Confused about estrogen therapy?
July 19th, 2013
02:30 PM ET

Confused about estrogen therapy?

Hormone replacement therapy has been a controversial issue for a lot of women over the last decade. Many have rejected any type of hormone therapy since a large, federally funded study found hormone replacement therapy could increase a woman’s risks for heart disease and strokes.

Now, a new study out of Yale School of Medicine suggests anywhere from 18,000 to 91,000 women in their 50s who had hysterectomies may have died prematurely in the last decade because they did not take estrogen-only hormone replacement therapy.

A bit of background

Before 2002, it was standard practice for gynecologists to recommend estrogen therapy to women with hysterectomies. More than 90% of those patients used it to treat symptoms such as hot flashes and to prevent osteoporosis and other diseases related to menopausal hormone deficiency. But according to the Yale study, only about 10% of these women use estrogen therapy today.

The data analyzed for this study comes from the large Women’s Health Initiative trial. That study was designed to confirm the hypotheses that hormone replacement therapy not only provides relief for menopause symptoms, but also helps protect women from heart disease, osteoporosis and dementia. The WHI first looked at the benefit of taking two hormones - estrogen and progestin, and then examined the benefits of taking estrogen alone.

The first part of the study was stopped in 2002, when early results suggested the combined estrogen-progestin therapy was actually increasing the risk of heart disease, stroke, breast cancer and dementia. Researchers saw a sharp decline in overall hormone use afterward as women heeded their doctors' warnings and stopped taking all post-menopausal hormones, whether they had had a hysterectomy or not.

In 2005 and 2012, the U.S. Preventive Services Task Force recommended against using the combined therapy or estrogen alone to prevent chronic conditions in postmenopausal women, which may have deterred more women from asking their doctors about these therapies - or stopped doctors from offering it in the first place.

The study

In this new study, published Thursday in the American Journal of Public Health, researchers looked at data from the second portion of the WHI trial, which looked at estrogen-only therapy.

According to the Yale researchers, the increased risks discovered in the first part of the WHI study only applied to women who had not had a hysterectomy and were taking pills that combined estrogen and progestin. They say the dangers did not apply to women without a uterus who used estrogen-only therapy - but few understood the difference.

"Sadly, the media, women, and health care providers did not appreciate the difference between the two kinds of hormone therapy," said Dr. Philip Sarrel, lead author of the study and emeritus professor in the departments of obstetrics, gynecology & reproductive sciences and psychiatry, at Yale. "As a result, the use of all forms of FDA-approved menopausal hormone therapy declined precipitously."

The study noted that results from the second part of the WHI study were very different.

A series of papers published by the WHI between 2004 and 2012 showed that estrogen-only therapy had mostly positive health outcomes; they said women who received estrogen, compared to those who received a placebo, had fewer deaths each year for 10 years and were less likely to develop breast cancer and heart disease.

Each year, the death rate among those not taking estrogen was 13 more per 10,000 women. Most of those deaths were due to heart disease. This doesn't need to happen, the study authors say.

The takeaway

"Women need to know that estrogen replacement is an important part of therapy, especially for women who are in their 50s and have had a hysterectomy and their ovaries removed," says Dr. Holly Thacker, director of the Cleveland Clinic Center for Specialized Women’s Health.

She says it’s time for women who have had hysterectomies to "stop being fearful of estrogen.” She points to other recent studies that show starting estrogen therapy shortly after menopause is key to reaping the benefits of the drugs.

Because each woman's health issues are different, experts recommend that women talk to their physicians about estrogen and other hormone replacement therapy before they make a decision on whether to take it.

"Estrogen avoidance has resulted in a real cost in women's lives every year for the last 10 years — and the deaths continue," said Sarrel. "We hope this article will stir an overdue debate and raise consciousness about the health benefits of estrogen-only therapy for women in their 50s with no uterus."

soundoff (38 Responses)
  1. USA

    Hang on I'm having a hot flash. 🙂

    July 20, 2013 at 14:37 | Report abuse | Reply
    • PC

      Background: I"m biologist who directs a research group of 26 scientists, and I'm someone who is very tired of crappy medical research setting national health policy. The WHI study from 2002 is so scientifically flawed that it could be taught in classes on how NOT to do research. Among many problems with that paper...

      The sample size for that study was 16,608 women. Of these, 8,506 were in the HRT group, and 8,102 in the placebo group. The analyses are all conducted on this entire sample, and those analyses are based on the assumption that all women in those groups did what they were supposed to do for the duration of the trial (i.e. they either took hormones, or they didn’t take any). The hazard ratios (statistical analyses) given in the paper for each of the medical problems discussed, and the differences in these ratios between the HRT and placebo group, are all calculated on this assumption. With me so far?

