MD, PhD, FMedSci, FRSB, FRCP, FRCPEd

A recently published study was aimed at evaluating the efficacy and safety of potentized estrogen compared to placebo in homeopathic treatment of endometriosis-associated pelvic pain (EAPP). This 24-week, randomized, double-blind, placebo-controlled trial included 50 women aged 18-45 years old with diagnosis of deeply infiltrating endometriosis based on magnetic resonance imaging or transvaginal ultrasound after bowel preparation, and score≥5 on a visual analogue scale (VAS: range 0 to 10) for endometriosis-associated pelvic pain. Potentized estrogen (12cH, 18cH and 24cH) or placebo was administered twice daily. The primary outcome measure was change in the severity of EAPP global and partial scores (VAS) from baseline to week 24, determined as the difference in the mean score of five modalities of chronic pelvic pain (dysmenorrhea, deep dyspareunia, non-cyclic pelvic pain, cyclic bowel pain and/or cyclic urinary pain). The secondary outcome measures were mean score difference for quality of life assessed with SF-36 Health Survey Questionnaire, depression symptoms on Beck Depression Inventory (BDI), and anxiety symptoms on Beck Anxiety Inventory (BAI).

The EAPP global score (VAS: range 0 to 50) decreased by 12.82 in the group treated with potentized estrogen from baseline to week 24. Group that used potentized estrogen also exhibited partial score (VAS: range 0 to 10) reduction in three EAPP modalities: dysmenorrhea (3.28;), non-cyclic pelvic pain (2.71), and cyclic bowel pain (3.40). Placebo group did not show any significant changes in EAPP global or partial scores. In addition, the potentized estrogen group showed significant improvement in three of eight SF-36 domains (bodily pain, vitality and mental health) and depression symptoms (BDI). The placebo group showed no significant improvement in this regard. These results demonstrate superiority of potentized estrogen over placebo. Few adverse events were associated with potentized estrogen.

The authors concluded that potentized estrogen (12cH, 18cH and 24cH) at a dose of 3 drops twice daily for 24 weeks was significantly more effective than placebo for reducing endometriosis-associated pelvic pain.

The study is unusual in several ways. For instance, contrary to most trials of homeopathy, its protocol had been published in ‘Homeopathy’ in August 2016. Here is the abstract:

BACKGROUND:

Endometriosis is a chronic inflammatory disease that causes difficult-to-treat pelvic pain. Thus being, many patients seek help in complementary and alternative medicine, including homeopathy. The effectiveness of homeopathic treatment for endometriosis is controversial due to the lack of evidences in the literature. The aim of the present randomized controlled trial is to assess the efficacy of potentized estrogen compared to placebo in the treatment of chronic pelvic pain associated with endometriosis.

METHODS/DESIGN:

The present is a randomized, double-blind, placebo-controlled trial of a homeopathic medicine individualized according to program ‘New Homeopathic Medicines: use of modern drugs according to the principle of similitude’ (http://newhomeopathicmedicines.com). Women with endometriosis, chronic pelvic pain and a set of signs and symptoms similar to the adverse events caused by estrogen were recruited at the Endometriosis Unit of Division of Clinical Gynecology, Clinical Hospital, School of Medicine, University of São Paulo (Hospital das Clínicas da Faculdade de Medicina da Universidade de São Paulo – HCFMUSP). The participants were selected based on the analysis of their medical records and the application of self-report structured questionnaires. A total of 50 women meeting the eligibility criteria will be randomly allocated to receive potentized estrogen or placebo. The primary clinical outcome measure will be severity of chronic pelvic pain. Statistical analysis will be performed on the intention-to-treat and per-protocol approaches comparing the effect of the homeopathic medicine versus placebo after 24 weeks of intervention.

DISCUSSION:

The present study was approved by the research ethics committee of HCFMUSP and the results are expected in 2016.

END OF QUOTE

As far as I can see, this study has no major flaws (I do not have access, however, to the full article). It seems to suggest that highly diluted homeopathic remedies are efficacious. I am aware of the fact that this will be difficult to accept for many readers of this blog.

So, what should we make of this new trial?

Should we recommend homeopathic estrogen to women suffering from endometriosis? I don’t think so. On the contrary, I recommend a healthy dose of scepticism. Clinical trials can produce false results sometimes by chance or through fraud. In any case, we hardly ever rely on the findings of a single study. The sensible course of action always is to wait for an independent replication (and, of course, study the full text of the paper).

