Hormone Therapy? No To Prevent Disease, Yes To Ease Menopause Woes

Dr. JoAnn Manson considers the evolution of menopause management and hormone therapy (Brigham & Women’s Hospital)

Here’s how we usually describe the medical pendulum swings on hormone treatments for menopausal women:

A couple-three decades ago, some doctors were touting hormone “replacement” therapy as a fountain of youth that might beat back not just hot flashes but many diseases that come with aging. Then research turned up more and more potential risks, from blood clots to strokes and breast cancer. Perhaps, researchers posited, hormone therapy might be okay in younger menopausal women but not in older? The rule became, “It’s complex; talk to your doctor.”

It’s still complex, but a new paper just out in the Journal of the American Medical Association at long last refines 13 years of intense research by the Women’s Health Initiative into a form that I can easily wrap my mind around. In short: Whether you’re in your fifties or beyond, no woman should be taking hormone therapy long-term, in hopes of preventing diseases of aging. Those benefits don’t outweigh the risks. But younger menopausal women with hard-to-take symptoms like hot flashes and night sweats can still consider taking hormones to alleviate them short-term.

To quote Dr. JoAnn E. Manson, the lead author of the new paper and chief of Preventative Medicine at Brigham and Women’s Hospital:

“This is the most comprehensive evidence base available for clinical decision making and it does suggest that hormone therapy should not be used for long-term chronic disease prevention — but it remains an appropriate option for short-term management of menopausal symptoms in early menopause.”

Got that? I asked whether there might be a medical profile that might rule out hormone therapy even for younger menopausal women.



Yes, Dr. Manson said, “If a woman is at very high risk of cardiovascular disease — if she’s had a prior stroke or blood clots in her legs or lungs, or has multiple risk factors, she may not be an appropriate candidate for even short-term treatment. But most women who do have the very significant symptoms — of hot flashes and night sweats and interrupted sleep in early menopause — could be considered for short-term therapy to manage these symptoms.”

Only about 15 to 20 percent of newly menopausal women have symptoms severe enough to consider hormones, she said.

An additional note: If “short-term” use of hormone therapy for menopause symptoms may be all right, just how long is short-term? That remains controversial, Dr. Manson said, but it can be as long as several years.

It has surely been a long, zig-zagging journey toward what now looks like nicely definitive data on hormone therapy.

“The science has advanced in incremental steps,” Dr. Manson said, and it really required a large-scale randomized trial, such as the Women’s Health Initiative, to understand the balance of benefits and risks. And it’s taken a while; there have been many swings of the pendulum. Hormone therapy was once believed to be a fountain of youth, and then it was believed to be too dangerous for anyone to use, and now we understand that there are women who are appropriate candidates, for at least short-term use, and hormone therapy should not be used for long-term chronic disease prevention.”
From the Brigham And Women’s Hospital press release:

Boston – Researchers from the Women’s Health Initiative (WHI) Hormone Therapy Trials are providing the most comprehensive look at the findings to date and providing new information from extended follow up of 27,347 postmenopausal women in the two hormone therapy trials (estrogen plus progestin and estrogen alone).  The study presents information on a wide range of diseases and quality-of-life outcomes, comparisons of the two hormone therapy trials side-by-side and a full breakdown of results by age and time since menopause onset and is published in the October 2, 2013 edition of JAMA.

The researchers conclude that the findings from the two WHI trials do not support use of hormone therapy for prevention of chronic disease; however, researchers note that treatment is appropriate for symptom management in some women.  The results indicate that hormone therapy has a complex pattern of health risks and benefits and demonstrate that younger women (defined as ages 50-59) tend to have a more favorable risk-to-benefit profile than older women.  Other key findings include:

·         Combination estrogen plus progestin (in women with an intact uterus) had more risks than estrogen alone (used in women with hysterectomy), primarily due to an increased risk of breast cancer with the former but not the latter.

·         Both forms of hormone therapy increased the risk of stroke, blood clots in the legs, gallstones and urinary incontinence.

·         Benefits of hormone therapy include decreased risk of hip fractures, other fractures, diabetes and hot flashes/night sweats.

·         Estrogen plus progestin increased dementia in women ages 65 years and older, but neither treatment affected cognition in younger women.

