Transdermal Oestradiol (‘oestrogen patches’) as Androgen Deprivation for the treatment of patients living with prostate cancer

Androgen deprivation (ADT - the suppression of testosterone) is a key treatment in the management of patients with prostate cancer, typically involving the use of depot injections of LHRH agonists/antagonists (LHRHa). Many of the side effects experienced by patients come from the consequent suppression of male oestrogens (derived from testosterone) as opposed to the testosterone suppression itself.

As an alternative method of ADT, the PATCH and STAMPEDE trials tested transdermal oestradiol (tE2) – ‘oestrogen patches’ – in patients with locally advanced and metastatic prostate cancer.

Results confirm there is no significant difference in prostate cancer control in patients with locally advanced prostate cancer treated with tE2 compared with LHRHa [1].  Transdermal oestradiol gives patients a choice between different ADT options, with tE2 offering several potential benefits [2]. These include significantly improved bone mineral density and better cholesterol and glucose profiles [3,4] in patients receiving tE2. Patients also reported significantly fewer hot flushes and overall better quality of life, possibly secondary to reduced nocturnal hot flushes leading to better sleep quality and less daytime fatigue. No increased risks of cardiovascular events were observed with tE2 therapy [5]. There is an increase in patients reporting gynaecomastia.

Although transdermal oestradiol patches are currently not licensed for this indication, patients may wish to discuss this option, either when starting ADT or if experiencing significant side-effects from LHRHa and as such we offer the following guidance based on our experience from PATCH and STAMPEDE.

If commencing ADT, an induction regimen of four 100mcg/24hr oestradiol patches changed twice weekly (e.g. Monday and Thursday) for four weeks is recommended. Femseven and Progynova were the brands used within PATCH and STAMPEDE. Consecutive patches should be applied to different sites. It is recommended that patches are placed on dry, intact and hairless skin and on areas where little wrinkling of skin occurs e.g. shoulder girdle, upper torso, upper arms, back, buttocks, hip or abdomen.  Avoid the nipples and genital area.

Advise patients that to apply the patch, they should remove the protective liner and then press onto the skin immediately and hold for at least 30 seconds to ensure proper adhesion. If necessary, tape can be used to fix the patch in place. If the patch is applied correctly, the patient can bathe or shower as usual. However, the patch might come off in very hot bath water. Dermatitis can be a fairly common side-effect of the patches, especially in the first 6 weeks. This can usually be controlled by alternating patch sites. If the patches become dislodged, patients should not put on extra patches but apply their next set of patches when they are due to be applied.

The aim is to provide an increase in the plasma level of oestradiol which is sufficient to achieve a castrate level of testosterone (<1.7nmol/L). A blood sample should be taken at 4 weeks after commencement of treatment with tE2 to check testosterone and oestradiol levels.

If the testosterone is suppressed after this “loading phase”, patients can then be reduced to three 100mcg/hr estradiol patches changed twice weekly, with monitoring blood tests every 12 weeks for the first year, and then every six months assuming stable levels are established.

Testosterone should be maintained at castrate levels (<1.7nmol/L) and the serum estradiol (E2) level between 250 - 2000 pmol/L (70 – 580 pg/ml).  These serum oestradiol level recommendations are based on trough readings (i.e.: a blood test taken the day prior to patch change); if the blood test is taken at other times, the reading is likely to be higher.

The number of patches can be reduced from three to two if oestradiol rises above the target range (>2000 pmol/l) and testosterone remains suppressed.

The number of patches can be increased from three to four if the testosterone level is not completely suppressed and oestradiol levels are low.

Blood tests should be checked four weeks after any dose change or any change in brand of patches.

The duration/indication of patch use would be the same as standard ADT (LHRHa) use.

PATCH and STAMPEDE protocols recommended avoiding concomitant cyproterone acetate as this can affect the metabolism of oestrogens.  In addition, Tamoxifen cannot be used alongside tE2 (e.g. for prevention of gynaecomastia) due to its interaction with the oestrogen receptor.  PATCH and STAMPEDE did not include patients known to have BRCA mutations.

Download clinical guidance (pdf)

References

1. Langley RE, et al. Transdermal Estradiol Patches in Locally Advanced Prostate Cancer. N Engl J Med. 2026 Mar 25. doi: 10.1056/NEJMoa2511781.
2. Gilbert DC et al. A Repurposing Programme Evaluating Transdermal Oestradiol Patches for the Treatment of Prostate Cancer Within the PATCH and STAMPEDE Trials: Current Results and Adapting Trial Design. Clin Oncol (R Coll Radiol). 2024 Jan;36(1):e11-e19.
3. Langley RE et al. A Randomised Comparison Evaluating Changes in Bone Mineral Density in Advanced Prostate Cancer: Luteinising Hormone-releasing Hormone Agonists Versus Transdermal Oestradiol. Eur Urol. 2016 Jun;69(6):1016-25. doi: 10.1016/j.eururo.2015.11.030.
4. Langley RE et al. Cardiovascular outcomes in patients with locally advanced and metastatic prostate cancer treated with luteinising-hormone-releasing-hormone agonists or transdermal oestrogen: the randomised, phase 2 MRC PATCH trial (PR09). Lancet Oncol. 2013 Apr;14(4):306-16.
5. Langley RE et al. Transdermal oestradiol for androgen suppression in prostate cancer: long-term cardiovascular outcomes from the randomised Prostate Adenocarcinoma Transcutaneous Hormone (PATCH) trial programme. Lancet. 2021 Feb 13;397(10274):581-591.