What are bioidentical hormones?

Nick Panay discussed the confusion around bioidentical hormones. Bioidentical hormones are officially defined as “precise duplicates of estradiol, estriol, estrone, progesterone, DHEA and testosterone as synthesised by the human ovary and adrenal”. However some confusion has been generated by pharmacies who have used the term to market their own unregulated non-evidence based products in some cases suggesting that you can extract progesterones from wild yams and estrogen from soy beans ( this is not true they need to be chemically confirmed.) The use of the custom-compounded hormone therapy created by pharmacies is not recommended because of the lack of; regulation, rigorous safety and efficacy testing, batch standardisation and inaccurate purity measures.

After the release of data from the WHI study, there has been a lot of public discussion about bioidentical hormones, which have been heavily marketed in the media with celebrity health gurus from Oprah to Dr. Ox. The confusion around what bioidentical hormones really are led to the BMS publishing the following statement in the UK “The term ‘bioidentical hormones’ is misleading; when Hormone Replacement Therapy (HRT) is indicated, women should be advised to only take those hormone therapies that are regulated and approved by the MHRA, which include hormones which are natural and identical to those produced in the body.” It is thought that instead of using the term ‘bioidentical’, ‘body-identical’ hormones should be used.

The link with breast cancer risk

The IMS 2016 recommendations stated that the increased risk of breast cancer is primarily associated with addition of progesterone to estrogen therapy and linked to length of use. However 3 studies suggest that micronized progesterone or dydrogesterone could be associated with lower risk than synthetic progestogens. Data from the Finnish registry study showed no increased risk of breast cancer after 5 years with dydrogesterone but demonstrated an increased risk with synthetic progestogens. It is thought that this is because synthetic progestogens are associated with more proliferation, whereas dydrogesterone favours more apoptosis. The E3N French cohort and Finnish cohort studies also showed breast cancer risk was lower with natural progesterone/dydrogesterone, whilst the CECILE study, a population control study of more than 1550 menopause, over 700 of whom had breast cancer cases demonstrated that estradiol with micronized progesterone had no increased risk.

Micronized progestogens and VTE risk.

In an earlier presentation we heard about VTE risk from Eswald (catch up on the session here if you missed it). It is thought that progestogens may modulate the increased risk conferred by oral estrogen due to a venous dilatory effect which leads to increased risk of thrombosis. In the E3N cohort study there was no increased risk with micronized progestogens and in the ESTHER case control study, those using micronized or pregnane progestogens seemed to have a reduced risk of thrombosis.

The ideal MHT therapy?

Nick believes we need to take this data and try to work out what the ideal MHT therapy will be accounting for timing and dose. The KEEPS and ELITE studies have demonstrated that the benefits of MHT can be achieved with no adverse effects on surrogate markers and the current evidence suggests that body identical regimens appear to optimise the benefit/risk ratio but more data from large randomised clinical trials on cardiovascular/breast endpoints are required in “The Window of Opportunity” to confirm impact of body identical progesterone and transdermal estradiol.  The WHI study had the wrong population (elderly, obese, hypersensitive) and the wrong MHT regimen (use of MPA, dose too high for population) so it’s time for something new! Whilst the ELITE trial forms the basis of a good pilot study it isn’t large enough, Nick believes we need to go global with co-ordination from WHO and local governments contributing. Do you agree? Let us know your thoughts on the ideal trial in the comment box below.