The interest in bioidentical hormone therapy (BHT) has seemingly exploded of late, due in part to celebrity books and daytime television discussion. Suzanne Somers, author of multiple books on BHT, recently made her case for BHT on Oprah. According to Somers, BHT is a veritable “juice of life“; appropriate for women from their twenties right up to menopause and beyond. This article will look at the safety and effectiveness of BHT, and the responsibility of pharmacists and the pharmacy profession in its provision.
Bioidentical and natural is good, synthetic and conventional is bad right?
The term “bioidentical” refers to hormones that are not produced in the body, are but biochemically similar to hormones the body produces. Bioidentical hormones include estrone, estradiol, estriol, progesterone, dehydroepiandrosterone (DHEA), and cortisol. The FDA and Health Canada have approved several prescription products that contain bioidentical hormones.[1] [2]
But this isn’t what celebrities like Somers are promoting. In the popular media, bioidentical hormone therapy refers to products that are custom manufactured in a pharmacy. Bioidentical is often used synonymously with the term “natural”, inferring that bioidentical, compounded hormones are natural, effective, and therefore good, while pharmaceutical-company manufactured hormones (bioidentical or not) are unnatural, ineffective and dangerous.
“Natural” is a meaningless term with respect to BHT. All bioidentical hormones are manufactured using wild yams or soy as the starting ingredient, and all undergo chemical conversion in a laboratory to be synthesized to the final ingredient. [1] [3] There are no bioidentical hormones that do no undergo some sort of laboratory manipulation. Consequently there are no truly “natural” bioidentical hormones.
For the remainder of this article, we will refer to BHT to mean pharmacy-compounded hormones, and focus on estrogen and progesterone replacement approaches.
“Compounded”: What do you mean?
At one time, almost all prescriptions were custom manufactured, or compounded. The pharmacist combined raw chemicals into dosage forms like capsules, tablets, liquids and creams. Compounding allows complete customization of a prescription – from a new strength of a capsule, to a liquid form of a tablet, to creams with combinations of ingredients that can be completely individualized. Hormones are usually compounded into creams or gels, but also into troches (lozenges), and sometimes capsules.
These days, commercial manufacturers supply most drug products, and the need for in-pharmacy compounding has dwindled. At the same time, regulatory oversight, by agencies like Health Canada and the FDA, ensure product uniformity, purity, potency, efficacy, and safety standards for consumers. Most importantly, these regulators require manufacturers to demonstrate that a drug studied in clinical trials is equivalent to the one available in the pharmacy. This allows us to accept that the results of research studies are relevant to patients that will receive the drug. We cannot automatically assume this when a product is compounded in a pharmacy, due to the lack of quality control standards, and batch-to-batch variation from different techniques, recipes, and practices.
Any pharmacy is capable of providing compounded prescriptions, but some specialize, calling themselves “compounding pharmacies” and aggressively promote the service. Professional Compounding Centers of America, provides training, formulations (recipes), and raw ingredients to compounding pharmacies. Other companies exist to supply pharmacies with articles, brochures and handouts to promote BHT and other types of compounded prescriptions. To pharmacies and pharmacists, compounding is a business opportunity, and an ideal way for independent pharmacies to compete against large chain stores, which typically do not offer extensive compounding services.
So what’s the problem with regular hormone therapy?
Hormone replacement therapy (HRT) was routinely used in women for decades. Not only was it effective at reducing menopausal symptoms like hot flashes and sleeplessness, it was believed to reduce the risk of osteoporosis, and possibly even heart disease. There was data to suggest some risks existed, but the balance of risks and benefit was believed to favour the use of HRT.
The Women’s Health Initiative (WHI) study was designed to provide conclusive answers about the risks and benefits of HRT. One part of the WHI was a huge study of over 16,000 post-menopausal women (with an intact uterus). It compared women taking conjugated estrogens (Premarin) plus medroxyprogesterone (Provera), packaged as Prempro, to women taking a placebo. The trial was stopped early when it was observed that the HRT group had more breast cancer cases compared to the group taking the placebo. Overall, the risk and benefit was as follows: If 10,000 post-menopausal women take HRT for one year, compared to a similar group taking a placebo, there will be 8 more cases of breast cancer, 7 more heart attacks, 8 more strokes, and 18 more blood clots. However, there will be 5 less osteoporosis fracture, and 6 fewer cases of colorectal cancer. Overall there will be no difference in death rates. (A superb summary of the WHI is available here (PDF)).
