Alternate hormone treatment

We keep talking about Lupron or Zoladex, etc., for hormone depletion. Estrogen patches are occasionally mentioned to help control hot flashes. But is anyone looked at/using Estrogen, as patches or gel, as REPLACEMENT? Tested in England, it has seen some use, but it's hard to get info on. The knee-jerk argument has always been: "No! Clots!" But that does not appear to be the case with estrogen patches...and may not even be an issue with old diethylstilbesterol at the lower doses now being used. Besides, the more I read about LHRH agents, the more I read of "cardio events". So?

There are advantages: no hot flashes, no bone loss, no fatigue, others. Dr. (Ph.D.) Wassersug of Canada has been a proponent, but finding others has been difficult.

Herb S.

10 Replies

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  • There is a 2008 paper [1] on a Scandinavian study that compared "high-dose polyestradiol phosphate (PEP; Estradurin) with combined androgen deprivation (CAD)".

    By that time, "855 of the 910 patients were dead" & "There was no difference between the treatment groups in terms of biochemical or clinical progression-free survival or in overall or disease-specific survival".

    However, there was: "a significant increase in non-fatal cardiovascular events in the PEP arm ... predominantly caused by an increase in ischemic heart and heart decompensation events."

    On the other hand: "There were 18 grave skeletal events in the CAD group but none in the PEP group."

    From 2005, a paper [2] on a Phase II U.S. study of transdermal estradiol (TDE) (0.6 mg per 24 hours) in "androgen-independent prostate carcinoma (AIPC)" cases:

    "serum estradiol level increased from 17.2 pg.mL ... to 460.7 pg/mL"

    "In patients with APIC, TDE was well tolerated and produced a modest response rate, but was not associated with thromboembolic complications or clinically important changes in several coagulation factors."

    -Patrick

    [1] ncbi.nlm.nih.gov/pubmed/184...

    Scand J Urol Nephrol. 2008;42(3):220-9. doi: 10.1080/00365590801943274.

    Parenteral estrogen versus combined androgen deprivation in the treatment of metastatic prostatic cancer: part 2. Final evaluation of the Scandinavian Prostatic Cancer Group (SPCG) Study No. 5.

    Hedlund PO, Damber JE, Hagerman I, Haukaas S, Henriksson P, Iversen P, Johansson R, Klarskov P, Lundbeck F, Rasmussen F, Varenhorst E, Viitanen J; SPCG-5 Study Group.

    Collaborators (104)

    Abstract

    OBJECTIVE:

    To compare parenteral estrogen therapy in the form of high-dose polyestradiol phosphate (PEP; Estradurin) with combined androgen deprivation (CAD) in the treatment of prostate cancer patients with skeletal metastases. The aim of the study was to compare anticancer efficacy and adverse events, especially cardiovascular events.

    MATERIAL AND METHODS:

    In total, 910 eligible patients with T0-4, NX, M1, G1-3 prostate cancer with an Eastern Cooperative Oncology Group performance status of 0-2 were randomized to treatment with either PEP 240 mg i.m. twice a month for 2 months and thereafter monthly, or flutamide (Eulexin) 250 mg t.i.d. per os in combination with either triptorelin (Decapeptyl) 3.75 mg i.m. per month or on an optional basis bilateral orchidectomy.

    RESULTS:

    At this final evaluation of the trial 855 of the 910 patients were dead. There was no difference between the treatment groups in terms of biochemical or clinical progression-free survival or in overall or disease-specific survival. There was no difference in cardiovascular mortality, but a significant increase in non-fatal cardiovascular events in the PEP arm (p<0.05) predominantly caused by an increase in ischemic heart and heart decompensation events. There were 18 grave skeletal events in the CAD group but none in the PEP group (p=0.001).

