Jerome Burne and Bio-Identical Hormone Replacement Therapy: Part 3

Jerome Burne and Bio-Identical Hormone Replacement Therapy: Parts 1 and 2 covered some difficulties with Kent Holtorf’s review article, Are Bioidentical Hormones (Estradiol, Estriol, and Progesterone) Safer or More Efficacious than Commonly Used Synthetic Versions in Hormone Replacement Therapy?, relating to a potential conflict of interest (despite a statement to the contrary) and the completeness and quality of the review. For this final examination of Jerome Burne’s Should middle-aged women be taking natural HRT?, we focus on a paper for which we had to guess the identity: Unequal risks for breast cancer associated with different hormone replacement therapies: results from the E3N cohort study. (Again, This Really Is Not Good Enough or TRINGE.) We should reiterate, as per parts 1 and 2, that this post is concerned with research standards and scholarship, not the relative merits or demerits of HRT and bioidentical hormone therapy.

Jerome Burne wrote:

When HRT was first developed, one of its key selling points was that it protected women against heart disease.

While studies have since proved that it does not have this protective effect, bio-identical versions might… The key is progesterone…

However, in the past 18 months there’s been new evidence from a French study to suggest that a bio-identical form of progesterone might also protect against breast cancer and heart attacks.

As above, HolfordWatch believes that Burne is referring to this large-scale epidemiological study: Unequal risks for breast cancer associated with different hormone replacement therapies: results from the E3N cohort study.

The authors of the E3N cohort study actually conclude:

E3N is the first epidemiological study that we know of to be providing results indicating that estrogen–progesterone and estrogen–dydrogesterone combinations may be the least harmful estrogen–progestagen HRTs regarding breast cancer risk. However, more evidence is required before these results can be translated into firm clinical recommendations for the management of menopausal symptoms. In addition, the effect of these combinations in other diseases (e.g., coronary heart disease, venous thromboembolism and colorectal cancer) has also to be evaluated. We therefore encourage further studies and reflection on the links between estrogen–progesterone and estrogen–dydrogesterone HRTs and breast cancer.

The short-hand version of this is that dydrogesterone is synthetic, a retroprogesterone and progestin – it is not a bio-identical hormone.

To be clear, a so-called bio-identical version of progesterone and a synthetic version both yielded better results than other varieties of progestagens for these outcomes in this study. The study authors sensibly call for more research to in order to make appropriate, evidenced clinical recommendations.

Burne then mentions that:

Some French researchers believe progesterone might also lower your risk of dementia. ‘Oestrogen and progesterone both have a protective effect on brain cells, unlike progestins,’ says Dr Michael Schumacher, of the Kremlin-Bicêtre hospital in Paris.

The support for that suggestion would seem to be this review:Novel perspectives for progesterone in HRT, with special reference to the nervous system. A substantial amount of the reported research on the brain or brain cells seems to be from animal studies:

In conclusion, a substantial number of animal studies have documented neuroprotective effects of progesterone or its reduced metabolites in the lesioned or diseased nervous system of young adult rodents.

It might seem a little premature to suggest that interesting animal studies might be extrapolated to imply similar neuroprotective effects in women and that is not readily apparent from the present article.

For women who may be interested in CAM offerings for menopause symptoms, AP Gaylard has a number of detailed explorations of red clover, black cohosh and other offerings (such as magnetic pads).

As ever, women who are considering hormonal or CAM interventions for menopause symptoms should consider their options in discussion with a GP or other appropriate health care worker.

And this concludes our present assessment of the state of the evidence and scholarship in Jerome Burne’s: Should middle-aged women be taking natural HRT?

