Hormone-Replacement Therapy: Could Estrogen Have Saved 50,000 Lives?

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For more than a decade, doctors have cautioned women about the risks associated with hormone-replacement therapy. But those warnings may have put one group of women at increased risk of dying early, according to the latest study.

Researchers at Yale University say nearly 50,000 women may have died prematurely after they stopped taking hormone-replacement therapy (HRT) to treat menopause symptoms, following a much publicized 2002 study that revealed the treatment increased risk of heart disease and breast cancer.

The 2002 Women’s Health Initiative (WHI) study, a 15-year investigation into the factors that contribute to the health of postmenopausal women, was stopped three years early when a preliminary review of the data showed that women taking the combination of estrogen and progestin had a higher rate of breast cancer, heart disease and stroke than women taking a placebo. The results stunned both the public and the medical community, since doctors had been prescribing the hormones not just to treat menopausal symptoms like hot flashes, but for extended periods of time to protect women against heart disease.

Almost immediately, doctors and public-health officials began shifting women away from such long-term use of hormones, recommending that postmenopausal women restrict hormone use to the few months surrounding menopause to address the most intense symptoms. In 2012, the U.S. Preventive Services Task Force confirmed the WHI trial’s findings, concluding after a review of 51 studies published since 2002 that the risks of HRT outweighed the benefits, which were limited to a reduced risk of fractures.

But the WHI scientists had always cautioned that their findings might not be broadly applicable to all women past menopause. They noted that the trial included women who were at least a decade beyond menopause, and that the participants used one specific formulation of HRT called Prempro, which is a combination of conjugated estrogens and a synthetic form of progesterone known as medroxyprogesterone acetate.

(MORE: The Truth About Hormones)

The WHI also continued to evaluate women who had had a hysterectomy, and therefore could take estrogen alone; women with an intact uterus are not advised to take estrogen without the protective effect of progesterone since estrogen is linked to a higher risk of uterine cancer. In 2007, the WHI reported that women with a hysterectomy who took estrogen alone had fewer calcium-based plaques in their arteries, and therefore may have enjoyed some protection against heart disease. This finding was supported by a 2011 study published in the Journal of the American Medical Association (JAMA) that found a slightly lower risk of breast cancer and no significantly increased risk of heart disease, blood clots, stroke or early death among women taking estrogen only compared with women with hysterectomies who took a placebo.

Based on those results, the Yale scientists decided to study this group of women further, to determine whether widespread coverage about the risks of HRT — the combination of estrogen and progestin — had persuaded these women to stop taking their estrogen-only therapy, and whether that decision impacted their mortality. Could women without a uterus benefit in some way from estrogen-only therapy, and were they putting their health at risk if they avoided the hormone therapy?

Their analysis, published in the American Journal of Public Health, confirmed their suspicions. Before the WHI study, about 90% of women who had a hysterectomy would have relied on estrogen therapy to replace what their reproductive system no longer produced. Following WHI, however, 10% of these women used the hormone, and based on a formula the researchers created to estimate their survival rates, they determined that 50,000 women died during the study period, between 2002 and 2011, prematurely. Dr. Philip Sarrel, professor emeritus of obstetrics, gynecology and reproductive sciences at Yale University School of Medicine and lead author of the study, said in a video discussing the study that none of these women, who were aged 50 to 59 at the start of the study, lived to reach their 70s. Most died of heart disease, bolstering the connection that earlier studies had found between estrogen-only therapy and a lower risk of heart problems among women who had a hysterectomy.

(MORE: Heart Benefits From Hormone-Replacement Therapy?)

The analysis highlights the challenges in crafting and distributing public-health messages so that they are interpreted correctly and applied to the right people. Following the surprisingly negative effects of HRT that WHI revealed, most in the medical community focused on warning women away from hormone therapy en masse, and the more nuanced message that some women might be able to continue taking estrogen alone became lost in that effort. “All we really knew [in 2002] was that this one kind of HRT used late in menopause resulted in a modest degree of harm,” says Dr. David Katz, the director of the Yale University Prevention Research Center and one of the authors of the new paper. “We developed a cultural aversion to HRT and unfortunately it was shared by doctors and patients alike, and it extended to all women and all forms [of the hormones].”

Katz says it’s not just the media that is responsible for such overgeneralizing — research journals do it too. And he suspects that many patients probably never discussed the results of the 2002 study in depth with their doctors, to determine if the findings applied to them, heightening the perception that hormone therapy of any kind was not a good idea for any postmenopausal woman.

“We would like to think that physicians are a case apart, that we are always guided by high professional standards and meticulously reading the literature,” says Katz. “If that were the case, every doctor would’ve read the WHI study, every doctor would’ve read the 2011 study and we wouldn’t have this problem. But actually the practice of medicine is consumed in the prevailing current in our culture.”

(MORE: U.S. Panel Warns Hormone-Replacement Therapy Is Too Risky)

And as is the case with any scientific finding, not everyone in the medical community is convinced that the 50,000 women would have lived had they taken estrogen therapy. But most experts agree that the results should start a serious discussion about how to communicate public-health messages so they are applied to the right populations in the correct way.

