Should I use hormone therapy in menopause?

I have been in practice long enough to have seen the discussion, research, and prescribing recommendations with respect to use of hormone replacement therapy (HRT) evolve. When I was in medical school in the early 2000s, it was assumed (based largely on outcomes from studies such as the Women's Health Initiative) that hormone replacements were not safe and indeed contributed to cancer, such as breast cancer. Repeated studies showed conflicting results with respect to the Women's Health Initiative, with some demonstrating a protective effect of HRT but only if "bio-identical" hormones were used (and if estrogen and progesterone were co-administered) while others showed possible cancer risk.

Given conflicting results, how can you make a decision for your health on whether or not to use HRT?

I think the answer is not cut and dry, very individual, and based on your overall history and genetic expressions. While that is probably not what you wanted to read, it is the truth and I can simplify it.

The reason HRT is such a difficult therapy to understand much less make a decision about, is due to the complexity of the estrogen receptors (ESRs). Estrogen receptors have a relactionship to your DNA. Essentially, estrogen and its effect on ESRs is called nuclear regulation. This means estrogen is associated with your DNA in the nucleus of cells and as such, triggers cell division (transcription) when it binds to its receptor. In other words, one of estrogen's jobs is to find its binding spot (the ESR) and tell the cell to divide. Normal cell division is necessary for overall wellness--which is a reason women like to be on estrogen and feel good when they are.

However, the ESR gene is very suseptible to genetic changes (called a polymorphism). I think it is the relatively easy tendency for the ESR gene to change (which can change the way estrogen affects or does not affect the ESR). In a survey of 75 of my patients who have done a gene test that can show whether or not the ESR gene has changed, about 20% of them had NO changes to the gene while the other 80% did. This is interesting to me, because in most studies you read, it is generally reported that 20% of women have a decreased risk of breast cancer with HRT use.

The gene of interest is ESR2. The ESR2 gene change that in my patient population had changed is called ESR2-rs4986938 and ESR-2987983 heterozygous and homozygous (CT/AG or TT deletions/insertions). My mom is normal for the ESR2 gene, but I am not. I have the ESR2 gene polymorphisms CT and AG. My mom actually does well on a very low dose amount of estradiol cream, but I noticed adverse effects when I tried the same cream.

If you want to know what ESR2 gene changes you have, I recommend the gene test from Nutrition Genome. I don't use their recommendations report, but I do like the list of gene changes that comes with that test. It has been very helpful for me to better assist my patients and make clinical decisions as to what they need (or don't need).

This all being said, be careful about whether or not you should use hormone replacement. In general, because there is yet a debated risk of cancer with HRT use likely because of the ESR gene changes, I still try to steer patients away from it--including my mom even though she is normal for ESR2. I did have one patient pass recently from metastatic breast cancer. She and I had both suspected the cancer arose from use of high-dose HRT therapy (per another proovider) that had been prescribed for hot flashes. There is a lot you can do to treat hot flashes without the use of hormones. That will be the subject of another blog!