Why are cardiac effects different for... - Advanced Prostate...

Advanced Prostate Cancer

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Why are cardiac effects different for GnRH agonists and antagonists?

Tall_Allen profile image

I've always been troubled by the observation that GnRH agonists (like Lupron, Gosarelix, Zoladex, and Triptorelin) had a high risk of cardiotoxicity while GnRH antagonists (Firmagon and Orgovyx) did not. Why should they be different if they both lower testosterone? This RCT offers a good explanation. They found that certain proteins known to stabilize plaques increased with use of antagonists. While men taking agonists were more likely to have their plaques rupture.


90 Replies

Is this enough evidence that we should ask our MOs to make the switch?

Tall_Allen profile image
Tall_Allen in reply to treedown

If cardiotoxicity is a concern for you, you may wish to discuss it.

cesanon profile image
cesanon in reply to Tall_Allen

Pretty much all of us our age have to watch after our hearts.

It would seem to me that if this is true, the default should be Firmagon or Orgovyx, unless there is good reason otherwise.

Are there not scenariors where it might make sense to couple an agonist with an antagonist for a push-pull effect.

Are you aware of any clinical trials to that effect?

Tall_Allen profile image
Tall_Allen in reply to cesanon

There is no push-pull. They both lower testosterone. Agonists by negative feedback, antagonists directly.

Does Regolux work for Advanced METASTATIC prostate cancer?

mperloe profile image
mperloe in reply to Christopherg

It is not as effective in lowering hormone production.

JRPnSD profile image
JRPnSD in reply to mperloe

Mperloe - based on what research did you state Orgovyx is not as effective? My monthly Testosterone tests say otherwise...and I see no scientific basis for your statement. I have used both Firmagon and Orgovyx for 4 months each....and Orgovyx gave me lower T readings. I go forward with the no pain option of Orgovyx.

mperloe profile image
mperloe in reply to JRPnSD

Orgovyx is great Regulyx is approved for endometriosis and does aim aim for aggressive hormone lowering. Sorry for the confusion.

JRPnSD profile image
JRPnSD in reply to mperloe

AH..the other name for Orgovyx is Relugolix. I assume you are talking about a similar-sounding drug that is targeted for endometriosis for women? Perhaps edit your original post to minimize the confusion?

mperloe profile image
mperloe in reply to JRPnSD

It is a bad day Sorry. Egalolix is the less effective oral antagonist for endometriosis. Very similar medication but not as potent when it comes to shutting down GnRH.

Yes. It lowers testosterone by the testes.

cesanon profile image
cesanon in reply to treedown

I was thinking the very same thing

treedown profile image
treedown in reply to cesanon

I will address in the future as if all things remain the same my last shot will be in June. Should that not be the case then many things will need to be considered. Also no cardio issues I am aware after 1.5 years so more interested than concerned. Though if all things between the 2 types of ADT are equal whatsbthe upside to an agonist to the patient? Seems none at all and plenty of downsides.

Tall_Allen profile image
Tall_Allen in reply to treedown

Convenience of multi month shots.

treedown profile image
treedown in reply to Tall_Allen

Thats a plus for me, are the other 2 taken orally daily?

Tall_Allen profile image
Tall_Allen in reply to treedown

Orgovyx is oral. Firmagon is a monthly shot.

spencoid2 profile image
spencoid2 in reply to Tall_Allen

I live 4 hours (on a good day) from my MO. We decided on Firmagon and I was not sure why since i have to drive 8 hours each month just for this shot. I think i do remember discussing cardio and other side effects and Dr. Anderson recommended Firmagon. At least I get to go to the brewery with my dog (and husband)

ronronHU profile image
ronronHU in reply to spencoid2

Have you ever considered trying transdermal E2 gel or the 'Patch'? They both do the same thing without the CV risks of GnRH agonists. I use the gel since it is less expensive and more convenient than wearing a patch. I haven't been to a doctor for 3 1/2 years.

