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Relugolix and Depression

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User
Posted 02 Aug 2026 at 18:10

I had a successful RALP in 2024 for 2c prostate cancer and all has been good until earlier this year when my PSA went up to 0.2.  A CT scan didn’t reveal any tumours but with a post-op Gleason of 4+5 I was recommended 20 fractions of radiotherapy along with several months of hormone treatment using Relugolix tablets. I have a history of depression but have been okay and off anti-depressants for several years.


However after only a couple of weeks on Relugolix my mood swings became increasingly erratic, I started to become disassociated and ended up going to the oncology Same Day Emergency Care service for my own safety (and sanity).  Unsurprisingly the hormone treatment was stopped.  I’m now 4 weeks further on and have just finished the radiotherapy and (leaving aside the exhaustion and tenesmus) my mental health has finally started to stabilise albeit I’m feeling devoid of motivation and purpose (which may in large part be the fatigue).  I won’t know the results of the radiotherapy for another 4-5 weeks but have already decided that if I ever have to again choose between hormone therapy and cancer then I’ll take my chances with the cancer.


Having got all that off my chest I wondered if there are any other experiences of Relugolix acutely affecting mental health or whether I’m just unlucky and a statistical outlier?


Thanks

User
Posted 02 Aug 2026 at 20:42
Edward, I hadn't heard of this so I did a search and found only one paper looking at the question which failed to find any link in a sample of 87 patients. https://pubmed.ncbi.nlm.nih.gov/39896185/

I have also experienced salvage radiotherapy, but in my case the hormone therapy used was goserelin (Zoladex). I have to say that isn't something I would repeat from choice, so maybe your symptoms were due to the reduction in testosterone. The good thing about Relugolix is that recovery to previous testosterone levels is reported to be better than with other treatments so you may return to your previous quality of life. As you say though the fatigue impact of radiotherapy will also be a factor, so it may take another month or two yet.

Good luck.
User
Posted 03 Aug 2026 at 07:39

Thanks Guys.


@J-B: I similarly assumed that the effect was caused by the loss of testosterone although one of the CNS did mention that the tablets can also affect serotonin levels, I think simply as a consequential wider imbalance of hormones.  However I can’t find any other reference to this.  Either way I’m glad that the direct effect of the tablets might be reasonably short.  I’m still getting some weak hot flushes which I’m hoping will settle down soon.


@Peter: golly 2 years sounds frightening so I’m glad that you haven’t had the same reaction.  I also had the low libido but under the circumstances and for the short amount of time I wasn’t too concerned.  I can well understand your frustration though. I’m interested that you also have a Gleason of 9 but if I’m interpreting you correctly it sounds like you still have your prostate and this is what’s further increasing the risk of the cancer spreading?


Thanks and good luck to you both.

User
Posted 05 Sep 2026 at 21:38

We're cheering you on!


Take care ... Stephen

User
Posted 06 Sep 2026 at 15:16

Thanks everyone for the comments and words of support.  It’s really interesting to hear about the potential for a direct link between testosterone levels and depression rather than as a side effect of the Rx medication itself.  It’s now about 6 weeks since I finished the RT and 8-9 weeks since I stopped the relugolix and I’ve still got significant fatigue and muscle weakness.  I should have thought that my testosterone levels should have recovered by now, but I’m seeing the oncologist on Wednesday for the post-RT results so there’s some useful stuff here that I shall raise. 🤗

User
Posted 02 Aug 2026 at 18:10

I had a successful RALP in 2024 for 2c prostate cancer and all has been good until earlier this year when my PSA went up to 0.2.  A CT scan didn’t reveal any tumours but with a post-op Gleason of 4+5 I was recommended 20 fractions of radiotherapy along with several months of hormone treatment using Relugolix tablets. I have a history of depression but have been okay and off anti-depressants for several years.


However after only a couple of weeks on Relugolix my mood swings became increasingly erratic, I started to become disassociated and ended up going to the oncology Same Day Emergency Care service for my own safety (and sanity).  Unsurprisingly the hormone treatment was stopped.  I’m now 4 weeks further on and have just finished the radiotherapy and (leaving aside the exhaustion and tenesmus) my mental health has finally started to stabilise albeit I’m feeling devoid of motivation and purpose (which may in large part be the fatigue).  I won’t know the results of the radiotherapy for another 4-5 weeks but have already decided that if I ever have to again choose between hormone therapy and cancer then I’ll take my chances with the cancer.


