Effects of HRT: Alone, in Combination or Sequencing

After conducting thorough research, I’m not concerned about my breast cancer risk. I’m part of the "Wisdom" breast cancer study, which is open to women 74 and under. The study includes genetic testing for 29 mutations associated with breast cancer, and I don’t have any of these mutations. In 2012, I had a 23andMe test for BRCA1 and BRCA2, and I’ve since had it redone through the Wisdom study. I’ve always maintained healthy habits.

My main concern is my heart health. I have cardiovascular disease (CVD) and, not surprisingly, 15 genetic risks for CVD (such as Apo(a), APOB, APOE4, thin caps, etc.). I’m worried because my cardiologist is not up-to-date on hormone knowledge. He believes estrogen causes breast cancer, but I know that’s incorrect. Given that he’s misinformed on this topic, I’m unsure if I can trust his advice about using a .05 estrogen patch and 4mg of testosterone. Does he fully understand the risks of hormone replacement therapy (HRT) for someone with my cardiovascular risks?

It’s possible he wasn’t educated about women’s hormones and their relationship to cardiovascular health during medical school. I could seek a third opinion, but what if that cardiologist also advises against HRT? How do I know which doctor to believe? I had to wait five months for an appointment with my current cardiologist and four months for my first one. Should I wait another five months for a third opinion?

It took me two and a half years to find a doctor willing to prescribe HRT. Navigating the healthcare system, staying informed about current HRT options, osteopenia/osteoporosis, and the latest CVD research has felt like a full-time job. If it weren’t for forums and knowledgeable doctors sharing information through social media podcasts, I would feel lost and alone.

I find some reassurance in knowing that cardiovascular events for older women who begin HRT usually occur in the first year of use and tend to diminish after that. I’m currently in my ninth month of HRT.

I acknowledge that this is a tough decision, especially since the risks and benefits for women over 70 starting hormones are not well understood. I appreciate everything you’ve shared and am grateful for forums like this one.

There’s a lot here to unpack. Apo-E (Apolipoprotein E) is involved in the metabolism of fats. Every human inherits one copy of the gene. There are three variants of the ApoE protein: e2, e3, and e4. The combination of these variants determines your ApoE genotype. For example, you could have a 2/2, 2/3, 3/3, or 3/4 genotype, among others. Some combinations can be protective, neutral, or harmful. I have the ApoE 3/4 genotype, which is associated with an increased risk of both Alzheimer's disease AND cardiovascular diseases. The most feared one is 4/4 genotype.

Apo-E binds to lipids to form lipoproteins. To simplify things, because of my APOE 3/4 allele, my body struggles to clear LDL efficiently. This causes LDL to linger longer, leading to oxidation and increased inflammation.

My understanding of Lp(a) and APOB is the same as yours except
Lp(a) is treatable with three medications available today. However, these medications cannot fully address Lp(a) in a way that is highly effective for those with high levels of it. They are approved for lowering LDL and not specifically for Lp(a). Despite this, I believe they should still be used. Statins, for example, can increase Lp(a) by 8-24%.

Repatha can reduce Lp(a) by an average of 27%, Praluent can reduce it by about 25%, and Leqvio can also lower it by around 25%. Both oral and transdermal estradiol can reduce Lp(a) by up to 22% in postmenopausal women, but as we know, both estradiol and Lp(a) can also contribute to plaque instability in postmenopausal women who have heart disease.

Most doctors want to increase statin dosages to lower LDL to very low levels with people that have heart disease and not address Lp(a). But why not use one of these three medications to treat both high LDL and Lp(a) until newer Lp(a) drugs are released? The main obstacle is the complex approval process and insurance challenges. Repatha and Praluent are covered under Medicare Part D, while Leqvio is covered under Medicare Part B and is generally easier to get approved. I have been approved for Leqvio but still waiting to start it.

I’m not sure if calculators are always helpful. You can have a CAC score of 0 and still experience a heart attack. My MESA score with CAC is 4.5%.

I had a hysterectomy (uterus and cervix removed) when I was 44, 1994. Afterward, a coworker gave me a book about bioidentical hormones, and I became aware of the potential for bone loss, even with intact ovaries. Around 1995, there was some news about testosterone helping women with bone health and libido.

I used the compounded bioidentical hormone doctor my coworker recommended for estradiol for about a year and also a had a Dexa scan for a baseline. Then I added testosterone cream a year later after hearing about it in the news. After a year of testosterone I had another Dexa scan (I was paranoid about osteoporosis). The results showed improvement with the testosterone. Two years later, the doctor moved to a different state, and when I tried to find another doctor to prescribe testosterone, many of them were horrified and I couldn't find anyone who would prescribe it.

I became overconfident and went for about 12 years without a DEXA scan. In 2022, I had one and found out I have osteopenia. I had another scan June 2024, and the results showed minimal change. The last June scan, I had only been on the Estradiol 0.025 patch for about 2-3 months, so I don’t think it had any effect on my DEXA results. I do believe that adding testosterone and increasing my estradiol patch to 0.05 will make a difference, but I won’t know for sure until June 2026.

I’ve seen two endocrinologists that don't believe in bone markers. I would like to have them done, but I’d have to find a doctor who would actually perform them. There isn't any facility here doing TBA scoring for cortical bone. Both doctors said they wish there were but it was about $.

When I found out about my osteopenia, I was very focused on preventing osteoporosis. I joined Mayo osteoporosis forum to learn more. After reading people’s experiences with osteoporosis and medications, I became scared. That fear kicked off my journey with hrt, which ultimately led me to discover I have cardiovascular disease. It’s been quite a journey.

I am 76 and I cannot find a dr who will prescribe hrt estrogen and progesterone. instead the thick uterine lining is being probed. I sense through much research that the hrt is enough.

I am very interested in how your treatment with Transdermal HRT goes. I did 24 months of Forteo in 2016. Follow up with Evista for 5 years, now doing Forteo again, but not sure how many months I will do that as there seems to be no research on the safety of extended use. The only study I found was for folks with an underlying condition where other meds were not effective. HRT seems to be the least intrusive and without side effects? I was to follow up with Evenity but not liking some of the side effects mentioned as well as it being the same manufacturer as Prolia? And acts similar to Prolia after the first few months? Prolia gave me jaw problems and loss of two molars, so would not like to try that again, but have to say Prolia worked wonderfully for my sister, who has been on it for 10 years now and moved from Osteoporosis to Osteopinia.
Keep us posted of your journey!! And thank you for sharing. All the best to you. : )
PS. I am 67 and T score of -3.5 on hip. Cannot do spine due to prior fractures.

I read low doses are best for people over 65

My mother was on HRT into her nineties. She didn't break any bones and her mind was as sharp as a tack until she went off a few years before she passed away at 97. I'm a believer in HRT. Like so many things in women's health, there is a lot of misinformation and nonchalance about doing what is best for us!

Fascinating. So have you exclusively used HRT? In treating osteoporosis? Sorry if that’s what you said, but I’m trying to unravel what others are doing, as my path is currently not working or changing anything.

Fascinating. So have you exclusively used HRT? In treating osteoporosis? Sorry if that’s what you said, but I’m trying to unravel what others are doing, as my path is currently not working or changing anything.