I've been looking at tamoxifen dosing, and how it works.
When I started developing tenderness and breast buds, I asked for it, and got a prescription from oncology for 20mg daily, but with the suggestion to try 20mg twice a week to start with. I didn't ever speak with whoever prescribed it, so was somewhat short on any more detailed instructions.
The 20mg twice a week only relieved the tenderness (which I didn't much care about anyway) for that day, and the breast buds continued to grow. I adjusted the dose up in steps to 20mg/day, and that did work, but by that time the breast buds had grown, and it took time for them to shrink.
I subsequently tried modifying the dose according to symptoms, but the results didn't match what I expected.
This caused me to go off and do some research on tamoxifen dosing, and it's much more complicated than I had imagined, but I'll go through it, because it might be useful to understand this for some people.
The active ingredient is tamoxifen citrate, 3/4 of each tablet (the rest being inactive things to make it into a tablet). When you take a tablet, it takes 5-7 days for your liver to breakdown half of the tamoxifen citrate (this is known as the chemical's half life), according to manufacturer data. They also give some other figures of blood concentrations after many months, from which I could work backwards to 5.4 days half life. This means if you take one tablet, 5.4 days later, half of it is still in your system, and after another 5.4 days, 1/4 of it is left in your system, and after another 5.4 days, 1/8th of it is left in your system, etc. This type of logarithmic decay is typical of the way most drugs are removed from the body (alcohol being a notable exception), although all drugs have different half lives.
Since the half life is quite a bit more than the dosing frequency (certainly for daily doses), this means the quantity of tamoxifen citrate in your blood once you've been on it a while will actually correspond to several day's dosage, because several days worth add together before they get removed by the liver. The dose is calculated to take this into account.
However, tamoxifen dosing is more complicated than this simple model. Tamoxifen citrate is metabolised (broken down) by the liver mainly into N-desmethyl tamoxifen. This works just as well as tamoxifen citrate to block estrogen, so although the liver has broken down half the tamoxifen citrate in 5 days, the breakdown product continues working as an estrogen blocker.
It gets even better... The N-desmethyl tamoxifen has an additional half life of about 14 days meaning almost 3 times as much builds up in the body as the original tamoxifen citrate, so it is actually the N-desmethyl tamoxifen which is the main estrogen blocker, rather than the tamoxifen citrate.
This combination is known as a biphase decay, because it relies on the half life decay of a second follow-on decay product.
However, because of this biphase decay, and in particular because it's the metabolite which produces most of the estrogen blocking effect, it takes a long time for the active concentration level to build up in the blood. I modeled this in an Excel spreadsheet, and it takes 3 months to build up to the final stable blood concentration level, and probably at least 2 months to get near enough to be working well.
Now, this probably works fine if you start taking it when you start on HT as you won't need it to be effective for a few months, but if you start taking it in response to breast pain and growth as I did, this allows quite some considerable time before it builds up a strong enough concentration in the blood to stop growth, and start reduction.
Using my Excel spreadsheet model, I can play around with dosing and see the impact it has on blood concentrations. For a target concentration level corresponding to 2 x 20mg/week, you can get there in 8 days by starting off with 20mg/day for the first 8 days, and then dropping back to 2 x 20mg/week, and this is probably what I would have done if I'd known this at the outset. (I did end up doing something not very dissimilar to get the effect I wanted, but I didn't realise I could have pulled the dose back down so quickly after 8 days, not knowing the mathematical model behind the dosing at the time.)
Now, this is totally non peer reviewed private research, so I'm certainly not suggesting anyone else should try this, particularly if your oncologist has prescribed a specific dose (mine didn't). But you might talk with your oncologist if you are starting out on tamoxifen due to breast pain/growth having started. I couldn't find any such research on dosing, probably because use in men for gynaecomastia is not covered anywhere near as well as use for breast cancer treatment.
I have another interest in making my dose as small as I can get away with. My liver is not overly happy with tamoxifen, which has raised my alanine aminotransferase levels. This means tamoxifen could give me non alcoholic fatty liver disease (NAFLD) with long term use. There are other potential side effects from it too, such as blood clots. I don't want to have to come off it, so I'm hoping minimising my dose will keep me safe on it, and the mathematical modeling may help me do this.
50% of women taking tamoxifen after breast cancer treatment for 5 years to reduce chance of recurrence do end up with fatty liver disease. There is also an interesting correlation in that those women who do get NAFLD are also only half as likely to get a breast cancer recurrence as those on tamoxifen who don't get NAFLD, although the mechanism behind this correlation are not known.
[EDIT 18/4/2019: Correct description of N-desmethyl tamoxifen blood concentration.]
Edited by member 18 Apr 2019 at 16:31
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