You raise some valid points, but I am a big fan of both Occam's Razor and the process of elimination as problem solving tools.
What I mean is, when faced with an unknown question and inadequate evidence or knowledge to make a clear assessment, I find it useful to work through systematically by starting with the simplest or most common explanations, exhausting solutions for each one at a time, and then moving on to the most experimental and esoteric approaches only once all the basics have been exhausted.
In actual fact, I think you have done this very well up to this point. In brief:
- Biopsies have ruled out an auto-immune cause with fair certainty.
- Iron infusions and extensive bloodwork has ruled out a nutritional cause or other general medical condition.
- Most recently, the use of daro+duta+cypro has ruled out with fair certainty (in my opinion) that this is a primarily androgenic issue, or that antiandrogens can likely solve your problem.
In my opinion, that workflow logically leads next into a deeper evaluation of your female hormones and how well the balance of them could be affecting your hair.
It is certainly possible that there is a far more esoteric cause such as the cortisol issues you describe. However, I do not think you have remotely enough data or trials to first rule out the contribution of estrogens to the problem. I also don't think you have run nearly sufficient trials to be able to say you've evaluated the female hormone issues with the same thoroughness you have evaluated the other preceding possibilities listed above.
The fact that you have experienced dramatic sheds of hair when switching estrogens/progesterones actually provides some strong evidence that this is where your problems are coming from. If the female hormones were not a major factor, they wouldn't have such a powerful effect on your hair.
I don't think it's correct that excessive estrogen causes hair loss by converting to testosterone. "Although testosterone can be converted to estradiol, the reverse does not happen."
https://www.americanscientist.org/article/testosterone-in-women
Estrogen is very complicated when it comes to hair and the research we have is very poor. But in essence, from the information we do have, estrogen can be fairly considered to have a Goldilocks effect on hair - too much is bad and too little is bad as well. (Laser therapy for hair has been shown to exhibit a similar Goldilocks effect.)
Estrogen must also be considered with finesse in that each type of estrogen works differently from the others and these differences extend to how they also work in different parts of the body.
Estrogenic activity within a tissue is influenced by the type of estrogen and the subtype of estrogen receptor found within that tissue,[20]as well as by the distribution of cofactors and corepressors of the estrogen-receptor complex within the tissue.[21] With estradiol as the standard, binding affinity for both estrogen receptor (ER)-α and -ß is equal at 100.[20] Estrone has a binding affinity for ER-α of 60 and for ER-ß of 37. Estriol binds to ER-α with an affinity of 14 and to ERß with an affinity of 21. Therefore, estradiol has the strongest binding affinity for both ER-α and -ß.
https://www.medscape.com/viewarticle/571299_6
This is where the greatest argument for bioidentical hormones comes from.
Ethinyl estradiol does not work the same as natural estrogens. Ethinyl estradiol is a primary ER-alpha agonist, and it triggers very different tissue responses from the natural estrogens which have a much more balanced function:
Differential effect of estrogen receptor alpha and beta agonists on the receptor
In the current investigation, we examined the effect of three estrogens with different potency for specific estrogen receptors (ER) on RAGE expression in human microvascular endothelial cells (HMEC-1). Of the three estrogens tested,
ethinyl estradiol (EE), an estrogen receptor alpha (ERα) agonist, was the strongest inducer of RAGE expression in HMEC-1. By comparison, 17-epiestriol, an estrogen receptor beta (ERβ) agonist and
17-β-E2, an ER agonist that is almost equally potent for ERα and ERβ were less effective in stimulating RAGE expression
https://www.sciencedirect.com/science/article/pii/S0167488905000467
There is a simple study which proves incontrovertibly that ethinyl estradiol does not work the same on body tissues as natural estrogens do. Also we can note that estriol, which is the most famous estrogen for hairg growth in pregnancy has a predominantly ER-beta affinity, while ethinyl estradiol has the exact opposite (high ER-alpha affinity)
If your primary estrogen (ethinyl estradiol) is so dramatically unbalanced and unnatural in its binding and tissue stimulation, how can you expect a natural response?
It is absolute fact that ethinyl estradiol is very different in the body compared to natural estradiol/estriol/estrone.
This provides a very clear and easy explanation for a lot of the problems you are having with good basic scientific principles behind it.
If you wish to test this hypothesis (which I think should be the next most logical step in your workflow), and you wish to avoid cycling hormones, then again an approach of Triest (estradiol/estriol/estrone) with a low dose progesterone IUD plus some topical and/or oral antiandrogens for insurance would objectively make the most sense.
Until you have tried a solution that involves a more balanced and natural stimulation of your estrogen receptors, it is not possible to say to what extent this is the issue. If the problem is the disproportionately high ER-alpha stimulation by ethinyl estradiol, then you will not adequately resolve that problem until you remove ethinyl estradiol from your body and replace it with something that provides a better balance of ER-alpha and ER-beta stimulation (eg. Triest).
That may be a difficult thing to conceive of doing, given the uterine pain and bleeding as well as shock losses you've suffered from prior shifts in estrogen in the past. But I think it's an absolutely necessary step to take at some point in this process, and I think it is the step with the highest probability of success given the facts discussed above.
In the big scheme of things (overlooking temporary pains and discomforts if we can), one of two things may happen if you do this: (1) the problem will be solved, or (2) you will have added imbalanced estrogen as yet another cause of your problem to have been ruled out.
In my opinion, only then would it make sense to start experimenting with your adrenal axis which is a much funnier system to manipulate and less likely to be the culprit in the context of the above.
Again this is all your choice. Whatever you do, don't stand still. Keep working logically through the system, as you are making progress whether you feel it or not sometimes. The process of elimination is a powerful problem solving tool of used correctlu. I recommend this approach next because I think there is the greatest evidence and highest probability that if you pursue it, it may be the last experiment you will need to run.