·         For estrogen alone, younger women had more favorable results for all-cause mortality, heart attacks, colorectal cancer, and combined chronic disease. Younger women’s overall risk-to-benefit profile on estrogen alone was more favorable than for older women.

·         Effects on quality-of-life outcomes with hormone therapy were mixed, with improvement in sleep and joint pain but increases in breast tenderness.

After stopping hormone therapy, most risks and benefits dissipated.  However, over the 13 year cumulative follow-up period, breast cancer risk remained slightly elevated for estrogen plus progestin but became significantly reduced for estrogen alone.  For estrogen plus progestin, a significant reduction in uterine (endometrial) cancer emerged during follow up and the risk of hip fracture remained significantly (but modestly) reduced.  For both forms of hormone therapy, there was no increase or decrease in the rate of total cancer (all types combined), cancer mortality, cardiovascular mortality, or all-cause mortality in the overall study population.

These findings indicate that the absolute risks of adverse events in younger women are much lower than in older women and, because menopausal symptoms are more common in younger age groups, the quality-of-life benefits are likely to outweigh the risks for many women who seek treatment for symptoms during the menopause transition. However, the study’s findings do not support long-term use for disease prevention.

“It is important to distinguish between the use of hormone therapy for symptom management and its use for the purpose of chronic disease prevention.  Short-term use of hormone therapy to manage moderate-to-severe hot flashes or other symptoms in early menopause remains appropriate, and the WHI findings should not be used as a basis for denying women such treatment”, said Manson.   Among women in the 50 to 59 year age group, fewer than 1 out of 100 had adverse events during five years of hormone therapy use, while the risks were four to five times higher among the older women.

“Although studies of other hormone therapy formulations, doses and routes of delivery are needed to find treatments with fewer risks, these medications are now among the best studied treatments in medical history. Clinicians can share information from the WHI trials with their patients and help them make more informed choices,” Manson said.

More of our recent coverage on hormone therapy:
Managing Menopause: Top Takeaways After Ten Years
Five New Rules Of Hormone Therapy For Menopause

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  • Liza Knowlton Dufresne

    Still no distinction made between synthetic and bio-identical hormones. Synthetic estrogen is made from the urine of mares. This “medicine” can cause cancer, as proven in the WHE 2002 study. BIO-IDENTICAL hormones, made from yams, do not cause cancer. They HAVE been found to prevent disease, including cancer and osteoporosis. The media persist in obfuscating the difference between HRT and BHRT. Let’s get it straight!

  • itasara

    I wish I had been in this study. I have been on HRT since maybe just before menapause ( I’m guessing 18 years plus or minus)and that was many years ago. I am still on it and am now 65. A paper like this leaves me with questions and worries me that should I have to change doctors the next one will not allow me to get HRT which I really like not to mention the insurance companies (that play doctor these days!) I keep on HRT particularly because I am a singer and although now singing is a little more difficult than it use to be I am pretty sure I maintain my higher notes because of HRT. I also have read that estradiol is a positive hormone that keeps people with MS in remission found out i had 8 years ago. I can’t take estradiol alone because I have not had a hysterectomy. Now to the important part, why did you not study sequential HRT which is the alternative to combination HRT? I always felt (especially with my background in nursing) that b/c the body inherantly runs on a cyclic calendar that combination therapy would be a really bad choice. So I continue to use sequential HRT despite the one disadvantage of getting a period. Also what about genetic propensity toward breast cancer? My daughter joined one of those sites to have her genes read and a propensity toward breast cancer was one that our f0(female side of my family and my husband’s family) does not have. And as far as I know I have not heard of any of my relatives having ever had a dx. of breast cancer. So how many in the study had a family history of breast cancer? I’d be intereted to know that.

    • Liza Knowlton Dufresne

      itasara–are you doing HRT or BHRT? There is a big difference. Have you read any of Suzanne Somer’s books? She has done a great job of explaining the difference between synthetic and bio-identical hormones. You can find a doctor near you who specializes in BHRT at foreverhealth.com. Also, please see my post above. I’m taking bio-identical progesterone and it is helping me a lot. I am 52, peri-menopausal. Good luck to you.