“What makes it a challenge is that there is not a simple set of evidence. There is not one truth about estrogen,” says Andrea LaCroix, the co–project director of the Clinical Coordinating Center for the Women’s Health Initiative and author of the 2011 study. “Anytime something is less straightforward and more complicated, it’s difficult in a quick media sound bite to get the message across. We tried very hard when we published that data to show that the findings were different for different age groups of women. In terms of the challenge, I actually agree with these authors that there was a lot of media attention when the 2011 paper came out, but there was not a lot of discussion about translation for women afterwards.”

In that spirit, LaCroix says the Yale results should not necessarily drive all women who have had a hysterectomy to take estrogen pills. More research will need to tease apart how estrogen may or may not be contributing to premature death in these women. “I find it incredibly brash in a way and almost arrogant to recommend the use of a pill to prevent death in women when it is totally unproven to do that in women of any age group. If the results of this paper were true and has public-health significance, we would’ve seen deaths in U.S. women age 50 to 59 increase concomitant with the decline in estrogen use,” she says. “The death data exists, and it would be important to do a study relating the decline in estrogen use to changes in mortality directly in our country.”

(MORE: Hormone-Replacement Therapy After Menopause: What Women Need to Know)

In the meantime, women should be asking their doctors about hormone therapy, and whether any version of the treatment is right for them. These discussions that could clear up confusion over what the latest data shows about the risks and benefits of hormones. “The primary messenger for all messages ought to be the doctors to the patients,” says Dr. Georges Benjamin, executive director of the American Public Health Association. “The public hears a lot from trusted messengers that may not be knowledgeable.”

20 comments
stemarks8
stemarks8

What is the take away from this study? I don't have a scientific background but it seems as though the information they published could not be on any practical use or am I missing something? I have a few articles on my site about http://www.dranabolics.com/high-estrogen-symptoms/, estrogen and how to combat estrogen in general. Feel free to check them out. Would love to hear your thoughts.

AnneyAuster
AnneyAuster

Menopause is a period of years in a normal woman’s life in which gradual hormonal changes bring about a shift away from the physical powers of childbearing, in favor of a more mature condition of mental development. Read more about menopause and hormonal changes at: http://tinyurl.com/lrq5vue

Loribean
Loribean

I can honestly say that HRT SAVED MY LIFE.  I was 47 and my cycle sporadic, I was bipolar, sleepless, my blood pressure had soared to 160/100, I had heart palps, was getting trouble with co-workers and tried to run my sister over with my car due to a bout of uncontrollable rage (what I lovingly refer to as my Jerry Springer moment in history), this started me on a SHAME SPIRAL of sickness and guilt, I became suicidal and sick or being sick and tired.  NOT ONE DOCTOR asked me if it was my hormones! even my endo at a famous teaching hospital!  I have thyroid issues.  Anyways, I realized that it was hormone imbalacne on my own thank you very much primary care provider that had known me for 20 years! thanks for offering my anti-psychotics, anti-depressents, cardiac meds, sleeping pills....oh yeah those are WAY SAFER than a naturally occuring substance in my body!  I should have run my docs over!  I demanded a transdermal patch and progesterone cream.  I cut the patch in HALF it's only .025mg!  thats it!!  and I AM CURED!!! I love my life, I am happy, productive, I don;t cry and pee myself every five minutes.  I am APPALLED that women are not getting the helpo they need from estrogen therapy.  they call it therapy for a reason!!  I am so happy my BP is down to 117/70.  No PVC's.  tons of energy to excercise...tell me that it's not healthy now!  strong bones and heart, muscles, sleeing like a baby...I famous law professor in my town just killed herself at 48.  same age as me.  All of the reports and articles talked about how she had gone to a dark place over the past year...from a mother or two super achiever to suicide?  that spells hormones to me! NOT ONE ARTICLE in our papers mentioned hormones...all about depression and mental illness.  I wish I wish I wish she had been as lucky as me (tears).  BRAVO estrogen.  I will take you until I'm 80 and bring on the breast cancer and stroke....I do not even care,.  I eat right (vegan) hike every day do not drink do not smoke never take anything except for supplements (lets talk Vitamin D very imp too!) and I feel healthier than ever thanks to my teeny weeny estrogen dose!  thank you god and evil pharmeceutical companies!  

DavidEm
DavidEm

Does the Yale study state whether they were using synthetic or bio identical hormone replacement therapy? Also, if you are going to supplement with estrogen and progesterone, you need to replenish with testosterone as well. Hormone Replacement Therapy is about optimizing all hormone levels AND balancing all the hormones in the body. You can't simply pick and choose which ones you want more/less of. html and her


Dr. Shira Miller also has a great article about why not to fear hormone replacement therapy and shows the benefits that can come with it.


Hope I was of some help to some of you out there. Remember, research these kinds of subjects in depth and then make a educated decision yourself. There are a lot of financial benefits to be made/lost in topics such as this.


P.S. - MenopauseMoxie makes some very good and try points. Make sure to read her comment as well if you haven't already.

GPS2007
GPS2007

I'm hoping that soon these studies will take into account the effects of estrogen-mimicking environmental compounds which are so prevalent.  How can we understand the complicated mix without looking at the plastics, pesticides and other contaminants in the system?