 

33 Responses to Homeopathic estrogen for endometriosis? Let’s wait for an independent replication!

  • This study is interesting with regard to several points. First, they used a discrete and limited measure, a score, and I am not sure if the applied statistical method is appropriate for that. Second, if one looks at the graphs, one sees distinct differences between the groups at the start of treatment in figures 3 and 4, especially with regard to pain and depression symptoms.The verum group scores much higher (1.33 resp. 1.5 fold). If one looks at table 1, one gets the impression that the verum group is generally worse off (lower social functioning, etc.) My guess is that they have a sampling and/or randomization problem. Since pain and mental functioning have a major psychosomatic component, patients being worse off might display a higher placebo effect than healthier patients.

    • You’ve put your finger straight on the problem, Thomas. Reading the post I wondered why the authors chose to use score reduction statistics rather than differences in mean scores at the end of treatment. The answer is, like you say, because the scores for most measures in the verum group were way worse at baseline for the verum group than for the placebo group. From table 2, although the individual means for the two groups were comparable, it’s clear that, for all five measures of symptomatic pain the verum group was worse off than the placebo group. From the figures, the differences in measurements not included in table 2 were considerable.

      It’s an underwhelming study, to put it in the least unfavourable light I can.

      • Careful Frank. This is paired testing. Paired testing almost always boils down to test the difference of something, in this case before – after. Anyway, the reduction is evident, even without statistics. However, since the baselines are so different (pointing towards a sampling and/or randomization problem) and they use measures heavily influenced by psychology, the question is is it homeopathic estrogen or psychology ? Taking into account the prior probability of homeopathy i’d say it’s psychology.

        • Thanks for the warning, Thomas. My point was simply that, if the groups started at the same point, most investigators would not rush to use a paired (differences) test. The baseline means in many cases are (statistically) huge but there is very little difference between group means at the end of treatment.

  • Skepticism can be helpful when it is unbiased; otherwise it’s a mechanism to deride competing professions even when particular evidence is published which might indicate that there is some value hidden within them. Here Edzard has been forced to acknowledge that a homeopathy study appears to have been well done..and with a positive result. Yet he negatively spun the result with his faux “concern” that the positive result might have been due to chance or fraud. LOL

    I wish such a skeptic had been vocal during “modern medicine’s” estrogen scam. The 1970’s brought us news that HRT(estrogen) caused uterine cancers. Drug makers circumvented this issue by adding progestin….and profits soared! One of Wyeth Pharma’s medical quacks, the esteemed Dr. Robert Wilson, M.D., was a great proponent of HRT(he was paid handsomely for his “ethical” contributions to the science of HRT benefits). The drug maker financed all of the medical quack’s relevant book-writing expenses as well as those of the quack’s research foundation. Once it was discovered that these products might help osteoporosis, marketing increased almost exponentially to physicians’ offices. Despite there not having been any real scientific evidence at the time that HRT prevented heart disease or stroke, marketers for the quack-supporting Wyeth(and other drug makers) stormed the offices of physicians within the medical profession to proseletize the claims. Not coinicidentally, the prescribing of the products increased substantially.

    It has been evinced that the greatest influence on physicians’ prescribing practices is their drug reps; how scientific a way to gather information about chemicals doctors will be prescribing for their patients! it’s unfortunate for the women in the 90’s who suffered CV problems and breast cancer resultant to their “modern medicine” recommendations, based strictly on observational studies and no RCT’s BTW, that more skepticism was not prevalent. Oh well, the physicians and the drugmakers made money…all was good! It seems that “patient protection” and “maintenance of medical standards” is going well for those in “modern medicine” who profit from the dearth of skepticism Edzard recommends, at least when such pertains to paramedical discliplines. It’s a shame that Edzard’s demands of paramedical research have not been and are not now fastidiously adhered to when it comes to medical products which can actually harm patients.

    • I have access to the paper and have written about potential problems above. The main problem is in my opinion that the verum group is clearly significantly worse than the placebo group.

  • This study is not a study of homeopathy. Haha, I am laughing so much now Edzard!

    Just because a substance is serially diluted (12CH etc) does not make it homeopathic.

    This is more evidence that Edzard does not have a CLUE what homeopathy is.

