Estradiol, QoL and inflammation

[Cliff-hanger]

Although I have been following the exchanges of this group for several months, this my first posting. I have (at 79) learned a lot from the pooled knowledge and experience of the group members. My inquiry ties in with posts regarding estradiol and the PATCH trial that have appeared the last couple of days.

After PCa diagnosis I started on Firmagon (June 2022, PSA 45), followed by SBRT. PSA was 7 in December 2022 and rose to 27 in May 2023. After Zytiga and Medrol were added. PSA declined to .40 in February 2024.

While I have been happy with recent treatment, the meds brought on joint and muscle pain and aggravated mobility issues (previous back surgery, three collapsed vertebrae). Together with fatigue and depression, I was desperate to regain at least part of my life and started with estradiol patches to reduce side effects (one 50 mcg patch every four days—finding the right dose was rather hit and miss). This led to great improvement of my physical and mental state, also much appreciated by my family.

There are, however two developments that are a bit unsettling. Whereas I had experienced some discomfort from the monthly Firmagon shots, this was easy to manage. After I started with estradiol early this year, the January and even more so the February Firmagon shot caused serious discomfort-- shivering and feeling unwell for more than 24 hours. Is Firmagon trying to tell me to cut it out, as its task has been taken over by estradiol?

The other change is more disconcerting. I have looked at signs of inflammation measured from blood samples for nearly ten years, in particular CRP (C-Reactive Protein), which should stay below 5. When it rose to low 20s seven or eight years ago, I received no satisfactory explanation. CRP then declined steadily for years, reaching .8 in January 2024. In February it suddenly jumped to 63.9. Although a mild lung infection started around the time the sample was taken, my primary care physician thought it was not significant. Did estradiol play a role? I obviously want to avoid endangering the course of treatment. As a high CRP can only lead to nasty consequences, I hope to be able to rule out a possible role of estradiol (and then find the real cause) before moving further down that road.

I don't know whether anyone ever looked at these issues, but I’m sure I’m addressing the right company.

[Tall_Allen]

Two different uses of estradiol patches:

(1) low dose - to help with some side effects of traditional ADT - bone mineral density loss, hot flashes, mood changes

(2) high dose - to replace traditional ADT. It causes the testes to stop producing testosterone.

We are awaiting the results of the PATCH/STAMPEDE trial that will demonstrate if it is indeed as effective as traditional ADT at prolonging survival. So far, we only have toxicity data. It has shown that it does not cause an increase in blood clots, which was a concern of oral estrogens. Unfortunately, it will not tell us whether the combinations with other hormonals (Zytiga, Xtandi, Erleada and Nubeqa) with chemo or with both are as effective.

[Gabby643 in reply to Tall_Allen]

Thanks T A!

[Cliff-hanger in reply to Tall_Allen]

Thanks for your response. I interpret the Estradiol dosage used in the PATCH trial as being about 10 times higher than what I am using now. The trial aims specifically at replacing standard ADT with high dose Estradiol. I have not found any evidence of there being a conflict between Firmagon and low dose Estradiol intended to reduce ADT side effects. Yet that is what my recent use might point at. Hence my inquiry whether anyone else combining the two experienced more severe reactions than usual.

[Break60 in reply to Cliff-hanger]

I’ve been on three .1 mg estradiol patches changed weekly and one 80mg Xtandi tablet since 2021. Results have been great. T of <3.0 and psa of <.1.

Incontinence is my big problem.

[MBACHE]

I had almost the same symptoms from the Firmagon shots as you did. Although they lasted only a few hours and would start during the night while I was sleeping. I experienced very violent shaking and also was very cold. This occurred after taking firmagon for several years. The shaking episodes at first happened sporadically and then continuously. I then switched back to Lupron with no further issues.

[Cliff-hanger in reply to MBACHE]

Were you using Estradiol at the time? Perhaps your body rebels after it has received Firmagon shots for a long time. My inquiry was more specifically whether any Firmagon users started experiencing adverse reactions after also adding Estradiol.

[janebob99]

I looked at a some papers, and found a good one:

ahajournals.org/doi/10.1161...

It says:

"After 6 months, C-reactive protein was increased by 10% in the group with the estrogen patch and by 48% in the group taking the oral estrogen pills. At 12 months, the C-reactive protein levels were 3% in the group on the patch and 64% in the oral estrogen group."

This makes sense, because the patch skips going through the liver, where all the bad effects of cardiovascular problems are created (e.g., blood clots).

You could consider stopping Lupron and just castrate yourself using High-Dose Estrogen. The patch study used 3 patches per week. I don't know how many you are using. You should monitor your estradiol and testosterone levels to demonstrate that you've castrated yourself. The goal should be <10-20 ng/dL, not 50 ng/dL (which is too high).

Bob