Transdermal Estradiol update - edited 10/30/2018

[E2-Guy]

A few months ago I had asked if anyone had experience with transdermal estradiol (tE2) and Richard Wassersug, PhD responded to my post with some very interesting information. Richard is extremely knowledgeable on the subject, has authored two books on 'Androgen Deprivation Therapy' and has written numerous papers on ADT. He is also a PCa survivor and is experiencing great results with tE2. He has since become my mentor in this tE2 experiment. The numerous side effects and expense of LHRH agonists/antagonists that many of you have mentioned prompted me to look into a less expensive and 'perhaps' milder form of ADT. I have been experiencing a relatively slow increase in my PSA after my recent sacral lymph node surgery and in an attempt to lower it, I have been reading every article that I can possibly find on DES, the 'patch', parenteral and transdermal estrogen.

Nine weeks ago I started applying ~1¼ mg of tE2 gel daily plus taking 0.5 mg of Avodart (the Avodart was suggested by Dr. Myers) every other day and my PSA has declined from 0.71 [4/01/2018] to 0.046. My alkaline phosphatase has also has gone down from 117 [7/13/2017] to 82. In addition to those numbers my T level has decreased from 455 [7/13/2017] to 72, (still a way to go to the castrate level), and my E2 is at 258. I may reduce the Avodart dosage to every three days due to its long half-life. These numbers do not appear to be significantly remarkable; however, they may at least be a start. At this point in my journey I am totally asymptomatic and the only side effects I am experiencing are nipple tenderness and a slight amount of gynecomastia...neither is of any consequence. It is my understanding that the tE2 will not cause bone density loss, hot flashes/flushes or increase CV risks. The CV risks were the major reason for the discontinuation of DES in the early 80s.

The transparent gel is extremely easy to use, causes no skin irritation (major complaint about the patch), dries in a matter of minutes and is relatively inexpensive. One 80 g tube lasts about a month.

Below I have included a brief summery of my history...I have previously posted more detailed info in case any of you are interested. I will keep you apprised of my future progress or 'lack of'!

Robotic RP - 12/27/2004

Post RP PSA - 0.03

No adjuvant therapy

68Ga-PSMA scan identifying metastasis in three sacral LNs - 5/23/2017

My more recent PSA results:

7/2013 - .21

5/2014 - .36

8/2014 - .39

10/2014 - .40

2/2015 - .50

5/5/2015 - .61

8/19/2015 - .69

9/14/2015 - .50?

10/27/2016- .71

4/12/2017 - 1.00

7/18/2017 - 1.30 [pre sacral excision]

9/11/2017 - 0.54 [post sacral excision]

10/11/2017 - 0.57

11/20/2017 - 0.657

12/29/2017 - 0.641

4/1/2018 - 0.71

6/19/2018 - 0.49

8/3/2018 - 0.19

10/30/2018 - 0.046

T levels:

7/13/2017 - 455

6/19/2018 - 349

8/3/2018 - 106

10/30/2018 - 72

Alkaline Phosphatase levels:

9/2015 - 78

7/2017 - 117

6/19/2018 - 97

10/30/2018 - 82

E2 level:

6/19/2018 - 31

8/3/2018 - 123

10/30/2018 - 258

[pjoshea13]

Hi Ron,

I'm somewhat confused by your numbers. The use of estradiol [E2], as in the PATCH trial [1] is, of course, intended to lead to castration. {"Exogenous administration of E2 inhibits the hypothalamic‐pituitary axis (thereby suppressing testosterone) as well but maintains E2 levels"} An E2 of 31 is not going to achieve that. And, as you say, with testosterone [T] at 349, you have a way to go. Some would say the E2 & T are still in the normal range & the therapeutic affect has yet to occur.

As T declines, less Avodart is required to control DHT converted from T. A small minority of men do continue to produce DHT when castrate, according to Dr. Myers. The main reason to use Avodart when castrate, IMO, is that the road to CRPC can involve the production of DHT via a pathway that does not involve T.

Incidentally, while I never comment on typos, 'Androgen Depravation Therapy' is just too good to let pass. My definition: the use of testosterone supplements to induce a priapic state (persistent erections).

Good luck with the therapy!

-Patrick

[1] onlinelibrary.wiley.com/doi...

[E2-Guy in reply to pjoshea13]

Thanks Patrick for the reply and for catching the 'a'! That's what I get for not proofreading. I am increasing my E2 dosage to ~2 mg of E2 until my next blood work results in about two months.

