By this logic, it is not worth measuring testosterone either, because testosterone does not exert its effects in serum, only in tissues. The fact is, the hormones we are measuring, circulating in serum, make their way into tissues and exert effects there. This is equally true for both testosterone and estradiol, and that is why it is worth measuring and concerning yourself with both hormones.
There is no unidirectional transporter in tissues that only allows E2 produced locally via aromatization to travel out from that tissue to the serum. E2 can just as easily pass from serum INTO tissues and exert effects as an endocrine hormone.
One of the best models in men to prove that is with estradiol administration in the context of androgen deprivation therapy (ADT). In these scenarios, men with prostate cancer are chemically castrated, reducing both T and E2 to nil, and then estradiol is administered to relieve men of some of the negative side effects.
When you restore serum E2 to physiological levels in men on ADT, their markers of bone health improve. Bone resorption is halted and bone density increases. There is no aromatization of testosterone occurring in these men. This is E2 measured in serum, traveling from the serum into the tissue, exerting endocrine effects. The same physiologic serum E2 levels will also relieve vasomotor symptoms like hot flashes in these men.
Relative to placebo, E2 treatment increases some measures of bone density and bone strength in men and reduces bone remodelling, effects that occur in the absence of endogenous T.
pubmed.ncbi.nlm.nih.gov
In men with castrate levels of E2 and TS, daily transdermal E2: 0.9-1.8 mg increased median serum E2 concentrations into the reference range reported for healthy men, but with substantial variability. E2 treatment reduced hot flushes and bone resorption. Larger studies will be required to test...
pubmed.ncbi.nlm.nih.gov
What happens when you go beyond physiologic serum E2 levels in men on ADT with estradiol administration? Gynecomastia. You are basically performing a gender transition on them, as the endocrine effects of high serum E2 work their magic in the tissues, in the absence of T and DHT to balance it.
Nipple tenderness was noted in 1 of 12 men receiving 0.9 mg, 2 of 12 men receiving 1.8 mg
and none using placebo gel in this study. In the PATCH trial, 75% of men receiving a high dose transdermal E2 regimen, sufficient to induce castrate T concentrations without GnRH analogs, experienced gynaecomastia compared to 19% of men receiving GnRH analogs (8). It is unknown to what extent long-term low dose transdermal E2 add-back will increase the incidence of breast adverse effects above that caused by GnRH analogs alone.
Basically what the anti-AI crowd has done is taken the nugget of truth that E2 often or even primarily functions as a paracrine hormone in men, and said that is the ONLY conceivable thing happening with E2. We will deny that high serum levels of E2 could ever possibly have undesired endocrine effects. We will bury our heads as far in the sand as necessary, creating carefully policed echo chambers on the Internet, such that we never have to consider that possibility again.
Just because AI's are not a safe and effective solution to undesirable effects of excessive E2 doesn't mean it is impossible for excessive E2 to cause undesirable effects. You've thrown the baby out with the bathwater.