BHT advocates cite the results of the WHI as proof of the harmfulness of HRT. However, the results of the trial actually tell otherwise. Some illnesses increased, some decreased. While overall the benefits do outweigh the risks for many women, especially if taken for long periods, the WHI results continue to be studied, and we’re now seeing physicians using HRT in an evidence-based way. For example, there is a renewed interest in using HRT right around the time of menopause. No other therapy has been shown to be as effective for menopausal symptoms, and the overall risks when used for short periods (i.e., less than five years), are low. In fact, the risks of breast cancer from HRT, while increased, are similar to that of other lifestyle risks, including alcohol consumption, obesity, and physical inactivity. ( See this statement from the Society of Obstetricians and Gynecologists of Canada.)
One unfortunate consequence from the WHI was the sense of betrayal women taking HRT felt from health professionals, regulators, and pharmaceutical companies. Those struggling with menopausal symptoms went looking for alternatives. Enter BHT, celebrity endorsements, and compounding pharmacies.
What are the purported benefits of BHT?
A quick search of the internet reveals all kinds of claims for BHT. If you believe what you hear on Oprah, BHT offers a “fountain of youth” for women, with none of the side effects but all of the benefits of conventional HRT. Advocates boldly state that BHT can prevent or cure heart disease, Alzheimer’s disease, and even breast cancer. [4]
BHT advocates argue that the WHI results were due to the choice of hormones studied, Premarin and Provera, (called PremPro in the US and PremPlus in Canada). Premarin is a mix of bioidentical and other estrogens derived from pregnant horses (PRegnant MARes urINe, hence the name). Provera is medroxyprogesterone, a version of progesterone that is commonly used because bioidentical progesterone is poorly absorbed. BHT advocates describe Premarin and Provera as “unnatural” and the reason for the problems with HRT. For example, Montreal Pharmacy’s website is typical, describing Premarin as “natural for horses but not for women”, and describes BHT estrogens as “anti-carcinogenic.”
Few physician advocates of BHT have any research or significant expertise in hormone replacement, women’s health, or endocrinology. ABC News noted that most of the sixteen physicians quoted in Suzanne Somer’s book,”Ageless – The Naked Truth about Bioidentical Hormones,” have not published a single paper on hormone replacement therapy. Additionally, three of these “cutting edge” physicians have had disciplinary action taken against them.
There are a significant number of supportive articles on BHT in pharmacy compounding journals, with a few appearing in more mainstream medical journals.[5] [6] [7] [8] A close analysis reveals that the evidentiary base relied upon is weak. A consistent theme is the cherry-picking of supportive studies, and the extrapolation of weak data into broad elaborations of the safety and effectiveness of BHT.
What does the science say?
There are no large well-controlled clinical trials that have evaluated BHT to the extent that HRT has been evaluated. Consequently, there is no conclusive evidence to demonstrate that BHT is either safer, has fewer side effects, or is more effective than HRT. [1] [9] [10]
BHT often contains combination of estrogens such as triest (estriol, estrone, and estradiol) and biest (estradiol and estriol). Both are arbitrary combinations of estrogens based on bad science. [10] [11] [12] There is no clinical evidence to show these combinations are appropriate. [11] While BHT proponents argue that estriol decreases the risk of breast cancer, there is no conclusive evidence to support this claim. [9] In fact, estriol has been shown to stimulate breast cancer growth to a greater extent than other estrogens. [9] Products containing estriol have not been approved in Canada or the United States, and given this data, its unlikely they would ever be approved. In fact, the FDA forbids compounding pharmacies from preparing products with estriol. [4]
A significant concern with BHT is the effectiveness of pharmacy-compounded progesterone. In women who have not had a hysterectomy, some version of progesterone must be given with estrogen to reduce the risk of endometrial cancer. Published reports have identified cases of endometrial cancer in women using BHT, possibly due to poor absorption from pharmacy-compounded progesterone products. [13] If this is the case, BHT carries significantly greater risks that HRT. Until there is evidence to show otherwise, compounded progesterone should be considered an unreliable source of progesterone. [14]
Overall, BHT has not been shown to prevent or cure any diseases. Statements of effectiveness for any medical condition, other than menopausal symptoms, are not supported by convincing evidence.
What about saliva tests?
So how do you know that your BHT is giving the desired effect? Some prescribers may order saliva tests to monitor a patient’s response to BHT. However, saliva tests are unreliable and considered by experts to be pseudoscience.[1] [10] [11] [12] [14] There is no persuasive scientific evidence that saliva tests are useful to monitor response to BHT or HRT. [12] The single best way to monitor hormone replacement is simply to see if menopause symptoms (e.g., hot flushes) are alleviated. [11] [14] BHT advocates argue that compounding and saliva allows patients to “balance” their hormones. But the science shows this is implausible. Estrogen and progesterone levels vary day-to-day and hour-to-hour. There are no published studies to demonstrate that single or multiple saliva tests reflect hormone need, or can be used to adjust doses accurately.
What about Big Pharma? Isn’t this just Wyeth reacting?
