Transdermal Estrogen and Bone Mineral Density

Transdermal estrogen patches are sometimes used as an alternative to the traditional Luteinising Hormone-Releasing Hormone Agonists (i.e. Lupron, etc.) drugs for hormone therapy (ADT).  Patches are successful in castrating a man, but unlike the LHRH agonists don’t cause bone mineral density loss.  This is important because bone health is vital in fighting prostate cancer.

See the Malecare Advanced Prostate Cancer Blog:


19 Replies

  • I may be wrong but they are not used as an alternative. 

    What they do is counter some of the side effects of androgen deprivation therapy. 

    And as such should probably always be used as part of androgen deprivation therapy unless there is a specific reason not to use them.

  • Originally ADT was accomplished by surgery or the oral use of estrogens (DES), however it fell out of favor because of very significant cardio-vascular issues and complications. 

    Today DES has basically been abandoned in favor of luteinizing hormone-releasing hormone agonists (LHRHa) since they produce castration levels of testosterone, however they too produce many toxicities including osteoporosis, fractures, hot flashes, erectile dysfunction, muscle weakness, increased risk for diabetes, changes in body composition, and CV toxicity.

    Increasingly, we are seeing an interest in an alternative ADT approach , using  parenteral estrogen, it suppresses testosterone, appears to mitigate the CV complications of oral estrogen by avoiding first-pass hepatic metabolism, thus avoids complications caused by the oral use of estrogen deprivation therapy.

    Estrogen is also used along with the LHRHa drugs to mitigate hot flashes, so it is used today for both purposes.

  • Joel, in English please LOL


  • Hello Joel (et al.),

    This is something I know something about, having personally used transdermal estradiol  (E2) for PSA control.  I used it continuously for over 15 years. My PSA right now is below the detectable limit.

    As you correctly point out, transdermal E2--compared to LHrH drugs--avoids hot flashes, osteoporosis, and may improve both cognitive function and libido.  Yes, it is not an approved treatment in the USA, but is in phase III clinical trials in the UK (i.e., the PATCH study). [You know all that.]

    The blood clot risk ;associated with estrogens appears to be dependent on the route of delivery...specifically associated with oral administration. [Again, you are corret about that.]

    What I can add to what you say is that transdermal E2 need not be in the form of patches.  I've used them, but much prefer the gel, Estrogel.  Email me directly if you have other questions.  My email address is not hidden on the internet. 

    Richard Wassersug

  • Richard, I've used patches and are planning on using them again later this Summer, in what way is the Estrogel better than patches?


  • Richard,

    I knew that you would chime in on this conversation.  Youare the  expert so I am glad that you have joinrd the conversation.  

    How do you dose the gel or the patches?


  • Joel,

    Dosing tE2 is a tricky topic, and made complicated by the fact that estrogens regulate their own receptor density.  That means that a constant dose applied to the skin may not end up as a constant serum concentration.  Personally I simply looked at my blood concentration.  While it fluctuated widely, I simply made sure that it was in the range of normal females that were premenstrual and not above the peak for that seen in their ovulatory cycle. 

    If you want more details, just email me with your telephone number and I can give you a call.

  • whenever the subject of oral estrogen is brought up, I think of Richard W. He is certainly an expert on the topic. For me it has been different, over the past decade I have used oral estrogen whenever a treatment I am on starts to Fail ie Nilandron, Ketoconazole, xtandi, zytiga, I add estrogen patches .1 mg once a day prepped with rubbing alchohol and many times that has given me an extra year on these therapies. and it works almost immediately for me. I am somewhat surprised others do not use these old therapies, I know there is a estrogen cream that can be wiped on arm to keep a guy castrate, however when I do it I am already castrate as I have been for years and adding the estradiol by climera patch stops my cancer and makes it stable.

