Here's some nice, reassuring news for menopausal women. (Now that's not a phrase you see every day.)
The longest, biggest randomized study on hormone therapy — the treatments for menopausal symptoms formerly known as hormone replacement therapy — finds no significant rise in the risk of premature death for women who took the hormones, compared with those who took placebos.
The study, just out in the journal JAMA, included more than 27,000 women who were randomized to take hormone therapy for a few years or a placebo, and 18 years of follow-up.
I spoke with lead author Dr. JoAnn Manson of Brigham and Women's Hospital and Harvard, who helped pioneer research into hormone therapy's effects, and came away with three main points:
1. Though each woman who considers hormone therapy must assess her own risks and benefits, the treatment is looking generally like a reasonable tactic for treating tough side effects of menopause — hot flashes, night sweats, sleep disruption.
2. The hormones are not looking anything like a fountain of youth, or even a reasonable tactic for trying to prevent disease, including heart disease or cancer.
3. This latest, longest study finds a surprising drop in deaths from dementia among women who took estrogen, but it's far too early to know what it means.
Our conversation, edited:
So this new study looks at "all-cause mortality," meaning deaths for any reason. Why is that important?
All-cause mortality is a critically important summary measure for an intervention such as hormone therapy that has a very complex pattern of benefits and risks. It increases the risk of some diseases, decreases the risk of others, but mortality rates are the ultimate bottom line in looking at the net effect of a medication on serious and life-threatening health outcomes.
We know that hormone therapy is effective in treating menopausal symptoms, reducing hot flashes, night sweats, and it also decreases the risk of hip fractures and other fractures. But it's been linked to increased risk of several health problems, including blood clots in the legs and lungs, stroke and certain cancers. So looking at all-cause mortality, and deaths from specific causes, really enables us to look at the net effect of hormone therapy on total mortality.
And your findings are reassuring, it seems, for women who've been on hormone therapy.
Yes, I think the main point is that the findings do provide reassurance, especially for the younger women who are more likely to have hot flashes, night sweats and menopausal symptoms, that hormone therapy is very appropriate for management of menopausal symptoms, and that there's no increased risk of total mortality, or deaths from cardiovascular disease or cancer.
How would you sum up what else is new in these findings?
In this study, we had 18 years of follow-up on over 27,000 women participating in the two hormone therapy trials of the Women's Health Initiative, and a total of more than 7,000 deaths, which is more than twice as many deaths as in our earlier report because of the longer follow-up.
And we found no association between hormone therapy and total mortality, or deaths from cardiovascular disease, cancer or other major causes. So I think that this is reassuring news that hormone therapy does not increase total mortality or cause-specific mortality. And in the younger women, age 50 to 59 at the start of the study, there was a trend toward lower mortality with hormone therapy than with placebo.
So the hormone therapy pendulum is swinging back toward the positive?
We don't think the pendulum should swing back to the use of hormone therapy for prevention of cardiovascular disease and for the express purpose of trying to prevent chronic disease. These findings provide reassurance for the use of hormone therapy for symptom management or treatment of hot flashes, night sweats and other menopausal symptoms that can impair quality of life and disrupt sleep. However, we're not recommending use of hormone therapy for the express purpose of trying to prevent cardiovascular disease or other chronic diseases.
And we don't think the pendulum should be swinging back to that point, but rather resting at a more appropriate place of reassurance about use for management of menopausal symptoms.
We think that these findings provide support for clinical guidelines from many professional societies that endorse the use of hormone therapy, especially among recently menopausal women, to manage bothersome hot flashes, night sweats and other symptoms. And these findings do provide some reassurance that these hormones will not increase mortality and that they are appropriate for treatment.
And, as always, discuss this with your doctor?
We do believe very strongly in shared decision-making between the patient and the clinician. The woman's preference for being treated with hormones or not being treated with hormones is tremendously important to factor in to the equation. So this additional information will be helpful to women in their own decision-making and in talking with their clinicians.
But there do seem to be some glimmerings or suggestions in your findings that in fact, hormone therapy may be leading to somewhat positive health outcomes.
We found that among the younger women, the women age 50 to 59 when they entered the study, there was about a 30 percent lower risk of mortality in the women who were treated with hormones compared to the women on placebo.
However, that risk reduction did not persist with long-term follow-up. So that provides further reason for not using hormones specifically for the purpose of trying to reduce chronic disease or decrease risk of mortality, because long-term, those benefits may not persist.
The study does provide evidence that over 18 years of follow up, there was no association between hormone therapy and total mortality or deaths specifically from cardiovascular disease or cancer. But there also was no clear benefit in the overall study population in terms of mortality, and the benefit that was seen during treatment in women in their 50s did not persist long term.
And there was an intriguing positive finding on dementia?
We did see, surprisingly, that the death rate from dementia — Alzheimer's disease and other forms of dementia — was about 26 percent lower among the women who were randomized to receive estrogen alone versus those receiving placebo, and a neutral effect on deaths from dementia among the women who were taking estrogen plus progestin.
But we consider these findings to be exploratory, and we need to delve much more deeply into them in order to understand what's happening. We certainly would not recommend that women start taking hormone therapy for the express purpose of trying to reduce their risk of dementia, because some other findings have suggested that there could be increased risk when looking just at diagnosis of dementia.
Overall, is this the biggest bottom line yet on hormone therapy?
This is the largest randomized clinical trial of hormone therapy that's been conducted. And now, with 18 years of follow-up, we have a very clear understanding of the balance of benefits and risks of these hormone formulations, and how that balance translates into all-cause mortality risk and risk of dying from specific causes, such as cardiovascular disease and cancer.
What we need now is additional research on some of the newer formulations of hormone therapy that are becoming more common in clinical practice, such as lower doses, different formulations and different routes of delivery, such as skin patches, gels or spray.