    Other commentators: please just leave Edzard to be in his ignorance.

    • Oh dear. Perhaps you haven’t bothered to read the paper?

    • Greg, oh dear. Estrogen is part of the homeopathic pharmacopedia of the US and therefore this *is* a homeopathic study. Seems as if *you* do not have aclue as to what homeopathy is, Greg.

    • @Greg

      I really don’t know anything about homeopathy. However, I thought this study regarded the effectiveness and safety of potentized estrogen in the homeopathic treatment of endometriosis. Would you educate me as to why, in your view, this was not a homeopathic study?

      Thank you

      • Doctor ‘Logos-Bios’, based on your comments on this blog, it is difficult to imagine that you don’t know anything about homeopathy.

        Avogadro’s response is adequate.

        There is no point for me to add further comments because the skeptics on this site are ‘die-hard’.

        • @Greg

          Perhaps you should have had read what the authors say in their introduction in the paper before penning your last comment.

        • @Greg

          I have never taken any classes on homeopathy and have never practiced it. Aside from knowing basic factoids about it that anyone could learn from casual reading, I’m quite ignorant of the profession, as are perhaps the majority of this forum’s posters. My comments to the skeptics relative to the many studies about which Edzard comments often deal with commenters’ inductive, all-encompassing, often ignorant statements that the conclusions of even encouraging study results don’t support the use of the therapy which had been studied; yet “modern medicine” continues to prescribe and utilize drugs and tests for which systematic reviews have revealed the same paucity of evidence Edzard claims is characterized by paramedical disciplines’ treatment protocols.

          My question to you was an earnest one: it simply seems to me that this was a study of a homeopathic product. You seem to believe otherwise. Please explain.

  • Does Estrogen, undiluted or diluted, cause symptoms of endometriosis in healthy subjects?

    If not, then it’s not given according to the ‘law’ of similars.

    Also, I would think a statistician could tell us about the chances of p-hacking.

    lastly, each group had 25 women. not exactly a large sample

  • The etiology of endometriosis is not certain. High estrogen levels can certainly worsen the condition, so effective medical treatments are aimed at regulating estrogen levels and reducing endometrial proliferation. However, not being a homeopath myself, I don’t know whether potentized estrogen in this case would represent an example of a substance within the domain of the “law of similars” because high estrogen, to my knowledge, has not been found to be a cause of endometriosis.

    • If the study stated:
      OBJECTIVE: To evaluate the efficacy and safety of potentized estrogen compared to placebo in treatment of endometriosis-associated pelvic pain

      it would have not have been ‘controversial’.

      If potentised estrogen helps endometriosis sufferers, what difference does it make if it is ‘homeopathic’ or not?

      It cannot be stated that this is a ‘homeopathic’ study of potentised estrogen because first you would need studies to show that estrogen produces endometriosis. Are there any?

      • @Greg

        OK…so “potentized estrogen” is NOT a homeopathic substance, according to you, because it is not within the domain of the “law of similars”? Such a position would make sense and be consistent with your past statements. However, the authors of this paper seem to believe that diluted estrogen IS a homeopathic substance. It seems as though you disagree that “potentized estrogen” is a homeopathic substance and that the tested substance would be better classified as serially diluted “medical” estrogen. Please correct me if I am erroneously inferring from your statements.

        • The tested substance would be better classified as ‘serially diluted estrogen’ unless it can be shown that the base estrogen used in the ‘potentised estrogen’ or the ‘potentised estrogen’ itself can produce the five modalities of chronic pelvic pain (dysmenorrhea, deep dyspareunia, non-cyclic pelvic pain, cyclic bowel pain and/or cyclic urinary pain), or any one or more of them.

          • I agree with you that this is not homeopathic in the sense if ‘like cures like’. much of today’s homeopathy isn’t. crucially it was published as a homeopathic trial

          • The introduction to the paper states:

            The theoretical-practical model underlying homeopathic therapeutics is based on four pillars: therapeutic similitude (similia similibus curentur, likes heal likes); homeopathic pathogenetic trials (similar to phase 1 clinical pharmacological trials); use of potentized medicines (prepared through serial dilution and agitation); and individualization of treatment (drug selection based on the full picture of signs and symptoms exhibited by each patient). In clinical practice, patients are prescribed medicines previously shown to elicit similar signs and symptoms on healthy subjects (so-called primary, direct or pathogenetic effects of medicines) to trigger a homeostatic reaction (secondary, rebound or paradoxical effect) in the body against its ongoing disorders [14,15]. Any (natural or synthetic) substance might be used as homeopathic medicine provided it elicits similar pathogenetic effects (or adverse events, in the terms of modern pharmacology) on healthy subjects.

