2025 Survey – Estradiol Initiative

Key findings from the 2025 survey of prostate cancer patients’ interest in alternative forms of ADT

Background

Rush et al. (2025) published a focus group study that included 14 PCa patients with early-stage PCa who had never been on any form of ADT, and an additional 10 men of similar age (50+) who had never been diagnosed with PCa. https://bjui-journals.onlinelibrary.wiley.com/doi/10.1111/bju.16863

The men in the focus groups discussed their views on three options for ADT:

standard Luteinizing Hormone-Releasing Hormone (LHRH) agonist and LHRH antagonist depot injections,
the daily oral LHRH antagonist pill Orgovyx (= relugolix),
transdermal estradiol (tE2) administered following the PATCH/STAMPEDE trial protocol (NCT00268476), which involved wearing multiple tE2 patches changed twice a week.

Overall, the men favored having options for ADT. After receiving information about the side effects of the three treatments, 14 participants favored the pill, 8 favored the tE2 patches, and two preferred the standard depot injections.

Our E2-I team was aware of the Rush et al. study before its publication and felt we could extend their research. We took on the challenge of collecting more data on PCa patients’ interest in options for ADT

This led to our anonymous survey of PCa patients’ “Interest in Alternative Forms of ADT”. The study was funded by the Schellhammer Urological Research Foundation in Virginia USA and was for PCa patients primarily in Canada and the United States, where most of the E2-I team are based.

Upon receiving official institutional review board approval for the study we invited any man diagnosed with PCa to complete the survey online. We intentionally reached out to men with different PCa treatment histories in order to capture diverse perspectives (e.g., Active Surveillance, traditional ADT, no ADT, prostatectomy only, radiation, chemotherapy). The survey ran from March to May in 2025.

Here’s a summary of our major findings…

Participants

Over 800 men completed the survey: 45% from the United States, 41% from Canada and 14% from other countries.

Participants overwhelmingly (~95%) favored having tE2 as an approved standard-of-care option in their country.

Of the entire sample when asked about preference for one form of tE2 over another, 22% preferred the tE2 patches following the PATCH/STAMPEDE trial protocol. However, 47% of respondents preferred topical tE2 gel/cream products. 31% had no preference.
The highest overall interest in having tE2 options were among PCa patients who had never been on ADT.
Older participants reported significantly more interest in tE2 than younger participants.

Interest in other forms of ADT

16% of men ranked long term depot injections of the standard LHRH agonists (e.g., Lupron Eligard, Zoladex) as their first choice for ADT. 3% ranked Firmagon injections as their first choice.
However, 14% ranked the daily Orgovyx pill first and 16% ranked tE2 products as their first choice. Those who ranked the depot injections as their first choice for ADT reported low interest in tE2 products.

Perspectives on side effects of different forms of ADT

48% of participants expressed “much concern” or “extreme concern” about osteoporosis (i.e., bone loss) as a major reason for favoring tE2 products over standard ADT depot agents.
37% of participants expressed “much” or “extreme concern” about gynecomastia (i.e., breast growth and sensitivity), but only 17% reported much or extreme concern about dermatitis (i.e., skin irritation) from tE2 patches.

Willingness to overcome barriers to use of tE2

The highest interest in tE2 products was seen in men with no concern about the need for daily application of topical gels or creams.
Over 90% of participants reported a willingness to have more frequent blood tests when starting tE2.
Those who had the highest interest in tE2 as an option for ADT were the most willing to pay for it out of pocket and to pay the most for it; i.e., 40% were willing to pay more than $35 US dollars per month.
Over 70% of the men were willing to seek and pay out-of-pocket for off-label access to tE2.
Of the entire sample, 75% were willing to consult more than one physician about off-label tE2, if first declined a prescription from their oncologist.
Over 250 participants left additional comments about ADT.

Selected Comments from Survey Participants

The survey ended with an open-ended question: “Is there anything else you’d like to share about your views on alternative options for ADT?”

Many, though not all, comments included opinions about the perceived pros and cons of the standard drugs used to treat prostate cancer (PCa). Some participants also offered opinions on tE2 options for ADT.

Below are examples of comments left by participants, categorized as positive or negative opinions on the various forms of ADT. Many participants left us comments about their history with prostate cancer treatments or opinions on the survey itself. These were excluded from further analysis if they did explicitly present positive or negative assessments of one form or another of ADT.

The comments were categorized by two members of our team who conferred about their classification until there was 100% agreement on what constituted positive or negative comments. Below the representative quotes, we summarize the data to compare perspectives on the various forms of ADT.

We have sorted them into three categories, as numbered below.

