Morgentaler & Testosterone Flare

[pjoshea13]

New paper below.

Abraham Morgentaler's Saturation Model states that PCa cells have all the testosterone [T] they can use at T levels in the upper-hypogonadal range. Therefore if T = 350, 650 or 950 ng/dL, there is no difference in the effect on PCa proliferation.

The testosterone flare caused by Lupron, etc, should be irrelevant, except for men already in the lower-hypogonadal range, when a rise in PSA is possible. In any case, the subject appears to be much ado about nothing.

Firmagon is sometimes temporarily used to finesse the flare "problem". There is usually an immediate drop in T. Since castrate T is the aim, I don't see how the new paper would affect Firmagon being used in this way.

Casodex is sometimes temporarily used too, but there are reasons for continuous use too.

"Although T flare has been considered risky for 30 yr, a modern review of the evidence collected primarily in the 1980s and 1990s fails to support this view. Specifically, T flare does not appear to be associated with significantly increased PSA, disease progression, or adverse events, even in men with widely metastatic disease. These results are consistent with the saturation model, first introduced in 2006. There seems little value in adding AA to LHRH agonists, except possibly for men with extensive vertebral metastases and serum T concentrations well below the saturation point of approximately 250ng/dl (8.7nmol/l)."

-Patrick

ncbi.nlm.nih.gov/pubmed/287...

Eur Urol Focus. 2017 Jul 1. pii: S2405-4569(17)30159-1. doi: 10.1016/j.euf.2017.06.008. [Epub ahead of print]

Risk of Testosterone Flare in the Era of the Saturation Model: One More Historical Myth.

Krakowsky Y1, Morgentaler A2.

Author information

Abstract

CONTEXT:

When luteinizing hormone-releasing hormone (LHRH) agonists were introduced in the 1980s, it was universally believed that the initial transient rise in serum testosterone (T), termed T flare, caused rapid prostate cancer (PCa) growth and led to disease progression, complications, and death. It became routine to offer antiandrogens (AAs) to prevent these risks. However, over the last decade, it has become recognized that androgens have a finite ability to stimulate PCa growth (the saturation model), providing a theoretical challenge to the risks of T flare.

OBJECTIVE:

To review evidence for the risks associated with T flare from a modern perspective, specifically prostate-specific antigen (PSA) flare, disease progression, and spinal cord compression.

EVIDENCE ACQUISITION:

An Ovid Medline database search was conducted to identify articles related to "testosterone flare", "disease flare", and "PSA flare" associated with LHRH agonists. The literature review included papers published from May 1, 1980 through May 1, 2016. Key search terms included, luteinizing hormone-releasing hormone, gonadotropin-releasing hormone, and antiandrogens.

EVIDENCE SYNTHESIS:

Initial administration of LHRH agonists uniformly results in peak increases in serum T by 40-100% on days 2-3, returning to baseline by days 7-8, after which T declines to castrate levels by approximately 2-3 wk. Of six LHRH agonist studies reporting PSA during the period of T flare, five showed no significant rise in PSA despite the presence of advanced disease with mean baseline PSA as high as ≥500ng/ml. Evidence for disease flare was limited to one report of greater bone pain with LHRH agonists alone versus LHRH agonists with AAs. Three other RCTs reported no disease flare. Rates of spinal cord compression were no greater for LHRH agonists alone compared with castration or estrogen treatment. We identified no studies of men treated with LHRH agonists versus placebo/no treatment to assess the effects of LHRH agonists compared with the natural history of advanced PCa.

CONCLUSIONS:

Although T flare has been considered risky for 30 yr, a modern review of the evidence collected primarily in the 1980s and 1990s fails to support this view. Specifically, T flare does not appear to be associated with significantly increased PSA, disease progression, or adverse events, even in men with widely metastatic disease. These results are consistent with the saturation model, first introduced in 2006. There seems little value in adding AA to LHRH agonists, except possibly for men with extensive vertebral metastases and serum T concentrations well below the saturation point of approximately 250ng/dl (8.7nmol/l).

PATIENT SUMMARY:

A review of the literature reveals no evidence for increased risks associated with testosterone flare from the initiation of luteinizing hormone-releasing hormone (LHRH) agonists. This appears to be an unsupported belief from an earlier era when our understanding of testosterone's relationship to prostate cancer was less sophisticated. Except in rare instances, there appears to be no need to use an androgen blocker when beginning treatment with LHRH agonists.

Copyright © 2017 European Association of Urology. Published by Elsevier B.V. All rights reserved.

KEYWORDS:

Androgens; Flare; Prostate cancer; Prostate-specific antigen; Risks; Testosterone

PMID: 28753828 DOI: 10.1016/j.euf.2017.06.008

[Sisira]

Interesting and useful finding. Nevertheless confusing when different views are held from time to time. I think it is better and safer to start with Firmagon or add an Androgen Blocker at the start of ADT in the interest of our life and let the Pundits continue their research and arguments. Why take a risk with a with a T-flare in any case? Safety at all times will protect us.

Thanks for for the post and new learning too is much appreciated.

Sisira

[rococo]

Still many mo"s stlll hold this view My previous mo thought low dose AA monotherapy wasn't sufficient to block psa reccurrence. I intellecualized the less androge receptors to block the less blockade necessary and it worked for 7+ years even though T soared to1000. So the question is if adt is sufficient what use are AA. I think that these blockades can be used to extend the adt off cycle. The best to all. Rocco

[Hidden]

I had read about the merits of administering casodex to tamp down the "T flare" associated with lupron/eligard. I insisted on the casodex prescription. It worked out well for another, silly reason -- the dang insurance company dragged their feet for weeks in approving the eligard. I was happy to have any kind of prescription going to work while forced to wait for the eligard shot.