Cardiovascular side effects of Lupron?

[Jamesrh]

I have had premature ventricular contractions show on stress EKG's for 40 years; doctors said "harmless". When RP failed after 7 years, I started Lupron 2 months ago on top of vitamin C and alpha Lipoic acid infusions, and many supplements. There was a period when pulse rate fell in 40's, but now back to normal. However, there are interruptions in the pulse. Blood pressure normal. Internet reportes Lupron has cardio effects. My MO dismissed idea of connection and I have a meeting with my cardiologist coming up. Any experiences with significant effects of Lupron on cardiovascular system?

[tango65]

No personal experience, but these 2 summaries may be of some help on this subject:

Eur Urol. 2014 Mar;65(3):565-73. doi: 10.1016/j.eururo.2013.10.032. Epub 2013 Nov 1.

Cardiovascular morbidity associated with gonadotropin releasing hormone agonists and an antagonist.

Albertsen PC1, Klotz L2, Tombal B3, Grady J4, Olesen TK5, Nilsson J6.

Author information

Abstract

BACKGROUND:

Androgen deprivation therapy (ADT) is associated with increased cardiovascular morbidity.

OBJECTIVE:

To determine whether cardiovascular morbidity differs following initiation of gonadotropin-releasing hormone (GnRH) agonists compared with an antagonist.

DESIGN, SETTING, AND PARTICIPANTS:

Pooled data from six phase 3 prospective randomized trials that recruited 2328 men between 2005 and 2012 to compare the efficacy of GnRH agonists against an antagonist. Men recruited had pathologically confirmed prostate cancer, an Eastern Cooperative Oncology Group score <2, a minimum life expectancy of 12 mo, and were naïve to ADT. Men were excluded if they had a prolonged baseline QT/corrected QT interval, other risk factors for heart failure, hypokalemia or a family history of long QT syndrome, or had another cancer diagnosed within 5 yr.

INTERVENTION:

Men were randomized to receive a GnRH agonist or an antagonist for either 3-7 mo (n=642) or 12 mo (n=1686). Treatment groups were balanced for common baseline characteristics.

OUTCOME MEASUREMENTS AND STATISTICAL ANALYSIS:

Event analysis was based on death from any cause or cardiac events. Data documenting adverse experiences were classified based on the Medical Dictionary for Regulatory Activities. The following conditions defined a cardiac event: arterial embolic or thrombotic events, hemorrhagic or ischemic cerebrovascular conditions, myocardial infarction, and other ischemic heart disease. Kaplan-Meier curves and log-rank tests were used to compare time to a cardiovascular event or death.

RESULTS AND LIMITATIONS:

Among men with preexisting cardiovascular disease, the risk of cardiac events within 1 yr of initiating therapy was significantly lower among men treated with a GnRH antagonist compared with GnRH agonists (hazard ratio: 0.44; 95% confidence interval, 0.26-0.74; p=0.002). Since our analysis is post hoc, our findings should only be interpreted as hypothesis generating.

CONCLUSIONS:

GnRH antagonists appear to halve the number of cardiac events experienced by men with preexisting cardiovascular disease during the first year of ADT when compared to GnRH agonists.

-----------------------------------

Sci Rep. 2016 May 18;6:26220. doi: 10.1038/srep26220.

Treatment with a GnRH receptor agonist, but not the GnRH receptor antagonist degarelix, induces atherosclerotic plaque instability in ApoE(-/-) mice.

Knutsson A1, Hsiung S1, Celik S1, Rattik S2, Mattisson IY2, Wigren M2, Scher HI3, Nilsson J2, Hultgårdh-Nilsson A1.

Author information

Abstract

Androgen-deprivation therapy (ADT) for prostate cancer has been associated with increased risk for development of cardiovascular events and recent pooled analyses of randomized intervention trials suggest that this primarily is the case for patients with pre-existing cardiovascular disease treated with gonadotropin-releasing hormone receptor (GnRH-R) agonists. In the present study we investigated the effects of the GnRH-R agonist leuprolide and the GnRH-R antagonist degarelix on established atherosclerotic plaques in ApoE(-/-) mice. A shear stress modifier was used to produce both advanced and more stable plaques in the carotid artery. After 4 weeks of ADT, increased areas of necrosis was observed in stable plaques from leuprolide-treated mice (median and IQR plaque necrotic area in control, degarelix and leuprolide-treated mice were 0.6% (IQR 0-3.1), 0.2% (IQR 0-4.4) and 11.0% (IQR 1.0-19.8), respectively). There was also evidence of increased inflammation as assessed by macrophage immunohistochemistry in the plaques from leuprolide-treated mice, but we found no evidence of such changes in plaques from control mice or mice treated with degarelix. Necrosis destabilizes plaques and increases the risk for rupture and development of acute cardiovascular events. Destabilization of pre-existing atherosclerotic plaques could explain the increased cardiovascular risk in prostate cancer patients treated with GnRH-R agonists.

[GeorgeGlass in reply to tango65]

What is the takeaway from these results? Aren't all the ADT drug option for adv. PCx in the agonist category? Are there any in the antagonist category for lowering the testosterone?

[tango65 in reply to GeorgeGlass]

Yes, there is Firmagon which is an antagonist. The only one approved in the USA.

[Jamesrh]

Thank you for your prompt reply with such thought provoking materials which will be a help to me and my physicians.

