Costs & Effectiveness of tE2 Products

Introduction

Recently, it has been demonstrated that transdermal estradiol (tE2) patches are as effective as luteinizing hormone releasing hormone agonists (LHRHa) for androgen deprivation therapy (ADT) [Langley et al. ESMO 2024; James et al. ASCO-GU 2025; and Gilbert et al. EAU 2025]. Prostate cancer (PCa) patients using tE2 patches for ADT experience few, if any, hot flashes and have overall better quality of life. Estradiol (E2) also protects bone mineral density, eliminating the need for using bone protective agents, with no increase in cardiovascular morbidity.

However, no tE2 products are approved as standard of care (SoC) for men. Thus, tE2 is an off-label ADT option, with physicians being reluctant to prescribe and payers being resistant to reimburse. Many patients nevertheless explore various tE2 formulations for ADT with little supporting data on efficacy or safety. Recognizing that problem led us to present a poster at the April 2025 annual meeting of the American Urological Association, titled:

The case For, And Challenges To, Using Transdermal Estradiol For Androgen Deprivation Therapy.

The abstract is copied below, but here we compare various commercially-available tE2 formulations, delivery systems, application protocols, and costs when used for ADT. From this we derive guidelines for uro-oncologists in discussing tE2 as an option for ADT with their patients.

General Conclusions

The reduction in testosterone serum level from using E2 is not proportional to E2 serum levels.
Serum E2 levels depend linearly on the applied tE2 dosage.
Serum E2 levels can vary by a factor of 3 X between different brands of patches, for the same nominal patch strength (0.1 mg E2).
E2 gel or cream may be effectively substituted for E2 patches.
tE2 products for ADT can be as much as 1000 times cheaper than LHRH agonists or antagonists.

Clinical Guidelines

E2 blood draws should be done at the same time since the last application.
E2 is absorbed fastest through the skin that has the least amount of subcutaneous fat.
E2 gels/creams may be absorbed better when applied to a smaller area rather than a larger area of skin.
Insurance coverage is often available now with letter to insurance carrier.

Currently there are no tE2 products on the market that are licensed to treat men with PCa. But there are many products on the market for women.

The citation is:

Watson, Robert; Wassersug, Richard; Schellhammer, Paul. IP26-37 THE CASE FOR, AND CHALLENGES TO, USING TRANSDERMAL ESTRADIOL FOR ANDROGEN DEPRIVATION THERAPY. The Journal of Urology 213(5S):p e1374, May 2025. | DOI: 10.1097/01.JU.0001110200.18879.65.37

Below are the key questions we asked, along with our key findings related to the comparative cost and effectiveness of the various tE2 products on the market. We also explored the implications of how and where the tE2 is applied to the body.

What is a reasonable target for serum estradiol levels to achieve adequate testosterone suppression?

Traditional castration levels of T < 50 ng/dl can be achieved with a serum E2 > 100 pg/ml, on average.
Sub-castrate levels of T < 20 ng/dl can be achieved with a serum E2 > 250 pg/ml, on average.

Can Estradiol Gel be substituted for E2 Patches?

Yes, equivalent serum E2 levels can be achieved with either E2 patches or E2 gel/cream.

How and where should Estradiol Gel be applied?

E2 gel absorption is maximized when the applied surface area is minimized (blue curve).
In general, E2 is absorbed fastest through skin that has the least amount of underlying fat (e.g., thumb side of the forearm, jawline, or scrotal skin).

Which are the most effective brands of E2 Patches?

Alora, Vivelle, Evorel, and Climara brands have the highest maximum and average serum E2 levels, for the same patch strength = 0.1 mg E2/24 hrs.
Serum E2 levels varies by a factor of 2-3 X between different brands for the same patch strength of (0.1 mg E2/24 Hrs).

Which are the cheapest bands of E2 Patches?

Costs vary by a factor of 10 X for the same patch strength (0.1 mg E2).
Evorel and Vivelle Dot are the cheapest brands.
However, the four separate bars for Vivelle Dot reveal the large variation in price between Canada and the USA, and also the large variation between pharmacies.