            To broaden the scope of action of similitude-based treatment, starting 2003, we developed a systematic method of application of the curative rebound effect of modern drugs. Within this context, we suggest giving patients drugs that induce adverse events similar to the full picture of their signs and symptoms, but in highly diluted doses (i.e., homeopathic potencies) to trigger a curative (homeostatic, rebound or homeopathic) reaction [16-18]. The resulting proposal is available at an open-access website (http://www.newhomeopathicmedicines.com) [19].

            In the present article, we describe the results of the just mentioned method to individualized homeopathic treatment of EAPP according to a pre-set protocol [20,21]. There we consider using potentized estrogen for EAPP treatment, because this hormone elicits, as adverse events (or pathogenetic effects), a set of signs and symptoms very similar to the one of endometriosis, including endometrial hyperplasia, pelvic pain, depression, anxiety, insomnia and migraine, among others.

          • @Greg

            Very good! Thank you for your explanation. I understand your position more clearly now.

          • Alan posted the intro to the paper. It appears that the authors don’t know that the cause of endometriosis is not known; ergo the cause could not currently be estrogen. Ergo, potentized estrogen would not be a true homeopathic substance, at least as I am able to understand what truly constitutes a homeopathic substance.

          • so much confusion!
            oestrogen is not homeopathic in this situation, I agree.
            but you are mistaken when you think that ‘like cures like’ means using causal agents.

          • @Edzard

            I’m quite happy to sit and watch the homeopaths argue over it. Having said that, it’ll no doubt still be used uncritically to promote homeopathy…

          • You guy’s have lost me here? As far as I am concerned, the water in my tap or the sugar cubes in my cupboard, are homeopathic if I or anyone else says so. I can definitely promisethat the water molecules that fed the sugarbeets were, if not actually there, at some point in time in turbulent contact with water molecules that went through and got admixed with the estrogen in the urine of young Queen Elisabeth and then got seriously diluted and shaken during the following decades. Potent stuff if you ask any water shaking expert, right? Or am I missing some finer points of importance?
            I dare claim that no one will be able to distinguish it homeopathically from a preparation of potentised estrogen made by any respected remedy retailer.
            What is the point? The nincompoops who wrote up this excercise in irrational thinking say it is homeopathic and potentized. Why doubt them?

  • And more specifically, studies to show that estrogen produces: endometriosis-associated pelvic pain (EAPP).

    That would be ‘homeopathic’.

    • The authors refer readers to this website. I’m used to the concept of ‘no true chiropractor’ since no two of them seem to agree about what chiropractic is or should be. Do we now have to enter the world of ‘no true homeopath’? (cf. ‘no true Scotsman’).

        • What a depressing link! Indeed it shows we’re already there with ‘no true homeopath’.

          Though Homeopathy’s overall effectiveness is low due to its bad application by most of its practitioners, in the minds of the people it has been established as a form of medicine that is better and more effective than conventional medicine with its side-effects and complications.

          In the minds of which people has homeopathy been established as a better and more effective form of medicine? The adjectives ‘ignorant’ and ‘gullible’ concerning science and medicine spring to mind.

          • What? It has been stated ad nauseum in previous threads by Edzard and his claque that some people get better with homeopathic care not because of the allegedly bogus medicines but BECAUSE OF THE HOMEOPATH(good listener, empathetic, etc.). Here you have quoted a comment which avers that homeopathy’s purportedly low effectiveness is due to homeopaths’ “bad application” of homeopathy. It would be nice to see some consistency in skeptics’ explanations regarding this matter.

  • It took me a while to procure the full text of this study, therefore maybe a little late.

    Did anybody figure out how the authors did their power calculation, which they claim ended with a fairly small number of participants? The authors apparently applied some correction from literature data (reduction of 2.16 instead of 2.58) and that is all they give us. Unfortunately G*Power will not run on my computer due to some unknown issue, otherwise I would try play around a little to find out the effect size the authors expected.

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