[Tall_Allen]

I like Richard as well. I'm glad the estrogen is working for you. What is his opinion about taking Tamoxifen at the same time to counter the breast effects? It blocks estrogen in breast tissue but is estrogenic in other tissues. There may be too much of a risk of blocking the estrogen receptor in the tumor tissue.

[E2-Guy in reply to Tall_Allen]

Allen,

Thank you for your reply/s...always much appreciated! I thought that I was fairly well versed in PCa; however, you and some of the other people on this site make me look like a kindergartner! Regarding the use of tamoxifen, I had asked Richard this question some time ago and here is a copy of our correspondence:

Hi Richard,

Sorry to bother you again, but I would like your opinion regarding taking 10 mg/day of tamoxifen to prevent gynecomastia and nipple sensitivity. Could that be counterproductive in conjunction with the oestrogel? I'm currently not aware of any breast enlargement; however, I sleep on my stomach and I am experiencing some degree of discomfort in my nipples.

From: "Wassersug, Richard"

To: Ron Pitelka <[e-mail]>

Sent: Tuesday, May 29, 2018 3:18 AM

Ron,

See attached. This paper suggests that it might be safe. However I am not convinced and I personally would avoid taking tamoxifen. That is a personal opinion as there are no data one way or the other to say that it is safe in the long term.

Richard W.

-----------------------------------------------------------------------------------------------

Correspondence:

Erik Wibowo, Level 6, Gordon & Leslie Diamond

Health Care Centre, 2775 Laurel Street,

Vancouver, BC V5Z 1M9, Canada.

E-mail: [e-mail]

Keywords:

adverse events, antiandrogen, breast cancer,

gynecomastia, infertility, males, prostate cancer,

tamoxifen

Received: 18-Sep-2015

Revised: 9-Mar-2016

Accepted: 12-Mar-2016

doi: 10.1111/andr.12197

Tamoxifen in men: a review of

adverse events

1E. Wibowo, 1P. A. Pollock, 2N. Hollis and 3R. J. Wassersug

1Vancouver Prostate Centre, Vancouver Coastal Health Research Institute, Vancouver, BC, Canada,

2Solid Organ Transplant Clinic, Vancouver General Hospital, Vancouver, BC, Canada, and

3Department of Urologic Sciences, University of British Columbia, Vancouver, BC, Canada

SUMMARY

Tamoxifen is an off-label option to treat men for breast cancer, infertility, and idiopathic gynecomastia. Lately, tamoxifen has been

proposed as a treatment to prevent gynecomastia in prostate cancer patients receiving antiandrogen therapy. We reviewed the

adverse events (AEs) reported in studies of men prescribed tamoxifen for these conditions to better understand its side-effect profile.

We searched PubMed for randomized controlled trials (RCTs) that included safety data of tamoxifen treatment in men with prostate

cancer, breast cancer, infertility, and idiopathic gynecomastia. Non-RCTs were also reviewed. The results demonstrate that the AE

profile in tamoxifen-treated male populations varied. Excluding breast events, gastrointestinal, and cardiovascular problems were

the most commonly reported AEs in prostate cancer patients, whereas more psychiatric disorders were reported in male breast cancer

patients. Few AEs have been documented in men receiving tamoxifen for infertility and idiopathic gynecomastia. Less than 5% of

men withdrew from tamoxifen therapy because of toxicity. This suggests that for most men, tamoxifen is well-tolerated. Of those

who discontinued tamoxifen, the majority were male breast cancer patients, and cardiovascular events were the most common reason

for stopping tamoxifen treatment. Unfortunately, in many cases, the reasons for withdrawing tamoxifen were unspecified. Based

on the available evidence, tamoxifen’s AE profile appears to vary depending upon which male population is treated. Also, the frequency

at which AEs occur varies – less AEs in men with infertility and idiopathic gynecomastia compared to men with prostate cancer

or breast cancer. Long-term studies that rigorously document the side-effect profile of tamoxifen in men are lacking.

[PCaGoAway]

Hi Ron

Right now I don't have time for a detailed reply; I don't log in much so let me write something to start. You wrote that you are dosing ca 1 1/4 mg but you mean grams I assume? I finally bought a Salter diet scale that weighs to 0.01 g for ca. $25 online. But there is also a packaging of the gel that has a pump that reliably doses 1.25 g. I am in the US but close to Mexico which is where I buy the gel - no prescription. I have used both patches (6 weeks) and more recently the gel - the patch adhesive irritates my skin. Long story short, I started using the gel and dosing so as to give the same amount of active ingredient as the daily amount delivered by patches. But I find that for whatever reason I have to use significantly more. You need to experiment for yourself. I talked to Richard W also. He monitors T, E2, and PSA. E2 levels are tricky. I am not sure how long E2 stays around in blood - it could be the continuous delivery by the patch is what makes dosing seem different. Therefore most recently I split my daily dose in half, once in morning and once at night. Too early to conclude. T and free T are what I am having measured.

