Bio-identical HRTs - are they better, do they have to be expensive?
Lately I have been encountering numerous patients who are spending a lot of money each month on a variety of compounded hormone replacement therapies (HRT). Their principle motivation is universally to either avoid perceived risks attached to pharmaceutical products or alternatively to have access to a more natural product. This is a complex area...and apologies that the rest of this blog is far from a light read. If there is one thing that I would say to summarise my thoughts on the matter:
"Women do not have to spend a fortune getting scripts filled at compounding pharmacies to gain the benefit of safer HRT".
A common clinical scenario that all gynaecologists, and general practitioners for that matter, encounter is the question of how best to provide aid to the woman struggling with symptoms of menopause. This has proven a fraught area of medical practice, not least as a consequence of historical studies that have arguably been misinterpreted in terms of the perceived risk profile associated with HRT for most women. The most high profile of these was the Womens Health Initiative which seemed to demonstrate a marked increase in breast cancer and stroke associated with the then standard combination HRT - conjugated equine oestrogen + medroxyprogesterone acetate. Almost overnight, clinicians and their patients dramatically, and understandably, reduced the uptake of HRT spawning a search for alternatives and an industry in menopause therapies proclaiming various answers. One of the largest has been the evolution of 'bio-identical' hormone replacement alternatives. So what are these bio-identical hormones and how do they compare, in terms of efficacy and safety, to modern pharmaceutical options?
The term 'bio-identical' means various things depending upon who you talk to. One widely accepted definition is "compounds that have exactly the same chemical and molecular structure as hormones that are produced in the human body" (The Endocrine Society). The production of such compounds aims to address concerns as to the 'artificiality' or 'foreignness' of 'synthetic' hormones, though the the term synthetic is misleading as nearly all available products, regardless of their labeling, are derived from artificial chemical precursors. However, the distinction does carry weight in distinguishing between hormones that are chemically identical to those the body produces as opposed to those such as equine products that are chemically different though potentially functionally similar. At a chemical level, bio-identical oestrogen is 17beta-estradiol (rather than conjugated oestrogen) and progesterone is typically micronised progesterone (rather than progestogen).
There is a certain elegant simplicity to the notion of bio-identical hormones - clearly there is a logic to the notion that a substance identical to what the body produces should be safer than one that is structurally different to what the body produces. But are they safer? Well, before asking that question, a quick summation of the risks associated with the non-bio-identical hormones:
Breast cancer - With conjugated oestrogen alone (such as post-hysterectomy), no increased risk. When combined with synthetic progestogens, the risk seems to vary depending on the product but in any case is relatively low, equivalent to the increased risk associated with obesity or consuming 1-2 standard drinks of alcohol every night;
Stroke/blood clots - Risk varies depending on the preparation and predominantly seems to be related to the route of oestrogen uptake. Oral preparations of oestrogen increase risk (around 1:5000) while transdermal preparations have no associated increased risk, making transdermal the gold standard in terms of safety.
To summarise, breast cancer risk relates to the progesterone and stroke risk predominantly relates to the type of oestrogen (there are exceptions depending on the product).
And what are the benefits of HRT? After-all, if there are no benefits why have the discussion in the first place? In summary:
Improved quality of life - addressing the burden of menopausal symptoms, such as hot flushes, insomnia, emotional lability and sexual comfort, can have a profound and positive effect upon a woman's life;
Reduced osteoporosis risk;
Reduced cardiovascular risk;
Reduced risk of dementia.
These benefits are stronger the earlier a woman transitions through menopause.
So, are bio-identicals safer? The evidence remains somewhat lacking, however, there is no denying that a growing evidence base is tending to demonstrate increased safety with specific products, particularly over a 5 year time frame. In fact, in my own practice I now preferentially recommend the combination of:
Transdermal oestrogen - either gel or patches to remove the stroke/clot risk;
Micronised progesterone - a bio-identical product that appears not to increase breast cancer risk.
This combination is available on a standard script from any chemist.
