ADT & thromboembolic events.

[pjoshea13]

New meta-analysis below.

"Deep venous thrombosis (DVT) was found significantly associated with gonadotropin-releasing hormone (GnRH) agonists alone (HR = 1.47 ...), GnRH agonists plus oral antiandrogen (AA) (HR = 2.55 ...), and AA alone (HR = 1.49 ...), but not with orchiectomy (HR = 1.80 ...).

"In addition, pulmonary embolism (PE) was significantly associated with GnRH agonists alone (HR = 2.26 ...) and orchiectomy (HR = 2.12 ...)".

Cancer itself brings its own risk.

It seems prudent to periodically have a D-dimer test. A number close to zero will rule out a blood clot. D-dimer can be elevated for reasons other than a blood clot, but in the context of ADT it is best to assume the worse IMO. Nattokinase breaks down the fibrin in a clot faster than plasin in the body can. In the short term, D-dimer will rise as the clot dissolves, but ultimately, it will fall, provided that the rate of breakdown exceeds the rate of acretion.

Some men take 2,000 FUs (fibrinolytic units) daily as a prophylactic, but a higher dose will be needed to treat a significant clot.

-Patrick

ncbi.nlm.nih.gov/pubmed/299...

Prostate Cancer Prostatic Dis. 2018 Jul 9. doi: 10.1038/s41391-018-0059-4. [Epub ahead of print]

Association of androgen deprivation therapy with thromboembolic events in patients with prostate cancer: a systematic review and meta-analysis.

Guo Z1, Huang Y1, Gong L2, Gan S3, Chan FL4, Gu C3, Xiang S3, Wang S5.

Author information

Abstract

BACKGROUND:

Whether androgen deprivation therapy (ADT) causes excess thromboembolic events (TEs) in men with prostate cancer (PCa) remains controversial and is the subject of the US Food and Drug Administration safety warning. This study aims to perform a systematic review and meta-analysis on previous studies to determine whether ADT is associated with TEs in men with PCa.

METHODS:

Medline, Embase, and Cochrane Library databases were searched for relevant studies. These studies comprised those that compared ADT versus control to treat PCa, reported TEs as outcome, and were published before January 2018. Multivariate adjusted hazard ratios (HRs) and associated 95% confidence intervals (CIs) were calculated using random- or fixed-effects models.

RESULTS:

Five retrospective population-based cohort studies involving 170,851 ADT users and 256,704 non-ADT users were identified. Deep venous thrombosis (DVT) was found significantly associated with gonadotropin-releasing hormone (GnRH) agonists alone (HR = 1.47, 95% CI: 1.07-2.03; P = 0.017; I2 = 96.3%), GnRH agonists plus oral antiandrogen (AA) (HR = 2.55, 95% CI: 2.21-2.94; P < 0.001; I2 = 0.0%), and AA alone (HR = 1.49, 95% CI: 1.13-1.96; P = 0.004; I2 = 0.0%), but not with orchiectomy (HR = 1.80, 95% CI: 0.93-3.47; P = 0.079; I2 = 94.8%). In addition, pulmonary embolism (PE) was significantly associated with GnRH agonists alone (HR = 2.26, 95% CI: 1.78-2.86; P < 0.001; I2 was unavailable) and orchiectomy (HR = 2.12, 95% CI: 1.44-3.11; P < 0.001; I2 = 57.2%). This relationship was also supported with subgroup analyses based on different continents and races.

CONCLUSIONS:

GnRH agonists alone, GnRH plus AA, and AA alone cause excess DVT in men with PCa after controlling the demographic and disease characteristics and other confounding factors, although statistically significant difference was not observed in orchiectomy group. Additionally, GnRH agonists alone and orchiectomy can increase the incidence of PE.

PMID: 29988099 DOI: 10.1038/s41391-018-0059-4

[cesanon]

Patrick,

So ADT and Vitamin K might not mix so well? Correct?

[pjoshea13 in reply to cesanon]

No. Vitamin K is fine. It is not implicated in abnormal coagulation.

There are many factors involved in coagulation. Doctors do not try to figure out what's behind a dysfunctional system. All they do is try to slow (increase) clotting time. This puts the patient at risk for a bleed out, but it gives the body time to remove the clot naturally.

To increase clotting time, one inhibits production of one of the many coagulation factors. Warfarin blocks the enzyme that restores oxidized vitamin K (Vitamin K epoxide reductase). This causes a K deficiency which affect clotting factors II, VII, IX, and X.

People with cancer have chronic coagulation dysfunction & often become Warfarin lifers. Living with vitamin K deficiency means having weaker bones & arterial calcification.

-Patrick

[snoraste]

Patrick- I may have asked this question before. Is the function of Nattokinase supplement solely for the arterial/blood clots? Or does it also function to slow metastasis?

[pjoshea13 in reply to snoraste]

A number of researchers claim that circulating microclots are essential to metastasis. Nattokinase quickly eliminates microclots.

-Patrick

[jimbob99999]

So, you have lower risk of embolism if you go orchiectomy versus ADT?

[pjoshea13 in reply to jimbob99999]

"... pulmonary embolism (PE) was significantly associated with GnRH agonists alone (HR = 2.26 ...) and orchiectomy (HR = 2.12 ...)

So the risk for orchiectomy is lower than for GnRH agonists alone, but it is still a doubling up on risk.

-Patrick

[hansjd]

Just wondering whether an ADT antagonist such as firmagon (degarilix) would prove a better option than an agonist to avoid DVTs and PEs. In the USA the ADT option always seems to be an agonist rather than an antagonist despite antagonists having better outcomes in many ways.

[NewAgeBrother in reply to hansjd]

That's a good question. There has been always a FDA warning on increased cardiovascular diseases with agonist drugs but not any on the Degarelix. However, the warning does not mention specifically DVT. So, this may be different.

fda.gov/Drugs/DrugSafety/uc...

[Mkeman in reply to NewAgeBrother]

Earlier this week I was diagnosed with atrial fib and put on a blood thinner. The condition wasn’t there last October in an EKG taken before I started ADT. I have had Casodex, Trelstar, Eligard, Zytiga, prednisone and Zometa. Did One or more of these drugs cause the problem? Can’t prove it...but the timing is suspicious. I would definitely ask for an EKG periodically. If the a-fib hadn’t been discovered the first major symptom might have been a fatal blood clot.

[NewAgeBrother in reply to Mkeman]

Eligard is an agonist drug. But, the warning does not mention DVT. See section 5.4.

accessdata.fda.gov/drugsatf...

[BigRich in reply to hansjd]

It is the cost in dollars that many institutions do not use an ADT antagonist- long term.

Rich

[Don1157]

Yea, CVD event within a year of ADT the first time, blood clot in heart following the second start of ADT,rapid growing cataracts within a year of second visit to ADT, and a gain of 30lbs! Never “want” to do that again!

[chhs1976]

All cancers are associated with increased risk of Thromboembolic events.