[E2-Guy in reply to PCaGoAway]

Dear PCaGoAway,

Thank you for your reply and the suggestion regarding "splitting the daily dose". As I have mentioned, I am new to this regimen and and it will probably take some time to get my numbers 'dialed in'. Richard is using the gel pump dispenser with the same 1.25 g dose; however, the tube that I am using comes along with a ruler-applicator which has two markers, each measuring 4 cm equal to 1.25 grams of the gel. 1.25 g is supposed to deliver .75 mg of E2. I have been using ~6½ cm of the gel which should equate to ~1¼ mg of E2. I am increasing my dosage to ~10 cm (a bit less than 2 mg of E2) until I have my next blood tests in about two months.

P.S. How are you doing with the gel?

[PCaGoAway in reply to E2-Guy]

Oh one more thing. My E2 level has never been above 100. My level before applying any E2 was about 17 pg/mL and now it varies between 2x that and up to 5x that. I see petercraig2 has a much higher level (only if the units are the same). I have not tried pushing it. My goal was to try it, and then just as a stopgap measure until something like Firmagon. If I hate Firmagon I may be back to E2 !!

[E2-Guy in reply to PCaGoAway]

How much do you pay for 80 g of the gel in Mexico?

[PCaGoAway in reply to E2-Guy]

Hello

The gel is about $25 - 30 US in Mexico. Manufactured by Besins in France, with labeling and instructions in Spanish. Richard W gets gel from Besins. How about you in Thailand?

As for how I am doing, my case and history is unusual. My PSA is about 30 now. It was rising and up to about 50 when I started gel. It took me a while to up the dose of gel enough but finally I got my T down to 1/3 of original, free T dropped by a factor of 6 or 8, and PSA was cut in half. It's gone up a bit because I cut back on the gel dose to 1.25 g gel 2x per day (I was up to 4 or 4.5 g per day). I am pretty much resigned to going on Firmagon w Zytiga in the near future....and save E2 gel for hot flash minimization.

[E2-Guy in reply to PCaGoAway]

The gel that I am using is also from Besins in France...see pic in my first post titled 'Transdermal Estradiol update'. As I had previously mentioned, Richard W. was battling PCa with all of the normal protocols for several years before he started using tE2. He was able to get his PSA down to a very low level with Lupron and then switched to tE2 to keep it down. About 15 years ago when he started using the gel, he would use about 5 squirts (1.25 g per squirt, each squirt delivering ~.75 mg of E2) gradually reducing the dosage to 3 to 4 squirts. His PSA remains undetectable and he believes that the lower dosage currently needed is partly due to T levels naturally declining with age.

[PCaGoAway in reply to E2-Guy]

Oh, about the dosing with the plastic ruler. The mass of gel depends a lot on the diameter of the bead of gel. You can be off by at least 50%. That's why I finally bought a Salter diet scale for $25 online, that weighs to 0.01 g.

[E2-Guy in reply to PCaGoAway]

I agree with you that" The mass of gel depends a lot on the diameter of the bead of gel."; however, I try to keep my bead as constant as possible even though I may not be getting exactly 1.25 g per 4 cm on the ruler. Depending on my next blood test results, I will make adjustments until I'm able to get my numbers where they should be. I obviously have to increase my dosage since my T level is still too high and my E2 level is way too low. I started out with a relatively low dosage (I'm guessing ~1.25 mg) just to see if it would have any effect, and also in hopes of keeping the gynecomastia and nipple tenderness at a minimum.

[E2-Guy]

Thank you Nalakrats...I follow your posts religiously!

[Joeym1040]

I recently ended a year clinical trial using estrodoil cream, applied to the shoulders daily. It worked wonderfully for me, however I do not know the dose I received. At anytime during the trial if your T went over 50 you were out of the trial. My T went to 0 and my psa was undetectable. Of the 4 people in my group 2 of us made it through and 2 were dropped. Trial ended in Jan. Have not heard anything since then, but if it appears as a product I am on it!

[E2-Guy in reply to Joeym1040]

Joe, I apply the gel to my inner thighs and my lower abdomen. Are you currently using any form of ADT?