      It is rather surprising, therefore, to find on page 326 that “a substantial number of women had stopped taking study drugs at some time” or that some women in the placebo group “initiated hormone use through their own clinician”. How substantial is “substantial”? Turns out it that a whopping 42% of those in the HRT group stopped taking HRT at some point, while 10.7% of those in the placebo group actually started taking hormones at some point before the end of the study. These figures are termed “crossover rates” and the authors note that the rates in both directions “exceeded design projections”.

      Despite this massive methodological complication, the study blithely goes on to analyze all 16,608 women as if nothing had happened, and to calculate relative risk between HRT and placebo accordingly. Then, in one of the more twisted examples of spurious logic I’ve seen in a paper, they actually go on to state that:

      "the lack of adherence would tend to decrease the observed treatment effects. Thus, the results presented here may underestimate the magnitude of... adverse effects on cardiovascular disease and breast cancer"

      The logic is that, since a lot of the women in the HRT group actually stopped taking hormones, the observed risks would have been even greater if they hadn’t.

      This is the scientific equivalent of having your cake and eating it too. First, you produce results concerning risks and clinical outcomes of hormone therapy based on a sample of 8,506 women, even though 42% of that sample didn’t adhere to the treatment. Then you act as if the results were strictly valid for the entire sample and claim that they would have been even more marked if everyone had adhered to the protocol. The problem, of course, is that almost half of them didn’t, so it’s inappropriate to report disease rates for these women and to ascribe a connection to HRT.

      The simple solution to this problem would of course be to remove all non-adhering patients from the sample (together with the several hundred women from the footnote for which complete follow-up information was not available) and then analyze what was left. This is known as censoring data; typically you’d use information on the women concerned only up to the point where they “crossed over”. Why this elementary step was not taken is the biggest mystery in this study. The paper does not tell us whether they attempted to do this, nor what impact the smaller sample (and lower statistical power) would have had on the results.

      It is papers like this (though this really is one of the worst) that explain why one frequently sees headlines that are variations on the theme of "New medical study contradicts results of previous medical study". Until doctors stop going on giant poorly designed fishing expeditions and instead learn to formulate biologically sound hypotheses and to analyze data with appropriate rigor, their work will continue to misinterpret small effects and chance variations, to the detriment of us all.

      July 26, 2013 at 12:59 | Report abuse |
    • Arrow Durfee

      HRT will continue to be high risk endeavor until conventional doctors get it right. They routinely use the wrong hormones and in wrong proportions to each other; they refuse to include DHEA and later in life; low levels of testosterone; they dont understand the role of iodine in breast and ovary health and its protective mechanisms regarding toxic estrogens. Estrodials and estriols generally must be used in combinations based on levels of individual deficiency in each woman, therefore prepackaged medicines must be ruled out and only individually compounded replacement regimens used. Also, women should take monthly break of 5 to 7days to mirror their previous monthly cycle. The body was designed for this break period. See the work and writings of Drs Abraham from UCLA on Iodine as well as Bernstein for iodine therapy and BHRT, and Dr Jonathan Wright of Washington state regarding Bioidentical Hormone Replacement Therapy. Someday CNN will start reporting medical truth instead of what pharmaceutical companies dictate. Do we have to wait for Sanjay to have another awakening from his brainwashed state of mind?

      August 14, 2013 at 10:40 | Report abuse |
  2. CF Fan

    This information is not based on any clinical or national mortality data – it is a mathematical model based off of an unreliable secondary analysis of the WHI trial in which researchers went back, spliced up the patients by age, and then tried to tease out a benefit for estrogen not seen in the group as a whole. Sarrel, who created these dubious calculations, is a paid consultant for Noven Pharmaceuticals, which just HAPPENS to manufacture an estrogen patch.

    The WHI has been maimed repeatedly by critics who simply didn't like the study's results, which showed no reduction in heart disease and an increased risk of stroke, blood clots, and dementia. The age analyses were never part of the study protocol. And regardless, they remain statistically insignificant. It's more than a little suspect that there remains a cadre of gynecologists (many of whom have vested financial interests in the sale of estrogen drugs) who are trying to revive hormone therapy as some all-purpose elixir. But their relentless efforts are not terribly surprising in lieu of the 90% drop in estrogen prescriptions over the past decade. Women's lives and overall health have been SPARED, not compromised, by the avoidance and/or limited use of hormone therapy after menopause, including estrogen alone.

    July 20, 2013 at 15:37 | Report abuse | Reply
    • mg maryland

      I agree with CF Fan .Cannot believe all the traction these ??calculations are recieving.