Having got all that off my chest I wondered if there are any other experiences of Relugolix acutely affecting mental health or whether I’m just unlucky and a statistical outlier?


Thanks

User
Posted 02 Aug 2026 at 21:24

I have been on Relugolix for 14 months and had 20 sessions of radiotherapy. I have not noticed any change in my mental state or any depression. My beef with Relugolix is that I am fed up with the side effects eg low libido etc. I am supposed to stay on it for 2 years and I asked if I could come off it and monitor PSA. They said that I was Gleason 9 and that there was a risk that cancer might spread somewhere else rather than prostate. I am staying on Relugolix for now but we will see.


 

User
Posted 12 Aug 2026 at 03:47

Originally Posted by: Online Community Member


I had a successful RALP in 2024 for 2c prostate cancer and all has been good until earlier this year when my PSA went up to 0.2.  A CT scan didn’t reveal any tumours but with a post-op Gleason of 4+5 I was recommended 20 fractions of radiotherapy along with several months of hormone treatment using Relugolix tablets. I have a history of depression but have been okay and off anti-depressants for several years.


However after only a couple of weeks on Relugolix my mood swings became increasingly erratic, I started to become disassociated and ended up going to the oncology Same Day Emergency Care service for my own safety (and sanity).  Unsurprisingly the hormone treatment was stopped.  I’m now 4 weeks further on and have just finished the radiotherapy and (leaving aside the exhaustion and tenesmus) my mental health has finally started to stabilise albeit I’m feeling devoid of motivation and purpose (which may in large part be the fatigue).  I won’t know the results of the radiotherapy for another 4-5 weeks but have already decided that if I ever have to again choose between hormone therapy and cancer then I’ll take my chances with the cancer.


Having got all that off my chest I wondered if there are any other experiences of Relugolix acutely affecting mental health or whether I’m just unlucky and a statistical outlier?


Thanks



I started it in February 2025, and within about 2–3 weeks I noticed a significant change in my mood — irritability, anxiety, poor concentration and a feeling of being emotionally detached that was very unlike me. I initially wondered if it was simply the stress of treatment, but the symptoms became noticeably worse the longer I stayed on it.


My oncologist stopped Relugolix in March 2025, and over the following 3–4 weeks my mood gradually improved. By around April, I felt much more like myself again. I had never experienced such a rapid change in my mental state from a cancer treatment before.

User
Posted 05 Sep 2026 at 23:19
Thanks so much for sharing Edward. My husband (about same age as you) had similar scary episodes about 6 months after starting Prostrap 3 (after RP and RT). Thankfully these calmed down and he found a way forward with training his thinking and exercise. He didn't have a choice to stop HT for 2 years.
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User
Posted 02 Aug 2026 at 20:42
Edward, I hadn't heard of this so I did a search and found only one paper looking at the question which failed to find any link in a sample of 87 patients. https://pubmed.ncbi.nlm.nih.gov/39896185/

I have also experienced salvage radiotherapy, but in my case the hormone therapy used was goserelin (Zoladex). I have to say that isn't something I would repeat from choice, so maybe your symptoms were due to the reduction in testosterone. The good thing about Relugolix is that recovery to previous testosterone levels is reported to be better than with other treatments so you may return to your previous quality of life. As you say though the fatigue impact of radiotherapy will also be a factor, so it may take another month or two yet.

Good luck.
User
Posted 02 Aug 2026 at 21:24

I have been on Relugolix for 14 months and had 20 sessions of radiotherapy. I have not noticed any change in my mental state or any depression. My beef with Relugolix is that I am fed up with the side effects eg low libido etc. I am supposed to stay on it for 2 years and I asked if I could come off it and monitor PSA. They said that I was Gleason 9 and that there was a risk that cancer might spread somewhere else rather than prostate. I am staying on Relugolix for now but we will see.


 

User
Posted 03 Aug 2026 at 07:39

Thanks Guys.