If you don’t mind sharing

How much gel do you use?

And is it daily?

Thank you so much


Hi Chris, One tube lasts me about three weeks and I apply it to my lower abdomen and inner thighs in the morning and before I go to bed. Richard Wassersug has been using it as his only form of ADT for about 20 years and only applies it once/day.

onajourney profile image
onajourney in reply to spencoid2

I would ask my MO if the injection could be given by a facility closer to you? I receive my injections from the nurse at my MO's office. It seems that nurses in other offices could also give the injection?

6357axbz profile image
6357axbz in reply to onajourney

My MO writes order for the injection and I’ve had it filled in different hospitals/doc offices. I’m a plane flight away from my MO.

spencoid2 profile image
spencoid2 in reply to onajourney

I should ask about that. When I was traveling in France, it was no big deal. Got a script from my Father's doctor, filled it at the pharmacy and the doctor did the injection himself. The biggest shock was the cost. For two office visits blood work ekg prescription and administration it was less than $200. I didn't even bother submitting it to insurance. Should be able to do the same here? I will ask my primary if she would like to do it. She is a real take charge type of doctor, she will love it.

Ausi profile image
Ausi in reply to onajourney

My Zoladex injections / implants are every 3 months (here in Australia). Though it is in TA’s hit list as an agonist.

There is a significant cost difference for many men with Medicare between the new Orovyx and Lupron.

The study listed which specific cardiac history were significant.

What is the cost difference?

Depends on your insurance lupron is free to us. The pills right now were going to cost $600 per month.

There are grants available to help cover Orgovyx costs.

Thank you that makes sense. Seems if the costs weren't different we should all abandon lupron on favor of these.

Tall_Allen profile image
Tall_Allen in reply to treedown

In the US, injections by the doctor are covered Medicare by Part B, pills by Part D.

Thanks!!..TA.....Do statins help in reducing these plaques caused by GnRH

Tall_Allen profile image
Tall_Allen in reply to SPEEDYX

Statins help stabilize plaques.

Thanks TA for posting. They wanted to switch me from firmogon to Lupron and I refused it and told the nurse Practitioner that the cardiovascular profile is better with firmogon Becuse I had read about it and she said “ No, there was a no proof “, now , she can’t argue:-).

There was always some suggestive evidence, but now there's a rationale:



More definitively, there was a large RCT called "PRONOUNCE" that has completed and will probably be published soon:


There's also this comparison of Lupron and Orgovyx that found a " 54% lower risk of major adverse cardiovascular events.”


Schwah profile image
Schwah in reply to Tall_Allen

So.....what’s the downside of switching to (or starting ) Orgovyx over Lupron? If both are equally effective when combined with Zytega, and one is much safer, seems like a no brainer to use Orgovyx. Am I missing anything TA?


Tall_Allen profile image
Tall_Allen in reply to Schwah

For some, compliance is better with a shot, And much less long-term experience with Orgovyx.

rmarkley profile image
rmarkley in reply to Schwah

The only problem is that Orgovyx is not approved for use with abiraterone. I am currently on Firmagon and abiraterone. My MO wants to put me on Orgovyx, but the insurance did not approve that. A study is currently ongoing with Orgovyx and abiraterone, with results due at year end. If anyone has been able to convince their insurance company to approve both Orgovyx and abiraterone, please let me know. My MO would dearly like to hear about that, so he can go beat on insurance.Note that Orgovyx will be more expensive than Firmagon. Firmagon is free at the hospital, while Orgovyx comes from the same specialty pharmacy as the abiraterone. My abi is $85/mo, except that I found an outfit that covers the copay.. Hopefully the same for Orgovyx when I am able to go on that.

Tall_Allen profile image
Tall_Allen in reply to rmarkley

My friend just got Orgovyx and abiraterone - fully covered. Maybe your MO can appeal.