    Sartor has said that he has seen DES work when patches quit, lower doses of DES 1mg have had many studies and are not as toxic as the 3 or 5 mg dES and still work, why do we abandon these old therapies just because there is newer therapies. advantage as both Richard and Joel have stated is that Transdermal bypasses the liver to  stop the blood clot risk.

    dx 2006, stage4,bpsa148, gs 10, at age 49 metastatic disease to bone at dx

  • I meant to say whenever the subject of Transdermal Estrogen is Brought up I think of Richard, apparently I am having some cognitive issues this

    sorry Dan

  • Thanks, Dan, for sharing your experience. Did you mean .1mg or 1mg of the dosage?



  • The dosage I have always used is .1 mg patch, 1 new one every day 6 out of 7 days and to leave them on for 7 days, I use climera, I am currently doing one every day as I think after being on them for a long time you do not get the absorption

  • Joel, on a related issue, what role does a falling alkaline phosphatase play?    Can you explain in simple terms, not getting too technical?      My reduced cognitive issues and memory make it difficult for me to grasp some concepts.      I believe that it has to do with bone health, and I'm on Xgeva injections monthly.

    Thank you,


  • Alkaline phophatase (AP) is a normal enzyme produced  within the body. Everyone produces some of this enzyme regardless of their state of health, gender, or age.

    The tissues that produce the most alkaline phosphatase are the bones and liver.  When prostate cancer spreads to the bones, its most common site,  it tends to break them down, releasing AP into the blood where it can be measured.

    When cancer, including prostate cancer, spreads to the bones the  bony tissue in the cancerous areas breaks down and releases increased levels of alkaline phosphatase into the bloodstream. 

    Increasing and decreasing levels of alkaline phosphatase in the blood stream reflects the amount of, and the activity of the cancer in the bones.  So, a decreasing alkaline phosphatase level in the blood serum probably reflects decreasing cancer activity in the bones. In other words decreasing is the way you want to go.


  • Dan 59,

    My husband is on Xtandi, and I fear that we will lose the funding for it as we are not seeing a decline in his PSA(13.80) anymore, but a levelling. Had CT Scan today, but will not see onco for a further month( Ray has had an amazing journey on Xtandi, the biggest drops for some time) Perhaps these patches are something that we could pursue, he used DES previously after failure of ADT and got a result for a further 18 months.


    Reasuring about the AP, as in last month we see a decline..


  • Carol, that is certainly something to discuss with your Oncologist, I have been on xtandi for a long time, In my mind leveling or being stable is a good thing, even slowing the rate of increase is a good thing. For me these patches have worked every time I revisit them after being off for about a year. How long ago was it that you were on des?

  • Carol,

    The best way to know about the potential continued effectiveness of Xtandi and Zytiga, other then PSA which is not that reliable at the beginning of the development of resistance) is by evaluating the existence of the androgen splice variant 7 (ARV-7).  Generally, this test id not available yet, however it is possible to have it evaluated at Johns Hopkins (Baltimore Md.)  This is the only place that I knew that is currently able to do the test and I am not sure what the cost would be or if it would be covered by insurance.


  • Carol, some months my psa is up and some months it is down still I believe it is relatively stable, locally it has been between 39 to 49 and back down to 40, at my center of excellence it is 32.081 last week and 4 months ago it was 32.077. I think what I am saying is that my psa fluctuates up and back down, I do not think it is always a precise test, and that they like to judge by scans at this stage , but they too are not precise, and I think to many give up on xtandi or other treatments to early, but yes what could transdermal estrogen hurt, many Drs. do not know that the transdermal approach bypasses first pass of the liver and does not have  the blood clot issues of oral estrogen, I say it is certainly worth a try and that it worked for me many times.

    If you need peer reviewed papers on oral estrogen I can find it for you, What Richard is doing does seem even better to just have some cream to wipe on your arm.


  • Dan59,  Ray was on 3mgDES plus warfarin from 6 Jan 12 -4/8/13, when he started on Zytiga. I would love to read the papers so that I am prepared for when we see onco. Haven't looked to see whether the cream is available here in New Zealand, but will do so.

    Thanks for you time.


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