MenopauseMoxie
MenopauseMoxie

Alexandra,

You didn't gather all the data.  There are more advanced ways to restore estrogen, and more effective than the one-size-fits-all, pharmaceutical industry approach to hormone balancing.  You mentioned nothing about the Panacea Protocol or the Wiley Protocol.  These advanced methods of hormone replacement therapy is designed to restore estrogen back to healthy levels, protecting the body from the degenerative diseases of aging, including menopause.  

It's estrogen deficiency in women and testosterone deficiency in men that cause osteoporosis and can be easily reversed if hormones are restored.  Current medical protocols in hormone replacement therapy suggest to dose enough hormones to treat the symptoms of estrogen deficiency but not enough to restore the depleted hormones to healthy levels.  

PMS, Endometreosis, Perimenopause, and menopause are a direct result of estrogen deficiency, and I think it's barbaric to withhold the very thing from women that can give them back their lives, and rid their bodies of disease and symptoms. It is clear in the non-pharmaceutical data that if we restore estrogen to healthy levels, these conditions would be rare instead of the norm.  The medical industry's mindset is keep the patient estrogen deficient, and the illnesses estrogen deficiency causes, so we can manage the symptoms with the drugs we manufacture.  

Why manage the symptoms of estrogen deficiency when we can get rid of estrogen deficiency by restoring hormones to healthy levels?

Hel1959
Hel1959

If the WHI finds it so difficult to get a simple message across it should not be running a study. I've had a hysterectomy and take HRT. I'm British. When I came to the US the WHI studies made it difficult to find a doctor willing to prescribe HRT as the WHI recommended alternative is bone building drugs to protect against osteoporosis with possible side effects including jaw bone death. The WHI knew in 2006 there was no increased risk of heart disease or breast cancer for women in this subgroup so they've had plenty of time to figure out how to explain it, and should have stressed from the start results for these women could be very different from those who did not. They only react as their data is torn to pieces by other studies including international ones. They failed to keep up with HRT trends both in terms of type of oestrogen and administration. 50,000 women may have died, others had their lives shortened and gone through unnecessary stress and all the WHI does is whine about communication?!?  

ikatejira
ikatejira

Should exercise and diet could protect this one? 

vgupta123
vgupta123

To the TIME editor: Could you please indicate 

1. Who funded the study, and 

2. What are the financial conflicts of interest of the researchers involved.

If women are going to make life-impacting changes based on just one study while ignoring the USPSTF's recommendation based on 51 studies, they deserve to know at least this much. Thank you.

eagle11772
eagle11772

Hey !  Ya gotta die of somethin ! :)

JaniceD'Amico
JaniceD'Amico

The picture of the pills are not the HRT noted in the study and are regular birth control pills.  These are made from yams, I think. The HRT study was initially misinterpreted and was on older women with heart disease. The newest analysis notes that estrogen alone may help prevent some heart disease. This is only given women without a uterus. Premarin is from pregnant mares and is the only estrogen from this source, all others are vegatable derived.  Given the huge numbers of women using HRT, you just dont see the huge corresponding increase in cancer expected. The bioidentical hormones are probably the biggest scams in medicine for older white women to spend money on in the youth quest. Suzanne Summers  (?sp) needed to stick with the thigh master and not practice medicine.

ErsieCourea
ErsieCourea

I am the furious curious cancer survivor on google and a few days ago I wrote a post titled A great confession. I n it I present a convinving argument that bioidentical hormone saved my life. In my five year cancer journey I also came across a piece of research thst said that it is certain brands of HRT that cause cancer - see toxic patents. I believe this. Also if you expect horse urine to save you you are in for a disappointment. Try a gkass of your own urine.

NoCFan
NoCFan

This information is not based on any new clinical trials or national mortality data - it is an estimation generated from a mathematical model that is 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. 

KarenW
KarenW

I find it incredibly brash that Ms  LaCroix  assumes that mortality would be the only data to examine.  Surgery and other treatments for heart disease have improved significantly.    Found some very preliminary data that does show a concomitant increase in heart disease in women but why didn't she do the research before replying?

dklloyd
dklloyd

This article did not mention Bioidentical Hormone creams.

SusieT
SusieT

@MenopauseMoxie Endometriosis is a direct result of estrogen deficiency? What? Do you Have credible source links for this?

Hel1959
Hel1959

@vgupta123 Could the TIME editor also include the financial interests of the WHI?

Hel1959
Hel1959

@NoCFan The WHI's own studies showed in 2007 that women who had a hysterectomy were not at increased risk but they've repeatedly failed to communicate it to the one sub group that has most at stake. Sorrel's study supports the WHI finding for that category of women. I had a hysterectomy at 26. That is a very different situation from taking HRT for a short period of time to help with natural menopause for which the average age is 51.

Hel1959
Hel1959

@NoCFan The WHI may have helped some women who had not had a hysterectomy on older forms of oestrogen only HRT for long periods of time, but killed 18,000 - 91,000 in the sub group and that is just from heart disease. The only thing they've been relentless about is failing to provide clear information.