his colleagues abusing drugs, we have to take another look at what enabled Armstrong to do so. There is a long history of coaches and trainers' seeking means to enable their athletes to have a competitive edge. While drugs have legitimate medical applications, there are always effects that will improve sports performance and endurance. Anabolic steroids have had the longest history of sports abuse, with the East Germans and Russians purported to be the first to use them in the Olympics. Steroid use was curtailed in the Olympics by the late 1970s, but it has continued in professional sports including American baseball through the mid-2000s. Recent concerns in veterinary medicine have focused on the use of powerful NSAID agents administered to injured horses to keep them competitive on the race track. There appears to be an endless effort to find new agents, even unlicensed drugs, to improve athletic performance. Growth hormone (a drug medically indicated only for the treatment of dwarfism), used by anti-aging physicians to counter anti-aging effects, has also been illicitly used by athletes. Should the standards that apply for drug abuse in sports also apply to anti-aging medicine?
Much as one might argue that more regulation, more inspection, and more policing curtail our freedoms, it would appear that those efforts are exactly what is needed to control the unbridled efforts of the unscrupulous in the sports world.
The New England Compounding Pharmacy Mess-up
By late October, more than 250 individuals had contracted fungal meningitis as a result of injections of compounded methylprednisolone manufactured by the New England Compounding Center. At least 25 individuals had died from the infection, while 14,000 persons in 25 states worried about developing the illness. Physicians were asked to assess "risk" in patients who had received spinal or joint injections of the steroid. Those thought to be at high risk were recommended to undergo a spinal tap to look for the rare disease-causing black fungus Exserohilum. In the event that the fungal diagnosis was confirmed, intravenous or oral antifungal medication would be prescribed, with a serious risk for developing kidney, liver, or bone marrow toxicity. Additionally, the NECC appeared to have manufactured other adulterated products used in different treatment procedures. All in all, the contaminated compounded injectable appears to have been responsible for one of the largest iatrogenic medical disasters on record. And, needless to say, our brethren in the legal profession are hard at work.
It is hard to imagine a more "mea culpa" incident in medicine. As the Hippocratic oath decrees, "First, do no harm." Of course, we are now receiving daily reports of this unfolding disaster in the media. The CDC, the FDA, state medical agencies, and federal and state investigators are probing the matter. The medical profession and the public are at high alert for learning the extent of the noncontagious outbreak. Learning whether there is further contamination with other NECC compounded products is under way. It has been determined that fungal contamination of compounded steroid products in an unrelated pharmacy was noted at least in one incident nearly 10 years earlier; however, there was no massive doctor-caused fungal infection. Still, the fact that fungus is capable of contaminating injectable steroid products is unsettling, given the widespread use of injecting patients with corticosteroids.
In fact, media probing of injectable drug manufacturers reveals that there are widespread sloppy, unhygienic, and faulty practices afoot in many production facilities licensed by the US. These facilities are not compounding pharmacies but production lines of major injectable drug manufacturers. Many of these companies are producing injectable in building sites that are old, with inadequate sterility in their production rooms. Onsite inspections at numerous companies have found injectable products with insect matter, soil, and dust contamination and other debris within the vials. Although the government inspectors have reported these findings and authorities have been made aware that there are high incidences of injectable contamination, little has been done to correct these manufacturing practices. Recently there have been some efforts to stop the contaminated production and a few manufacturers have begun building new facilities with sterile production facilities. However, these buildings are still in development. As a result, many manufacturers have halted production of injectable medical products. Supposedly chemotherapy agents are being manufactured in sterile facilities – but manufacturers have discontinued injectable steroid production. Hence, with a shortage of manufactured steroids, compounding pharmacies have stepped in to "compound" the injectables. It is a stretch of the imagination, however, to claim that one is compounding a steroid injection when one is making tens of thousands of vials.
It is one thing if NECC sloppily manufactured the methylprednisolone, allowing fungal contamination. It is altogether a different matter if, in fact, the product was manufactured elsewhere in the US or internationally and simply labeled as compounded by NECC. It is one thing if NECC conducted quality-control studies and somehow did not find fungus as a contaminant. It is quite another if the pharmacy conducted no quality control of its manufacturing. It is one thing if NECC did not know that its product was contaminated and distributed it in good faith; it is quite another if it knew that there was contamination and distributed it with knowledge of the contamination. A recent report indicated that NECC workers were aware of injectable vial contamination at their facility.
Quality control is a time-consuming, expensive, and intensive process that takes away from the bottom line. There is no additional profit from knowing that one's product is sterile and biologically and chemically safe. We complain about the high cost of pharmaceuticals, but one of the givens of using pharmaceuticals is that the drug companies guarantee their quality control. The compounding pharmacies have fought the FDA and FTC and government authorities for their right to offer physicians and patients compounded products. With that right comes the responsibility of maintaining rigorous quality-control standards. Not only must compounding pharmacies assure that there is quality-control testing, but such practices should be available in a detailed discussion of methodology employed. The quality-control testing procedures should be available not only to authorities but also to physicians ordering products. As an aside, quality-control procedures should also be obligatory for all vitamin, nutraceutical, and herbal manufacturers. Such testing procedures should be made available to physicians ordering supplement products for distribution; companies failing to provide detailed quality-control procedures should be shunned for supplement purchasing.
Estrogen Metabolite Ratio and Breast Cancer Risk
I know that when one turns 60, one is free to retire and enjoy one's golden years. I'm reluctant to give up my medical practice and the Townsend Letter,so no one should have any worries that I will be disappearing in Costa Rica. Still, becoming an old fogey makes one a little resistant to relearning – especially when one is convinced that one's beliefs are based on solid science. I was ill prepared this month to read Tori Hudson's column challenging the medical shibboleth that 2-hydroxyestrone to 16-alpha-hydroxyestrone ratio gives us useful information about assessing breast cancer risk. Hudson's examination was provocative; Jacob Schor, ND's review was shocking. Schor's title says it all: "Estrogen Metabolite Ratios: Time for Us to Let Go."
Go? Like, give up the ratios? No, I can't do that, I'm thinking. The estrogen metabolite ratio is the way that I decide whether hormone replacement therapy is safe or not. The estrogen metabolite ratio is the way that I decide that breast cancer risk is higher or lower in a woman. The ratio determines whether I need to make a recommendation for increased DIM supplementation. According to Hudson and Schor, that is wrong, wrong, wrong!
We're told that the ratio of estrogen metabolites 2-hydroxyestrone to 16-alpha-hydroxyestrone ratio should ideally be 2.0 or greater. Turns out that an increased ratio does not lower breast cancer risk. In fact, there is evidence suggesting that breast cancer risk may be higher in the women with ratios greater than 2.0. In fact, the ratio just did not make any difference in a women's breast cancer risk. In a small subgroup, in women who have estrogen and progesterone negative receptors, an increased ratio actually increased the risk for developing breast cancer! Another study suggested that the metabolite which was thought to be predictive, 2-hydroxyestrone, actually increased the risk for breast cancer; contrariwise, the 16-alpha-hydroxyestrone metabolite lowered breast cancer risk. Schor and Hudson show that one cannot be certain with any measurement whether the risk increases or decreases for breast or endometrial cancer.
Schor wants old fogeys like me to dump this estrogen metabolite ratio theory in the garbage. It doesn't predict breast cancer risk. He also wants new NDs to do the same. Time to learn a different approach to assess breast cancer risk.
Jonathan Collin, MD