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15 Comments

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15 responses to “Jerome Burne and Bio-Identical Hormone Replacement Therapy: Part 3

  1. Pingback: Jerome Burne and Bio-Identical Hormone Replacement Therapy: Part 1 « Holford Watch: Patrick Holford, nutritionism and bad science

  2. Leslie

    Interesting that hundreds of studies (physiologic, animal or human) show that bioidentical hormones are safer (although many may not be perfect studies) but none show that synthetic hormones are safer. All it takes is a little common sense as to what I would want to use. I think it is, as they say, a no brainer.
    Why would I use synthetic as the current evidence shows they may (likely) carry more risk and, at best, they carry the same risk.

    • As I said, this is not a post about the menopause or bio-identical hormones, it is about the scholarship of the article and the research upon which it relies.

      • Leslie

        I can appreciate that but think it is a classic case of missing the forest for the trees where individual points of a study are debated ad nauseam but the obvious answer is starring one in the face. Think it demonstrates the perversion of the term evidence based medicine and the lack of common sense in medicine today.

  3. Allo V Psycho

    Leslie, it seems a little extreme to say that this ‘demonstrates the perversion of the term evidence based medicine’. On the contrary, you are relying on evidence based medicine in order to come to your conclusion about treatment regimes. The ‘hundreds of studies’ you mention are, well, evidence. The blog author made it clear several times that s/he was not addressing the biology of HRT, but a quite different ‘forest of trees’ – that of the process of science. That is both legitimate and interesting. It would be generally wrong, for instance, not to declare a conflict of interest, or to cite selective or misleading evidence, no matter what the subject matter. If a scientist funded by a big pharmaceutical company failed to declare this as an interest, for instance, this would be interesting and important, independently of the results they were describing. Do you think it at all possible you might have missed the point here?

    • My interest in this is (as you recognise) solely in the process of reviewing and evaluating evidence. If you are going to review evidence and adopt a stance based on it, then the evidence must be scrutinised in its entirety.

      Bertolt Brecht pithily summed up the rationale for scrutinising evidence: Life of Galileo:

      The aim of science is not to open the door to infinite wisdom, but to set a limit to infinite error.

  4. @Leslie

    Unfortunately, there is no evidence to persuasively and conclusively demonstrate that the risks with bioidentical hormones are any less significant than with conventional hormone therapy. Consequently, an evidence-based approach is to apply the WHI risk and benefit findings to all hormone therapies.

    Consumers that select pharmacy-compounded bioidentical hormones face additional risks, beyond that of the WHI – most importantly, batch-to-batch variation, and formulation differences, which means that safety and efficacy data, even from trials that have studied bioidentical hormones, cannot be considered to be applicable.

    Bioidentical hormones that are commercially manufactured (yes, there are several) are subjected to evaluations of product quality, safety, efficacy, etc. All carry appropriate warnings consistent with the findings of the WHI study.

    • Strongly agree. There have been too many occasions when an intervention seemed like commonsense but it wasn’t borne out in practice. One example today is a revisiting of guidelines for fetal monitoring: it seemed that it would reduce the incidence of Cerebral Palsy etc. but in widespread practice, it is possible that it does more harm than good.

      As you say, commercial BIH are regulated and carry warnings; it seems absurd that competitor products are not bound by similar standards when they hope to have a pharmaceutical effect but bypass the need for regulation by representing themselves as a different industry.

      To quote Chris MacDonald:

      The side-effects of drugs…only become known *because* they are carefully studied and monitored. Sometimes such discoveries are made later rather than sooner — but better that it’s well-studied than not.

      …Drug companies are forced, by the legal and ethical standards that government them, to design drug trials carefully to rule out the dozens of ways in which personal, first-hand observation is likely to be biased. If drug companies were allowed to market a drug based solely on mere anecdotes from happy customers, can you imagine just how bad that would be?

    • Rachel S

      “Unfortunately, there is no evidence to persuasively and conclusively demonstrate that the risks with bioidentical hormones are any less significant than with conventional hormone therapy. Consequently, an evidence-based approach is to apply the WHI risk and benefit findings to all hormone therapies.”

