Why might someone suddenly become resistant to testosterone therapy?

Hello:

I'm a 50 year old male with primary hypogonadism. This stems from losing one testicle when I was 25 to torsion and a case of epididymitis in my late mid 30s that had spread p to the testicle and (is suspected by my doctors to nave) damaged the Leydig cells that produce testosterone (T). A few years after that I started showing the classic symptoms of hypogonadism (loss of sexual interest, ED, low energy, depression and irritability and weight gain.) When they did a T panel and measured my levels of estradiol (E2), follicle stimulating hormone (FSH) and leutenizing hormone (LH), my total T was about 250 with correspondingly low free and bioavailable T, normal sex hormone binding globulin (SHBG), normal E2 levels and sky high LH and FSH. The endocrinologist I saw at the time put me on two pumps of Androgel daily and things returned to normal for about 10 years with my T profile returning to normal for my age.

Roughly 6 months ago, however, I noticed a return of the symptoms I had before being put on hormone replacement. I was referred to an andrologist who tested my T profile and levels of FSH, LH, E2 and prolactin (Pro.) The last being to rule out a pituitary tumor. My T profile had dropped way down again (total T of about 225 with corresponding drops in free and bioavailable T, significantly elevated E2 (85) and normal values for SHBG, FSH, LH and Pro. My andrologist increased my dosage of Androgel to four pumps a day and put me on 0.5 mg of generic Arimadex twice a week to lower the E2 values to safer levels. This initially caused a huge rise in the whole T profile (total T of 850, free T of over 100.) The E2 levels only dropped to 45 rather than the desirable range of 20-30, so the Arimadex was doubled. This had no effect on my E2 levels, though, and my T profile rapidly dropped down to 300 (which would be fine if I were 80-100 years old.)

So it's like my body is fighting to keep my T abnormally low and my E2 high. My andrologist gave a generic diagnosis of pituitary insufficiency of unknown origin but admits he's never seen anything like this before. After some quibbling with the insurance company, he wants me to start on six pumps of Androgel and isn't quite sure how to address the elevated E2 levels. My fear is that I'll see another sudden jump in the T profile followed by another rapid drop.

So I'm wondering if anyone in this forum has experienced something similar, how it was treated and how that treatment worked for them.

Thanks very much and apologies for the long post.