[Joeym1040]

I have been on holiday since the trial ended end of Dec. My psa <.02 and my t was 0 in Jan. In march my t was 30 and psa. 08I so I usually wait until psa get to about 4-5 before starting ADT again. I am scheduled for a visit with my oncologist in August. Depending on my levels they may want to start me on Lupron again. I have been on and off Lupron since 2011. If this gel can keep psa under control at my current levels that would be GREAT. Probably never go on Lupron again. Thoughts

[E2-Guy in reply to Joeym1040]

IMO I would not wait until your PSA reaches "about 4-5". I would start using the gel now since your March PSA was up to 0.081. Based on your January to March increase, your PSA could be up to ~0.2; however, just a wild guess. Since the side effects of the gel are considerably less than Lupron, I see no reason why you would want to wait. When my PSA had reached 0.71, I asked Richard Wassersug for his opinion as to when he would recommend starting the tE2 gel regimen? He said that I may have to start with larger doses to drive my PSA down which could cause elevated nipple sensitivity. He did state that he was already on Lupron (I'm assuming he wanted to bring his PSA to a very low level) before starting tE2 gel.

[Joeym1040]

sounds like a good idea. I already had radiation to the breast before I started the clinical trial so that should not be a problem for me. How much do you use each application? and where should I buy it?

[E2-Guy in reply to Joeym1040]

As I have mentioned, I am new to this regimen and and it will probably take some time to get my numbers 'dialed in'. Richard is using the gel pump dispenser with the same 1.25 g dose; however, the tube that I am using comes along with a ruler-applicator which has two markers, each measuring 4 cm equal to 1.25 grams of the gel. 1.25 g is supposed to deliver .75 mg of E2. I have been using ~6½ cm of the gel which should equate to ~1¼ mg of E2. I am increasing my dosage to ~10 cm (a bit less than 2 mg of E2) until I have my next blood tests in about two months.

'PCaGoAway' is buying the gel in Mexico...I just asked him how much he is paying?

Richard Wassersug paid $55 in Canada.

Amazon has it for $40.

I pay $9.50 in Thailand.

[Herman_PSA in reply to E2-Guy]

What's the brand name on Amazon? Thanks!

[petercraig2]

I've been on Estradiol patches x4 1.56mg and change every 3-4 days. and monthly numbers below. My Dr. has given me a script with Lifelabs for bloodwork every four weeks to cover PSA, Estogen, FSH and Testosterone so we can both see results and respond quickly if required otherwise I see him every three months.

Both PSA dropped very quickly and and testosterone to castrate <.1 which was pretty dramatic result. Both have slightly increased over the last three months and met with Dr. on Friday and we agreed to increase patches to x3 every other day. We're hoping an increase in Estrogen will bring numbers back down otherwise it's some other ADT such as Firmagon.

Patches work very well for me even though I have to pay for them they are cheap compared to anything else. No cardiac issues and minimal guy boobs.

Had robotic and post op PSA 3.3 and climbing so found a Dr who would let me use Estogen patches after I had provided Oncology literature to his satisfaction.

PSA Test Estrodiol

21-Aug-17 7.700 1402

8-Sep-17 2.100 0.5 1084

29-Sep-17 1.600 1.00 925

20-Oct-17 1.400 0.60 254

10-Nov-17 1.900 0.80 891

1-Dec-17 0.820 0.10 1698

22-Dec-17 0.340 0.10 642

12-Jan-18 0.260 0.10 445

2-Feb-18 0.170 0.10 1099

27-Feb-18 0.110 0.10 914

28-Mar-18 0.092

25-Apr-18 0.100 0.10

23-May-18 0.170 0.50

20-Jun-18 0.200 2.70 490

Peter

[E2-Guy in reply to petercraig2]

20-Jun-18 0.200 (2.70)? (490)?

What are the numbers in parenthesis?

[petercraig2 in reply to E2-Guy]

OK so first number is the date, second is PSA, third is Testosterone and third number is Estrodiol/Estrogen.

Does that make more sense?

As a possiblre indicatoe of problems I also have FSH test in monthly bloodwork but didnd't include this data set

Peter

[E2-Guy in reply to petercraig2]

IMO your E2 level may be a little high...I don't think that you would want it to go above the normal high for a premenopausal females which is around 350 pg/mL.

Also your T level could go up a little but not over 50. Some of the PCa gurus on this forum may suggest otherwise.

[petercraig2 in reply to E2-Guy]

I would agree in principle however over last three months PSA, FSH and T. have done a turn around and are all increasing.

My guy doesn't know what's happening as bone scan last week didn't seem to show anything so actually increasing Estrogen to see if it knocks all of these numbers back down.

