Our special thanks to Hans Casteels, Ruth Langley, and Duncan Gilbert for helping write these FAQs!
1. What is ADT and why is it important to me?
Androgen Deprivation Therapy (ADT) is a standard treatment for high risk prostate cancer (PCa). By depriving the cancer cells of the androgen, testosterone (T), they stop growing and stop secreting prostate-specific antigen (PSA). This causes PCa tumors to shrink and can lower PSA, if the cancer is still hormone-sensitive (i.e., dependent on T).
2. What is Estradiol and why is it important to me?
Estradiol (E2) is one of four hormones called “estrogens”. E2 is the most potent of the four, and it is made by converting T to E2. E2 plays important roles in your health, including regulating: 1) brain health and mood, 2) bone health, 3) cardiovasular health, 4) sexual function, and 5) body fat composition.
3. Why should I use tE2 for ADT instead of standard ADT drugs?
Transdermal estradiol (tE2) is delivered into the bloodstream through the skin. At high enough doses, tE2 suppresses T as effectively as standard ADT drugs. Also, tE2 ADT reduces or eliminates most side effects from standard ADT drugs, such as: hot flashes, osteoporosis, fatigue, brain fog, elevated blood pressure, elevated lipids, and elevated blood glucose levels.
4. How effective is tE2 ADT at reducing T?
The PATCH/STAMPEDE team reported that more than 90% of men who used tE2 for ADT reduced their T < 50 ng/dl (traditional castration level) after 12 weeks of treatment.
5. How effective is tE2 ADT at reducing PSA?
The PATCH/STAMPEDE Phase-III trial reported that men who used tE2 for ADT reduced their baseline PSA by at least 90% after 12 weeks.
6. Can tE2 ADT reduce the size of prostate cancer tumors?
Most likely, yes. Because PSA serves as a biochemical marker for prostate cancer, the observed 90% decline in PSA associated with tE2 ADT suggests that prostate cancer tumors may shrink significantly.
7. How effective is tE2 at controlling PCa?
In a head-to-head comparison, the 14-year, Phase-III, PATCH/STAMPEDE randomized controlled trial conclusively demonstrated that using tE2 for ADT was equally good at controlling PCa as standard ADT drugs, in terms of having essentially the same Metastasis-Free Survival (MFS). MFS is defined as the length of time after diagnosis, or start of treatment, during which a patient is alive and has no evidence of cancer spreading (metastasizing) to distant sites.
Note: These survival results were limited to locally advanced PCa patients: 1) whose cancer was hormone-sensitive, 2) who had no metastasis at diagnosis, and 3) who did not use Androgen Receptor Pathway Inhibitor drugs (ARPI’s) or Orgovyx™ (relugolix) pills.
8. Are tE2 products FDA-approved for men?
Generally, no. Most tE2 products are not currently FDA approved for men, but they are FDA approved for postmenopausal women. The tE2 products approved for women can be legally prescribed “off-label” for men. Off-label access requires negotiating with your prescribing physician. However, injectable forms of E2 (e.g., estradiol valerate) are currently FDA approved for palliative care of men with advanced prostate cancer.
9. Are tE2 products listed as a Standard of Care for PCa in the National Comprehensive Cancer Network (NCCN) guidelines?
No. The NCCN is a consortium of 33 leading cancer centers in North America that formally sets Standards of Care (SOC) guidelines for cancer treatments. The NCCN has not yet endorsed the use of tE2 ADT as a SOC. However, tE2 products are legally prescribed off-label by a growing number of physicians.
10. Can using tE2 reduce hot flashes caused by standard ADT drugs?
Yes. UsingtE2 will reduce both the frequency and severity of hot flashes caused by standard ADT. You will likely sleep better, too. That means less fatigue and less brain fog during the day from having fewer hot flashes that disrupt your sleep at night.
11. Can tE2 ADT protect my bones?
Yes. The PATCH trials showed that tE2 ADT generally increases your bone mineral density (BMD) over a period of 1-2 years, unlike standard ADT drugs that cause a loss of BMD during that time. The loss of BMD increases your risk of a fracture, such as a broken hip, should you fall. Protecting your bones helps prevent surgeries and hospitalizations, which ultimately helps to preserve your independence.
12. Does tE2 ADT have an increased risk of blood clots or other cardiovascular problems compared to standard ADT drugs?
No. The PATCH/STAMPEDE trials found no increased risk of blood clots or other cardiovascular events when tE2 was used for ADT (following the trial protocol), as compared to standard ADT drugs.
13. Can using tE2 products cause my breasts to grow larger?
Yes. About 80% of men who use tE2 for ADT have some breast tissue growth (gynecomastia). However, breast growth is typically less than what you might imagine. Studies of genetic males who take high-dose estrogen as part of gender-affirming treatment (i.e., trans women) report that their breasts are typically smaller than an A-cup size. Larger breast growth is rare and generally increases with obesity. Gynecomastia is primarily a cosmetic concern and does not have adverse health consequences. If breast growth concerns you, then there are preventative and surgical measures that you can discuss with your physician.
