As I experiment with BAT (to the horror of some), one of my doctors has strongly told me to limit Anastrozole to 0.5 mg once every two months or, at most, 0.5 mg at the time of injection and 0.5 mg one week later, saying
“anastrozole only stops the conversion to estradiol. 2-OHE1 and 16a-OHE1 are more deleterious than estradiol.”
1. Anyone have any guidelines for an appropriate dosage of anastrozole? I have started searching the BAT clinical trials, but it is a tedious process and I have not come up with any specifics yet. Of course one can measure estradiol for guidance. I think there has been general agreement that we want estradiol to be about 20 pg/mL, less than 30 and certainly more that 12. My most recent measurements, away from BAT, were 20, 13, and 15. During BAT, however, estradiol levels after injection, despite taking anastrozole, have been 58 and 108. Not sure if these temporary surges are significant or not.
2. As for 2-OHE1 and 16a-OHE1, Patrick has covered this well, including
“DIM: There was an "increase of 47% in the 2-OHE1/16alpha-OHE1 ratio from 1.46 to 2.14 ..."
“Results of experiments in multiple laboratories over the last 20 years have shown that a large part of the cancer-inducing effect of estrogen involves the formation of agonistic metabolites of estrogen, especially 16-alpha-hydroxyestrone. Other metabolites, such as 2-hydroxyestrone and 2-hydroxyestradiol, offer protection against the estrogen-agonist effects of 16-alpha-hydroxyestrone."
“There are two major hydroxylation metabolic pathways for its elimination: the "2" path (2-Hydroxylation) & the "16alpha" path (16a-Hydroxylation). The latter produces metabolites that are thought to be carcinogenic. The "2" path produces benign, & perhaps even protective, metabolites.”
So I guess the problem is that by using anastrozole to limit estradiol there is greater usage of the 16alpha-OHE1 hydroxylation pathway.
Any thoughts are appreciated.
Written by
cigafred
To view profiles and participate in discussions please or .
The role of estrogen is still not completely understood in PCa. Estrogen is acted on by two distinct receptors, ERα and ERβ. Friedman in his book points to ERα being the bad actor and ERβ being somewhat protective. As the paper linked below indicates there is some controversy about this claim. The ratio of the two is likely deterministic of positive or negative effects.
The research paper linked below from 2018 provides a good overview of the estrogen receptors. This passage below should serve as a caution against letting E2 get too high. I seem to remember that both Patrick & Nalakrats settled on a range around 20 as the target and use some form of SERM or AI as needed to keep it around that. (And also help keep those man-boobs in check.)
Preclinical findings have shown that estradiol levels play an important role in PC pathogenesis. In aromatase knockout (KO) mice, which cannot metabolize androgens to estrogens, high testosterone levels only lead to prostatic hypertrophy and hyperplasia. In contrast, high estrogen and low testosterone levels induce inflammatory events and premalignant lesions (17). These findings are corroborated by epidemiological studies, suggesting that estradiol serum levels and estradiol/testosterone (E/T) serum ratio impinge on PC initiation and progression. African-American men, who have high serum estradiol levels, exhibit a greater risk of developing PC (18), and PC incidence increases during aging, since it is often diagnosed in elderly rather than young men (19). In elderly males, testosterone production by the testis declines, while estradiol concentration remains constant (20). Consequently, the ratio between circulating and intraprostatic E/T increases.
The full paper is here:
Estrogens and Their Receptors in Prostate Cancer: Therapeutic Implications - Fronteirs in Oncology, Published online: 2018 Jan 18
FWIW, I've tested E2 on four occasions since my BCR#2 in the middle of last year. Those labs were done after a short test treatment with bical alone (27.9), after 30-day trial with bical + Avodart (19.5), and 5 weeks before and after 2 months of Lupron mono (10.9 b, 11.9 a). Testosterone ranged from 643 to 530 for those labs. All were done at same Labcorp facility and all blood draws were done at mid-morning in a well-rested, well- hydrated, and fasted state. It might be worth noting that the high E2 was after a short 10-day test treatment with bical alone - and after combining bical with Avodart, E2 came right down to the 20 target. DHT also dropped from 52.0 to 8.3 due to Avodart - and all the above treatments resulted in a non-durable <0.1 PSA.
Labcorp's range for E2 is 7.6-42.6 pg/mL. Seems to me that keeping in the lower half of that range (unless treating with E2) would be a good idea, esp. when T is low.
Stay Well - Ciao - K9
Illustrates the putative role of ER (α or β) in PC.
Thanks for this multi-faceted answer. Yes, my reference to "20 pg/mL, less than 30 and certainly more that 12" was partly based on the writings of P and N. I am comfortable that, away from BAT, I am in that range, but do not know how aggressive to be in combatting the surge that comes from T-cyp injections.
As I am sure smurtaw has seen, but others maybe not, our discussion has also been going on in the "other" healthunlocked advanced PC web site, and my responses to his information-filled offerings are there (only because that is where I first saw one of his answers to me).
I do not measure blood levels of estrogens while I am on BAT. They don’t apply. There action is complex with the different receptors and can change over time. Estradiol is your friend until it is your enemy. (Like a lover???)
I choose to follow PSA levels and occasional scans to know which, rather than reference blood levels that were not established for my situation. But each to his own - no absolute right or wrong answer yet. SARMs May offer an alternative pathway to balancing ER and AR effects. 🤷🏼♂️
Thanks and yes, I am coming to a similar conclusion--more work to do, but I will post something once I have finished. By the way, I think Patrick used a similar phrase when he posted "My attitude was that DHT was my friend ... until it wasn't." healthunlocked.com/advanced...
Content on HealthUnlocked does not replace the relationship between you and doctors or other healthcare professionals nor the advice you receive from them.
Never delay seeking advice or dialling emergency services because of something that you have read on HealthUnlocked.
BAT in the UK: does if officially exist