    CONCLUSIONS:

    PEP has an anticancer efficacy equal to CAD and does not increase cardiovascular mortality in metastasized patients, but carries a significant risk of non-fatal cardiovascular events, which should be balanced against the skeletal complications in the CAD group. It is feasible to use Estradurin in the primary or secondary endocrine treatment of metastasized patients without prominent cardiac risk factors and especially those with osteoporosis.

    [2] onlinelibrary.wiley.com/doi... [Full text]

    Cancer. 2005 Feb 15;103(4):717-23.

    Phase II study of transdermal estradiol in androgen-independent prostate carcinoma.

    Bland LB1, Garzotto M, DeLoughery TG, Ryan CW, Schuff KG, Wersinger EM, Lemmon D, Beer TM.

    Author information

    Abstract

    BACKGROUND:

    Oral estrogen therapy has activity in patients with hormone-naive and androgen-independent prostate carcinoma (AIPC), but its utility is limited by the associated risk of thromboembolic toxicity. Parenteral administration may be safer as it avoids "first pass" liver exposure to estrogen. The authors tested the safety and efficacy of transdermal estradiol (TDE), as well as the effect of therapy on hot flashes, sex hormones, the procoagulant cascade, and bone turnover in patients with AIPC.

    METHODS:

    Patients with prostate carcinoma progressing after primary hormonal therapy received TDE 0.6 mg per 24 hours (administered as six 0.1 mg per 24-hour patches replaced every 7 days). Serum prostate-specific antigen (PSA) and hormone levels, coagulation factors, markers of bone turnover, bone density measurements, and a hot flash diary were collected at regular intervals.

    RESULTS:

    Three of 24 patients (12.5%; 95% confidence interval [CI], 0-26%) had a confirmed PSA reduction >50%. The Kaplan-Meier estimate of median time to disease progression was 12 weeks (95% CI, 4.6-19.4 weeks). Toxicity was modest and no thromboembolic complications occurred. The mean (+/-95% CI) serum estradiol level increased from 17.2 pg.mL (range, 14.8-19.6 pg/mL) to 460.7 pg/mL (range, 334.6-586.7 pg/mL). The total testosterone level remained stable in the anorchid range during treatment, but the free testosterone level decreased as a result of increased sex hormone binding globulin. No change in factor VIII activity, F 1.2, or resistance to activated protein C was observed, whereas a modest decrease in the protein S level was observed.

    CONCLUSIONS:

    In patients with APIC, TDE was well tolerated and produced a modest response rate, but was not associated with thromboembolic complications or clinically important changes in several coagulation factors.

    Copyright (c) 2005 American Cancer Society.

    Comment in

    Phase II study of transdermal estradiol in androgen-independent prostate carcinoma. [Cancer. 2006]

    PMID: 15641029 DOI: 10.1002/cncr.20857

    [PubMed - indexed for MEDLINE]

  • Patrick: Thanks; these two references, even though "old" seem to prove the point, First paper (IM administration) shows a cardio effect. Earlier paper used patches, no cardio effect. The problem seems to be getting docs to change their viewpoint. My own oncologist, who I think participated in a [more recent] trial of patches, still had the knee-jerk reaction when I first asked him: "clots!" When I asked him about the study all I got was "mumble, mumble."

    For those who may want to rush off for patches, do note that estradiol patches do seem to fail just like LHRH agents. My concern has been trying to find appropriate dosing...while the question of level vs peak/value pattern remains unresolved.

    Herb s.

  • Just to clarify, I have indeed personally used high dose transdermal estradiol (tE2) for ADT, but:

    1. It is an off-label use in Canada.

    2. I prefer the gel to the patches, as I found it much easier to manage.

    3. I only did it do avoid hot flashes, osteoporosis, full suppression of my libido, and the mild cognitive impairment that I experience when on LHRH drugs.

    4. Gynecomastia is a definite side effect, which is inconsequential for some men but intolerable for others.

    5. It may be dangerous if one is into the castrate resistnet stage of the disease

    That said, I did tE2 for ~ 15 years with complete PSA control. HOWEVER I don't actively promote tE2 either in person or in the ADT book as I am not an MD and believe that it doesn't help my credibility as a research scientist to go about promoting medical treatments based on N=1 data.

