In this article, originally published by RACGP, Dr Karen Magraith and I share insights about bioidentical hormone therapy.
Two experts answer common questions on compounding bioidentical hormone therapy for menopause.
In the wake of recent warnings about bioidentical hormone therapy, RACGP Quality Care committee member Dr Magdalena Simonis and Dr Karen Magraith from the Australian Menopause Society (AMS) answer questions about a controversial therapy sometimes offered as an alternative to traditional menopausal hormone replacement therapy (MHT).
What is compounded bioidentical hormone therapy?
Dr Karen Magraith:
This term refers to hormone treatments that are compounded products which are marketed as hormones that are identical to those produced by the body. The production of these products is not subject to the regulatory conditions of approved pharmaceutical products.
The hormones are often given as creams, troches or pessaries and are promoted as being ‘natural’. Women are attracted to the idea of something that is natural and interpret it as being therefore safe. The preparations often contain a combination of oestrogens, progesterone, testosterone and other hormones.
It is unclear how many of these prescriptions are written or what the preparations actually contain.
This needs to be distinguished from the prescription of approved pharmaceutical products such as oestradiol and progesterone. These Therapeutic Goods Administration-approved [TGA] products are hormones that are known as ‘body identical’, i.e. they are the same as hormones produced by the human ovary, and are available in Australia. Other approved pharmaceutical options are also available. Together these products are known as [menopausal hormone therapy] MHT.
Dr Magdalena Simonis:
The term ‘bioidentical’ has been defined by the Endocrine Society as ‘compounds that have exactly the same chemical and molecular structure as hormones that are produced in the human body’. The term ‘body-identical’ is used here interchangeably. Some prescribed MHT is ‘bioidentical’ and some is not.
The term ‘bioidentical’ can be misleading because it has been used to differentiate between MHT that is considered ‘natural,’ which patients may assume to mean ‘safer’ than traditionally prescribed hormone therapy (HT), which it is not.
A more comprehensive term is ‘body identical’, which ascribes the appropriate meaning being, ‘identical to the hormones produced by the body’. There are approved body-identical hormones that can be prescribed and unapproved body-identical hormones. Doctors should understand the difference between these and be able to advise their patients accordingly.
The gross misconception amongst the public is that MHT is ‘synthetic’ or unnatural and bioidentical hormones are ‘natural.’ In truth, both are synthesised in a laboratory – but only MHT is strictly regulated for quality and safety.
What are the concerns about the use of bioidentical hormone therapy?
Concerns around ‘bioidentical’ hormone therapy include the following issues:
- the safety of production, which encompasses the compounding process, the quality, purity and safety of the products used
- the lack of regulation around production of the compounds
- misinformation amongst women that ‘bioidentical’ is synonymous with ‘safe’
- the unnecessary cost
- the lack of reliability of salivary testing to titrate doses and formulations
- the unscientific basis around the mix of chemical compounds used for conditions other than menopausal symptoms
- the lack of large-scale studies and supporting peer-reviewed research
- the estimation of compounded formulation doses that are bioequivalent to conventional HT is difficult.
Compounded bioidentical hormone therapy is not produced under the usual strict pharmaceutical regulations. More often, they are prepared by pharmacists referred to as ‘compounding pharmacists’, in varying concentrations and proportions, which may vary from week to week, month to month based upon levels measured through expensive salivary fluid tests, as specified by the healthcare provider, who is usually a GP, or naturopath.
Compounding can allow for a variety of delivery mechanisms to be provided in a form that is better tolerated by the patient such as topical gels, creams, soluble tablets, powder, troches, [and] vaginal creams; however, the compounded hormones are not required to undergo rigorous pharmaceutical and TGA testing and there can be large variability in the concentrations of active and inactive ingredients, hence their efficacy is variable. There is evidence to suggest that levels of progesterone prescribed might not be sufficient to prevent endometrial hyperplasia, putting women at increased risk of endometrial carcinoma.
The ‘bioidentical’ hormone therapy is described as being more similar to naturally occurring hormones than synthetic preparations and can include a combination of a variety of oestrogens such as oestriol, ‘biest’ (oestradiol and oestriol) and ‘triest’ (oestradiol, oestrone, oestriol), in combination with progesterone and other hormone compounds which may include DHEA, pregnenolone (a precursor to cortisol), testosterone, thyroxine, melatonin and growth hormone. These other compounds may be required for conditions other than menopausal symptoms and can cause undesirable side effects.
Australian Menopause Society members are concerned for a number of reasons.