1. How do the patients describe the challenges of PCa treatment with standard ADT agents (i.e., LHRH agonist/antagonist depot Injections and the oral drug Orgovyx)? ☹️

I’ve been on ADT (Eligard and Abiraterone) for 7 years. Most of the common side effects went away within the first year. Muscle mass loss and depression are the two side effects I still struggle with, and depression in particular I have had minimal support for, from either my urologist or family doctor. It’s very frustrating.
It’s a bitch but I’m on the right side of the grass.
Had ADT – developed osteopenia (undiagnosed) – fell – 3 pelvic fractures plus spinal damage leading to fusion – alternatives to ADT urgently needed.
It seems like [ADT] impacts patients somewhat differently. It seems like it has a varied impact on me over the past 30 months, perhaps accumulative. The longer I have been on it, the more difficult it is for me to live a normal, active life.
There is no information here on the emotions caused by ADT. This is important to me as it was the most difficult side effect to deal with. I eventually worked with a mental health professional to work through it.
Lupron worked but was a quality-of-life disaster for me.
It would be great if we could come up with a treatment that would eliminate the hot flashes, loss of libido and other side effects.
I’d really be happy to have an ADT treatment without hot flashes.
I was on Lupron for two years after focal SBRT. Lupron took all the living out of life. My get-up-and-go, got-up-and-went. Cancer has returned in the other side of the prostate. Currently I have refused returning to Lupron because of lifestyle degradation.
My ADT – Zoladex – made me tired throughout the course. I could not find “tiredness index” associated with the various drugs available in Canada. If I could, I would choose a drug that would make me the least tired. Perhaps they are all the same by driving testosterone to zero.
More options the better, as PC treatments are harsh on the body, to minimize any of the side effects such as osteoporosis. [I]t is critical options of this nature are made available.
Anything that works without the side effects from Lupron, especially for patients with prior heart condition.
If I ever have to go on ADT again, I will choose early death if no other options are available. It was the worst experience of my life. I was only on it for six months and now I have severe osteoporosis, when my Dexa [scan] was normal pre-ADT, [and] my penis shrank. I’ve been off Orgovyx [for] six months and my testosterone is still hypogonadal and I was told it may never recover…I’m severely depressed.
ADT has been, by far, the worst part of my treatment. Doctors absolutely did not prepare me adequately for the side effects.
More options for men who require ADT are very important.
I wish I had known more on ADT before starting it.
ADT Eligard has too many bad, life-altering side effects even though it keeps PSA at .01. Make anything else that works but has no mood swings, hot flashes, muscle loss, ED, bone loss, fatigue, and joint pains.
I was previously on Orgovyx for 24 months. If I had to go back on ADT, I would strongly consider orchiectomy as first choice over medical castration. This is a topic that I do feel needs more discussion as an alternative form of ADT but has been eliminated from discussions by many patients and physicians.
I had an awful experience with Lupron. I had almost every side effect. ANYTHING that can be less debilitating and yet still reduces T to fight PCa seems worthwhile to me.
ADT has been brutal on me. I wish Oncologists presented more info on ADT options and side effects prior to start as well as a better means of dealing with them. It is only from me seeking information from different sources that have led me to suggest options to my oncologist. I started on monthly Lupron and did some research and then switched to Orgovyx. Also consulted with urologic oncologist when radiation oncologist didn’t offer any means to deal with side effects. No baseline measures of T or bone density taken prior to [treatment]. I advocated for DEXA scan and have major density loss. The list goes on and on. Need more support when diagnosed.
Having had Lupron injection treatment, and experiencing most of the side effects, I will not consider any of the options if continued treatment is deemed necessary.
Fatigue is a killer. Omg.
Side effects from ADT are very serious and this info is not easily available from your urologist prior to starting your treatments.
I can’t have an erection; I have hot flashes; I’m moody; I’m scared. But, I’m alive!
ANYTHING would be better than current forms of ADT. I was only on it six months and have been off it quite awhile now but my T didn’t return. I have osteoporosis, my penis shrunk considerably, and I’m extremely depressed and angry about all of these things. The worst is DOCTORS NEVER TOLD ME THESE THINGS COULD HAPPEN.
I do have osteoporosis as a result of long-term ADT. A[n] effective ADT drug that minimizes bone loss would be of very significant benefit to me. I am also experiencing muscle loss, which is beginning to impair my activity level. An ADT drug that minimizes muscle loss would also be very interesting.

2. What do the patients envision as the benefits of ADT with LHRH agonists/antagonists? 😊

I am doing very well on standard treatments, Xtandi plus Eligard, so [I] would be very reluctant to switch. [P]resently, I think that my oncologist feels the same way. If I am responding so well, why change?
If something works, don’t fix it.
The ADTs are known products, with known side-effects, and known methods of minimizing/avoiding side-effects; the newer patch/gel products mentioned have no local track record. That would be a problem for me to choose them.
I find Orgovyx easy to take one pill a day and I tolerate any adverse effects ok. It would remain my treatment of choice.
I have been on Lupron (injection every 4 months) for 12 years and am 80 years old, so [I] am unlikely to change as it has kept PSA at a reasonable level (currently 0.58).
Done so well on Eligard + 100 supplements (Patrick, Nal, etc.) that no need to change to the superior E2. Plus there seems to be some question about the use of E2 after metastases are found (common iliac and para-aortic nodes).
The Question “If you wanted to use tE2 for ADT, how many additional physicians would you be willing to consult if your current doctor declined to prescribe tE2 “off-label” for ADT? (pick one)” should also have the option: None, because I trust the advice of my doctor.
I am happy with, through meds, no hot flushes and no pains despite having metastasized cancer in hip and back. The quarterly Zoladex injections seem to work fine. Yes, I have osteoperosis [ and am] getting Prolia injection. I believe I get the best care possible at Princess Margaret Hospital. I am grateful for all the assistance I do get. I am also on Apalutamide, Tamsusolin. finasteride, Blood thinner 60 mg, Cyproterone.
For short-term ADT (6 months) I would prefer the pill type so I could recover testosterone faster, but if I have to go on long-term, life-long ADT, I would probably go for the injection style.

