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Effects of HRT: Alone, in Combination or Sequencing

Posted by mayblin @mayblin, Jan 17, 2025

Have you used HRT as the sole modality for osteopenia or osteoporosis? How about using it in a therapy sequence or in combination with another osteodrug, either an anabolic or an antiresorptive? What is the outcome of such choice(s)?

After a diagnosis of osteoporosis nearly 3 years ago, I elected Forteo as my first drug therapy then transitioned to HRT afterwards. Forteo gave me a jump start on building bones: lumbar bmd +8.6%, hips r/l +4.8/2.2%, femur necks r/l +8.9/3.4%. Bmd improvements are as follows after 22mo Forteo followed by 6mo HRT (scans were done with same machine and by same tech):

Lumbar spine bmd +18%, T score from -3.4 to -2.3;
Right hip bmd +9%, T score from -2.3 to -1.8;
Left hip bmd +4.1%, T score from -2.1 to -1.8;
Right femur neck bmd +16%, T score from -2.4 to -1.6;
Left femur neck bmd +9.8%, T score from -2.5 to -2.0;
TBS from 1.264 to 1.322

So far so good but I know this is just the start of a long road ahead.

I’m very grateful for the existence of Mayo Clinic Connect. Without this forum I’d never thought HRT would be in the cards as I’m more than 10 years past menopause. Many thanks to @vkmov for initiating the thread “Transdermal HRT”, @teb for her generous sharing of personal experiences, and countless members for their in depth discussions and suggestions.

The inclusion of HRT in the management of osteoporosis isn’t mainstream, in fact it is not approved for the treatment of osteoporosis so data and evidence are lacking. It will be helpful if we could share the outcomes of HRT among those of us who have chosen to use HRT under the care of our team of physicians. Dexa results possibly with bone turnover markers and/or TBS info if available will be nice. By the way, my CTX trended down to 163 after 6mo HRT from a high of 793 at end of Forteo treatment, a change I didn’t anticipate at all.

Any comments or analysis are welcome; and best luck to us all no matter what therapy path(s) we choose!

Interested in more discussions like this? Go to the Osteoporosis & Bone Health Support Group.

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teb | @teb | May 13 5:07pm

@mayblin Glad you are doing well!

I've been on HRT now for about 8 years and I believe it is the major contributing factor to maintaining/possibly building my bones. I started at .025 transdermal estradiol and was on that for many years which helped to keep my spine at -2.8. Gradually, over the years, I have increased the dose and am now at .05. My most recent dexa indicated my spine was -2.5 but I don't believe I had been on the higher dose long enough to have that kind of impact. It was also a new Dexa machine for me but almost every dexa machine I have used has been different due to moving quite frequently over the last 7 years. From my understanding, an estrogen blood level of 40 is the point at which you can build bone. My last level was 40 when measured. In addition to HRT, I do cardio dance 3X a week, gym weights 2x a week, 30 minutes core/daily, hike on hills 1x a week and eat a whole foods/organic diet. I do believe it's a combination of all these things that have contributed to keeping the loss at bay though before the hormones (and Forteo before that) I ate a clean diet and exercised, I just increased/improved everything I was doing previously.

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mayblin | @mayblin | May 14 10:32am
In reply to @debbie1956 "@mayblin , Yes, I recall you starting the estradiol patch and micronized progesterone around the same..." + (show)
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@mayblin , Yes, I recall you starting the estradiol patch and micronized progesterone around the same time that I did, approaching 2 years ago at age 67, and that we were on the same doses. My response has been very similar to yours. To CTX tests since starting show that the CTX has come down from 688 to close to 100 within a year. This is a phenomenal reduction as I have never taken anti-resorptive nor anabolic osteoporosis medication. My t-score spine bmd went from -.3 to -2.6. I am due for another bone scan soon as well to see if these gains have held or maybe further improved. When I began HRT, my greatest hope was to stop my staggering progression of bone loss, so this gain was an unexpected bonus.