Wyeth, the manufacturer of Premarin, suffered a huge decrease in sales due to the WHI results. And Wyeth did petition the FDA in 2005, requesting the regulation of BHT compounding by pharmacies. The FDA studied the issue and subsequently took action against compounding pharmacies. While this action has been opposed by several pharmacist and pharmacy compounding organizations, many large medical and public organizations, with no vested interest in HRT or in Wyeth, have spoken out against BHT and strongly support the FDA’s action:
The American Medical Association – representing 135,000 physicians
The Endocrine Society -14,000 members in 100 countries – [position paper]
The American College of Obstetricians and Gynecologists – 52,000 members
The American Association of Clinical Endocrinologists
The North American Menopause Society
Public Citizen an outspoken critic of both FDA and no friend of the pharmaceutical industry, is one of the strongest critics of BHT, labeling it “DO NOT USE” on their worstpills.org website. They went on to say the following:
“Compounding pharmacies have their own financially driven interest in selling untested BHRT drugs. The pharmacies do, in fact, make unsubstantiated claims about the safety and effectiveness of their BHRT products. The overhead is probably quite low for producing, promoting and selling drugs that are not FDA-approved and are made from bulk drug substances (powdered drug) of unknown quality from sometimes questionable sources.”
They continue,
“Proponents of BHRT, those benefiting economically from their sale, maintain that the right of women and their doctors to choose must be protected. This is a perversion of consumerism often put forward by producers of shoddy products. There is a more fundamental right that is being violated by compounding pharmacies: the right to a marketplace free of potentially dangerous untested products promoted for unsubstantiated uses.” [Source]
So what’s the bottom line?
BHT is the alternative that isn’t. It isn’t safer, it isn’t more effective, and it isn’t based on sound or convincing science. Celebrity advocates and anecdotal evidence are easy to find, but the scientific data to support the broad claims of BHT advocates is absent. Without reassurance about risk or benefit, BHT is not an appropriate or safe option for the overwhelming majority of women.
I’m a patient. What should I know?
BHT therapy means more unknowns than HRT. These risks could have serious long-term health consequences. Despite what you may read on the internet or what you are told by your physician or pharmacist, you must assume the risks of BHT are at least equivalent to that of HRT.
Remember that some Health Canada/FDA-approved types of HRT contain bioidentical hormones. By taking commercially-manufactured HRT, (bioidentical or not) you and your physician will have better information about expected benefits and risks of treatment. You can then make an informed decision based on actual scientific data. With HRT, you will have access to products that follow highly rigorous and regulated manufacturing standards. Compounded products, on the other hand, mean a decision based on less scientific evidence and risks that equal or possibly exceed that of HRT. Essentially you’re in a clinical trial of one person: you. Regardless of your decision, any HRT, bioidentical or not, should be prescribed at the lowest possible dose and for the shortest duration possible.
In exceptional situations where commercially-manufactured products are intolerable, or for some reason, inappropriate for managing your menopausal symptoms, compounded BHT may be an acceptable option. If this is the case, choose your pharmacy carefully. Ask about the pharmacist’s experience with compounding BHT. Preparing BHT involves the measurement of very, very small amounts of raw materials, approaching the error limits of most pharmacy scales. Consequently unless the pharmacy consistently prepares large volumes of BHT creams, you are more likely to receive a product that varies from batch to batch. Remember that pharmacies are not required to disclose warnings with BHT. However the FDA has made it clear that these risks are real, and should be considered equivalent to that of HRT. Review the data on the WHI study.
The term “Hormone Consultant” is a undefined title that provides no assurance that someone is a qualified health professional, or is capable of providing evidence-based and science-based information on hormone replacement. [14]
Pharmacists or physicians that recommend saliva tests as part of your evaluation are not providing advice that is supported by science.
Most insurance plans refuse to pay for BHT. You may be required to pay cash for your prescription. The costs can be expensive.
Advice for pharmacists?
It is inappropriate to assume that a lack of data with BHT is evidence of safety. Claims cannot be made that BHT is superior with respect to efficacy or safety until these claims have been demonstrated in randomized controlled trials. Further, claims of reduced breast cancer risk, improved cardiovascular protection, improved adherence to therapy, and fewer adverse effects have not been substantiated and are misleading.
Following the release of the WHI, the FDA required all HRT manufacturers to include the same information about risk and benefit of HRT, unless evidence could be provided to demonstrate a different risk profile. Given the size of the WHI it is reasonable to conclude that this data will not emerge for BHT. There is no comparable evidence to demonstrate either improved efficacy or reduced risk with BHT compared with HRT. Consequently it is appropriate to provide the same risk/benefit information to patients taking BHT.
