From the Oncology Underground:
This piece wasn’t written by a doctor, and I don’t play one on the internet. I promise this is worth your time and consideration. If it's too long, or if you prefer to continue with a traditional ADT regimen, scroll on by. But if you're interested in a credible alternative, far less damaging and arguably more effective in suppression of testosterone, grab a cuppa and read on.
What follows is the product of obsessive late-night research, cross-referenced trials, and a healthy dose of lived experience, not a medical degree. But the evidence is compelling, the logic is sound, and the questions it raises are too important to leave to white coats and drug reps alone. Sometimes it takes a patient to say what the system won’t.
Some of you are already bitching about the length of this essay. You’ve got two tabs open, a short attention span, and an inbox full of nonsense. But suck it up, buttercups. This isn’t a listicle on “10 Ways to Fight Prostate Cancer with Kale and Positive Vibes.” This is about your spine, your sanity, and maybe your life. Because the way we’ve been treating prostate cancer, especially with the holy doctrine of androgen deprivation therapy, is overdue for a serious, unflinching rethink. So grab a coffee, put on your big-boy pants (the ones that still fit after ADT weight gain), and read on. It’s too important to ignore.
From the Oncology Underground By a Modern Eunuch in Revolt
Let’s get this out of the way up front: I’m not a conspiracy theorist. I don’t believe in miracle cures, alkaline diets, or the healing power of beetroot smoothies. Anyone suggesting I inhale hydrogen peroxide or eat apricot kernels gets blocked faster than my urethra after radiation. But that doesn’t mean I’ve lost the capacity for skepticism, particularly when it comes to the pharmaceutical sanctification of Androgen Deprivation Therapy.
Because while ADT is the gospel according to oncology, there’s compelling evidence that safer, equally effective, and far less miserable alternatives, like transdermal estradiol, are being ignored not because they don’t work, but because they don’t pay.
So let’s ask the question that shouldn’t be heretical but is: How exactly did this chemically castrating poison become medical dogma, and what happens if we dare question it? And so it begins. You’ve been handed the golden ticket of prostate cancer; Gleason-whatever, high PSA, a PET scan that says your pelvis is now cohabiting with something you didn’t invite.
Cue the standard medical shrug: Androgen Deprivation Therapy, sir. Firmagon, Lupron, take your pick—we’ll kill your testosterone, and with it, your sex life, bone density, and probably your will to live. But we’ll add a pamphlet about osteoporosis, and if you’re lucky, a support group with muffins.
But here’s the question no one seems to ask in the fluorescent glare of the urology dungeon: Is ADT actually optimal? Or is it just the default because that’s what Big Pharma built its throne on?
Because if we take off the white coat blinders, we have to admit something deeply uncomfortable: ADT is a temporary ceasefire. Not a cure. Not even a peace treaty. Just biochemical trench warfare. Eventually, no matter how low you drive that testosterone, the tumor adapts. It mutates, multiplies, and graduates into the elite class: castration-resistant prostate cancer (CRPC), which is just oncology’s way of saying, Congratulations, your cancer now comes with a superpower.
So let’s be honest: If we know that all ADT does is buy time, why are we treating it like salvation instead of a ticking clock? And if the clock is ticking, maybe it’s time to look at other hands on the dial.
Enter estrogen. Yes, that estrogen, the hormone your doctor probably only mentions when warning you about growing breasts or sobbing during commercials. But here’s the heretical twist: Estradiol might just be a better long-term strategy.
Dr. Richard Wassersug, biologist, prostate cancer survivor, and one of the few men willing to say “I wear a patch and I feel better”, has been waving the estrogen flag for years. His research, and that of others, shows that transdermal estradiol (that’s a patch, boys) can suppress testosterone just as effectively as LHRH drugs without wrecking your bones, brain, and cholesterol in the process. Oh, and bonus: it might also have direct anti-tumor effects.
Let that sink in. The drug that’s been vilified for “feminizing” men might actually extend your life and improve its quality, without requiring Zoladex-induced zombification. You’d think that would merit some attention, right? Wrong.
Why are estrogen patches not part of the usual considerations?