    If one wants to explore though going on tE2 with their physicians, they should check out what Paul Abel and his team in London have published on the PATCH study. PATCH is now a phase 3 study rolled into the larger and endless STAMPEDE clinical trial.

    If folks want more information on my reaction to tE2 they can go to the Journal of Sex and Marital Therapy and pull up the essay "Prostate Cancer, Gonadal Hormones, and my Brain" which I published there a couple of years ago. The essay is, I believe, freely available as a download from the journal's website.

    Richard W.

    PS: Paul Schellhammer MD (past president of the American Urological Association) has a new essay out which mentions E2 use for patients on ADT. It is his personal view on PCa as a patient and PCa expert. It was invited by the Turkish Journal of Urology, It is also freely available online.

  • Hi Herb1,

    My husband used diethystilbestrol 2mg plus warfarin 2mg from 16/1/12 to 4/8/13 where his PSA initially fell from 45 to16, but this was discontinued once PSA reached 38 and Zytiga was commenced. There was some breast enlargement which he had radiated. I wish you luck Herb.

    Carol

  • When I was first on Lupron, I had hot flashes, & told my urologist. He prescribed megestrol (generic Megace). It worked. After some time passed, I realized I didn't get hot flashes anymore even without the megestrol.

    I haven't seen it mentioned in this forum, although I haven't searched for it. Maybe it's not being used anymore? Anyway, it worked for me.

  • Neal-yes, megace is a recognized treatment for the hot flashes. There is another agent also,but I can't think of name. Both are in the hormone class. My flashes on Lupron initially were never bad enough that I wanted to add another hormone to my treatment--I just bought a few pocket-sized fans!

    Unfortunately, as far as I know neither Megace nor other drug does any good for other side effects such as: cognition problems, bone density loss, etc.

    Herb

  • Hi, I have been on the Estrogen patches for three years now and they have been great for me. My PSA is 0.12 and has been at that level for two and a half years. I put two 100mg. patches on every four days and that is all the maintenance we do. When I get depressed or down, I take a ten day break from the patches and go back on them with no side effects what so ever. I have written on this subject three times in the past, but it seems only us Canadians are using the patches with any success? If anyone wants to contact my doctor in London ON., please just drop me a line and I will be glad to help to give you the doctors name and point you in the right direction. Scoreo

  • Hi sawmill: Thanks for responding and I'm glad to see it's working well for you. Richard, does that make it N=2? :-). Sawmill, what were your pre-estrogen, pre any hormone treatment statistics: GS, psa, when diagnosed, other treatment, etc.?

    I don't know if estrogens are the answer for any, some, all, but I do think it's important that patients AND DOCTORS are kept aware that there are alternatives.

    Herb

  • Thnx Herb1, before trying the Estrogen I had tried all the hormone treatments out there and I mean all and my body rejected them. Finally my Oncologist in London said there was no treatment left and I should go home and make peace with myself. Two weeks later he called me in and said they had this new path to try if I wanted to be the first to wear it? My PSA was 136 and climbing every week and I felt there was nothing to lose by giving it a shot. One month later my PSA had dropped to 75 and two months later it was 31. I felt great and I had forgot what it was like not to suffer from all the side effects I had endured over the past 13 years. Six months passed and I was down to 0.91 and I started with four patches of Estradot 100 and now was down to two patches changing them every four days. Today I am 0.12 and I have few if any hot flashes and take nothing else for the Cancer other than healthy eating. I can't say enough about the Estrogen, as it works for me and I am in my 16th year with the beast. Good luck and I will share anything with anyone who needs help on this site. Sawmill.

  • Sawmill: Sounds great, keep going! What are the specs (concentration or dose) of your patches, do you change them both on the same day, and have you determined your blood serum estrogen levels?

    herb

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