These compounded products do not have safety data and the appropriate dose of these products is unknown. In particular, it is not known if the doses of progesterone used are sufficient to provide endometrial protection. Inadequate progesterone dosing can lead to endometrial dysplasia and cancer. It is also unknown whether the products maintain bone density.
Prescribing often occurs by doctors who are not the patient’s usual GP, making it more difficult to perform a thorough assessment. This is a particular risk with telephone or online consultations. This practice can also lead to fragmentation of care.
Some women believe that by taking bioidentical hormones they are taking a natural or herbal product, and avoiding potential risks from conventional MHT products. Women often have expensive and unproven blood or saliva testing to adjust doses.
Women often spend large sums of money on compounded hormone treatments when they could be receiving appropriate MHT from their usual GP for a lower cost.
There is misunderstanding in the community about the risks of conventional MHT and about what compounded bioidentical hormones are. This makes some women vulnerable to expensive, unproven, and potentially dangerous treatments.
Bioidentical hormones often do relieve women’s symptoms because they contain real hormones. This is different to other ‘alternative’ treatments that are sometimes thought of as being expensive placebos. However, having real hormones in the wrong balance also raises the potential for harm.
What caused the increase in bioidentical hormone use?
The dramatic increase in interest for bioidentical hormone treatment followed the findings of the Women’s Health Initiative study (WHI) in 2002. The key findings of this study indicated that use of combined conjugated equine oestrogen therapy with medroxyprogesterone acetate therapy for more than eight years in postmenopausal women, was associated with an increased risk of breast cancer, heart disease, stroke and thromboembolic events.
Within three months of the release of these findings there was a 63% reduction in prescribed HRT in the USA and the Australian reaction mirrored this. Women sought alternative treatments to manage the symptoms of menopause and lost trust in the FDA-approved forms of therapy.
Likewise, their treating GPs were equally concerned about exposing their patients to further risks of disease and found there was little available information at the time to support them in guiding their patients. The media sensationalised the findings ahead of the medical profession being properly informed so that a lot of effort on the part of GPs especially, was required to reassure or educate their patients around the WHI (2002) findings.
Several years lapsed before the findings of the WHI (2002) study were put into perspective, giving GPs the comfort to prescribe HRT for their patients again.
It became increasingly difficult to assure them that the risks for 5–8 years of HRT was not significantly increased, and that this was often all that was required to help women through the perimenopause and menopause.
It was during this time that ‘bioidentical’ hormones were falsely marketed as being ‘safer’ than MHT traditionally prescribed, giving rise to an unregulated, multi-billion dollar industry.
There are concerns by the Australasian Menopause Society that women who are prescribed bioidentical HT believe it to be safer, with fewer side effects, lower risks of cancer (breast and endometrium), ischaemic heart disease (IHD), thromboembolic events and stroke, such as those associated with traditional forms of hormone replacement therapy.
A consequence of this, is that regular breast screening, chronic disease screens and bone density testing might be neglected and they might be prescribed these for much longer than the recommended maximum period of eight years.
It is now widely agreed by menopause experts that the risks of MHT reported in the WHI trial were misunderstood and overstated. For example, the risk of breast cancer attributable to the combined oestrogen plus progestogen treatment in the study amounts to less than one extra case per thousand women per year compared with placebo.
In addition, there [are] now options which are likely to carry a lower risk than the formulations that were used in the WHI trial, including the availability of micronised progesterone which can be used instead of synthetic progestogens.
Unfortunately the belief that MHT is risky has persisted and many GPs and women still perceive MHT to be unsafe. In fact, the International Menopause Society states that the risks are very low and the benefits greater when initiated under the age of 60 to symptomatic women who have no contraindications.
Special mention should be given to women with premature ovarian insufficiency, who need thorough assessment and support. For these women MHT is advised until at least the age of 51 in the absence of contraindications.
Dr Karen Magraith is a board member of the Australian Menopause Society.
Why are some GPs continuing to prescribe bioidentical hormones instead of MHT?
The flawed media representation of the WHI findings in 2002 scared patients, and GPs had to respond quickly to their concerns.
GPs were inundated with concerned patients seeking alternative treatments and at that time, the only over-the-counter, non-hormonal medication that had received some acceptance by the medical profession was the use of Black Cohosh, for hot flushes. Women sought support for the sleep deprivation and mood disturbance, resulting in many requiring oral antidepressant therapy to help them cope with their symptoms.
During this same time, the opportunity for another market arose which included unregulated treatments branded as ‘safe’ and ‘natural’. There was a tendency for women to see naturopaths and homeopaths for their menopausal symptoms and through this avenue, received a lot of misinformation which was fed back to their GPs.