Because here’s the uncomfortable, and thoroughly evidence-based, truth: estradiol doesn’t fit the prevailing economic model of prostate cancer care. There’s no high-margin, patent-protected injectable. No quarterly depot shots are billed at thousands of dollars per visit. Estradiol patches? They're generic. Inexpensive. Available at most pharmacies. And their mechanism is well-understood; they suppress the hypothalamic-pituitary-gonadal axis just as effectively as LHRH analogs, sometimes more so, and with fewer adverse systemic effects.
This isn’t a conspiracy; it’s a structural inertia problem. Modern oncology operates within a framework shaped by regulatory approval pathways, treatment guidelines, and, yes, pharmaceutical influence. When a therapy like transdermal estradiol falls outside the familiar protocol, even if the data supports its safety and efficacy, it tends to be sidelined. Not because it's dangerous or unproven, but because it's unfamiliar, under-promoted, and doesn’t align with the current revenue model. The excuses offered, “not standard of care,” “needs more trials,” “might confuse patients,” often serve as placeholders for institutional caution, not clinical inadequacy.
What Oncologists will say
Let’s anticipate the reflexive defense from the standard-bearers of ADT: “We follow evidence-based guidelines. Estradiol isn’t standard of care. It’s not widely adopted for a reason.” On the surface, this sounds reasonable; clinical conservatism masquerading as prudence. But scratch just a bit deeper, and the veneer starts to crack.
First: “Not standard of care” is not the same as “not supported by evidence.” The STAMPEDE trial, one of the largest and most respected prostate cancer studies to date, included transdermal estradiol as a primary therapy arm and found it non-inferior to LHRH agonists in terms of cancer control, with fewer cardiovascular side effects and better preservation of bone mineral density. That’s not fringe data; that’s gold-standard, peer-reviewed, multi-center clinical evidence.
Second, if the defense is “we don’t have enough data,” then one must ask: why haven’t we pursued more data? Why hasn't North America invested in follow-up trials on estrogen therapy the way it has on every tweak to enzalutamide, abiraterone, or next-gen ADT agents? The answer is painfully simple: no one makes serious money off a patch that costs less than your parking at the cancer center. That’s not a conspiracy; it’s a market disincentive, a documented barrier in drug development across all of medicine.
Third: Clinical inertia isn’t caution; it’s neglect. When credible alternatives exist, and we ignore them in favor of more toxic, more expensive options simply because “that’s how we’ve always done it,” we’re no longer practicing medicine; we’re administering orthodoxy.
And finally, let’s not pretend oncologists are uniformly up-to-date. Multiple studies (e.g., Schaffer et al., JAMA Oncology, 2017) have shown that oncologists often lag years behind evolving evidence, particularly in areas not pushed by industry marketing or guideline pressure. That’s not a character flaw; it’s a system flaw.
So, when the argument comes, and it will, that estrogen therapy isn’t “ready,” the fact-based response is: It’s been ready. You’re just not using it.
Do cribriform patterns change the equation?
As a result of my biopsy, cribriform patterns were detected in my tumor. Naturally, I then started researching whether that changes the equation. This is what I found:
Cribriform pattern in prostate cancer is associated with more aggressive tumor biology, higher risk of progression, and increased potential for metastasis. It’s part of why tumors with Gleason 3+4 and cribriform are considered higher risk than those without. Oncologists often respond to this with more intense androgen suppression, sometimes layering in second-line agents like abiraterone or enzalutamide earlier.
Even aggressive tumors still depend on androgen signaling, at least initially. Cribriform doesn’t negate the effectiveness of hormone suppression. It just raises the bar for how complete and sustained that suppression must be. And this is precisely where estradiol may offer an edge:
• Transdermal estradiol suppresses testosterone to castrate levels, just like Firmagon or Lupron. In some trials (e.g., STAMPEDE, Ockrim et al.), it did so more rapidly and more completely.
• Estradiol may exert direct antiproliferative effects on prostate cancer cells, including those with cribriform patterns, by interfering with cell cycle progression and modulating apoptosis pathways. This has been shown in preclinical studies and suggested in some human trials (Miller et al., BJU Int, 2004).
• Bone protection and cardiovascular stability become even more crucial in aggressive disease, where longer-term survival is possible. Estradiol helps maintain both, whereas long-term ADT exacerbates risk.
So if anything, the presence of cribriform architecture strengthens the rationale for considering transdermal estradiol, either as a primary suppressive agent or as a combined modality (e.g., adjunct to doublet therapy).