At this point, an important distinction needs to be made between pharmaceutical bio-identical products, available from any chemist, and compounded bio-identical products, only available from a compounding pharmacy and, generally speaking, significantly more expensive reflecting the loss of efficiency of scale when production is taken outside of a factory. And it is this distinction that partially prompted me to raise today's topic. Regardless of your thoughts as regards 'big Pharma', and I am by no means naive to the sins of the industry, both here in Australia and in most first world countries, before a product reaches your chemist it has been through a stringent array of vetting processes to ensure safety and consistency (dosing) of the product. Compounded products are not subject to the same stringent processes. This is not to suggest that compounding pharmacies are dangerous, however, there is an unavoidable variance in product consistency inherent in their process and quality of product will vary from one compounding pharmacist to the next - in my own practice there are only a couple of compounding pharmacists that I recommend as they have a locally proven track record for product quality. Equally there are compounding services that I prefer my patients not to obtain their products from. As I have implied, there is in fact a role for compounding pharmacies, and an important one at that. For some patients the standard delivery vehicles for a particular drug, including HRT, is just not appropriate and compounding pharmacies offer the option of providing the desired medication in an alternative, tailored format. Secondly, some medications simply are not available in a mass produced format. So compounding certainly remains an important tool in any clinician's prescription armament.
But should patients seeking HRT be directed towards compounded products? I don't think so, and I am aware that there are a number of clinicians, and patients, who would disagree with me. My take on the issue is simple. Since the Womens Health Initiative, pharmaceuticals have come a long way. The combination of conjugated oestrogen and medroxyprogesterone acetate is no longer the only option available from a standard chemist. Indeed, commercially available transdermal oestrogen (bio-identical) and micronised progesterone (bio-identical) are now readily accessible and come with the added certainty of stringent pre and post market surveillance and quality assurance, often at significantly less cost than a compounded equivalent.
I've limited my discussion to oestrogen and progesterone replacement. I do want to raise two additional issues that I have observed at increasing frequency amongst women who come to see me. The first is women who are prescribed progesterone only to address their menopausal symptoms. The rationale seems to be on the assumption that progesterone alone can alleviate hot flushes in particular. I have spent this evening trying to find evidence to support such an assertion and struggled to find anything that could be described as quality. Indeed, an effect beyond placebo seems hard to find in either the evidence or on the basis of our (meaning a gynaecologist's) understanding of what progesterone does. Given the safety of transdermal oestrogens and their proven efficacy I am at somewhat of a loss why some women are directed to procure expensive compounded progesterone trouches and the like for their menopausal concerns.
The second issue I wanted to address is the rise in DHEA prescriptions, again an expensive therapy obtained from a compounding pharmacy. DHEA is a precursor molecule that the body converts into both oestrogens and androgens (male hormones). The theory then is that by providing this precursor the body itself will then replace deficiencies in oestrogen and testosterone. These effects are principally driven by the ovaries which continue to produce androgens, but not oestrogens, after the menopause. Androgens, such as testosterone, are then aromatised in the body to oestrogens. The benefits are meant to be three-fold; improved sexual function, improved energy levels and improvement in symptoms of menopause. Frankly, the evidence is lacking, to negative. DHEA as a vaginal preparation has been shown to improve genito-urinary symptoms (sexual dryness and bladder dysfunction) but otherwise has no proven benefit when taken systemically. Again, potentially no more than placebo. For those women who are seeking to address libido/sexual function concerns, a better consideration is transdermal or subcutaneous implants of testosterone, for which some, though limited, evidence of benefit is at least available.
Menopause is a challenging time in many women's lives and as with all challenges in life there is a large industry that has grown to service those challenges. Today's blog entry is not meant to serve as the definitive discussion of HRT but rather to cast a brief light on the conversations that women should be having with their clinicians when seeking treatment. The fears that women have regarding HRT are well established though the impact of the Womens Health Initiative and similar historical studies should have been overtaken by the advances in HRT safety. For those who are looking for a good place to start seeking information I would suggest the following:
The Australian Menopause Society - https://www.menopause.org.au/
Your general practitioner or gynaecologist.