If that doesn't work than it's onto something like Fermagon.

It's a big worry as Estrogen was doing very well for me with minimal side effects.

Maybe someone else has more knowledge & experience in this and open to all suggestions?

Peter

[Dan59 in reply to petercraig2]

Peter, years ago when I was on Climera .1mgX6 per week, my estradiol level was around 900 at times, It fluctuated, but the patches worked very well for me, with several successful rechallenge in CRPC, I used in conjunction with zolodex. Your e2 number looks more ideal than what I had IMO.

Dan

[E2-Guy in reply to petercraig2]

Hi Peter,

Haven't heard from you for some time...how are you doing? Give me a little update on your latest numbers and what you're taking/doing.

[petercraig2 in reply to E2-Guy]

Thanks for asking and all seems to be going very well.

Following an unexplained hiccup PSA has continued downward and now at 0.016 with T still <0.1. Alk Phos test every three months is in normal range. Hoping to have DHT in next monts bloodwork just to make sure it is still inline and not feeding the little buggers.

My only grumble is a return of incontinence which I blame on delayed resctiin to radiatioin a year ago. So I'm on a rigorous schedule of Kegal excercises which I hoping will nip that in the bud.

Are you still doing well on the Estrogen gel and keeping PSA in decline?

Peter

[E2-Guy in reply to petercraig2]

Peter, Happy to hear that are doing well with the exception of the "incontinence". I am going to send you a message on my experience with incontinence. What are you currently taking/using?

May latest blood test results as of 10/30/2018 using only tE2 gel and one Avodart every third day:

PSA - 0.046

T level - 72

E2 level - 258

Alk phos - 82

[PCaGoAway]

Hi ronronHU,

I’ll be interested in what you find.

Like I said I think I’ll be switching to a standard of care protocol, and maybe use lower tE2 doses against side effects. One thing Richard W and I talked about is cycling the dose over a month, much like what happens in women. I wonder if that would guard against developing resistance.

I hope the tE2 works well for you. I know another man in my support group who wants to try it - he also talked w Richard W.

I was encouraged by Joey saying he was in a clinical trial. Hopefully this treatment can be further improved!

[E2-Guy in reply to PCaGoAway]

Hi mate, How are you doing? Can you give me an update on your latest regimen/numbers?

[PCaGoAway]

Hi - July I had some scans done at NIH - PSMA-PET scans - they showed cancer in my bones in about 15-20 places, although some of those spots were still quite small. Early August my PSA was at a record of 73 and I started Firmagon and Zytiga. It's worked very well! 73 to 5.7 to 1.5 to 0.77 to 0.46 (the last reading is from today). I may start applying E2 gel in lower dose to help reduce chance of bone loss, though I have been going to the gym with a trainer as another way to help. I tested myself for E2 and my reading is below 6 (my T is below 3 (!!)) .

[Break60]

Hi Ronru

I’ve been on estradiol patches now for six weeks and am having second thoughts due to lower back pain, enlarged breasts and nipple soreness , flu like symptoms, fatigue and weakness . I’m applying four .1 mg patches twice weekly . I also take avodart, metformin, rosuvastatin , celecoxib. Total T is very low (6.9) and free T even lower. PSa is .192 . E2 was around 75.

I feel worse than when I was on trelstar.

Am I taking too high a dose?

Bob

[E2-Guy in reply to Break60]

Bob,

Sorry to hear that you are not doing as well with the E2 patches as you were with Trelstar.

I shared your post with Richard and his opinion is that the nipple symptoms are from the E2, but the flu like symptoms and back pain are probably not. And the fatigue may be due to the low T. Some of that may just be due to aging. I have so far been most fortunate in that I have ONLY the boobs and nipple tenderness as side effects from the tE2 gel. My most recent blood work indicated a PSA of .014, E2 level of 145 and a T level of 70. If you felt better on Trelstar than on tE2, perhaps you might consider switching back to Trelstar.

IMO, E2 should help maintain your bone density as well as denosumab would...R. Wassersug, TA, Alan Meyer, Patrick, etc. are better able to answer this question.

My best,

Ron

[Break60 in reply to E2-Guy]

Actually I’m doing better on E2. All the other S.E. are gone but I need to Lose a lot of weight!!

[E2-Guy in reply to Break60]

Just talked with Richard...He said to tell you that you are welcome to call him if you have any questions that he can help you with.

[Break60]

Ron

Since using estradiol instead of SOC adt doesn’t it make sense that Xgeva would be unnecessary ?

Bob