It is the responsibility of pharmacists to offer evidence-based information to patients who are seeking health information. It is also the pharmacist’s responsibility to protect patients from unnecessary risk. It has been argued that the line of professional ethics is crossed when a practitioner promotes his or her own therapy as a “product” which is not considered the standard of care. [15] Menopausal women are vulnerable to anecdote and misinformation as they seek treatment for what can be very debilitating symptoms. [15] This puts an additional onus on pharmacists to provide ethical, science-based care.
Conclusion
All forms of hormone replacement must be held to the same standard and level of evidence. Given the limitations of data on BHT, and the potential risks, it is doubtful that BHT will ever be considered an accepted, appropriate therapy, or the standard of care, until important questions of safety and efficacy are addressed. Consequently, the onus is on pharmacists and pharmacies that profit from BHT, and the colleges that regulate them, to ensure that patients receive accurate, evidence-based information about this controversial therapy.
Fears and mistrust of HRT are largely unfounded, and propagated in part by advocates for BHT who may not be providing evidence-based information on the facts of HRT and the additional risks of compounded therapies.
The proliferation of compounding pharmacies specializing in BHT has become a largely unmonitored supply chain of untested products, responding to, but also driving demand for, products that are not the standard of care. It is time for the pharmacy profession to reflect on its obligations to patient care and reevaluate the provision of bioidentical hormones.
For More Information
Sasketchewan’s Academic Detailing Program, RxFiles, prepared a summary of clinical data following the WHI events of 2002. While somewhat dated, it provides a good overview of alternatives from a Canadian perspective. Sasketchewan’s drug information service published a good overview of the BHT issues in 2003.
British Columbia’’s Therapeutics Initiative prepared a nice summary of the WHI following the publication of the key clinical data.
Dr. Harriet Hall examined BHT in Skeptic magazine in 2007 and in the Science-Based Medicine blog in 2008.
FDA’s Q&A on compounding provides their perspective on the practice.
Pharmwatch’s take on Bioidentical Hormone Therapy.
References
[1]. Pinkerton JV. Bioidentical Hormones. What you (and your patient) need to know. OBG Management 2009;21(1):43-52.
[2] Health Canada. Drug Product Database (Database on the Internet). Available at: http://www.hc-sc.gc.ca/dhp-mps/prodpharma/databasdon/index-eng.php . Accessed March 10, 2009.
[3] Harvard Women’s Health Watch. “What are Bioidentical Hormones” 2006;13(12):1-3.
[4] Food and Drug Administration. “Bio-Identicals: Sorting Myths from Facts” Available at www.fda.gov/consumer/updates/bioidenticals040808.html. Accessed March 10, 2009.
[5] Schwartz ET, Holtorf K. Hormones in wellness and disease prevention: Common practices, current state of the evidence, and questions for the future. Prim Care Clin Office Pract 2008;35:669-705.
[6] Hortorf K. The bioidentical hormone debate. Are bioidentical hormones (estradiol, estriol, and progesterone) safer or more efficacious than commonly used synthetic versions in hormone replacement therapy? Postgrad Med 2009;121(1):1-13.
[7] Paoletti J. Correcting misconceptions about compounding bioidentical hormones: A review of the literature. Int J Pharmaceutical Compounding 2007;11(4):269-72.
[8] Wepfer S. The science behind bioidentical hormone replacement. Int J Pharmaceutical Compounding 2001;5(6):462-4.
[9] Boothby LA, Doering LA. Bioidentical hormone therapy. a panacea that lacks supportive evidence. Curr Opin Obstet Gynecol 2008;20:400-7.
[10] Sikes CK. Bioidentical hormones for menopausal therapy. Women’s Health 2008;4(2):163-71.
[11] Cirigliano M. Bioidentical hormone therapy: A review of the evidence. J Women’s Health 2007;16(5):600-31.
[12] Boothby LA, Doering PL, Kipersztok S. Bioidentical hormone therapy: a review. Menopause 2004;11(3):356-67.
[13] Eden JA, Hacker NF, Fortune M. Three cases of endometrial cancer associated with”bioidentical” hormone therapy. Med J Aust 2007;187(4):244-5.
[14] MacLennan AH, Sturdee DW. The ‘bioidentical/bioequivalent’ hormone scam. Climacteric 2006;9:1-3.
[15] Rosenthal MS. Ethical problems with bioidentical hormone therapy. Int J Impot Res 2008;20:45-52.
March 14, 2009 at 11:03 pm |
Thanks for posting a comment on my blog and thanks for taking the time to post such a thorough and well-referenced blog post.
There are many things I disagree with you about in this posting and I hope to be able to make my case on each specific item as I have more time to write, but I just want to challenge you on a couple of key points.