      July 20, 2013 at 22:15 | Report abuse |
  3. WS

    Where's the reporting on the alarmingly high rate of unnecessary hysterectomies and ovary removals? A woman's ovaries are the equivalent of a man's testicles. A 2000 study determined that 76% of hysterectomies don't meet ACOG criteria – http://www.ncbi.nlm.nih.gov/pubmed/10674580. Healthy ovaries are removed during hysterectomy about 73% of the time despite lifetime ovarian cancer risk being less than 2% (same as testicular cancer risk).

    The uterus and ovaries have non-reproductive (lifelong) functions. Hysterectomy is a destructive surgery causing anatomical, skeletal, hormonal, and sexual damage. The uterine ligaments are the structural supports for the pelvis, the severing of which compromises external anatomy / skeletal structure. The uterus keeps the bladder and bowel in their rightful positions for proper function. It is key to sexual function – desire, arousal, response (Masters and Johnson). The ovaries are the gonads and produce hormones into a woman's 80's if she's intact. Just as a man's sex organs are essential his whole life, so are a woman's.

    It's time that the media report on this grossly overused surgery.

    July 21, 2013 at 10:01 | Report abuse | Reply
    • mary

      Totally agree.. They are not throw away organs.. they are vital to a womans over all health and well being..
      Doctors have, and do .And in my case did.. Know that I did not want a hysterectomy unless I had cancer. .When I woke up to hear no cancer...I immediately heard. " I did a complete hysterectomy, I did what I FELT was best for you"..
      Many woman have been done this way in the past.. And I hope not today.. But I was shocked when it was done to me.. I thought I had the right to decide.
      Then came the hormone replacement situation and women having problems getting their doctors to prescribe it..
      Even though women have told doctors for years how this surgery effects them. They continue to Poo poo it..
      Its infuriating..

      July 23, 2013 at 15:47 | Report abuse |
    • Jess

      Hysterectomies and oophorectomies (removal of the ovaries) are indeed very serious and life-changing surgeries, and should not be taken as lightly as I think many do. My aunt had to have her ovaries removed a year or so ago (I can't remember the exact reason, but it was a necessary one) and that's a hard thing for a 38 year old woman to do. She has two beautiful daughters and three stepdaughters so there is certainly no shortage of children in her life, but it's basically instant menopause.

      Luckily, her doctor didn't convince her that it was a good idea to take her uterus too, so I'm sure that saved her quite a bit of issues, but still. I can imagine it is psychologically and physiologically difficult to deal with.

      July 23, 2013 at 17:24 | Report abuse |
  4. furiouscuriouscancersurvivor

    Word needs to get out that excess estrogen is an inevitable side effect of the Western way of life including a diet low in plant fibre which keeps the colon free of too manyestrogens, too many dairy products, red meat and lack of physical exercise. I am following a natural approach to cancer, avoided toxic treatments and believe that a bio identical hormone of Harvard university fame saved my life.

    July 21, 2013 at 15:11 | Report abuse | Reply
  5. Pippa

    I'm about to become a royal auntie;-)

    July 21, 2013 at 15:38 | Report abuse | Reply
  6. Boo

    Oh really???? My OB/GYN refuses to give ANYof his patients hormone replacement therapy.

    July 22, 2013 at 14:46 | Report abuse | Reply
    • mary

      Find one that does.No woman should be forced to suffer..

      July 23, 2013 at 15:40 | Report abuse |
  7. Sherri

    Have just gone off Estradiol after having a severe reaction to it causing major depression, severe diarrhea, stomach pain etc. It is not for everyone. Tried Femhrt also and it caused major depression. It was worse than the hot flashes. If you start having problems as listed above, talk to your doctor but they will probably not associate the problems with the meds. Start with lowest dose possible and see how you do before increasing. If you are prone to depression, these may not be the meds for you.

    July 22, 2013 at 18:13 | Report abuse | Reply
  8. mary

    I woke up after surgery without ovaries. Doctor told me he did what he felt was best for me.. I was young. I knew immediately it was NOT ok.. I went through hormone he... and it was HE***L...~! As he upped it and then took it down and played with even taking me totally off it.. I miserably complained, if he did not know how to replace them, then why did he take mine out.. Long story short.. I ended up hospitalized with depression that turned into an anxiety disorder to go along with it.
    The doctor told me I was depressed to the point that I might possibly never get above the gray area.. A lifelong situation that might very well lesson my enjoyment of life.
    I went to a woman doctor out of desperation . I knew it was hormones..And I knew horse estrogen was NOT the "same thing".. I was given bio identical estrogen. And in two days I knew my hormonal HE.. was over..
    Due to the situation the stress and the depression..I had to stay on anti depressants and anti anxiety for years.. I still need anti anxiety.. As sometimes the brain does not ever become chemically balanced either.
    So long story short..I NEVER stopped estrogen.. And I still argue at times to stay on it. I hope this helps with my continued (unfair) fight ~!
    I never want to risk depression ever again. I don't want the bone medications.. Or any of the other medications to solve the problems estrogen solves.They all carry HUGE side effect risks.
    Its our bodies.. The quality of life goes down after menopause. Our bodies are made to have estrogen in them. Putting back bio identical estrogen , what it has lost, and feeling good. Is NOT something to be afraid of.

