HRT after 60

Whose ready to kick a hornet’s nest? I guess I am. Like most areas of medicine where there is alot of controversy, this is one in which we desperately need more research. I’m going to detail how I counsel pateints but this is one where you can expect to get a range of opinions from doctors. In the absense of evidence, you get a range of opinions. Much of the dogma is expert opinion and well, that’s worth something - not saying what exactly, but surely something.

So, the average age of menopause is 51 and we will assume for the purposes of this conversation that we are first talking to a woman who went through menopause at 51, started HRT within 5 years of menopause and is now 60 and deciding what she needs to do. We will then have a conversation with a second fictional 60 year old who missed HRT in her 50s and is now wondering if its right for her.

Ms. A

So, to start Ms. A is a 60 year old who started HRT in her early 50s. She is now using an estrogen patch 0.05 and takes progesterone 100 mg at bedtime. She is doing well and comes in for her annual. “Do I need to stop now that I’m 60?” We pull up a chair because this isn’t a short conversation. First, the benefits - continued prevention of bone loss/osteoporosis, improved cardiovascular outcomes on women who start HRT close to menopause and improved all cause mortality. The downsides. As we age, we can develop and increased risk of blood clots and even topical estrogen application is not without risk. However, with all cause mortality comind down on the side of HRT, it’s likely of overall benefit. Now, how do you feel when taking it? If you were to not have it, would you have menopausal symptoms? would you have vaginal symptoms? would you have aging in your skin and face and loss of muscle mass? The answer to all of these is yes, but to what extent and if that would be bothersome is very woman to woman dependent.

Is there another way to achieve the benefits you desire? For the vaginal stuff yes - and let me say this again, vaginal estrogen is fine at any age and stage of peri/post menopause. Bone and muscle mass? There isn’t a good way. You can train and exercise and eat healthfully and you will still likely develop the rapid bone loss that is common to all postmenopausal women. For the skin, I’d dab some of your down there cream on your face and then there’s always the medspa.

Do you need to be on the same dose? Maybe not. This is an excellent time to consider coming down to 0.0375 and if you do fine, I’d stay at that dose for a year or two until your next bone density is due and see where your bones are at. I cannot stress this enough, but bone density and preention/treatment of osteoporosis is critical for maintaining quality of life in your 80s. Assume you will get there and want a skeleton that is still functioning when you do.

Ms. B

Ms. B when through menopause at 51 and saw an uncaring doctor who told her to suck it up because she didn’t want breast cancer did she? So, she’s bought fans and sucked it up and is now turning 60. Having heard about all the newly admitted HRT benefits and finding out that it doesn’t cause breast cancer she wants to know if shes a candidate. She had her first DEXA scan this morning and has some mild osteopenia with a normal FRAX score (meaning no prescription therapy is indicated).

So, we start by quickly dispelling again the breast cancer myth - it was never a statistically significant increase in risk and was an artifact of an oddly low breast cancer rate in the placebo group. Next, we say, great news, the WHI is really helpful for answering the question of what to do with you becasue the average age of patients in that trial was 63. What we saw there was a bump in cardiovascular risk in year one, evened out in year 2 and diminished in year 3. (This can at least partially be attributed to the use of oral premarin, which is about 10x more likely to make you throw a clot than oral estradiol and today, we use topical estrogen, which are even less likely to cause a clot.) There have also been some subsequent trials that suggest there may not be much of an improvement in CVD risk, but one of the biggest issues when looking at these trials is that what we call “HRT” could be about 12 different things and how much dose dose matter? You have oral estradiol (3 doses, but can be combined for many more options), oral premarin (2 doses I think, but I’ve literally never written a rx for it and never will), patch estradiol at 5 different doses, vaginal ring, evamist, divigel, compounds and on and on and on. We see in WHI that there is no statistically significant difference in all cause mortality for women starting therapy age 60-69 and fewer hip fractures and colon cancer. Quality of life was also significantly improved. There was an increased risk of thromboembolic events and like I said earlier in the paragraph, don’t use oral premarin over 60.

So, should we go forward? I generally take the approach that if someone is suffering from something - still having hot flashes, can’t sleep at night, etc, then treatment offers real benefits. We also have the mild osteopenia that can be reversed with HRT and esp if she has a family history, I’d probably lean toward treatment. If she says, “No, I feel great and I’m really enjoying my life right now,” then I would not lean towards prescribing more medicine for a much slimmer chance of benefit. I think doctors have gotten themselves in a lot of trouble historically doing that sort of thing.

The most important thing to notice about the answer for Mrs. B is that it’s nothing like the conversation I would have had with her 51 year old self. There does seem to be a clear all cause mortality benefit from HRT when started at the time of menopause. Our arteries get harder, we become more insulin resistant and there is a shift in lipids to look much more like that of man and the result of this combination is that approximately 10 years later, heart disease will have set in. If early intervention can stop that, we definitely need to know.

If anyone at the NIH is reading this and trying to figure out what to do with your women’s health budget, can I propose WHI 2? WHI 2 would be a trial of women aged 48-58 and they would be started on HRT at the start of perimenopause up to within 3 years of menopause and continued on HRT for 10 years - and maybe an option for an additional 5 year extension if there are significant differences in outcomes favoring HRT. We should attempt to find a trial director who is either agnostic or slightly pro HRT since the last guy poisoned the well for a generation based on … a lack of statistical significance. And, for the love of all that is holy, use an estradiol patch at 0.05 or 0.075 and micronized progesterone as this is what the majority of women getting HRT are taking.