With regard to the WHI, just because all-cause mortality did not increase with the CEE/MPA arm doesn’t mean that the treatment arm is safe. The authors of the trial stopped it for a reason. They concluded that “overall health risks exceeded benefits from use of combined estrogen plus progestin for an average 5.2-year follow-up among healthy postmenopausal US women.” JAMA. 2002;288:321-333. Now proponents of conventional HRT are recommending using lower doses for only 1-2 years. Where is the scientific evidence to back that up? And since when did women suffering from menopausal symptoms only have them for 2 years?
Second, I assume you are a pharmacist who dispenses medications. So, next time you are putting your initial on a prescription that is going to a patient, ask yourself, where is the clinical evidence to support that drug’s use. Have you ever dispensed atenolol for hypertension, orlistat for obesity, or donepezil for Alzheimer’s disease? I would estimate that about one-third do one-half of the drugs behind a typical pharmacy counter do not have solid clinical evidence to support its use. I’m not saying that all these drugs should never be used. The existing clinical evidence needs to be weighed against the patient’s specific circumstance and integrated with our knowledge of physiology and pharmacology to make the best choice for the patient. Why else did we go to pharmacy school to learn that stuff?
Anyway, I appreciate your willingness to put your thoughts out there into the blogosphere so we could have this debate. I look forward to more postings.
Peter Koshland, Pharm.D
March 19, 2009 at 9:08 pm |
Hi. Thanks for the comments and feedback.
The current positioning of HRT as reasonable option for short durations is one that does have published clinical evidence to support it. Here is some further information to support that statement.
Most women use HRT for less than 5 years. The risk of breast cancer returns to normal after discontinuation. In the WHI, women who had not used HRT prior to enrolment showed no increase in the risk of breast cancer over the duration of the study. Consequently, the evidence suggests that short-term HRT use (i.e., <5yrs) carries little incremental risk.
Many modifiable and unmodifiable breast cancer risks are similar to that of HRT. For example, failing to exercise regularly is as risky as HRT, with respect to breast cancer. Consequently the incremental risk of hormone replacement (bioidentical or not) needs to be put into this context.
These statements are based on the following clinical practice guidelines:
Menopause and Osteoporosis Update. Journal of Obstetrics and Gynaecology Canada. 31(1): January 2009
as well as
Estrogen and Progestin use in postmenopausal women: July 2008 Position Statement of the North American Menopause Society (PDF).
Regardless of one’s perspective on the evidence supporting short-term use of HRT, I am unaware of any data with compounded BHT that demonstrate the risks are any different. As I noted, the use of compounded products introduces several more risk factors that must be considered without persuasive evidence of additional clinical benefit.
With respect to the level of evidence supporting other prescription drugs, that’s an ad hominem tu quoque argument. The focus of this article was BHT. Perhaps I’ll get to the cholinesterase inhibitors in a future article….thanks for the suggestion!
March 27, 2009 at 4:07 pm |
I joined your blog today and this was the first article that came up. As a female who has underwent treatment for stage 3 breast cancer, I can tell you first hand that the effects of all the chemicals and radiation and surgeries have taken their toll on my body. At age 39 the chemotherapy put me into a post-menapausal state (sort of) which left me feeling fatigued, mental cloudiness, hot flashes (unbearable at times), sleep disturbances, I could go on and on.
I am almost 3 years out since my diagnosis and I do credit my oncologist for saving my life. However, he now only wants to give me antidepressents and anti-inflamatory drugs to help with the serious fatigue that I experience. I am so sick of taking pills!
A few months ago I attended a symposium on nutrition and it’s effects on our bodies. This led me down the path to discover how important hormones are for our bodies and how powerful their effects are.
I just finished blood test and saliva testing for hormone levels and the saliva test were very similar to the blood test results that my oncologist ordered. I have been reading and investigating these issues (BHT and other hormone replacements) for a couple of months and talking to others who have used BHT.
If you look at the articles that are against saliva testing they are all funded by pharmaceutical companies (100%) compared to independent studies that found saliva testing to be useful and accurate (92%). I now know my cortisol and progesterone levels are seriously low and my estrogen levels are very high. This is consistent with estrogen dominance – which I now believe to be a large factor to my getting breast cancer in the first place.
I am looking forward to Peter K. disputing each point that you make with scientific evidence, but I will tell you first hand that when given the choice of Prometrium or a compounded progesterone, I will choose the compounded progesterone that is specific to my needs. One point to make is that a good compounding pharmacist will have samples tested by an independent lab for potency and accuracy.
I know many women (and their husbands) who would NOT be happy and healthy if it were not for them taking BHT. Tell me why there are no scientific studies on the BHT??? Because the pharmaceutical companies can NOT make any money on these products.
April 25, 2009 at 6:58 am |
Thanks for your comments. I suppose it’s easy and convenient to blame “Big Pharma” for suppressing bioidentical hormones. But rather than trot out conspiracy theories, let’s keep the discussion focused on the science. If you have substantive evidence that refutes the science, please post it here for further discussion. I am particularly interested in seeing the results of your systematic review of the funding sources of articles that examine saliva testing. Please feel free to post your search strategy, citations, and funding sources here.