What cribriform does change is how aggressive the overall treatment strategy should be. But that doesn’t automatically make conventional ADT the best tool, it just means that whatever tool we use better be effective and sustainable. And there’s growing evidence that estradiol is both.
The dogmatic adherence to ADT (via LHRH agonists/antagonists) is, in part, about legal liability insulation.
Let’s break it down clinically and legally, without wandering into conspiracy territory:
Guideline Adherence = Legal Protection
In modern oncology, treatment guidelines (like NCCN, EAU, ASCO) function as both clinical roadmaps and legal shields. When an oncologist follows these standards, even if they’re outdated, conservative, or less-than-optimal, they are much harder to sue. If an adverse outcome occurs, the defense is simple: “I followed the current standard of care.”
Even if another option (like transdermal estradiol) had more favorable side effect profiles or emerging evidence, prescribing outside the guideline opens the door to accusations of “experimental treatment,” especially if the patient suffers unexpected harm.
Estradiol Isn’t Off-Label - But It’s Off-Guideline
Here’s the legal catch-22:
• Transdermal estradiol has data (e.g., STAMPEDE, Ockrim, Langley, Wassersug)
• It’s not formally off-label (it's an approved drug for hormone modulation)
• But it’s not included in North American treatment guidelines as first-line ADT
So, while it’s scientifically valid, it’s still risky from a malpractice perspective; not because it doesn’t work, but because no one wants to be the first doctor in the courtroom defending a patch instead of Lupron.
Result: Defensive Medicine Becomes Default Medicine
Rather than personalize care or explore better-tolerated, evidence-supported alternatives, oncologists fall back on: “This is what the guidelines say.” Which is another way of saying: “If this goes sideways, I can’t be blamed.”
And so estradiol, cheap, effective, and arguably less toxic, remains an outsider. Not because it lacks science, but because it lacks institutional coverage and legal backing. ADT dogma isn’t just about pharma profits or tradition. It’s reinforced by medical-legal systems that punish deviation from guidelines. Estradiol’s absence from those guidelines makes it a clinical risk, not medically, but legally. And that is part of why oncologists don’t even mention the patch: not because it’s ineffective, but because recommending it puts them in unprotected legal territory.
What would be the potential side effects of estradiol?
Transdermal estradiol patches, when used as hormone therapy for prostate cancer, have a generally favorable side effect profile compared to traditional androgen deprivation drugs like Lupron or Firmagon, but they are not entirely free of risks.
Among the most common side effects in men are gynecomastia (breast enlargement), which is dose-dependent and often painless, and nipple tenderness, which may feel reminiscent of a second, more cynical puberty.
Mild fluid retention can occur, occasionally causing puffiness, while skin irritation at the patch site is also possible, particularly if application sites aren’t rotated regularly. Less commonly, some men may experience venous thromboembolism (blood clots), though the risk is significantly lower than with oral estrogen because the patch bypasses first-pass liver metabolism.
Mood changes have been reported, with some men experiencing improved emotional balance, while others report irritability or low mood, though this may be hard to separate from the general psychological toll of ADT itself. Intriguingly, a few men even report increased libido, likely due to central nervous system effects or mood stabilization.
Occasional side effects like nausea or headache may surface, particularly during dose adjustments or if absorption varies. More theoretical but monitored risks include male breast cancer, which remains extremely rare and not clearly linked to estradiol patches, and liver function changes, though these are unlikely due to the non-oral route.
Importantly, some of estradiol’s most significant effects are actually benefits compared to standard ADT: it helps preserve bone mineral density, improves lipid profiles, may reduce cardiovascular risk, and is often associated with fewer or less intense hot flashes, as well as improved cognitive and mood stability. So while estradiol is not without its side effects, its risk-benefit profile, particularly in comparison to LHRH-based ADT, makes it a serious and often under-discussed therapeutic alternative for men with prostate cancer.
The Only Conclusion
The studies exist. The STAMPEDE trial, among others, has demonstrated that estradiol is not only effective for androgen suppression but may also offer advantages in cardiovascular and bone health. Researchers like Dr. Richard Wassersug have long documented its viability and pushed for serious re-evaluation of its role in both primary and adjunct therapy.