    July 23, 2013 at 15:38 | Report abuse | Reply
  9. Mary

    I'm 55 years old and I still have my ovaries and uterus. But my menopausal symptoms made me miserable and deeply affected the quality of my life. I had hot flashes every 30 minutes or so, day and night. Those in and of themselves aren't so horrible, except that I was never getting a good night's sleep. I was exhausted, and I have to work full time so it was tough. I was also confused, anxious, and overly worried about things which added to my stress. I'm a natural sort of girl–vegetarian for 30 years, all natural child births, no medications, you name it. However, after 8 years of suffering and no end in site, I decided to trade being scared of cancer for having a real quality of life. I tried bioidential hormone cream, but it didn't really help. Now I take Prempro, estrogen and progesterone combo, and can't overstate the difference it has made in my life. I sleep, I'm calm, I have energy. I feel good. My OB-gyn said the 2002 study (or whenever it was) was done with women in their 70's and had misleading results. I don't know who or what to belief, and I'm trained in research methodology. So, that's my story. Not sure if I'm making the right decision, but I sure do like not being miserable. I guess we all do the best we can!

    July 23, 2013 at 21:57 | Report abuse | Reply
  10. christy

    No way no how am I ingesting horse urine. Where do you think Premarin comes from? Pregnant horses. The pee barns that produce Premarin are some of the most horrific acts of cruelty known to mankind. Breed horses to prevent women from going through a natural change of life, keep them trapped in tiny stalls to collect their pee, then turn them loose to birth foals destined to be slaughtered for overseas consumption.Horrific. Anyone selfish enough to buy Premarin deserves the side effects.

    July 24, 2013 at 16:55 | Report abuse | Reply
  11. alto53

    I had both hysterectomy and oophorectomy at 36 and took a low dose estrogen only until I was 56 when I went off and let nature take it's natural course. My doctor though had no problem if I wanted to stay on for the rest of my life, he always cited the studies were not focused on these complete surgeries and estrogen only replacement. The question is: What is the guidance on how long after these necessary surgeries should a woman who chooses this therapy stay on?

    I felt fortunate not to live my life suffering through immediate menopause and not be able to enjoy life with with husband young children. Also not have to fear ovarian and uterine cancer....ever.

    July 26, 2013 at 09:00 | Report abuse | Reply
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  14. Deir

    Publication of this article is utter BS. Using OpenPayments.CMS.gov, it's quite clear that Drs. Thacker and Sarrel and their universities (Yale? Really??) both received thousands from the drug manufacturers. Look for Wyeth. Look for Pfizer in NYC. Dr. Sarrel himself published a 2001 study that said older women who used estrogen after a heart issue had a 290% increase in the likelihood to have a fatal stroke using estrogen (The study was called: A clinical trial of estrogen-replacement therapy after ischemic stroke. Viscoli CM, Brass LM, Kernan WN, Sarrel PM, Suissa S, Horwitz RI. N Engl J Med. 2001 Oct 25;345(17):1243-9.), yet here he is giving us "results" of a non-study. Later he had the NERVE to publish the same paid-off nonsense from another angle saying women who were not using estrogen to manage hot flashes were costing their companies money!! He's absolutely sold out and it should be illegal. Pfizer lost a lot of money after the WHI study was published. Here's the deal. You my not be able to prove that younger women will encounter the same harmful effects as the older women from the study, but the fact that it hurt them isn't good! Pfizer was the one who paid with the NIH for those studies. They wanted a rubber stamp to claim that estrogen helped older women too so they could expand their market. Instead, it proved the opposite and now that profit is down by at least 50% since the news came out, they've been paying off corrupt doctors and hospitals to come out with reasons why women should still take estrogen. They are corrupt and the doctors are corrupt and anyone who publishes this without doing due diligence is just corroborating their lies.

    July 11, 2015 at 17:26 | Report abuse | Reply
  15. georgina

    Is hrt worth a try three years after a non agressive grade 1breast cancer ?i am 59 with terrible lack of energy insomnia foggy brain etc

    April 17, 2016 at 07:10 | Report abuse | Reply
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