July 6, 2009 at 10:15 am
You noted that there is no science on this “bio-identical” matter yet, so maybe that is why “no substantive evidence exists”. Where is you advocacy of finding answers to severe problems faced by menopausal women. You are stoked with reasons why it does not work. Wonder why such passion to debunk this?
Here is some form of evidence for you…women (including myself) feel incredibly better, are once again able to compete well in the professional workplace, be a better spouse, mother, daughter, friend — living life again.
I find that your comments and tone lack objectivity of a scientist. Furthermore, you as a man, lack the personal basis to tell women who have been helped that they are being dupped. Your position is lacking in substantive evidence as well.
April 18, 2009 at 1:56 pm |
Unless you are a woman and have actually tried some of these HRTs,then I would suggest that you think again about the benefits of bio-identical hormones. Prescriptions are not a one-size fits all for individuals. I personally have tried many products that contain estradiol, i.e. vagifem, evamist, estragel and found that I still had symptoms of hot flashes, trouble sleeping, and aching/tenderness in my abdomen. Once I tried biest cream – bio-identical hormones of 1.25 mg twice daily, my symptoms immediately improved and I am sleeping all night with increased sexual desire. Please do not generalize the benefits of natural hormones. I don’t care if the FDA approves them or not, why do they need to if they are natural.
April 25, 2009 at 7:01 am |
For health professionals interested in the WHI, I refer you to the following:
http://journals.lww.com/journalppo/Fulltext/2009/04000/Hormone_Replacement_Therapy__Real_Concerns_and.1.aspx
Here is the abstract:
April 26, 2009 at 7:08 am |
Great blog!
I know a doctor (he actually does have MD, but practices woo) who’s managed to make heaps of money by diagnosing just about every woman entering his posh clinic with ‘hormone imblalance’ and prescribing this garbage. This is a really great and informative post, and I’m adding you to my blogroll.
April 26, 2009 at 7:08 am |
[...] blogs in my blogroll with similar names (which are also always worth a look). Scott’s post on bioidentical hormones is a favorite of mine – a fellow family physician with an ‘alternative’ bent living in [...]
April 26, 2009 at 9:39 am |
Here’s another study you might be interested in: Bleeding profiles and effects on the endometrium for women using a novel combination of transdermal oestradiol and natural progesterone cream as part of a continuous combined hormone replacement regime. (BJOG, 2005).
The authors found that progesterone cream did not produce the effects on the uterine lining that naturally produced progesterone does. This study found the same thing, with the added bonus that the authors tested salivary progesterone levels, and found them to be “so variable as to be considered completely unreliable”.
So in at least one sense, that of endometrial composition, natural progesterone cream is NOT bioidentical and does not produce the same effects as naturally produced progesterone. Given that endometrial transformation and support is the primary function of progesterone in situ, it’s reasonable to question whether natural progesterone cream has any of the other purported effects.
May 15, 2009 at 9:28 am |
Congratulations on such a lucid and comprehensive report on these BHT “alternatives”. I have now been going through the menopause for SEVEN years and having recently been scared by multiple articles on, it now would appear, the ever increasing risk of HRT, I reluctantly stopped taking it. Three separate physicians have verified that I am one of those poor unfortunates suffering “severe syptoms” and I definitely fall into your category of “Menopausal women vulnerable to anecdote and misinformation as they seek treatment for what can be very debilitating symptoms”. So I thank you for your information on BHT. However, I am struggling to maintain a semblance of my true self – sleep, work, socialising is all a nightmare. Surely with all the advances we have made in modern medicine, there has to be an alternative to HRT?? To what degree do the risks associated with HRT increase with duration (7 yrs in my case)? I am in my third month without HRT – NONE of the known homeopathic options have worked for me and I’m just not sure how long I can continue in this way. If there was a specific “stop” point, it might be easier to bear, but my physician says he has one patient of 63 who is still suffering!!! (I am 52!) So if ANYONE out there knows anything to enlighten me – please let me know
) !
May 15, 2009 at 10:36 pm |
Jane, thanks for sharing your story. As a regular reader of this blog and registered pharmacist, I wish to answer some of your concerns. However, understand that any information found on forums or websites is not a substitute to good communication between you and your GP or specialist.
For starters, menopause can vary greatly with regards to symptoms, severity and duration. For example, some women may experience hot flashes for months to a few years after start of menopause (around 51 years or age), while others will suffer less from hot flashes but more vaginal-bladder problems, mood (ie: irritable, sleep troubles, depression), or sexual problems due to complications of low estrogen. Average duration is 6 months to 2 years, while some studies show a proportion or women can experience some extent of symptoms for as long as 10 years.