      That is not “evidence-based” science.
      To reach a conclusion that “all hormone therapies” must be considered to have the same risk on the basis of insufficient evidence to prove otherwise is nonsense.
      Simply because a hormone and hormone-like drug happen to operate on a common receptor hardly gives evidence-based justification to conclude the side effects are the same, or even similar, particularly when the metabolization and action of the metabolites are well known to be very different.
      Ask yourself, for example, why MPA is not given to sustain risky pregnancies rather than real progesterone.

      • You might be interested in the just released JAMA paper than finds a quantifiable (and small, 1 extra case per 8,300 women per year who are taking HRT) risk of ovarian cancer with all formulations of HRT including those that contain ‘bio-identicals’.

        News item about HRT and ovarian cancer (will replace with direct link to JAMA when it comes up).

        Update: Hormone Therapy and Ovarian Cancer.
        Lina Steinrud Mørch, MSc; Ellen Løkkegaard, MD, PhD; Anne Helms Andreasen, MSc; Susanne Krüger-Kjær, MD, DrMSci; Øjvind Lidegaard, MD, DrMSci JAMA. 2009;302(3):298-305.

        • Rachel S

          “You might be interested in the just released JAMA paper than finds a quantifiable (and small, 1 extra case per 8,300 women per year who are taking HRT) risk of ovarian cancer with all formulations of HRT including those that contain ‘bio-identicals’.”

          Really?
          It’s always useful to look at the actual paper before jumping to conclusions–particularly when sometimes imprecise terms such as “progestins” are used. Sometimes “progestins” refers to a patentable quasi-progesterone drugs as distinct from human progesterone. Sometimes it is used more nebulously to include human progesterone.
          Standardized use of nomenclature would be welcome from the health industry, but if bioidentical progesterone is included in the study perhaps you could point out the numbers as I only did a cursory reading.

          But we do get this statement:

          “Combined therapy with norethisterone was associated with an increased risk of epithelial ovarian cancer (RR, 1.55; 95% CI, 1.36-1.76), which was not significantly different from the RRs associated with medroxyprogesterone, levonorgestrel, or cyproterone acetate (Table 3).”

          Here “combined therapy” (the almost always necessary opposing estrogens with a progestogen) only references “progestins” in the form of patentable quasi-progesterone drugs.

  5. Ian Horsewell

    At the risk of pointing out something that has already been commented on – when checking the blog a lot of the names seemed vaguely familar and I went back to check my recent reading. I found an article – possibly a version of the one from the Maily Dail – in my father-in-law’s April issue of Reader’s Digest. It contains some of the same doctors (presumably private health practitioners) and the same vague references to research. Interestingly, the quotes in the article are from clients, talking about their lack of side-effects – getting the point over without any of the medical professionals having to be quoted telling less than the whole story.

    • Well, that’s getting bang for buck from the same piece if it can be placed in several publications. However, it sounds more disturbing if the quotes tend to be from the clients rather than the medical people. One imagines that the clients that one would speak to would be the ones who are pleased with the BHT rather than those who experienced some of the same health issues or side-effects as with standard HRT.

      I wonder how much of an expectation there is that might influence the client/patient perception that any irritating symptoms can’t possibly be side-effects?

      I must look out for the Reader’s Digest version as any differences might be interesting and quite an insight into the expected audiences. Was it the same author (Jerome Burne)?

      • Ian Horsewell

        Definitely same author – in fact, some of the text seems pretty much identical. Not surprising, I suppose, as Reader’s Digest prints edited/summarised articles that have originally appeared elsewhere. I can’t find it online but perhaps a trial subscription would show more content at the RD website.

        The doctors mentioned (Marian Gluck and John Moran) both show up online as having, umm, interesting ideas about treating menopausal symptoms and similar using nutritional supplements and offering a range of blood tests, details not given on the web site I saw.

        • Thank you. Seems a little odd that the Reader’s Digest came out before this Daily Mail piece but perhaps there is another book in the offing or an update to Food Is Better Medicine Than Drugs.

          Some very “umm, interesting ideas” – I should be inured to it by now but I’m not.

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