6357axbz profile image
6357axbz in reply to Tall_Allen

Good news!

rmarkley profile image
rmarkley in reply to Tall_Allen

My MO has appealed. What is your friend's insurance company? Maybe his doctor could talk to or email my doctor and they could figure out how to do it. My MO is open to anything that will allow him to put me on Orgovyx and abiraterone.

Tall_Allen profile image
Tall_Allen in reply to rmarkley

He has Medicare + Anthem Blue Cross supplemental. He had an anaphylactic reaction to his last Lupron shot, so maybe that had some influence. But Zytiga + castration (physical or chemical) is standard of care for mHSPC, so the insurance shouldn't care how the castration occurs. It's possible that your drug plan doesn't cover Orgovyx.

rmarkley profile image
rmarkley in reply to Tall_Allen

Is there some way that we can get your friends MO to contact my MO or vice versa? My insurance is Anthem Medicare Preferred. I would really like to figure out a way for the 2 MO's to discuss this.

rmarkley profile image
rmarkley in reply to rmarkley

Thanks for your help. I will contact my MO.

6357axbz profile image
6357axbz in reply to rmarkley

Good important info. Thank-you

rmarkley profile image
rmarkley in reply to 6357axbz

I was put on Firmagon due to my lone atrial fibrillation. Made my cardiologist happy.

Deadstick profile image
Deadstick in reply to Tall_Allen

All I know is that after 4 years of Lupron, I'm going back to my cardiologist for my 3rd cardiologist conversion to hopefully get me out of A-Fib.....again

Thanks for posting this. Very timely. I am due for my 6-month Eligard shot next week and will have a discussion with my doctor.

Are there GnRH antagonists (Firmagon and Orgovyx) versions with longer than 30-day cadence doses? I assumed the driver behind Lupron was to push out the appointments to 90 or 180 days cycles. Stopping in monthly for a Firmagon shot is no issue for me. I'm not sure about insurance coverage (I'm US private insurance; not Medicare). However, the immediate Firmagon side effects were more pronounced (its felt like a flaming baseball for the first couple days). I'd deal with the discomfort for less cardiotoxicity. Thanks.

Tall_Allen profile image
Tall_Allen in reply to rm9x

Orgovyx is a daily pill.

rm9x profile image
rm9x in reply to Tall_Allen

Thanks. Does Firmagon come in a dose longer than 30 days?

Tall_Allen profile image
Tall_Allen in reply to rm9x

No - only 30 day. Injection site reactions are worse on the first 2 doses.

It is easy enough to test in any individual by sequential testosterone tests. Did my own: after a single shot of 120 mg Firmagon my T remained castrate <20 for three months. (No starter dose of 240.) Suspect that many men could go to every other month without emerging from castrate.

Can anything be done to reduce the pain of the injection sites?

ice before and after may help.

MateoBeach profile image
MateoBeach in reply to rm9x

See my reply to TA below in this thread. Worked for 3 months for me.

Which one is Tak-700 please?

Tall_Allen profile image
Tall_Allen in reply to Lulu700

TAK-700 (Orteronel) was an experimental hormone therapy that acts much like abiraterone. It didn't improve pain or survival, and was scrapped. Why do you ask?

Lulu700 profile image
Lulu700 in reply to Tall_Allen

Because I’m still on it .

Tall_Allen profile image
Tall_Allen in reply to Lulu700

It's interesting stuff. It increased progression-free survival but didn't increase overall survival. I thought Takeda stopped supporting it.

Lulu700 profile image
Lulu700 in reply to Tall_Allen

They did but they still provide it free to the few of us still on it? Thanks

I believe you could also avoid this issue with an orchiectomy if you wanted to avoid the shots altogether.

I realize that it's not a solution for everyone, but for those who have to be on ADT permenantly anyway, I might be a good option.

6357axbz profile image
6357axbz in reply to gregg57

Very good point gregg

spencoid2 profile image
spencoid2 in reply to gregg57

There was a fair amount of largely positive feedback on orchiectomy. At this point I have little attachment to my balls, they worked well for many years but they are no longer needed.