14. Can my breasts become sensitive when using tE2 products?
Yes. Breast soreness and nipple sensitivity (i.e., mastalgia) can occur when using tE2 for ADT. The increased soreness is typically mild, and nipple sensitivity is manageable. The soreness and sensitivity generally disappears over time and is not permanent.
15. Can tE2 ADT help cause less fatigue and brain fog than standard ADT?
Yes. Because tE2 reduces the frequency and severity of hot flashes (and may eliminate them altogether), your sleep quality may improve significantly from not being awakened by hot flashes. The improved quality of sleep may help to reduce daytime fatigue and brain fog.
16. How much do tE2 products cost?
tE2 products (patches or gels/creams) generally cost about $1 US/day (without insurance coverage). However, the costs of E2 patches can vary by a factor of ~10 X for the same strength of patch. So, you should shop around for the lowest price, and use a discount pharmacy card, if available. Also, check with your health insurance provider, because some insurers cover the costs of patches (e.g., Aetna, and some Medicare Advantage plans).
17. Can tE2 ADT help lower my blood pressure?
Yes. The use of tE2 can help to lower your blood pressure by a modest amount because estradiol is a vasodilator. In contrast, standard ADT drugs generally increase your blood pressure.
18. Can tE2 ADT help to reduce my “bad” cholesterol and increase my “good” cholesterol (HDL)?
Yes. The use of tE2 can lower your “bad” cholesterol and increase your “good” cholesterol (High Density Lipids, HDL) by a modest amount. In contrast, standard ADT drugs generally increase bad cholesterol and decrease good cholesterol.
19. Can tE2 ADT help lower my blood glucose levels?
Yes. The use of tE2 may help lower your blood glucose levels by a modest amount, as compared to standard ADT drugs, which generally increase glucose levels. This reduction in glucose may help prevent insulin resistance and “metabolic syndrome,” which can be a precursor to diabetes.
20. Can tE2 ADT affect my sex life differently than standard ADT drugs?
Perhaps. All forms of ADT will lower T and, hence, depress libido. However, there is some evidence that tE2 ADT can preserve sexual interest to a greater extent than standard ADT drugs. Sexual relations will change with any form of ADT (as it does with aging), but intimacy doesn’t have to change. Intimacy with your partner can be preserved if you and your partner stay well-connected emotionally.
21. Can my fracture risk be lower on tE2 ADT than standard ADT?
Most likely, yes. As a baseline, 1 in 5 healthy men will experience an osteoporotic fracture in their lifetime due to loss of Bone Mineral Density (BMD). For PCa patients, the PATCH/STAMPEDE trials reported a 25% incidence of osteoporotic fracture requiring hospitalization, over a 10-year period, when using standard ADT drugs. We expect that the fracture risk will be lower on tE2 ADT simply because BMD generally increases when tE2 is used for ADT. In contrast, BMD decreases when patients use standard ADT drugs.
22. What is a desirable target level for suppressing testosterone?
T < 50 ng/dL is traditionally considered a castrate level. However, even lower levels (T < 20 ng/dL) have been shown to further delay progression of PCa and improve overall survival. Suppressing T to < 20 ng/dl will generally require a higher dose of tE2, however.
23. What blood labs should I get, and how often?
T, E2, and PSA are the most important blood labs to routinely get. This should be discussed with your doctor, but we suggest getting monthly T and PSA blood tests for the first 3 months when starting tE2 therapy (or when changing doses), and then quarterly after these levels stabilize.
24. What other lab tests should I get?
Lipids profile, liver enzymes, fasting glucose, blood pressure, and bone mineral density scans (DEXA or equivalent) are also important to get on a regular basis (including baseline measurements), if one is on ADT long term.
25. Can I use tE2 products at the same time while also doing standard ADT?
Yes. A lower dose of tE2 may be combined with standard ADT drugs to help reduce or eliminate hot flashes, improve sleep quality, reduce fatigue and brain fog, and fight the loss of bone density that is caused by standard ADT drugs.
26. Where can I go to learn more about the side effects of ADT and how to manage them?
For more information, written in laymen’s language, on ADT side effects and how to best manage them, see Androgen Deprivation Therapy: An essential guide for prostate cancer patients and their loved ones! It is available at https://www.springerpub.com/androgen-deprivation-therapy-9780826184023.html and from Amazon.com. Also, you can go to: www.LifeOnAdt.com.
27. Will tE2 ADT make me a “soprano”?
No. Your voice will not change.
28. Will I lose my facial hair using tE2 for ADT?
No. Your beard and mustache will remain. Body hair may thin, but your scalp hair may actually be preserved. Your skin will be softer, too.
