New study damns results of WHI report on Premarin family of drugs

by JANE ALLIN

New Study

Another new study published September 12, 2017 in the Journal of the American Medical Society (JAMA) has made headlines claiming that HRT is not the villain it was once thought to be.

Per the investigators, a statistical review of the results of the damning 2002 WHI study showed that the women taking the hormones did not die earlier or have higher incidence of chronic illness than those taking a placebo.

In fact, to the contrary, this new study asserts that these women experienced a profusion of benefits as a result of taking the HRT – improving the quality of life, preventing osteoporosis, heart disease and Alzheimer’s, and of course a satisfying sex life among other advantages.

An author who penned an article in the Huffington Post by Erika Schwartz MD, self-described as a physician who is a hormones and prevention expert, even goes so far as to tout them as miracle drugs. Laughable at best.

“Hormones are great for you. You are better off with any kind of HRT (bioidentical estradiol, testosterone, conjugated equine estrogen, etc.) than nothing. The WHI study was a most horrific insult to women’s health in recent history. It hurt and still does millions of women. Women are suffering because money was more important than pure science and honest medical discourse.” [1]

Pfizer World Headquarters. Reuters.
Pfizer World Headquarters. Reuters.

How was money more important than science and honest medical discourse? If anything, the WHI resulted in huge losses in profits for Big Pharma, notably Wyeth, now a wholly owned subsidiary of pharmaceutical giant Pfizer.

Moreover, Wyeth was guilty of covering up the truth about HRT and its link to increased incidences of cancer, heart disease and other life-threatening ailments in pursuit of higher profits at the expense of women. A classic example was the use of ghostwriters hired by Wyeth for this very reason.

“The articles, published in medical journals between 1998 and 2005, emphasized the benefits and de-emphasized the risks of taking hormones to protect against maladies like aging skin, heart disease and dementia. That supposed medical consensus benefited Wyeth, the pharmaceutical company that paid a medical communications firm to draft the papers, as sales of its hormone drugs, called Premarin and Prempro, soared to nearly $2 billion in 2001.” [2]

In any case, the study: “Menopausal Hormone Therapy and Long- term All-cause and Cause Specific Mortality; The Women’s Health Initiative Randomized Trials” in its entirety is available here  and a brief overview and summary of results can be found here.

The study was an observational follow-up of more than 27,000 postmenopausal women aged 50 to 79 years who were enrolled in the 2 WHI randomized clinical trials between 1993 and 1998 and followed up through December 31, 2014 – a cumulative total of 18 years.

These two trials — the original WHI study, and a second WHI study published two years later — found that taking estrogen plus progestin (Prempro) HRT increased a woman’s risk of heart disease and breast cancer while taking estrogen alone (Premarin) increased the risk of stroke, dementia, and other health dangers including endometrial cancer.

Trio of Rescued Premarin Foals. Photo: Vivian Grant Farrell
Trio of Rescued Premarin Foals. Photo: Vivian Grant Farrell.

The new study published in JAMA on September 12, 2017 strongly supports the claim that hormone therapy with CEEs (conjugated equine estrogens) in combination with progesterone (e.g. PremPro) and CEEs alone (Premarin) are not associated with “all-cause” mortality. In other words, they are trying to convince women that HRT therapy is not harmful, will not kill you nor shorten your life – those women who took the drugs to alleviate the symptoms of menopause were no more likely to be dead after 18 years than those who didn’t.

“Among postmenopausal women, hormone therapy with CEE plus Progestin (PremPro) for a median of 5.6 years or with CEE alone Premarin for a median of 7.2 years was not associated with risk of all-cause, cardiovascular, or cancer mortality during a cumulative follow-up of 18 years.”  [3]

Specifically, HRT taken for 5 to 7 years was not associated with risk of long-term “all-cause” mortality.

So they say.

Yet in the same breath, they continue to advise restrictions on its use based on the age of onset of menopause, the lowest dose possible, for the shortest duration possible, not to be taken with existing risk of cancer and heart disease, blah, blah, blah . . .

“Although these findings lend support to practice guidelines endorsing use of hormone therapy for recently menopausal women with moderate-to-severe symptoms, in the absence of contraindications, the attenuation of age differences with longer follow-up and potential health risks of treatment would not support use of hormone therapy for reducing chronic disease or mortality. Moreover, it is unclear whether benefits would outweigh risks with longer duration of treatment.” [4]

As with other prescription medications and the plethora of warnings, contraindications and precautions, how safe are these drugs, particularly given past studies other than the WHI trials have also shown them to be harbingers of heart disease, cancers and other maladies?

As a matter of fact, according to their analysis, the researchers found that there was indeed a “statistically significant” increase in breast cancer incidence in women who took the combination CEE and Progestin HRT (Prempro) – the same findings as the WHI and other independent studies of which there are many.

