Connect
Darolutamide Impact on Testosterone Utilization
I did 13 months of ADT (Lupron injections) with darolutamide (Nubeqa) while doing chemo then radiation. Now I’m on darolutamide only. While my testosterone is increasing, I’m slow to regain strength, especially in my legs. My understanding is darolutamide is a testosterone blocker. So I’m curious about it blocking testosterone utilization other than by cancer cells as related to my ongoing weakness.
Like
Helpful
HugInterested in more discussions like this? Go to the Prostate Cancer Support Group.
Connect
@mmacaulay, you are wondering if in addition to darolutamide blocking the use of testosterone by the tumor cells, it may also be blocking uptake of testosterone in healthy cells and thereby causing general weakness. Am I understanding your question correctly?
I see others like @kam23 @sam60 @john6stodolka @digby2023 @lorenbk @ssaftler @hergiew and more have written about leg weakness related to Lupron in these discussions:
- Lupron Depot: Weakness and instability side effects
https://connect.mayoclinic.org/discussion/lupron-depot/
- Lupron: Anyone have muscle weakness and severe leg pain?
https://connect.mayoclinic.org/discussion/lupron-muscle-weakness-and-severe-leg-pain/
For some the weakness resolved over time. @mmacaulay, How long has it been since you stopped treatment with chemo and Lupron? How long have you been on darolutamide?
-
Like -
Helpful -
Hug
2 ReactionsYes. I am having leg weakness. Is it improper to attribute this to Lupron?
It is my understanding that all the lutamide drugs block all the body's cells uptake of 'T' (testosterone), not just the PCa cells. Thus, even if you return to 'T' production after removal of other ADT drugs, the lutamides will not allow your body to use it as all the body's cell receptors are blocked from uptake of the replenished 'T'.
Again, this is my understanding of the lutamides. Please feel free to add to or correct me if needed.
Charlie
-
Like -
Helpful -
Hug
2 ReactionsThanks! I was wondering why nobody commented. Your understanding reinforces my suspicion that darolutamide is the reason why I remain weak even though my T is trending back up since I stopped Lupron. I especially have difficulty with stairs.
-
Like -
Helpful -
Hug
2 ReactionsI‘ve been off Lupron injections since March 1, after 13 months of once-per-month sticks. I started the injections shortly before doing six sessions of chemo (toxotere). Started darolutamide pills when I started chemo and am still doing the pills now for about sixteen months.
Glass is half full. Shouldn’t complain.
-
Like -
Helpful -
Hug
1 ReactionI’ve never heard of anybody doing the Nubeqa without the standard ADT(such as Lupron). I’m on both after completing chemotherapy and Pluvicto. It is my understanding I’ll be going off the Nubeqa within the next year and continue on the Lupron.
-
Like -
Helpful -
Hug
2 ReactionsWhile I'm hesitant to share with a large group, I noticed your are "director". So I assume you are associated with Mayo and having some much-desired credibility.
I've was diagnosed with Gleason 9 about three years ago with metastases in lymph nodes, including near my heart. My prostate specialist is Dr. Eugene Kwon of Mayo and my oncologist Dr. Hujec of Minnesota Oncology. I started with Lupron before doing chemo. Dr. Hujec prescribed Nubeqa when I did six sessions of chemo infusions with Dexter. Soon thereafter I did 24 sessions of SBRT at Mayo's facility in Northfield. My PSA went from 25 to less than 1.0 ng/dL and has stayed there for about two years. Meanwhile I've done bloodwork, PSMA PET scans and meetings with Dr. Kwon every three months at Mayo and more bloodwork and vists with Dr. Hujec also every three months.
So I've done Lupron and Nubeqa for 13 months followed by Nubeqa-only for another 17 months. My T has returned to about 350 and leveled off.
The reasons for this communique are about my state of chronic fatigue and development of gynecomastia. I've tried to exercise on a machine and hand weights. I've also gone to physical therapy sessions. But the fatigue continues, particularly in my legs. I have trouble with stairs. I love golf but now I have to use a cart. As related to the gynecomastia, I recently had some radiation at MN Oncology as the suggestion of Dr. Hujec. I haven't noticed any change for the better.
I'm 75 years old. I recognize that I should otherwise accept the inevitability of aging. But I'm determined that my fatigue is related to Nubeqa. Four pills a day. I keep wondering if the Nubeqa is preventing the onset of CRPC.
I'm about to do my three-monthly meetings with Drs. Kwon and Hujec. While I have tremendous respect for their abilities and knowledge, I sense I need to push back. I perceive that I might improve my quality of life for the few years I have left if I stop taking Nubeqa. Maybe a three-month or longer vacation? Or maybe at least reduce the dosage?
I'm also aware that my case is somewhat unique because blockers like Nubeqa are relatively new and certainly Nubeqa-only is ground-breaking.
Who can I turn to for independent counsel without offending the folks who have saved my life?
I' stopped Lupron after
-
Like -
Helpful -
Hug
1 ReactionI have the same doctors and treatment going on as you but only been off Lupron 4 months and my testosterone has yet to recover any. I too have the same problems going on as you and was hoping the return of testosterone would alleviate them. Dr.Kwon was not recommending me going off Lupron but I have found he is approachable to patients being proactive in their own care which he will go along with if test results are favorable to more than one treatment path. Dr.Hugec had previously talked to me about eventually tapering off the Nubeqa so I think if you present the way you feel to them I think they will work with you. Just my opinion. Good luck 🙏
My oncologist says gynecomastia can be stopped and maybe reversed chemically rather than with radiation. Maybe Tamoxifen? It’s worth asking.
I also have Dr. Hugec as my oncologist as well as oncologist Dr. Ian Okazaki, Masonic Cancer Center UofMN, MHealth Fairview. I am Gleason 9, had prostatectomy July 2024 and started Eligard (lupron) injections Nov 1 2024 which made lung nodules disappear. I started Nubeqa in January 2025 and declined triplet therapy at MN Oncology with chemo(docetaxel) due to neuropathy in feet and wanting to have quality of life without the effects of chemo. June 2025 "Arasens" trial results also support doublet therapy without docetaxel as a viable treatment for both metastatic and non metastatic prostate cancer, although OS is greater with triplet...granted if you can take the chemo. I have tolerated both Eligard and Nubeqa quite well and wonder if that may be because I have not had chemo?
QUESTION: Could the results of chemo cause more fatigue and leg weakness and not necessarily the Lupron/Nubeqa?
My PSA at MN Oncology has been .06 since November and .01 since November at Masonic Cancer Center - different results with different testing methods. Both are still "detectable" but not rising. Testosterone is 6. My LDH Panel has been rising since October and now is 230, so a concern.
I see Dr. Hugec next week to review test results and perhaps reconsider triplet therapy, although I am well beyond the 8 week recommended timeframe from introducing Nubeqa and Docetaxel together. Perhaps he will recommend continuing on Eligard and Nubeqa or adding chemo? No end to the scenarios.