Transdermal HRT

Hi mayblin, I'm happy to share. I've been on the 0.05 mg estradiol / 0.14 mg norethindrone acetate Combipatch since last March. My new gyno will start me off on the equivelant dosage of the estradiol patch (0.05 mg) and the oral prometrium (100 mg) then gradually increase the dosage. I have epilepsy, so we have to proceed with caution. She says it's easier to get the dosages where they need to be with these HRTs than it us with Combipatch. To be honest, I didn't ask why that's the case. I'm just happy to have a doctor willing to do it.

I don't have any articles or research to site on the combination of HRTs and bisphosphonates. I've chosen to do both so to counter Evenity rebound with the low dose Reclast infusion while increasing HRT dosage. I'll continue having my BTMs tested every 3 months to determine when to move on to Alendronate. The idea is to improve my bone metabolism while tapering off of osteomeds. I'm making decisions based on my knowledge of how the various treatments work and how my body is responding. So far so good!

From the American College of Obstetricians and Gynecologists re stroke and transdermal HRT:
https://www.acog.org/clinical/clinical-guidance/committee-opinion/articles/2013/04/postmenopausal-estrogen-therapy-route-of-administration-and-risk-of-venous-thromboembolism
“Studies that compared oral and transdermal ET have demonstrated that transdermally administered estrogen has little or no effect in elevating prothrombotic substances and may have beneficial effects on proinflammatory markers, including C-reactive protein, prothrombin activation peptide, and antithrombin activity. Also, in contrast to oral ET, transdermal ET also may have a suppressive effect on tissue plasminogen activator antigen and plasminogen activator inhibitor activity 2324 25 26 27 28 29.

The Estrogen and Thromboembolism Risk study, a multicenter case–control study of thromboembolism among postmenopausal women aged 45–70 years, demonstrated an odds ratio for venous thromboembolism in users of oral and transdermal estrogen to be 4.2 (95% CI, 1.5–11.6) and 0.9 (95% CI,0.4–2.1), respectively, when compared with nonusers 10. Transdermal estrogen had no increased risk compared with nonusers. Similar results were reported elsewhere 30 31 32 33 34 35 and of particular importance, in women who were stratified for weight 36 and the presence of prothrombotic mutations 37.”

Hello! I sure have mentioned transdermal hrt to my functional medicine aprn, pcp and gynecologist. All say no because I carry the gene factor v leiden heterozygous which puts me more at risk for blood clots. There are no studies in the United States including women with this genetic disorder. It has been approved in United Kingdom for women at risk for blood clots and had/have cancer. Bioidentical transdermal hrt is the safest way to go. My main cause of osteoporosis is loss of estrogen. Took Teriparatide then had to stop after 6 months due to high levels of calcium in 24 hour urine. Had my first Reclast infusion last month. Just have to take one day at a time. I'm due to have a Dexa scan in 2025 with tbs so hopefully some improvements since this years testing though I never had tbs with my dexa before, so hoping I have good quality bones.

Does anyone know if there have been newer studies re: transdermal estrogen & cardiovascular/stroke risks? And if so, do they support the same conclusion as this 2023 study?

I have Factor V also and found out only in 2000, when I had a knee replacement and my entire leg clotted afterwards. Fortunately the Genome Project had just completed its work, so Factor V was a known thing and one of the specialist called in for my knee issue ordered a test. I've had other clotting but so far only post-surgically. I'm now 86 and have had a second knee replacement and recent broken femur surgery without incident though I always have a hematologist on the case.
I've also taken transdermal bioidentical estrogen and progesterone for several decades now. It was recently upped a bit for the osteoporosis diagnosis. One of my doctors who approved its use for me is the founder of the lab system for Functional Medicine at the Cleveland Clinic. Another is endocrinology royalty, in the direct family line of the discoverer of hormones - her late father and her brother are also endocrinologists. They're Belgian, so a little out of the mainstream. If you can find someone to prescribe it for you, I don't think you should worry about it, and you will feel better and presumably your bones will have a bit of an advantage as well.
What you SHOULD worry about with Factor V is eye surgery, especially if you're on one of the newer drugs like Xarelto. I lost an eye that way in 2018, when I was assured by the hematology establishment that I should be off it for only two days for a drainage tube insertion. I'm leery of Xarelto, so I stayed off it for four days. Still I had a huge bleed from a collapsed eye wall several weeks later, plus more surgeries to remove blood. A year later, the retina guy explained that the blood vessels are teeny and weak, and you need to be off these newish drugs for at least 10 days. I had researched everywhere and seen nothing like this, and when I asked him why he said that, he said when you're a retina specialist you see a lot of older people and quite a few of them are on these drugs. "It's my experience." My three doctors were going to write a case report about this but one thing and another kept them too busy and they didn't. When it turned out the optic nerve was too damaged, the hematologist said, that's because Factor V makes an especially hard clot that's really difficult to dissolve. I'm now on 10mg of Xarelto, which is a fairly recent lowering of the dose recommended for genetic clotting patients.