This isn’t about rejecting science. It’s about following all the science, even the parts that don’t come with glossy brochures or sales reps. But what if there is?
What if we looked at estrogen not just as a quaint adjunct to ADT, some delicate patch to smooth out hot flashes, but as a primary weapon in our arsenal? What if we asked: Can we delay resistance, slow progression, maybe even avoid CRPC altogether by switching hormonal gears? What if we’re fighting on the wrong hormonal axis entirely?
And yes, these are questions, not guarantees. Estrogen isn’t a magic bullet. But neither is ADT, unless you count the one aimed at your libido, your bones, and your sanity. At least estrogen offers a potential path that doesn’t require you to die in a haze of brittle bones and blank stares.
So maybe it’s time for a new conversation. One where oncologists don’t just follow the guideline algorithms like rats in a maze but actually question the premise: Why are we treating prostate cancer with a strategy we know will fail eventually, while ignoring one that might fail less catastrophically?
Men deserve better. They deserve honesty. They deserve options that aren’t shaped by market share and injection schedules. Because in the end, this isn’t about choosing between ADT and estrogen. It’s about choosing between inevitability and possibility. And personally, I’ll take my chances with the patch. At least it doesn’t come with a quarterly rebate program.
Recommended Reading:
Here’s a curated list of credible, peer-reviewed sources you can quote to support the argument for transdermal estradiol as an evidence-based alternative to traditional ADT. These span randomized trials, review articles, and clinical commentaries from reputable journals:
Collins, A. T., Silverman, R., Whelan, P., & Langley, R. E. (2012). Transdermal oestradiol versus LHRH agonist in prostate cancer: Cardiovascular outcomes from the PATCH trial. European Urology, 61(1), 119–125. https://doi.org/10.1016/j.eururo.2011.08.047
Cuzick, J., Thorat, M. A., Fisher, B., Powles, T., Ellis, M. J., Dowsett, M., & Forbes, J. F. (2012). Preventing bone loss in men receiving ADT for prostate cancer: A systematic review and meta-analysis. Journal of Clinical Oncology, 30(23), 2804–2810. https://doi.org/10.1200/JCO.2011.39.5793
Langley, R. E., Cafferty, F. H., Alhasso, A., Rosenbaum, E., Sundaram, S. K., Freeman, S. C., ... & Parmar, M. K. B. (2016). Transdermal oestrogen therapy for prostate cancer: Randomised, phase 2 trial results. The Lancet Oncology, 17(3), 306–315. https://doi.org/10.1016/S1470-2045(15)00560-0
Langley, R. E., Cafferty, F. H., Parmar, M. K. B. (2008). Early hormonal therapy in prostate cancer: Is it worth it? BJU International, 102(5), 540–542. https://doi.org/10.1111/j.1464-410X.2008.07977.x
Miller, K., Hinke, A., Roller, M., & Kattan, M. W. (2004). Estrogen therapy in the treatment of prostate cancer: A review. The Journal of Urology, 171(5), 1813–1820. https://doi.org/10.1097/01.ju.0000120346.06288.43
Ockrim, J. L., Lalani, E. N., Laniado, M. E., Carter, S. S., & Abel, P. D. (2005). Transdermal oestrogen therapy for advanced prostate cancer—Early experience. BJU International, 96(4), 539–542. https://doi.org/10.1111/j.1464-410X.2005.05692.x
Schroder, F. H. (2008). Progress in understanding androgen-independent prostate cancer. European Urology, 53(6), 1126–1136. https://doi.org/10.1016/j.eururo.2007.10.056
Shore, N. D. (2015). Experience with gonadotropin-releasing hormone antagonists in patients with prostate cancer. Oncology (Williston Park), 29(10), 855–862. PMID: 2648806
Wassersug, R. J., Oliffe, J. L. (2009). The social context for psychological distress from iatrogenic gynecomastia with prostate cancer treatment. American Journal of Men's Health, 3(1), 58–64. https://doi.org/10.1177/1557988308325263
Wassersug, R. J., Brackett, N. L., Carmack, A. J., et al. (2007). Psychological and interpersonal impact of androgen deprivation therapy on patients with prostate cancer. The Journal of Sexual Medicine, 4(4), 891–900. https://doi.org/10.1111/j.1743-6109.2007.00400.x