Scott did partly adress your concern of HRT risk in this post. However, your physician or community pharmacist can explain that the risk is low and is dependant on which HRT combination you were taking (also, for how long).
Jane quote -
“Surely with all the advances we have made in modern
medicine, there has to be an alternative to HRT??”
As for other treatments, there are various options available. however, they are best determined by what type of symptoms you are experiencing (ie: hot flashed, bladder-vaginal or mood problems?) and by reviewing benefit vs. risk of each treatment by you and your physician. If you think you may need a referal to a specialist, feel free to ask. They are often times more up to date with recent research than your GP.
Questions to ask your GP or specialist:
-Are my symptoms (ie: sleep,work, socializing) related to menopause or might be related to something else?
-Of all the medications I’ve tried, are there others that you think I could try?
-Would you recommend certain lifestyle changes that may be worthwile?
If I may suggest further reading, try a reputable health advocate society like Mayo Clinic(1), or the Society of Ob-Gyn of Canada supported website (2) or the UK’s NHS (3).
1)http://www.mayoclinic.com/health/hormone-therapy/WO00046
2)http://www.menopauseandu.ca/index_e.aspx
3)http://www.nhs.uk/Conditions/Menopause/Pages/Treatment.aspx
May 15, 2009 at 11:26 pm |
[...] Bioidentical hormones: estrogen, testosterone, progesterone (See my previous analysis of the pseuodoscience of bioidentical hormones.) [...]
May 16, 2009 at 9:31 am |
Hi Nicolas! Many thanks for the time taken – it is much appreciated. I am generally very unhappy with my physician, but the system is such in the UK that it is very hard to switch. I will follow your advice and try to get a referral. My main problem is just being hot and flustered virtually all the time – the sweat just pours off me – which can be very embarrassing in some social situations, and which prevents me sleeping through the night. The flashes can be so bad that they are akin to panic attacks. My brain often feels like cotton wool and I have trouble focusing on matters or concentrating. I am suffering from depression – for which I am now receiving treatment – exacerbated I feel due to my constant state of “fluster” and the weight I gained as soon as I went on HRT (around 15 lbs – which has failed to come back off again!). Finding the motivation to exercise to lose the weight is extremely hard, especially when the sweat’s already pouring off me without lifting a finger! I’m also extremely depressed because it has lasted so long, I have now been suffering in this way for seven years and it all just seems so endless …
May 16, 2009 at 7:17 pm |
Respect for your very detailed attack on bioidenticals but as a medical journalist whose done some research into them I’d like to make a few points in reply. The first is that, like many such attacks, it glosses over just how striking is the chemical difference between the HRT versions of oestrogen and progesterone and the bioidentical ones. Can’t reproduce it here but there are some very accessible diagrams on the web.
What they show is that that if you compare the structure of bioidentical estradiol with testosterone (the hormones responsible for differentiating males and females) they are remarkably similar, far more similar than the structures of estradiol and premarin (a major HRT oestrogen). With hormones small differences can have large effects,
Even more striking is the difference between progestin and progesterone; it is also worth noting that while progesterone is present in large quantities during pregnancy that progestin is contraindicated during pregnancy as it can induce miscarriages.
A second point is that it is frequently repeated that there are no proper trials comparing HRT and bioidenticals however it is not that simple and the French experience in this respect is interesting. They are much more keen than the US and the UK on using both progestins and progesterone (the version they use is a micronized progesterone that has actually been licensed in the USA for some time (don’t have the details to hand) and and has recently become available in the UK where it is known as Utrogestan.)
A considerable amount of research into progesterone has been done by Dr Michael Schumacher of the Kremlin-Bicêtre hospital in Paris who cites a range of studies – much of it animal- showing that progesterone has beneficial effects on the breast tissue, on blood vessel function and in strengthening bone. Many of the benefits of progesterone, he says comes from the fact that while oestrogen stimulates cells, progesterone calms them down ( Michael Schumacher, Rachida Guennoun, Abdel Ghoumari et al “Novel perspectives for progesterone in HRT, with special reference to the nervous system” Endocr Rev. 2007 Jun;28(4):387-439)
Drawing on this work Schumacher believes that progesterone might lower the risk for dementia since oestrogen and progesterone combined have been shown to have a neuroprotective effect, unlike progestins which can reduce this protective effect.
He also suggests that progesterone may protect against breast cancer and this is supported by a trial that is almost unknown in US and UK comparing the effects of progesterone and oestrogen. It’s a big ongoing French study of 54,548 menopausal women comparing what happens to those who take progesterone in their HRT with those who get progestin. The latest report has found that after eight years while those on progestins have a raised risk of breast cancer, those on progesterone don’t. (Fournier et al “Unequal risks for breast cancer associated with different hormone replacement therapies: results from the (E.sib.3) cohort study” Breast Cancer Res Treat 2008: 107(1): 103-11) It’s not a controlled double blind etc but it’s far from negligible.