“Total cancer mortality did not differ significantly between intervention and placebo groups in either trial despite the increased incidence of breast cancer with CEE plus MPA34 and concerns about an increased risk of hormone-sensitive cancers with both regimens”. [5]

Yet this “critical finding” is obscured in the blanket statements in the many articles circulating the Internet that extol the benefits of HRT as a direct result of this study.

Sadly, often these warnings are not passed on to the unsuspecting patient and are glossed over, even by their physicians. One need only listen to the sweeping comments made by Erika Schwartz, MD, the hormone expert who authored the paper referred to above; “Principal Investigators of 2002 WHI Study Reverse Findings — HRT vindicated in new JAMA article”.

Not only does she recommend all forms of HRT to her patients, as well as making the ridiculous statement that women are suffering because money was more important than science when in fact, money had nothing to do with it — sales of Premarin and its derivatives plunged after the results were released — she has this little rant to add:

“Now oddly media coverage hasn’t really done this report justice. It has been casually covered as a ray of hope but not as the wake-up call it MUST be. While in 2002 the media frenzy killed HRT, the JAMA report was interpreted as light reassurance for HRT. That’s just not right. There is no doubt here. HORMONES DO NOT HARM WOMEN, the medical establishment dogma does.” [6]

Seriously?

The researchers themselves have underscored the limitations of the study, caution the interpretation of the results and warn that cause-specific mortality analyses should be considered exploratory. If that isn’t from the horse’s mouth what is?

So, what to make of this? What prompted these original researchers to revisit this 25 years after the fact? To right a perceived wrong in the hope that the whole debacle of the HRT debate goes away once and for all? To help lessen the stigma so that there will be a resurgence of sales of the Premarin family of drugs?

Your guess is as good as mine, but I am betting it has everything to do with Pfizer’s bottom line.

There is no reason to think that a new study is right and all the previous studies are wrong. But if they are profit driven this is exactly what the drug companies want people to believe.

Class Action Lawsuits

And what about all those class-action lawsuits? Are they suddenly moot? These were massive suits involving thousands and thousands of women, some surviving and others dying. If these drugs don’t cause cancer why on earth did Wyeth/Pfizer lose these lawsuits, many of which were unlawful death suits? Do people really think that companies such as Wyeth and Pfizer have no leverage? Money talks.

The science is there but it seems that there is always some new study funded by these mammoth pharmaceutical companies to cast doubt on the findings if they are not in support of pushing their drugs that make lucrative profits — money before patient safety. In fact, for this study, Pfizer was paid for consultancy and review activities.

Conflict of interest? You be the judge.

As Peter Gotzsche M.D., Director of The Nordic Cochrane Centre and author of “Deadly Medicines and Organised Crime: How Big Pharma Has Corrupted Health Care” points out:

“Much of what the drug industry does fulfills the criteria for organized crime in US law,” Dr. Gotzsche said in a recent interview. “And they behave in many ways like the mafia does, they corrupt everyone they can corrupt, they have bought every type of person, even including ministers of health in some countries . . . The drug industry buys the professors first, then chiefs of departments, then other chief physicians and so on, they don’t buy junior doctors.” [7]

Menopause Lane Street Sign. Author unknown.
Unattributed Google search result.

Lies, Damn Lies and Statistics

The approach to this study is not new and similar studies have been made in the past — for example, one in 2013:

Menopausal Hormone Therapy and Health Outcomes During the Intervention and Extended Poststopping Phases of the Women’s Health Initiative Randomized”. (http://jamanetwork).

One of the key points is that in these studies the results of the WHI are broken down by age groups, rather than individuals treated as a single cohort. The other principal factor is that the statistical analysis used in both the current and 2013 study was hypothesis testing (statistical significance) using “P values”. And in each case, the conclusions were the same — HRT is safe (with some restrictions).

While this age-stratified analysis is a good approach, what of the actual statistical method used to arrive at the conclusions?

Without going into detail about hypothesis testing and the use of “P values” to predict the significance of an event, this statistical method and its applicability to medical research has been shown repeatedly that conclusions based on calculating “P values” are frequently false. Just as statistical significance does not always mean a result is real, lack of statistical significance (which they are using in this study) does not mean that there is no effect.

In fact, observant experts have been pointing out serious flaws in standard statistical testing for decades. In recent years, the depth of the problem has become more apparent and better documented, yet the medical community continues to employ these methods simply because these methods have been embedded in the scientific process. In effect, it is not just medical research, but all research fields, that often draw erroneous conclusions.

Even the researchers warn of caution when interpreting these results:

“Finally, the nominal P values presented here should be interpreted cautiously, as multiple outcomes and subgroups were examined. Thus, cause-specific mortality analyses should be considered exploratory.” [8]

And yet, this new study is being promoted as leading-edge “feel-good” news for menopausal women across the globe via social media without recognition of the caveats associated with the results. Reckless endangerment at its best.

Yes, ladies, you can breathe a sigh of relief. Or not.