3. How do men view transdermal estradiol (tE2) products as options for ADT? 😊

I am currently on traditional ADT (Lupron + abiraterone) plus tE2 for symptom management. If I’d been starting my ADT today, I’d have chosen tE2 as the primary ADT.
Estrogen patches have [the] least…side [effect] risks. [tE2] provides bone health [protection]…and is a scalable therapy that can [be] increased/decreased incrementally subject to bloodwork testing.
Estradiol looks like a good one with lesser risk of truly bad side effects like muscle wasting, bone breakage, maybe less cancer brain fog and no sweats. Medroxyprogesterone was given to me after 5 months of terrible sweats and worked [in] a week. Why not sooner?
I would want to try [tE2] for the least side effects.
Much prefer [tE2] Patch over Lupron or the like. But hard to find a doc that will prescribe it.
I was previously on ADT (Orgovyx) for 24 months. Should I need to go on ADT again I would strongly consider orchiectomy. I would also be open to considering estradiol. Would need more information.
tE2 is, in my opinion, definitely the way forward subject to BIG PHARMA allowing it to be approved. The many benefits arising from it far outweigh, in my opinion, any potential downside. I am from the UK where it also is not approved; however, I am awaiting a meeting with my MDT to put forward my case for using tE2 as my first treatment following prostatectomy 3.5 years ago. I have been informed that there is a good chance I will be successful.
I realize that the Patch study results are relatively recent, but I am a little concerned about the medical community’s reluctance to adopt Estradiol earlier, since it was obvious that it mimicked the effects of Lupron with less side effects. I have difficulty sleeping on Lupron and hate the hot flashes that wake me up.
[I] would like consideration for Eligard plus lo[w]-dose estrogen patches to help with hot flashes and other side effects, but my urologist will not approve.
tE2 should be approved as SOC [standard of care] in the US. It would save many men from suffering from the undesirable SEs currently experienced and quite possibly prove to be more efficacious in providing durable remissions.
I love the ESTROGEN Patches compared to Lupron !!
I am using gel and am happy. Fifteen years since diagnosed and going strong.
I find that tE2 is a very effective, inexpensive, and painless, form of ADT. I highly recommend it.
Been on [tE2] patches for 3 weeks. Testing in 2 more weeks. Kaiser was reluctant to prescribe but City of Hope talked Kaiser into prescribing. So far, I like patches instead of Orgovyx. Patches are free at Kaiser.
Thanks for doing this. tE2 sounds like a great option.
Have been unable to get tE2 from a local doctor.
The [tE2] gel should absolutely be made an option for men. The more choices we have, the better the outcome.
Side effects of ADT…are not good. I am happy I am on estradiol gel as it does not have the side effects. Occasionally… some months, there is a spike in PSA, but that is, I believe, from missed dosing. Last 12 months there has been a slowly increasing PSA.
Thank you very much for bringing this information to our attention. It is important that tE2 gets approved and available in North America. I would definitely opt for it.
Happy to pay to reduce hot flashes.
When I was on ADT as part of my radiation treatment, I found the side-effects, specifically hot flashes, unbearable. It made life not worth living. Luckily, it was only for 6 months (but side effects lasted 1 year). I would not consider going on this same drug again, should there be a reoccurrence. So it’s good to know about tE2 as this would be an option I would take, even if I hadto leave the country or pay out of pocket to get this medication to reduce the hot flashes.
I am very concerned about ADT side effects, and loss of bone and muscle. Based on the study, I would prefer to use the “Patch”.

Summary of survey comments

Of the 74 comments that expressed opinions on the various forms of ADT, 84% were negative comments on the LHRH agonist and antagonist depot injections. Far fewer negative comments were presented for the LHRH antagonist pill Orgovyx or various forms of tE2. Two patients presented positive comments on the perceived benefits of an orchiectomy, but the sample size was too small to draw any conclusions in comparison to the drugs used ADT.

Comments about Orgovyx were about 3.7 times more likely to be positive compared with comments about traditional ADT.

	Total	Pro 😊	Con ☹️
Traditional ADT	74	12 (16%)	62 (84%)
Orgovyx	12	5 (42%)	7 (58%)
tE2	23	23 (100%)	0
Orchiectomy	2	2 (100%)	0