Menopause News Round-Up

The length of time between accessing and disseminating new medical information is inversely proportional to the immediate import of that information.

Which is another way of saying that I heard nothing at last week’s meeting of the North American Menopause Society that is going to impact my medical practice anytime soon, which may be why it’s taken me so long to blog about it.

Which is not to say it wasn’t an interesting meeting.

More Theorizing About Estrogen and the Heart

There was lots of talk about the recent publication of the WHI Coronary Artery Calcium Study. You know, the one the media hasn’t talked much about. The one that showed that women age 50-59 who took estrogen alone had 30-49% less calcifications in their coronary arteries than women who took placebo. This, combined with a non-significant trend toward lower rates of cardiac events in this age group, continues to fuel hope that hormone replacement begun in the early menopause may actually be a good thing for the heart. As opposed to HRT started 10 or more years later, which, as we all know, is not.

This data dovetails nicely with some very interesting recent research into estrogen’s actions on blood vessels. Let’s see if I can make this simple …

We’ve known for years that estrogen increase nitrous oxide levels in the endothelium (the lining of blood vessels), which leads to vessel relaxation, endothelial cell migration and blood vessel wall repair (all good things). We also know that estrogen raises the good cholesterol (HDL) and lowers the bad cholesterol (LDL). Another good thing. So how do we explain that women who took estrogen in the WHI had more heart attacks?

One reason might be the action of 27-hydroxy cholesterol (27 HC), a cholesterol metabolite found in the blood and in the plaque of atherosclerotic blood vessels. It turns out that 27HC acts like a natural SERM (selective estrogen receptor modulator) that blocks estrogen receptors in blood vessels. This interferes with estrogen’s favorable action on nitrous oxide synthetase and blood vessel repair.

So, in cardiac vessels free of blockage, perhaps those of a newly menopausal woman age 50-59, estrogen is free to do it’s good stuff. But in vessels that already have build-up of plaque, and that harbor 27HC, perhaps like those in women age 62 (the average age in the WHI), estrogen does no good. In fact, given estrogen’s additional action in increasing blood clotting, giving estrogen at this late date might even be harmful.

It all sounds very nice, but the problem is that the research on 27HC and estrogen has so far only been done on mice, not women. The other problem is that the Coronary Artery Calcium Study did not include women over 60, so we have no idea what really happened to the coronary vessels of older women on estrogen.

So all of this is just a hypothesis. A hypothesis that does not change the decision-making process around using HRT in real women today.

Low-Dose Transdermal HRT

It’s the new mantra – go low dose, and think transdermal.

Why low dose? Because for many women using HRT, lower doses work just as well as standard doses for menopausal symptom control and for treatment of bone loss, but are less likely to increase breast density and cause side effects such as breast tenderness and bleeding.

Low doses of estrogen given transdermally do not appear to alter clotting parameters, leading to the assumption that they may be safer and carry less risks of strokes and blood clots.

Actually, I’ve been prescribing low dose HRT for some time now, and use mostly transdermal preparations. Although we do not as yet have the large clinical trials to support its relative safety compared with the formulations used in the WHI, it just makes sense, and truth be told, I see no compelling reason not to use these preparations.

But be careful – Estrogen is still estrogen, and until we have further data, women using low dose transdermal preparations need to assume they are accepting the risks of HRT as defined in the WHI.

One exception could be the risk of clotting , which may be lower with low dose transdermal HRT. The data are compelling enough that a few practitioners will now prescribe low dose transdermal estrogen to women at increased risk for thrombosis. That’s a tough call given the FDA labeling, but if this is a choice you are facing, talk to your hematologist.

Measuring Bone Quality

There was talk of fancy new ways of assessing bone quality – things like MRIs that can be manipulated to show the reaction of a vertebra to stress, and lots of computer modeling that will allow for drug manufactures to compare their products using technology more exacting than a simple bone density.

This was all very nice, but in the end, not clinically applicable just yet.

Preventing Breast Cancer

As usual these days, there is lots of talk about breast cancer chemo-prevention, a conversation begun primarily by the folks at Lilly, who have been trying for sometime now to turn the results of the STAR Trial into some meaningful profit for their drug Evista. ( I blogged about this trial back in February) Evista has been FDA-approved for treatment of osteoporosis, and is now approved for prevention of breast cancer in high-risk women with osteoporosis.

IN the STAR Trial, Evista prevented breast cancers as well as Tamoxifen, with less adverse effects on the endometrium and less blood clots. However, both drugs increase blood clots and stroke risks relative to placebo, and Evista is not as good as Tamoxifen in preventing DCIS. Oh, and Tamoxifen increases cataracts but Evista does not. Not so simple, is it?

But the big question is this – what breast cancer risk if high enough to warrant taking a drug that is not risk-free for five years? The STAR trial used a five-risk of 1.66% as criteria for enrollment in that trial, a risk which is essentially that of any 60-64 year old woman. As one women commented at the meeting, are we to ask every woman over 60 to consider taking a drug to lower their breast cancer risk that will also increase their risk of stroke? Most of us seem to think not. But for certain very high risk women, it’s a consideration, especially if they are already looking to treat osteoporosis.

The Eli Lilly folks have been working overtime to sell breast cancer risk assessment as the lead-in to use of their drug. But selling chemo-prevention is a different story. It’s a hard sell, essentially convincing women to trade in one risk for another, and the nuances of the choice are complex.

I really hope Lilly does not try the DTC approach on this one…

The Media and Health Reporting

The highlight of the meeting for me was a talk by Tara Parker-Pope, health journalist and author of “The Hormone Decision”. Pope took on the medical establishment, asking us to accept our role in the media mess surrounding the WHI, and challenging us to begin to better communicate research findings.

Pope made two simple but profoundly important suggestions – Write your abstract with the public in mind, and stop reporting relative risk. Relative risk, while useful statistically, is meaningless to individuals who really just want to know their individual risk associated with a treatment or lack therof.

I thought Tara was right on, and look forward to reading her new column and blog in the NY Times.