@J-B: I similarly assumed that the effect was caused by the loss of testosterone although one of the CNS did mention that the tablets can also affect serotonin levels, I think simply as a consequential wider imbalance of hormones.  However I can’t find any other reference to this.  Either way I’m glad that the direct effect of the tablets might be reasonably short.  I’m still getting some weak hot flushes which I’m hoping will settle down soon.


@Peter: golly 2 years sounds frightening so I’m glad that you haven’t had the same reaction.  I also had the low libido but under the circumstances and for the short amount of time I wasn’t too concerned.  I can well understand your frustration though. I’m interested that you also have a Gleason of 9 but if I’m interpreting you correctly it sounds like you still have your prostate and this is what’s further increasing the risk of the cancer spreading?


Thanks and good luck to you both.

User
Posted 12 Aug 2026 at 03:47

Originally Posted by: Online Community Member


I had a successful RALP in 2024 for 2c prostate cancer and all has been good until earlier this year when my PSA went up to 0.2.  A CT scan didn’t reveal any tumours but with a post-op Gleason of 4+5 I was recommended 20 fractions of radiotherapy along with several months of hormone treatment using Relugolix tablets. I have a history of depression but have been okay and off anti-depressants for several years.


However after only a couple of weeks on Relugolix my mood swings became increasingly erratic, I started to become disassociated and ended up going to the oncology Same Day Emergency Care service for my own safety (and sanity).  Unsurprisingly the hormone treatment was stopped.  I’m now 4 weeks further on and have just finished the radiotherapy and (leaving aside the exhaustion and tenesmus) my mental health has finally started to stabilise albeit I’m feeling devoid of motivation and purpose (which may in large part be the fatigue).  I won’t know the results of the radiotherapy for another 4-5 weeks but have already decided that if I ever have to again choose between hormone therapy and cancer then I’ll take my chances with the cancer.


Having got all that off my chest I wondered if there are any other experiences of Relugolix acutely affecting mental health or whether I’m just unlucky and a statistical outlier?


Thanks



I started it in February 2025, and within about 2–3 weeks I noticed a significant change in my mood — irritability, anxiety, poor concentration and a feeling of being emotionally detached that was very unlike me. I initially wondered if it was simply the stress of treatment, but the symptoms became noticeably worse the longer I stayed on it.


My oncologist stopped Relugolix in March 2025, and over the following 3–4 weeks my mood gradually improved. By around April, I felt much more like myself again. I had never experienced such a rapid change in my mental state from a cancer treatment before.

User
Posted 05 Sep 2026 at 17:38

@edwardshephard. Thanks for sharing. Much appreciated. I've been on Relugolix for 5 months and was about to start a conversation asking "Is anyone else getting their butt kicked by Relugolix?" 


Thankfully, I have not felt Relugolix affecting my mental health, apart from occassional bouts of listlessness. But my physical health has definitely been hit - I have not felt a tiredness quite like this before. That in itself has been somewhat depressing, as has the chronic sleep disruption, which itself erodes physical fitness and mental sharpness. 


If I spend the morning running errands, grocery shopping, maybe some time spent tidying the garage, by about 2 or 3 I am nodding off while trying to read or type. And during physical activity I get almost a warning feeling, like my body is telling me I'm going to regret doing even one more physical chore.


From the reading I have managed to do, it seems Relugolix (Rx for short) has a couple of advantages in my situation. I have atrial fibrillation and Rx is considered one of the bettewr approaches to crushing testosterone without affecting heart rate. 


The rapid recovery of testosterone upon stopping Rx is also appealing. I don't say this as a guy who frets about "low T" because I've had relatively low T (12) for 10 years while maintaining normla sexual function and holding down a high pressure job with lots of travel.


However, what strikes me is that the oncologists say things like "I'd like to keep you on the Relugolix for 18 months" which makes sense for absolutely crushing testosterone, but no sense at all if quality of life is a factor in the equation. Even six months of nightly sleep disturbance is a health risk in my opinion. And unless you've been given advice about avoiding penile atrophy Rx is a threat to resuming sexual functionality. (For the record, I have not heard anything from anyone involved in my prostate cancer treatment on the subject of penile atrophy).


