By MacLennan, Alastair H; Sturdee, David W
So-called ‘bioidentical or bioequivalent hormones’ are increasingly being sold direct to women on the internet or through laboratories and compounding chemists, who encourage patients to obtain prescriptions for these unregistered and unproven concoctions from their doctor. Gullible doctors are often writing prescriptions dictated by outside agencies that have purportedly assessed the woman’s hormonal needs through salivary hormone testing. Women are being falsely informed on multiple internet sites or through media advertisements in various ways that ‘Bioidentical hormone therapy has all of the good effects of HRT with none of the severe side- effects that have caused so many women looking for menopause relief to steer away from traditionally administered HRT.’ Most sites start with fear tactics and may falsely represent the true risks of pharmaceutical HRT and then state or infer that their pharmacy- mixed hormones have similar or greater benefits, with no risk or no mention of risk. Quite correctly, they say that hormone therapies are best tailored to the individual and her needs, but the pseudo science is that they claim that a woman’s clinical need can be calculated from her saliva.
In truth, there is no scientific evidence to back claims for ‘bioidentical hormones’ that they have any advantage over conventional therapies, but there is evidence that they may sometimes be dangerous1. So-called ‘bioidentical’ hormones are claimed to be synthesized from many of the same sources as traditional HRT, e.g. yams. The hormone made by the ‘bioidentical’ manufacturer is often claimed to be ‘natural’ and, in advertisements, it is inferred that the identical estradiol, produced by the regulated pharmaceutical industry from the same yam source, is somehow different and not natural. Great play is often made of pharmaceutical estrogens produced from non-vegetable sources, e.g. equine estrogens, but there is little mention that these estrogens are mostly converted in the human into human estrogens. It should be clearly stated that there are no published peer-reviewed data to show that a single or multiple salivary hormone assays can accurately reflect the hormonal status or needs of a woman and, in particular, there has been no validation that they can be used to titrate hormone regimens to give an appropriate hormonal response. It is not been shown that hormonal blood levels are useful in adjusting hormonal therapies, and salivary levels also have not been correlated with clinical response. Most experienced clinicians realize that hormone regimens are best tailored by the clinical response and not by biochemistry reports.
The ‘bioidentical’ hormonal mixtures are compounded in buccal troches or transdermal creams and may contain estrogens (estrone, estradiol and estriol), progesterone, testosterone, dehydroepiandrosterone (DHEA), thyroxine, growth hormone and melatonin. Purveyors of these hormones use loopholes in some countries’ therapeutic goods regulations, where these hormones are either considered as complementary medicines (which are often poorly regulated) or where there are regulations that allow the importation of drugs that are not available in that country but are needed for a specific patient. In reality, the hormones are imported by compounding pharmacists before any patients are identified and, through various forms of advertising, women and doctors are attracted. Financial incentives are sometimes offered to doctors to prescribe the mixtures and to use laboratories, which claim without validation that they can effectively measure salivary hormones and thereby recommend the precise mixtures of hormones to be compounded to give the desired clinical effect.
The ‘bioidentica’ salesmen play on recent media hype about registered menopausal hormone therapies and the illusion that their hormones are somehow more ‘natural’ and therefore somehow safer than those synthesized by a pharmaceutical company. In reality, unlike the strict requirements for registered pharmaceutical products, the bioidentical products can be synthesized and imported without regulatory quality control evidence of purity, dosage, contamination, bioavailability, etc. They are compounded with other hormones and ingredients in local pharmacies without safety data concerning these combinations and doses and without adequate pharmacy audits of the compounding process. They are sold without evidence of the pharmacokinetics, clinical effect, sideeffects and drug interactions of these particular hormonal regimens. Some of the individual hormones used such as DHEA have not been approved by therapeutic regulatory authorities and have no quality data to justify their clinical use. In 2001, the FDA analyzed a variety of 29 product samples from 12 compounding pharmacies and found that 34% of them failed one or more standard quality tests2.