Both my MO and Uro will support me if i decide to go that route.

The Uro says it is a simple outpatient procedure, but not reversible :)

Is there any reason to not ditch the testicles? Fewer side effects, less driving? Any other benefits. I am getting myself ready for this.

gregg57 profile image
gregg57 in reply to spencoid2

I think the reason it's not done more is just the psychological aspect. In many countries in the world it's more of a standard, in part because of the cost issue. Yes it's not reversable, but then neither is stage 4 prostate cancer.

Lulu700 profile image
Lulu700 in reply to gregg57

Agreed 👍

Lulu700 profile image
Lulu700 in reply to spencoid2

Chop chop. I did it. No regrets. No taking those two back now. They were already a liability to me . Take care

ctflatlander profile image
ctflatlander in reply to gregg57

I agree. Just had it done.

Lulu700 profile image
Lulu700 in reply to ctflatlander

Whoop di Dooo ! Welcome to the club! 😳✌️

Cheerr profile image
Cheerr in reply to gregg57

Unless Firmagon comes in a similar 3-monthly or 6-monthly dose like Lupron, it’s hard to make a switch. Going in every month is hard and the injection site reaction for dad was always more painful with Firmagon.

Looks like more reasons to consider Orchidectomy after all. (For permanent ADT folks)

Tall_Allen profile image
Tall_Allen in reply to Cheerr

Orgovyx is a daily pill.

Cheerr profile image
Cheerr in reply to Tall_Allen

Thanks! Will explore this option 😊

Hi Tall Allen and gentlemen

I would be most grateful if you could advise on my question which is:

Are Bradycardia, premature ventricular contractions (PVC’s) and Tachycardia all considered cardiovascular diseases?

these are electrical problems of the heart

Hence should Firmigon be the best LHRH choice?

And what about the 2nd generation drugs? Which ones for heart problems?

With thanks and all best wishes

Arrhythmias are a different sort of cardiac problem. I don't know if agonists or antagonists are any different in that regard. This study says that cardiac tissues have GnRH receptors that may be stimulated by agonists:


But I don't know of any comparisons about arrhythmias.

Thank you so much for replying

You are more helpful than my MO

I will have to shake my cardiologist for a.direct answer

Thanks so much for the article

All best wishes


Thanks for the post....just getting ready to approach oncologist to make the switch. Good to have some published evidence..... they always seem so reluctant to deviate from the norm(what they normally prescribe)

My only hesitation in switching my husband to Orgovyx is the liver metabolism. Specifically the potential interaction with dexamethasone, as he takes that for 3 days each docetaxil cycle, but also just the potential effects on liver enzymes, especially as we contemplate adding abiraterone. His MO has never prescribed it, but is willing to do so.

My husband is currently on degarelix, but I know his MO plans to eventually switch him to Lupron.

What are your thoughts on liver impact?

Cooolone profile image
Cooolone in reply to bethdavis

The great thing with the "pill" is that if adverse liver reaction occurs, you can stop the pills immediately and the drug wears off fairly quickly and would allow then a switch. As opposed to adverse events with an injections whereas you'll need to await the dissipation of the drug over it's timeline for mitigation.

Otherwise, I'm currently on Orgovyx (Relugolix) and between my 5th & 6th cycle of Docetaxel. I do not recall any elevated liver indicators in my last blood work. But everyone is different, and that then shouldn't mean anything to you. I'm assuming there's an issue that there is concern on the "liver" enzymes...? If there is liver function concern, have you considered the use of "Milk Thistle"?