@Peter My feeling is that oncologists are not giving adequate thought to the Rx side effects. And neither they or the urology folks are monitoring treatment closely enough. While I am being treated by the NHS, I have paid privately for tests that I think I need. My journey/strategy has been as follows: in March I chose hormone + radiation over surgery in response to a finding of Gleason 7 (4+3). This was after a biopsy prompted by PSA 9 and an MRI showing changes from 2024.


Before starting Rx in April I asked the urologist if he was going to test my testosterone level. This would seem essential to get a proper picture of how Rx was performing, and to measure recover. But he just said "No need, the Relugolix will crush it." So I paid for a test and it was 9.4 before Rx. I paid for another test after 50 days of Rx and my T was down to 0.6 (chemical castration = 1 and target for radiotherapy is 0.67. (Also, my PSA was down to 2.68 just due to Rx. Thankfully, when I showed these numbers to my NHS oncologist he scheduled the start of my radiotherapy (RT) for July 1, three months after starting Rx and three months earlier than previously stated.


I am now awaiting the first PSA results after the 4x5 RT sessions in July. 


Good luck to you both.

User
Posted 05 Sep 2026 at 17:53

Interesting comments, thankyou. Food for thought for my next oncology discussion. I am thinking of toughing it out on Relugolix for another 9 months whilst trying to keep my sexual function going although it is a struggle.

User
Posted 05 Sep 2026 at 21:38

We're cheering you on!


Take care ... Stephen

User
Posted 05 Sep 2026 at 22:20

Long before my prostate cancer I was treated for depression due to low testosterone, when they finally tested me for Low T I had been through many years of unsuccessfully depression treatment.


My Timeline:


1996, Left testicle removed due to infarction.
2000, Diagnosed with Clinical depression
2000 thru 2009, Unsuccessfully treated for depression using multiple meds 
2010, Tested & confirmed a VERY low testosterone level, Diagnosed with “low T induced depression”
2010 thru 2011, tried various testosterone therapies, Androgel, Androderm patches but T levels did not increase enough, then found Injections in my butt every 2 weeks Increased T levels but was very painful.
2011, Started surgically implanted Testopel, 8 pellets every 90 days
2012, I was able to stop all depression meds
2011 thru 2023, continued surgically implanted Testopel with no depression meds needed (12 years!)
2023, March thru June, High PSA detected, prostate biopsy confirmed aggressive cancer, Gleason score of 9, (4+5), PET Pylarify Scan indicate cancer is likely metastatic. Testosterone therapy stopped. Prostatectomy Surgery on 9-June, 2023
2023 thru 2024, PSA levels remained low, I did not require any radiation or use of Relugolix but my Testosterone level was barely detectable, fearing a bad depression I contacted a mental health doctor and asked to go back on depression meds, by the time I started depression meds (2024) I was in a deep depression and had to have help pursuing mental health treatment (medication & therapy). The medications helped allot but still not the same as before my cancer diagnosis. 
2025, I asked my urologist if I could re-start my testosterone therapy, he agreed to start me on subcutaneous testosterone injections ounce per week that I give myself in my stomach.
Today:  
I am getting my subcutaneous testosterone injections every Friday and my testosterone is considered normal for a 68 year old man AND I am taking two different depression medications (Vyvanse & Viibryd), my depression levels are very low (probable normal for a USA citizen). I only recently started talking to my mental health doctor about phasing out my depression meds but I am a little worried about this plan as things are going well for me now, although it would be nice to get rid of the side effects of the depression medications. 


Not sure if my story helps....    


Good Luck!


 

User
Posted 05 Sep 2026 at 23:19
Thanks so much for sharing Edward. My husband (about same age as you) had similar scary episodes about 6 months after starting Prostrap 3 (after RP and RT). Thankfully these calmed down and he found a way forward with training his thinking and exercise. He didn't have a choice to stop HT for 2 years.
User
Posted 06 Sep 2026 at 15:16

Thanks everyone for the comments and words of support.  It’s really interesting to hear about the potential for a direct link between testosterone levels and depression rather than as a side effect of the Rx medication itself.  It’s now about 6 weeks since I finished the RT and 8-9 weeks since I stopped the relugolix and I’ve still got significant fatigue and muscle weakness.  I should have thought that my testosterone levels should have recovered by now, but I’m seeing the oncologist on Wednesday for the post-RT results so there’s some useful stuff here that I shall raise. 🤗

 
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