Wren and colleagues have conducted one of very few pharmacokinetic studies of bioidentical hormones delivered in a buccal troche and assessed both plasma and salivary levels, with the conclusion that salivary levels were highly variable and their accuracy and value were uncertain for therapeutic monitoring of hormonal therapy3. Wren and his colleagues also conducted a double- blind, randomized, controlled trial of transdermal progesterone cream, finding no clinical beneficial effect. Of greater concern, these authors found that this progesterone regimen had no measurable effect on the endometrium and thus would not suppress estrogen- induced endometrial proliferation4. There have been anecdotal reports of endometrial cancers following the use of bioidentical hormonal regimens containing ‘natural’ estrogens and progesterone. Thus, there is great concern that progesterone given by buccal or transdermal routes, in conjunction with estrogen, is not proven to suppress the risk of endometrial cancer induced by estrogen therapy. If the estrogens used in ‘bioidentical’ mixtures are the same and can reach bioequivalent serum levels, they are likely to have the same benefits as registered estrogens. However, they will also have the same risks. If the opposing progesterone used does not have a protective endometrial effect, it will have greater risks than conventional combined HRT.
The cost of the unproven ‘bioidentical hormones’ is usually several times greater than traditional menopausal hormone therapies and the patient often has to pay dearly for the salivary tests. Both the patient and her doctor may receive results of these assays from ‘hormone consultants’, whose qualifications are unknown, who have not seen the patient, and who give unvalidated interpretations of the results that they reflect abnormal adrenal, ovarian and/or thyroid function. In examples of these reports that we have seen, the ‘hormonal consultant’ advocates the precise hormonal mixtures and doses that the patient should obtain and the doctor should prescribe. This has huge medicolegal implications for the prescriber who takes the responsibility for the quality, risks and evidence for the use of this unregistered complementary and alternative therapy. In a recent Climacteric Editorial, Breen outlined the ethical responsibilities for those advocating and prescribing complementary medicines . The prescriber must inform the patient when a therapy is unproven, the patient must be fully informed of any risks associated with such therapy, access to proven therapies should not be denied, a second medical opinion should be offered if there are potential risks to an unproven and unconventional therapy, and doctors should not gain financially from the sale of these products.
Medical negligence could be claimed:
* If you were unaware of the published risks of the hormones in your prescription;
* If you have not fully informed your patient of these risks;
* If you were unaware of known drug interactions for these products;
* If you were unsure of the appropriate hormonal mixtures and doses you prescribed;
* If there is no supporting peer-reviewed academic data for your therapeutic regimen;
* If you had given the impression to the patient that ‘bioidentical hormones’ were safe.
There is some doubt that medical indemnity agencies will indemnify doctors if they prescribe unproven complementary products, especially if they have escaped any scrutiny by the relevant national therapeutic regulatory agency. In Australia, the Australasian Menopause Society wrote to the medical indemnity agencies in Australia and could not obtain any clear assurance that their members would be covered for the prescription of such products. The four agencies that replied had many caveats about the adequacy of evidence for the product and the extent that the patient was informed about its proven risks and benefits, and would not guarantee cover. Therefore, the prescriber may be at personal financial risk if litigation ensued because an adverse event, e.g. thromboembolism, was claimed to have been precipitated by ‘bioidentical’ therapy. In some countries, a doctor must be fully indemnified to be registered to practice medicine. So, they may also risk their medical registration. One wonders why prescribers of bioidentical hormones take such risks!
In Australia and the USA, there has been a recent proliferation of compounding chemists who have taken advantage ofpostmenopausal women’s need for and anxiety about conventional HRT and the loopholes in current legislation in these countries. These compounding pharmacies are now manufacturing ‘bioidentical’ hormonal mixtures and delivery systems in such proportions that they have effectively become a large, inadequately regulated pharmaceutical industry. It is time for the international drug regulatory authorities to regulate this industry, which is based on false promise, pseudo science and pecuniary interest without responsibility for the interests and health of the consumer.
1. Boothby LA, Doering PL, Kipersztok S. Bioidentical hormone therapy: a review. Menopause 2004;11:356-67
2. Beasley D. Use of “bioidentical” female hormones questioned. Reuters Health Information, Oct 31, 2005
3. Wren BG, Day RO, McLachlan AJ, Williams KM. Pharmacokinetics of estradiol, progesterone, testosterone and dehydroepiandrosterone after transbuccal administration to postmenopausal women. Climacteric 2003;6:104-11
4. Wren BG, Champion SM, Willets K, et al. Transdermal progesterone and its effects on vasomotor symptoms, blood lipid levels, bone metabolic markers, mood, and quality of life for postmenopausal women. Menopause 2003;10:13-8
5. Breen KJ. Ethical issues in the use of complementary medicines. Climacteric 2003;6:268-72
Copyright CRC Press Feb 2006