How Long Can You Safely Take Menopause Hormone Therapy?
Looking at combined therapy and the new study: Part 2
We have very little data on the use of menopause hormone therapy after age 65, so it was exciting to have a new paper that specifically looks at this age group. As the study provided much information, I addressed the estrogen-only aspect in the previous post (located here). Today, I will discuss the estrogen plus progestogen arm, also known as combination therapy.
One very important note. Most women using menopause hormone therapy take the type of regimen we are about to discuss, an estrogen plus progestogen. Unfortunately, some people primarily use the estrogen-only findings to talk about all menopause hormone therapy. This serves no one, as they are different regimens. Okay, maybe it serves people who have built a career around hormones solving everything. But that isn’t what happens here because you deserve facts.
Just a reminder, this is an observational study, so cause and effect can’t generally be inferred. For example, in this study, low-dose vaginal estrogen, products that do not raise the estrogen level above the menopausal range, reduced the risk of lung cancer by 19% and colon cancer by 20% (both results were statistically significant), but medium doses of vaginal estrogen (estrogen meant to be absorbed) did not have this effect. This seems biologically implausible and is likely a statistical artifact.
With any observational study, it’s important to consider the findings in context and be careful about projecting what we may or may not want the results to be.
Okay, let’s get into it.
Brief Intro
The study is a database review of electronic medical records from the US Centers for Medicare and Medicaid Services (CMS). The researchers looked at who received hormones and who didn’t and also evaluated a variety of important health outcomes: death, five different types of cancer (breast, lung, endometrial, colon, and ovary), cardiovascular disease (six different types, including stroke and blood clots), and dementia. A medium or standard dose of hormones was 0.625 of conjugated equine estrogens (CEE or Premarin), 1 mg of oral estradiol, 5 μg of oral ethinyl estradiol, a transdermal 50 μg patch, and a vaginal delivery of 50 μg estradiol. Women were not randomly assigned to hormones or a placebo, so many unknown variables exist.
There were many permutations and combinations of regimens. In addition, the grouping of some of the results in the paper could be confusing or misleading. For example, the oral estrogen plus progesterone or oral estrogen plus progestin categories both include estradiol and Premarin (conjugated equine estrogens or CEE). However, they are not the same hormones, and Premarin is not a major player in the menopause therapy market right now (outside of Duavee, and there is no data here on that drug combination). Premarin could give different results than estradiol, so they should really be looked at separately. Another example is the weird grouping of low-dose estrogen, which includes both low-dose vaginal estradiol (a product meant to stay in the vagina and not cause estradiol levels to rise over that seen in the menopause range) and low-dose transdermal estradiol meant to enter the blood and raise the levels. Therefore, I decided to dive into the supplemental data and gather information on the most common regimens. This means I focused on transdermal estradiol and oral estradiol regimens with either progesterone or a progestin. If you need a refresher on progesterone vs. progestins, read this post.
The following few sections will be pretty in-depth, so like my previous post on this topic, you can keep reading (and I don’t mean to discourage you from that) or skip to the “Putting it All Together” section if you feel your eyes glazing over.
Mortality and Cancer Risk
I created a table showing some of the key findings with the most common regimens used today. The findings represent the increased or decreased risk associated with the hormone regimens as compared to women over 65 not taking hormones. Hopefully, this provides a quick and easy way to look at the data. Results that were not statistically significant are in black type and have NS below the number (basically, consider these results as no change in risk). Numbers with a positive value mean an increased risk (bad) and are also highlighted in red. And, of course, numbers with a negative value mean a reduced risk (good) and are in green text. Values with an asterisk have a stronger statistical signal.
Table 1: Overall Mortality and Risk of Breast, Lung, Endometrial, Colon and Ovarian Cancer with Combined MHT