And for trial evidence that isn’t all. In the USA Dr Schumacher’s claim that progesterone can protect blood vessels and cut down the risk of strokes has just been supported in two small trials at Texas University. Researchers gave a progesterone cream or a placebo to 30 post-menopausal women for eight weeks. Not only did the cream improve their symptoms but there was no rise in various markers in the blood that make strokes more likely, such as inflammation and a tendency to form clots. Kenna Stephenson, Pierre Neuenschwander et al Transdermal progesterone: Effects on Menopausal Symptoms and on Thrombotic, Anticoagulant and inflammatory factors in post menopausal women International Journal of Pharmaceutical Compounding Vol 12 No 4 July/August 2008 (not on Pubmed but is on Embase, Emnursing, Compendex, Geobase, Scopus)
The second trial found a similar beneficial result from giving a cocktail of individualised bio-identical hormones to 75 patients and compared the results regular HRT. The women were tested after a year. The results were reported at the American Heart Association Scientific Sessions 2008, New Orleans, Nov. 8-12, 2008 by Kenna Stephenson, MD, department of family medicine, University of Texas Health Science Center, Tyler.
Now evidence like this doesn’t completely prove the case for BI and everyone agrees there needs to be more research. So will the big trials that doctors are demanding now be run? The depressing truth is that it’s unlikely without strong consumer pressure. Calls for such research are not new.
Thirty years ago an editorial in the Journal of the American Medical Association asked how long clinicians will to wait for proper clinical trials on the benefits of estriol, the weakest of the oestrogens. “Enough evidence has been accumulated,” it said “that we may say that it is safer than Estrone and Estradiol.” The trials have still not been done. (Follingstad A. Estriol the forgotten hormone? JAMA, 1978;239:29-30.)
What I’m still surprised about in these debates (firefights?) over the benefits of pharmaceutical vs (I use my terms carefully here) non patentable treatments is the assumption of scientific superiority on the pharmaceutical side. You must know that a cavalier attitude to evidence has been a hallmark of drug company marketing, frequently with fatal results. In light of the repeated assertions that there is no proper clinical trial evidence for bioidenticals it is worth remembering that until the WHI study there was none for HRT either – lots of observational stuff but no long term trial and the pills were prescribed in their millions.
But the fiddling was far more specific. Recently a particularly striking example fudging figures on HRT came to light as a result of investigations by Senator Grassley into “ghostwriting”. A report in the New York Times showed how Wyeth Pharmaceuticals and a medical writing firm produced ghostwritten journal articles–all signed by prominent gynecologists—that were designed to deceive doctors about the safety of Prempro. (THE NEW YORK TIMES December 12, 2008
“Drug Maker Said to Pay Ghostwriters for Journal Articles”)
One of these was published in The American Journal of Obstetrics and Gynecology in May 2003 – a year after the WHI study had found the increased the risk of breast cancer – saying that there was “no definitive evidence” that progestins cause breast cancer, adding that hormone users had a better chance of surviving cancer.
Finally although the anti bioidentical camp keep on playing down the HRT risks there is growing evidence that a falling incidence of breast cancer among postmenopausal women in the United Kingdom may be linked to lesser use of hormone replacement therapy (HRT). (See BMJ 2009;338:b791)
Jerome Burne
June 20, 2009 at 3:58 pm |
[...] principles, naturopaths believe they are primary care providers and want to be able to offer dubious therapies like bioidentical hormones. Oregon is where Ontario naturopaths want to be – with a long list of “real [...]
July 7, 2009 at 3:24 am |
[...] and soy rather than horse urine. As Scott of Science-Based Pharmacy puts it in his discussion of bio-identical hormones: Bioidentical is often used synonymously with the term “natural”, inferring that bioidentical, [...]
July 7, 2009 at 12:52 pm |
[...] we noticed that Burne had left a long comment, recommending his own research, on a post about The Alternative that Isn’t: Bioidentical Hormones at Science-Based Pharmacy. [...]
August 9, 2009 at 4:02 pm |
[...] be talking about pseudoscience in the pharmacy, bioidentical hormones, naturopathy, pharmacists that refuse to fill prescriptions for religious/moral reasons, [...]
July 6, 2009 at 11:16 am |
Thanks for your comments. I do no dispute that you feel better on hormones. Hormone replacement is much more effective than any other treatment for the relief of menopausal symptoms. The point of the article is the relative risk and benefit of pharmacy-compounded products, compared with conventional hormone therapy. I am unclear about your statement that the article is lacking in substantive evidence – the article is referenced, and the citations are at the bottom of the article. If you have data to dispute any statements, please feel free to post it.