Hi @bayhorse the article that you were referring to was from 2013, not 2023, I believe. It's related to VTE (venous thromboembolism). When one uses bioidentical form of estrogen (E2, or estradiol) topically either transdermally or intravaginally, there is very little added VTE risks since estradiol bypasses liver metabolism.

There are two well designed clinical studies for estrogen's effect on cvd risks: KEEPS (2019) and ELITE (2016). ELITE (Early verses Late postmenopausal Treatment with Estradiol) is of special interest to us: it concluded that "Oral estradiol therapy was associated with less progression of subclinical atherosclerosis (measured as CIMT) than was placebo when therapy was initiated within 6 years after menopause but not when it was initiated 10 or more years after menopause. Estradiol had no significant effect on cardiac CT measures of atherosclerosis in either postmenopause stratum. (Funded by the National Institute on Aging, National Institutes of Health; ELITE ClinicalTrials.gov number, NCT00114517.)". This is why many doctors are reluctant prescribing hrt if a woman is postmenopausal for more than 10 years.

During my exploration on the feasibility of hrt therapy (I was just a little over 10 yr past menopause at the time), one statement stood out - one can be 55 years old having a cardiovascular health of a 65 year-old, or, vice versa. So the key is to find a cardiologist who is familiar with this topic and to get an individualized cvd risk assessment.

You might already read the thread "HRT safety" where many members discussed the topic:
https://connect.mayoclinic.org/discussion/hrt-safety/

Hi, mayblin, and thanks much for your informative response. I am, as you were, a little over 10 years past menopause, and I have an implanted pacemaker/ defibrillator due to heart failure. But my recent echo and stress test results were very good, hence my willingness to venture into HRT to help my very poor bones. My cardiologist wouldn’t weigh in on the matter — he was honest and admitted he didn’t know enough to advise. So it looks like the task will be to find a cardiologist who does know enough. I am in Austin, Tx. If anyone can make a recommendation, I’d be grateful!

Does anyone know if there have been newer studies re: transdermal estrogen & cardiovascular/stroke risks? And if so, do they support the same conclusion as this 2023 study?

Here's one from October 2024:
Hormone Replacement Therapy
https://www.ncbi.nlm.nih.gov/books/NBK493191/
Gina Harper-Harrison; Karen Carlson; Meaghan M. Shanahan.
Author Information and Affiliations

Last Update: October 6, 2024.

See: Transdermal formulations

Conversely, transdermal estrogen bypasses the hepatic metabolism that produces activated protein-C resistance, negating the risk of blood clotting seen with oral formulations.[11] Transdermal estradiol offers several benefits, including avoiding the digestive system and liver metabolism, resulting in no changes to thyroid-binding globulin or hepatic coagulation proteins at standard doses. Transdermal delivery has minimal impact on the risk of VTE and is convenient, typically requiring application once or twice a week. This makes transdermal estrogen a better choice than oral estrogen for most women, especially patients who smoke cigarettes or have migraines. Additionally, transdermal estrogen has a neutral effect on blood lipids. However, topical forms may cause skin irritation or, rarely, allergic reactions, though this is less common with gels. Some women may experience poor absorption or forget to change the patch regularly.[8]