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Thank you debbie and teb for sharing your experiences and updates.

@debbie1956 its remarkable how closely our CTX ranges align in the low 100s. It really adds weight to the evidence that the low dose estradiol patch can be very effective for bone turnover suppression. @teb thank you for the update on your dosing change and your recent DXA trend. It’s nice to see how these adjustments play out over time.

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kfhoz | @kfhoz | May 14 12:08pm
In reply to @dmshope "@mayblin Thank you for the detailed and kind response. That gives me guidelines. I went off..." + (show)
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@mayblin
Thank you for the detailed and kind response. That gives me guidelines.

I went off Evenity at 11 months due to no reponse ( no dexa improvement) and continued fracture ( lower limb). It may not have been the evenity as much as the sequencing of evenity so close to tymlos and after a course of actonel. Evenity after tymlos has lower effectiveness but still should have some effectiveness.

I am hoping the HRT will improve cortical bone and nourish my body and manage normalizing CTX but as we know CTX increases with a fracture to promote healing; so we will have to moniter this and figure out what is best.

Good health to you.

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@dmshope Interesting. Romosozumab (Evenity) after a PTH drug (e.g. Tymlos=abaloparatide) is supposed to be good sequencing. Kudos to your doctor on that. But a bisphosphonate such as risedronate (Actonel) before Evenity is supposed to mute the response. So your suspicion of the Actonel seems on target, although I assume you had 18 to 24 months on Tymlos before starting Evenity. So that is a possible further reminder for us all that once you take a bisphosphonate long term the effects, good and bad, could be there for many years. But people respond differently. Thanks for sharing your history!

Reference, although not the best about bisphosphonates staying with you for years:
https://pmc.ncbi.nlm.nih.gov/articles/PMC3707342/
EXCERPT: "A reservoir of bisphosphonates accumulates after years of treatment that is gradually released over months or years ..."

Here is a reference from Dr. Doug Lucas about sequencing OP meds.

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debbie1956 | @debbie1956 | May 14 2:45pm
In reply to @mayblin "@dmshope I’ve been using transdermal estradiol 0.025mg/day patches and oral micronized progesterone 100mg daily at bedtime...." + (show)
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@dmshope
I’ve been using transdermal estradiol 0.025mg/day patches and oral micronized progesterone 100mg daily at bedtime.

My endocrinologist and a bone specialist originally advised titrating up to the standard 0.05mg/day patch dose (roughly the equivalent of the CEE dose used in the WHI study). However, when they saw my CTX drop to 302 after just 3mo, they had me hold at the lower dose. By 6mo mark, my labs confirmed that the 0.025mg/day was adequate for suppression. Please note that my 1st year BTMs were influenced by coming off Forteo, with a high turnover rate at the time; therefore, part of those initial CTX changes was likely due to that transition.

I’m nearing the end of my second year on HRT, and my CTX has consistently remained below 120 during second year. I won’t have my next DXA results until later this year to see the formal BMD impact.

Have you finished your Evenity course? If so, you may want to keep an eye on your CTX closely as it can take 6-9mos for estrogen to reach its peak anti-resorptive effect, if you choose HRT route.

There is evidence suggesting that low-dose and conventional-dose patches can be equally effective at preventing bone loss across all post-menopausal ages:
https://pubmed.ncbi.nlm.nih.gov/8706298/
I believe @debbie1956 used the same dosing as mine and I’ll tag her here. I’ll also tag @teb who has been on HRT for quite a long time and shared similar experiences in the past, just in case either of them has a moment to chime in with their experiences.

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@mayblin I so appreciate all your extensive research and studies that you post for us. I just read your PubMed study on low dose transdermal estrogen for women of all post-menopausal ages. This was such an encouraging study to read and really affirms our experience of Estradiol patch 0.025 with micronized Progesterone 100 mg. There seems to be very few studies on HRT for women over 67.

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