OK this is a very interesting and important update regarding the risks and benefits for post-menopausal women on hormonal therapy. I get asked almost weekly about the safety of taking hormone replacement therapy (HRT) after menopause. For years the standard of practice and general belief was that HRT after menopause helped protect women’s bones and reduce their risk of heart disease. Then is a tectonic shift in evidence based advise, the US Preventive Services Task Force suggested that the benefits did not appear to outweigh the risks for women over 50 experiencing menopause. Based on their new understanding of the data they in fact did not recommend HRT for most post-menopausal women. It was about this time that doctors began advising women to stop using HRT except in cases where their symptoms were intolerable otherwise.
This month an updated review of the literature was published by the same group in JAMA (2017 Dec 12; 318(22) 2234-2249 where over 40,000 women (mean ages 53-79) enrolled in 18 clinical trials (N=142-16,608) were looked at in a combined “meta-analysis” for an updated look at the potential benefits and risks of HRT. I wanted to try and summarize the results for you and then give you my thoughts on the impact.
The first group included women who were using “estrogen only” replacement. Looking at the the number of cases per 1000 “person-years” they found the following:
BENEFITS
Diabetes an average of 19 fewer cases/1000 patient years
Fractures an average of 53 fewer case/1000 patient years
RISKS
Gall Bladder Disease an average increase of 30 cases/1000 patient years
Stroke an average increase of 11 cases/1000 patient years
Thromboembolism an average increase of 11 cases/1000 patient years
Urinary Incontinence an average increase of 1261 cases/1000 patient years
The second group included women using a combination of estrogen and progesterone. Their data revealed:
BENEFITS
Colorectal Cancer an average of 6 fewer cases/1000 patient years
Diabetes an average of 14 fewer cases/1000 patient years
Fractures an average of 44 fewer cases/1000 patient years
RISKS
Invasive Breast Cancer an average increase of 9 cases/1000 patient years
Probable Dementia an average increase of 22 cases/1000 patient years
Gallbladder Disease an average increase of 21 cases/1000 patient years
Stroke an average increase of 9 cases/1000 patient years
Urinary Incontinence an average increase of 878 cases/1000 patient years
Thromboembolism an average increase of 21 cases/1000 patient years
The Task Force conclusion was that the data was inconclusive with there being some evidence of benefit but also significant evidence of risk as well. So what does all this mean?
First, what are “Patient Years”?
Let’s look at an example…
Let’s say you have 1000 patients who are followed in a study for 2 years. This would represent 2000 “patient years” of follow-up
Next let’s say half this group of 1000 patients who were followed for 2 years (500×2=1000 patient years) on a placebo or NOT on estrogen had 30 cases of diabetes. This would represent 30 cases/1000 patient years.
Now let’s say the other half of this group of 1000 patients was followed for 2 years on HRT (500×2=1000 patient years) and only had 11 cases of diabetes. This would represent 11 cases/1000 patient years.
So if you compared the two groups you could say that the HRT group had 19 fewer cases/1000 patient years than the control or placebo group
Now how do you understand the results?
- First this type of analysis is powered by the size of the patients included in the Meta-Analysis that lumps together results from a number of studies. These studies are interesting because they consider large groups of patients.
- The challenge is that each individual study in the “meta-analysis” was constructed differently with unique criteria for enrollment, controls for other diseases and even histories of previous disease. So you have to be careful interpreting the data.
- There is no way to attribute a causal relationship to any of the data. The best you can surmise is that there may be an association between the risks, benefits and the use of HRT in post-menopausal women between the ages of 53 and 79.
My Thoughts and Recommendation
Obviously I need to lead with the recommendation to discuss this with your doctor. Every woman’s situation is different and since the data is not conclusive, personal and professional judgement needs to be involved in each case.
What stands out to me in this review is that the benefits in both groups relate to diabetes and fractures, with a small colorectal cancer reduction in the combination HRT group. Compare these “benefits” to the “risks” which include stroke, thromboembolism (blood clot), breast cancer and dementia. Though the numbers are small in both instances, the risks seem far more consequential to me. It is possible to lower diabetes risk with diet, exercise and weigh loss! No need for HRT here. So my initial reaction to this new analysis is to not recommend taking HRT unless you have severe vasomotor symptoms of menopause. For those who are already on HRT because of post-menopausal symptoms I offer the following two observations.
First, all this data applies to women over 50 who have experienced menopause. For women under age 50 who have significant symptoms from “surgical menopause”, for women without contraindications, in general the data does not reflect excessive risk precluding HRT to relieve the very disruptive symptoms of menopause. I would still try a non-HRT solution first to address post-menopausal symptoms, though in the event this is not effective I believe HRT does not represent an unacceptable risk.
For women over 50 years’ old who have severe post-menopausal symptoms and no specific contraindication to HRT such as a previous blood clot or breast cancer, I believe HRT may be an alternative. Again, I would always suggest a non-HRT solution first and if you are planning on using HRT I suggest it be used for as short a time as possible, and at as low a dose as possible to alleviate your symptoms.
Because of the importance and magnitude of the issue this subject will continue to be looked at on a regular basis. Updated recommendations will likely be made stay connected to your doctor for any new analysis or clinical findings .