29. Can E2 patches irritate my skin?
Possibly. Only about 10% of men develop some local skin irritation from the adhesive used in E2 patches. Pretreating the skin with a steroid spray (e.g., Flonase™) may help prevent skin irritation. Alternatively, switching from E2 patches to E2 gels or creams will eliminate irritation from the patch’s adhesive. And, E2 gels/creams are equally as effective as E2 patches for ADT.
30. Can I gain weight using tE2 for ADT?
Possibly. In the PATCH/STAMPEDE trials, only about 10% of men gained weight using tE2 for ADT.Most men won’t gain weight, especially if they maintain a good level of physical activity and a good diet.
31. Do men normally have more E2 than postmenopausal women?
Yes. The reference range of E2 for healthy men is 10-40 pg/ml, which is greater than the reference range for postmenopausal women (0-20 pg/ml).
32. How many patches should I use at a time?
There are many different E2 patch brands commercially available with a doctor’s prescription. We recommend that you start by using one patch (changed twice weekly) and then monthly monitor your T for 2-3 months (Note: T normally decreases significantly over 1-2 weeks). Then, gradually increase the number of patches until a desired level of suppressed T has been reached (e.g., T < 20 ng/dl). In general, the guideline is to use the lowest dose of tE2 that maintains a suppressed level of T.
33. Is it a hassle to use E2 patches for ADT?
No. Wearing an E2 patch is less intrusive than having to get injections of standard ADT drugs, and they are easier to live with once applying the patches has become routine. They do need to be replaced once or twice a week, and about 10% of men can experience some skin irritation from the patch’s adhesive. Switching to E2 gels or creams can eliminate any skin irritation from patches, and they are equally as effective as E2 patches.
34. Where can I buy estradiol gel?
Estradiol gel is available online in the USA from Divigel.com (0.1% E2) and Estrogel.com (0.06% E2) with a doctor’s prescription. Most pharmacies that carry tE2 patches for women also sell these gel products, including Elestrin gel (0.06% E2). Alternatively, your local compounding pharmacy can custom-compound E2 gel (or cream) at the same, or higher, concentrations (e.g., from 0.1% to 1% E2), with a doctor’s prescription, and often at a reduced cost.
35. Is tE2 ADT just another Internet fad?
No. Unlike online “miracle cures,” the use of tE2 for ADT has passed rigorous, long-term, clinical trials (i.e., the 14-year Phase-III PATCH/STAMPEDE trials). This is evidence-based medicine, and the ability of estrogens to suppress T has been understood and reconfirmed over 8 decades…since at least the 1940’s.
36. What are some practical tips for using E2 patches or gels?
- Rotate patch sites to reduce skin irritation from the adhesive.
- Apply patches to clean, dry, and non-oily skin (e.g., after a shower or after cleaning the skin with alcohol).
- Similarly, apply E2 gels/creams after bathing or washing. Note: gels dry quickly and more rapidly than creams.
37. What if my oncologist won’t prescribe tE2 ADT because it is“not approved as a Standard of Care for men”?
If your oncologist dismisses tE2 ADT as “not approved for men,” don’t assume the conversation is over. Using tE2 for ADT is supported by peer-reviewed, long-term clinical trials. So, you might ask your doctor: “Have you seen the “PATCH/STAMPEDE trials results, summarized on the Estradiol Initiative website?” (estradiolinitiative.org)
If you feel stonewalled, consider getting a second opinion from a urologic oncologist, a Primary Care Practitioner (PCP), or a General Practitioner (GP). Alternatively, you can ask your local compounding pharmacy for recommendations of practitioners who routinely prescribe hormones for their patients. Also, you can reach out to an academic or one of the tertiary cancer centers that specialize in treating prostate cancer.
Patient advocacy groups and online PCa communities (such as HealthUnlocked.com) can also point you toward specialists who are familiar with prescribing tE2 products. You may also want to print the abstracts of recent publications and respectfully ask your provider to review them before your next visit.
Above all, remember: asking questions and advocating for your options isn’t being difficult. It’s part of a Shared Decision-Making process, where physicians listen to you and, in turn, you receive healthcare that you trust.
38. What’s the Bottom Line?
All medications have some trade-offs. For tE2 products, the major side effect is mild gynecomastia, which is cosmetic and has no health risks. ADT with tE2 may also cause breast soreness and nipple sensitivity, which typically diminishes over time. Safety and cancer survival rates for patients who use tE2 for ADT are equally as good when compared to standard ADT drugs. However, standard ADT drugs have many side effects that can substantially reduce a patient’s health and quality of life. Using tE2 for ADT can significantly reduce hot flashes and even reverse osteoporosis caused by standard ADT drugs. Sleep quality, fatigue, brain fog, insulin resistance and cholesterol levels may also be improved.
The bottom line is that using tE2 for ADT is not experimental. Rather, it is equally safe, rigorously tested, and significantly improves quality of life.