It was a double bind situation where GPs were reluctant to prescribe MHT due to the risk of being sued for cancer years down the track, and patients feared traditional HT or had lost trust in the GP also. We were all made to look like we were backtracking on the promise of relative safety we had given our patients.
In the USA, the FDA has issued statements warning against the practice of prescribing non-FDA approved drugs. By contrast, Australia’s TGA does not classify bioidentical compounding hormones as pharmaceuticals, which would require strict regulation.
Their position is that medicines that are extemporaneously compounded by a pharmacist for individual patient use are not required to be on the Australian Register of Therapeutic Goods (ARTG) and therefore, need not be assessed for safety and efficacy by them.
Without a clear statement from the TGA that classifies the bioidentical compounded hormones as potentially equivalent in activity to other pharmaceutical drugs – thus requiring rigorous controls in testing for purity and safety – this will remain open for misuse.
The TGA considers the process of compounding bioidentical formulations to be a Pharmaceutical Board of Australia (PBA) matter. The Pharmacy Guild of Australia (PGA) along with the PBA state that a pharmacist should ‘compound a medicine only when an appropriate commercial product is unavailable or unsuitable’.
The standards for compounding vary and there is no mandatory training, supervision nor quality assurance. This is very concerning as the quality of production, concentration of components and the mixing agents can vary enormously from pharmacy to pharmacy and even from day to day with the same compounding pharmacist.
I can’t say why GPs are prescribing compounded bioidenticals but I would remind them that the AMS does not endorse the prescribing. The FDA and international menopause bodies also recommend against prescribing. Suitable approved preparations are available for GPs to prescribe.
AMS would like to see an increase in education regarding menopause for medical students, GP registrars and GPs.
What advice should GPs give if a woman asks about the best way forward?
A woman who comes to her GP asking for treatment of her menopausal symptoms should be offered MHT, after evaluation of her symptoms and the impact they are having on her life emotionally, professionally, socially and physically. A thorough history should be taken to assess her risk profile for breast cancer, stroke, IHD, osteoporosis and the appropriate screens ordered.
Following this, where conservative treatment and lifestyle modifications have failed, or when she just simply wants something to help her as soon as possible, MHT can be offered.
If there are urogenital symptoms of the menopause alone, this can be treated topically. Where there are systemic symptoms such as hot flushes, sleep deprivation, mood changes, the broad range of options can be discussed with her regarding her choice of transdermal patches or gels, versus oral tablets and transvaginal therapy.
The GP can direct the woman to the Australian Menopause Society to find a doctor with the appropriate skills in managing her and maintaining adequate surveillance of her symptoms and ongoing screening.
Women presenting with symptoms around perimenopause or menopause should be assessed thoroughly. This should include an assessment of her symptoms, general health and risk factors. AMS provides guidance on appropriate assessment.
Focusing on the woman’s main concerns helps GPs to understand what she is seeking and to respond appropriately. Most symptomatic women can be offered conventional MHT.
For women who are seeking bioidentical hormone therapy, this can be provided by prescribing ‘body identical’ oestradiol and micronised progesterone. Using this combination has potential advantages over some other forms of MHT in terms of risk profile.
The treatment of menopausal women, including the prescription of MHT, should be within the realm of all GPs and can be seen as part of mainstream general practice. GPs are accustomed to discussing potential benefits and risks of new treatments with patients, and MHT should be no exception to this.
Where should GPs go for more information?
Dr Magraith has recently published an article on making choices at menopause in the Australian Journal of General Practice.
Originally published: racgp.org.au/newsgp/clinical/what-should-gps-know-about-compounded-bioidentical
Magdalena is the President of the AFMW (2020-) and former President of VMWS (2013 & 2017-2020), National Coordinator AFMW, MWIA Scientific and Research Subcommittee co-Chair, MWIA Mentoring and Leadership, Special Interest Group, Chair
Magdalena’s deep engagements with the RACGP over many years includes chair of Women in General Practice, is currently on the RACGP Expert Committee Quality Care, prior to that on RACGP eHealth Expert Committee. She is a regular media spokesperson on numerous health issues, being interviewed most weeks by mainstream and medical media. Magdalena has represented the RACGP at senate enquiries and has worked on several National Health Framework reviews.
Both an RACGP examiner and University examiner she supervises medical students and undertakes general practice research. Roles outside of RACGP include the Strategy and Policy Committee for Breast Cancer Network Australia, Board Director of Women’s Health Victoria and Chair of their Strategy and Policy subcommittee and the AMA Victoria GP Network Committee.
Magdalena has presented at the United Nations as part of the Australian Assembly and was recently appointed the Australian representative to the World Health Organisation, World Assembly on COVID 19, by the Medical Women’s International Association (MWIA).