[Don1157]

Oh my, you hit on a sore spot with me. I started on Lupron in March of 2009, in December of 2009 I had a triple bypass. I am sure that the beginnings were there before Lupron, but it seemed to facilitate the worsening of the disease. It seems to affect every system in the body, or the lack of testosterone does anyway, and affects them in a bad way. My MO talked in the sense of my concern, but he has gone as far as let me be on holiday, and was going to begin intermittent treatment, and now talks only about casodex and the post of research said antagonist therapy may be easier on the heart, but don’t know about that until after brachytherapy at the end of March. I believe and a search of the literature as already posted that it does have negative cardiovascular effects. I believe it also sped up a cataract in my right eye, and there it was seen in the forums and literature, of course I may be a rare huma ... good luck!

[Jamesrh in reply to Don1157]

Many thanks.

[Daddysdaughter]

My father was having chest pain not cardiac related and then converted to atrial fibrillation for 24 hours. After multiple tests and an angio there was no answer. The cardiologist and his MO all said it is not related to Lupron. I disagree! I believe it’s all because of the Lupron. He is still on it but no longer has any palpitations. Good luck in figuring it out!! Wishing you well!!

[Jamesrh in reply to Daddysdaughter]

Thank you, I will post my conclusions

[cbc-ppml]

In regard to premature ventricular contractions - I have always had "PVCs" on my stress EKG's for several decades now, and have always been told that they were benign.

[SUPERHEAT12 in reply to cbc-ppml]

I had heart disease prior to being diagnosed with pc. It was totally under control. I did not connect the ADT with heart disease but I had to have stents after a few years. I thought that was due to the stress associated with pc but now I wonder if it wasn't the ADT. Other factor, however, I did not get as much cardio exercise after PC. Just did not have the energy...

Superheat12

[herb1]

Jamesrh: Seems you takes your choice-helps or hinders! I've been on IADT since 2001, in 2004 cardiologist thought he saw heart damage on stress test and urged me to "stop any exercise". I changed cardiologist. In 2017, I collapsed at racquetball, at age 81, and had rush triple bypass. Still on IADT. Who's right?

[Hidden]

I take meds for atrial fibrillation. I was concerned about how eligard (similar to lupron I am told) would effect my heart. I had zero a-fib events during the six months I was on eligard. I typically have an event every couple of months.

[gottodealwithit]

I had a history of Atrial Fib in late 1990s and early 2000s. December 2005 I had a pulmonary vein catheter ablation procedure. Afterwards no more incidents of Atrial Fib UNTIL 4 weeks after my first Lupron injection June 2016, went for successful cardio conversion, then second Lupron Dec 2016 again within 6 weeks again Atrial Fib followed by successful cardio conversion. Then third Lupron Injection June 2017 and shortly after again Atrial Fib and successful cardio conversion. Then in August 2017 my cardiologist attempted catheter ablation but it was unsuccessful and I am now in permanent atrial fib and consequently a beta blocker med. My oncologist was in complete denial that there could be connection between the Lupron Shot and the incidents of Atrial Fib. I think it was far more than coincidence. However after consultation with cardiologist and since my PSA was undectable I decided to forego the 4th Lupron shot scheduled for Dec 2017 and will now monitor PSA levels every 6 months.

[Jamesrh in reply to gottodealwithit]

Wow, thank you,sounds like my MO.

[scarlino]

I have been on Firmagard and then Lupron since 2015 along with Zytiga, Aberiterone and Predisone since February of 2017 as part of a clinical trial. I had no indications of heart problems ever. At the end of 2017 I had long lasting palpitations with my BP fluctuating crazily. My heart rate has been low (~50 bpm). All tests indicated no heart attack but heart monitoring showed I had PVCs. One point my heart stopped beating for 5.2 secs, though I felt nothing unusual. I now have a pacemaker. I never heard anything about Lupron being the culprit. I will definitely discuss with my Cardio and Onc.

[Jamesrh in reply to scarlino]

Thank you, sounds like mine.Beats per minute dropped into 40’s about a month after first Lpron shot, but now are back to normal, a month after that.

[ARIES29]

Interesting talk about the connection of lupron & cardio desease. After my brief experience with that & cosudex tablets i noticed heart pain not previously experienced but maybe due to excessive weight put on due to inactivity due to this treatment. Now on cosudex tablets only,still sleep half day but no other side effects yet anyway.

Looking forward to the Lutetium-177 PSMA therapy to get rid of this terrible desease & the even more disgusting side effects of the treatment so far.

[Jeff54]

I was on Lupron after surgical removal of prostate in 2005. I was on this medication for 3 years and after 2 months of being off the Lupron had problems with heart! Was taken out of work with heart beat of 208 beats per minute! Went to see cardiologist and was diagnosed with S.V.T. Underwent 2 heart ablations ok for 1 year then problem turned into Atrial Fibrillation! I was put on Multaq 400 mgs 2 times a day. I am now on Hormonal Therapy 4 years 8 months! I am on Eligard every 4 months and so far no problems! I walk 2 hours steady Friday,Saturday and Sunday each day! This certainly helps me!

[Vitaminlover]

Spouse started on firmagon/ zytiga and developed a skipped heart beat and low heart rate. Cardiologist did adjust BP meds and that seemed to help. Just started Lupron with zytiga and gets light headed for a few days. Good luck and please update us on any changes.