Thank you for this vital information. My husband was diagnosed at the end of 2014. He was treated with the combination of chemo (doxetal), radiation, firmagon(first shot) and the lupron every six months. He has suffered 4 heart attacks. After the 3 rd one he began going to a cardiologist who has a specialty in the effects of can treatment. She talked to the MO to get him off the Lupron but the MO said there was nothing else. After the 4 th one in July 2019, the MO took him off. He has been doing great but his PSA began rising in Feb this year. It is now 0.05. His T is 288 serum and 3.9 free. The MO is watching this very closely. Don’t know what will happen next. He feels really great with the T rising as he had horrible fatigue from the Lupron.

What is interesting is the cardiologist knew right away what was going on but the MO was not convinced until #4.

He will be 69.

Thanks TA for the good info. I switched after 18 months from Firmagon to Orgovyx just a couple of month ago and have seen no discernible change in side effects i.e., fatigue and hot flashes. It seems I’ve read elsewhere that the antagonists also offer the benefit of lower impact on bone density depletion. That along with the lower CVD profile was enough to convince me to go with Firmagon in the beginning. The recent switch to Orgovyx, where you can take a daily oral pill in lieu of a monthly belly shot, was a no brainer. Thanks again for your invaluable input on this forum.

6357axbz profile image
6357axbz in reply to Stevana

Any problems with insurance covering Orgovyx?

Explorer08 profile image
Explorer08 in reply to 6357axbz

Regarding insurance coverage, I have CVS Caremark for my drug coverage and pay a $75 per month copay for Orgovyx which is delivered to my home each month. This coverage is under my Anthem BC/BS medical plan. It took a couple of attempts on the part of my MO to get approval. The main argument was the lower rate of heart problems with Orgovyx. I was approved for Orgovyx through 2024.

6357axbz profile image
6357axbz in reply to Explorer08

Good news. Thank-you.

Stevana profile image
Stevana in reply to 6357axbz

I’m on FEP Blue as ex-Fed employee. I also used Orgovyx’s premium copay assistance program and pay $10 per months supply. I’m approved by BSBS for one year and have to get another approval in 12 months. I’m receiving my drugs from Moffitt Cancer Center in Tampa who is using the Caremark system. I would recommend you start with Orgovyx’s customer assistance on what you need to do to get approval from your provider. I would have had a $110 per month copay but got it know down to $10 thru Orgovyx. Good luck.

6357axbz profile image
6357axbz in reply to Stevana

Thanks, good info. My MO would like to wait till there us more experience given I tolerate lupron (Eligard) pretty well

Stevana profile image
Stevana in reply to 6357axbz

From what I’ve read Orgovyx is more or less an oral form of Firmagon. I’ve really experienced no different in the two drugs. But I do understand your doc wanting to stick with what’s working for you. My feeling is the antagonist have a better overall (lower) risk profile. Good luck and stay strong. 💪💪

Because it uses different pathways to lower your testosterone I can't take lupron it I have too many side effects but from a femigon gives me a sore stomach for 3 days I tolerate it very well

Ok ta..im concernef about me heart...wouldnt want it to kill me before the cancer does that's a joke but I'm in the Titan trial the open-label part of it and I'm on Lupron / eligard/ erleada which I get at no cost for another year-and-a-half I would like to switch to the pill ADT but that means I'd have to drop out of the trials and it's been working for four years but maybe I wouldn't if the pill is still a form of castration am I answering my own question but I like it when you do because you're real smart

According to the TITAN specs, "the choice of the GnRHa (agonist or antagonist) will be at discretion of the Investigator." They also allow surgical castration. Both Firmagon (monthly injections) and Orgovyx (daily pills) are GnRH antagonists and have the same heart benefit. You should discuss this with your doctor.

The other thing worth considering is that Erleada has already been FDA-approved for mHSPC, so you can get the drug by prescription (with co-pay).

Yeah but even with co-pay I think it's about 500 a month cuz it cost 12 Grand regularly and I'm on a pretty tight budget so I may write it out for a while I did have a stress test and setup my heart wasn't going to kill me at the time but that was three years ago we all know that that Lupron is pretty tough on the heart thanks for responding t a

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