Effects of estradiol on bone in men undergoing ADT

[pjoshea13]

New Australian study below [1].

Seems a long time coming. ("6-month randomised, placebo-controlled trial")

"In men, many effects of testosterone (T) on the skeleton are thought to be mediated by estradiol (E2), but trial evidence is largely lacking."

"Relative to placebo, E2 treatment increases some measures of bone density and bone strength in men and reduces bone remodelling, effects that occur in absence of endogenous T."

Therefore, E2 replacement should occur, if necessary, before bisphosphonates, etc, be resorted to.

IMO, target E2 is 20 pg/mL when E2 is <12 pg/mL. Using the lowest dose E2 patch.

-Patrick

[1] pubmed.ncbi.nlm.nih.gov/356...

Eur J Endocrinol

. 2022 Jun 1;EJE-22-0227. doi: 10.1530/EJE-22-0227. Online ahead of print.

Effects of estradiol on bone in men undergoing androgen deprivation therapy: a randomised placebo-controlled trial

Nicholas Russell 1 , Ali Ghasem-Zadeh 2 , Rudolf Hoermann 3 , Ada S Cheung 4 , Jeffrey D Zajac 5 , Cat Shore-Lorenti 6 , Peter R Ebeling 7 , David J Handelsman 8 , Mathis Grossmann 9

Affiliations collapse

Affiliations

1 N Russell, Department of Endocrinology, Austin Health, Heidelberg, 3084, Australia.

2 A Ghasem-Zadeh, Department of Endocrinology, Austin Health, Heidelberg, Australia.

3 R Hoermann, Department of Medicine (Austin Health), The University of Melbourne Department of Medicine Austin Health, Heidelberg, Australia.

4 A Cheung, Department of Medicine (Austin Health), University of Melbourne, Heidelberg, Australia.

5 J Zajac, Medicine, University of Melbourne, Heidelberg, Australia.

6 C Shore-Lorenti, Department of Medicine, School of Clinical Sciences at Monash Health, Monash University, Clayton, Australia.

7 P Ebeling, Medicine, Monash University, Clayton, Australia.

8 D Handelsman, ANZAC Research Institute and Dept of Andrology, Dept of Andrology, Sydney, Australia.

9 M Grossmann, Medicine, Austin Health/ Northern Health, University of Melbourne, Heidelberg, Australia.

PMID: 35666800 DOI: 10.1530/EJE-22-0227

Abstract

Objective: In men, many effects of testosterone (T) on the skeleton are thought to be mediated by estradiol (E2), but trial evidence is largely lacking. This study aimed to determine the effects of E2 on bone health in men in the absence of endogenous T.

Design: 6-month randomised, placebo-controlled trial with the hypothesis that E2 would slow decline of volumetric bone mineral density (vBMD) and bone microstructure, maintain areal bone mineral density (aBMD), and reduce bone remodelling.

Methods: 78 participants receiving androgen deprivation therapy for prostate cancer were randomised to 0.9mg of 0.1% E2 gel daily, or matched placebo. The outcome measures were vBMD and microarchitecture at the distal tibia and distal radius by high-resolution peripheral quantitative CT, aBMD at the spine and hip by dual energy x-ray absorptiometry, and serum bone remodelling markers.

Results: For the primary endpoint, total vBMD at the distal tibia, there was no significant difference between groups, mean adjusted difference (MAD) 2.0mgHA/cm3 (95%CI -0.8 - 4.8), p=0.17. Cortical vBMD at the distal radius increased in the E2 group relative to placebo, MAD 14.8mgHA/cm3 (95%CI 4.5-25.0), p=0.005. Relative to placebo, E2 increased estimated failure load at tibia, MAD 250N (95%CI 36-465), p=0.02 and radius, MAD 193N (95%CI 65-320), p=0.003. Relative to placebo, E2 increased aBMD at the lumbar spine, MAD 0.02g/cm2 (95%CI 0.01-0.03), p=0.01, and ultra-distal radius, MAD 0.01g/cm2 (95%CI 0.00 - 0.02), p=0.01, and reduced serum bone remodelling markers.

Conclusion: Relative to placebo, E2 treatment increases some measures of bone density and bone strength in men and reduces bone remodelling, effects that occur in absence of endogenous T.

[Kentucky1]

What's the clinical significance of this study? Does this favor E2 over Xgeva or Zometa?

[pjoshea13 in reply to Kentucky1]

ADT harms bones by creating estradiol deficiency. It makes sense to correct the deficiency before starting heavy duty drugs.

There is no downside to low-dose E2 patches. No necrosis of the jaw risk.

Many men in the group, perhaps influenced by Dr. Myers, use low-dose E2 (such as the Vivelle-Dot 0.025mg applied to the skin twice weekly)

-Patrick

[Hidden in reply to pjoshea13]

My mo won’t give it to me . Instead prolia . Wtf? Standard of care .

[pjoshea13 in reply to Hidden]

Ironically, in the bad old days before Lupron, men on the synthetic estrogen DES (Diethylstilbestrol) for ADT did not suffer bone loss. DES was recognized by the body as a stand-in for estradiol [E2].

At the moment, LabCorp says my E2 is <5 pg/mL, i.e. 0-4.9. Would be a disaster for bone if I were on Lupron, but with DES, a spine doc told me that my spine was in remarkably good condition for my age. I credit vitamin K2-7 for that, but it's also anecdotal evidence that ADT bone loss is essentially due to E2 loss without some add-back mechanism (in my case DES.)

Docs who treat with Denosumab (Prolia/Xgeva) or Bisphosphonates (Zometa, etc.) are remarkably ignorant about the importance of E2 for bone in males.

-Patrick

[MateoBeach in reply to pjoshea13]

Wondering about the CV risk of DES. Do you think Nattokinase and low dose aspirin provides enough counter protection? Or something else in your toolkit?

[cesanon]

1. "effects that occur in absence of endogenous T."

What does that mean? What is its significance?

2. Therefore, E2 replacement should occur, if necessary, before bisphosphonates, etc, be resorted to.

Why would that be?

[pjoshea13 in reply to cesanon]

Check out the numerous threads on the topic - including the Dr. Myers vlog post.

[Hidden]

Hypogonadism is me .. adt 7 yrs , I tried an estradiol 2 gel last yr . By the time I finished that tube I was done with it . My tits increased and became painful for the first time . I dropped it . So much for self medicating .

[DenDoc]

No mention that the estradiol patch will help with the hot flashes too. I am in year 13 of ADT and bone health remains good.

[MateoBeach]

Studies of Zometa, a bisphoshonate, and especially denosumab, that have been previously cited, suggest that they alter the bone micro environment in ways that make them less hospitable for metastasis. Hence less likely to progress to new bone mets, perhaps especially in men with no known bone Mets yet. (My speculation on that last part.)By the end stage of APC 90% will have bone Mets and related symptoms such as pathological fractures and severe bone pain. Vs. the 5% or less who may develop ONJ.

Therefore I personally advocate and use denosumab proactively for over 5 years now and continue to have no known bone metastasis.

When I decide to go off it I will substitute at least intermittent Oral alendronate to protect from denosumab withdrawal effects.

And I also use estradiol patch when on my ADT cycles (1 out of 3 months off of T-cypionate mBAT), along with tamoxifen.

Thanks for all your insightful posts and perspectives. Paul