Tachyphylaxis and Hormone Resistance
Tachyphylaxis (stay with me, I promise the post gets better) is the medical term describing a sudden decrease in response to a drug after initial administration.
Vikram Talaulikar, a Specialist in Reproductive Medicine at UCLH & Hon. Associate Professor in Women’s Health at UCL wrote a brilliant post over on LinkedIn about Tachyphylaxis in relation to the current popular higher “off licensed” prescribed doses of HRT - I really recommend you take a read of the entire post.
What he beautifully explains (and I feel this is also very relevant in PMDD & endometriosis, with the natural ebb and flow of hormones) is Tachyphylaxis can occur when the bodies receptors for hormones; such as progesterone or oestrogen receptors or drugs (HRT, progestogens or the pill) don't react or respond in the intended or “normal” way. So, it’s easier to now refer to this phenomenon as a hormone resistance.
In some cases, the receptors become less sensitive to the medication or naturally produced hormones. In other cases, the number of receptors actually decreases, meaning there are fewer “docking stations” for medications /hormones to attach to create their effects.
If, for example one has a have progesterone resistance then this helps to explain why progesterone therapy in the form of birth control pills for endo or PMDD may not be working for you. Similarly If there are less “active” progesterone receptors, then your body will not recognize these additions.
Here’s a quick recap of how hormones and their receptors work. Think of the receptors as a lock and the hormone or drug, that resembles the hormone enough, as a key that fits into that lock. Once the “key” is metaphorically turned in the lock it’s starts a chain reaction, that we is called transcription, which facilitates an action. These receptor (locks) are positioned on the outside of cells membranes - located all over the body, waiting for the correct key (hormone or drug) to slot it, and elicit it’s response.
Tachyphylaxis therefore can be viewed as the locks no longer fitting the preferable key or less locks now being available for selection.
In the context of HRT, we simply do not know what the long term effects of dosing supraphysiological blood oestrogen levels are - that research has not to date been done, in fact our generation of menopause graduates are indeed walking research labs! As such I implore you to work with an informed menopause literate Dr that does not prescribe higher and higher doses of HRT on the basis that “ you are not absorbing it” as the side effects to this are unkown.
What I believe can provide some insightful answers as to why some women suffer with PMDD or are non responders to licensed HRT doses is looking into the nutrigenomic components to their personal lock and keys.
A hormone nutrigenomic report by @LifecodeGx will provide insightful information to the health of your oestrogen receptors, how well you are genetically set up to remove oestrogen from the body (a slow removal could predispose towards a receptor overwhelm sciario) together with the health of one's GABA receptor which is important when we look at progesterone.
As always, there is not one magic bullet, but, the more pieces of your personal health jigsaw collated - the closer we become to unlocking (excuse the dreadful pun) the correct support plan for you.
In health,
Tanyax