“The case against science is straightforward: much of the scientific literature, perhaps half, may simply be untrue. Afflicted by studies with small sample sizes, tiny effects, invalid exploratory analyses, and flagrant conflicts of interest, together with an obsession for pursuing fashionable trends of dubious importance, science has taken a turn towards darkness.” [9]

In truth, the best solution to determine the safety of HRT on the health of menopausal women would be to repeat the experiment without the flaws that existed in the original WHI studies. Unfortunately, often studies are too complicated, lengthy or expensive to repeat.

Or, as in this case perhaps, the drug company does not want to pursue a wholly comprehensive study as it will further affect sales if found to negatively impact the health of patients, just as it did originally – why take the time and money if only to find that HRT does in fact cause heart disease, cancer and the like.

That is both a financial risk and a precarious risk where damning results could leave a stain on the brand name and negatively affect profits if the results are published. However, drug companies publish only a fraction of the studies they fund — the ones that promote their drugs. Unwanted results are not published.

Sadly, doctors must rely on academic peer-reviewed medical journals to learn about prescription drugs and pass these findings onto their patients in the way of prescription medications. What choice do they have?

“Pharmaceutical companies know this and have worked hard to sway the leadership. Now the question comes up if we can trust the data that the leadership relies on. One wonders how deep the deception goes. In fact, the heavy influence of pharmaceutical dollars inspired the former editor-in-chief of the New England Journal of Medicine, Dr. Marcia Angell, to conclude, “It is simply no longer possible to believe much of the clinical research that is published, or to rely on the judgment of trusted physicians or authoritative medical guidelines.”  [10]

In the News

It is always tempting for journalists and scientists alike to report a finding that is contrary to popular belief. This is no exception.

For years after the damning result of the WHI study, and to this day forward, HRT has been a controversial subject. When a study emerges that defies previous findings, often the magnitude of the effect is overstated and the less likely the research findings are to be true.

Then there is the enticing phrase “Contrary to previous scientific belief . . .”.

“Ordinarily, “contrary to previous belief” should be a warning flag that the result being reported is likely to be wrong. Instead it is usually a green light to go with the story. So the general criteria of newsworthiness—a first report, in a hot field, producing findings contrary to previous belief—seem designed specifically to select the scientific papers most likely to be bogus.” [11]

Add to this, the HRT media campaigns by Pfizer and others that underplay the dangers of cancer and heart disease. These types of studies that shine a positive light on the use of HRT to control symptoms of menopause clearly add more arsenal to their strategy. Billions are spent on direct-to-consumer ads promoting drugs that Big Pharma say are intended to raise awareness of treatment options.
The truth is, direct-to-consumer advertising is used to drive choice rather than inform it – the ‘driving’ typically in the direction of expensive brand-name drugs. [12]

The only two countries in the world that allow direct-to-consumer advertising are the U.S. and New Zealand.

Survey’s carried out in both countries have shown that when a patient asks for a specific drug their family physician is likely to prescribe that drug over others such as generics or alternatives, for example.

But it is more insidious than this since the ugly truth is that doctors are being enticed by pharmaceutical companies to prescribe their drugs.

In a gullible nation that has been brainwashed by Big Pharma, and their physicians who receive 95% of their information from this very source, there is little difficulty persuading the masses that drugs are the answer to any “condition” although many of these so-called illnesses are treatable by lifestyle changes or, in effect, are not diseases at all. [13]

Such is the case for the ubiquitous Premarin family of drugs.

Prescription drugs are killing us. Arnold Seymour Relman. Image Source: True Activist.
“The medical profession is being bought by the pharmaceutical industry, not only in terms of practice of medicine but also in terms of teaching and research.” Arnold Seymour Relman. Image Source: True Activist.

So, I leave you with this.

“The medical profession is being bought by the pharmaceutical industry, not only in terms of the practice of medicine, but also in terms of teaching and research. The academic institutions of this country are allowing themselves to be the paid agents of the pharmaceutical industry. I think it’s disgraceful.” – Arnold Seymour Relman (1923-2014), Harvard Professor of Medicine and former Editor-in-Chief of the New England Medical Journal [14]

[1] [6] http://www.huffingtonpost.com/entry/principal-investigators-of-2002-whi-study-reverse-findings_us_59bf0771e4b06b71800c3aed

[2] http://www.nytimes.com/2009/08/05/health/research/05ghost.html?pagewanted=all

[3] [4] [5] [8] https://preview.thenewsmarket.com/Previews/JOUR/DocumentAssets/483786.pdf

[7] [10] https://www.thedailybeast.com/big-pharma-is-americas-new-mafia

[9] https://www.acsh.org/news/2015/05/19/science-publication-is-hopelessly-compromised-say-journal-editors

[11] http://nautil.us/issue/4/the-unlikely/sciences-significant-stats-problem

[12] http://www.who.int/bulletin/volumes/87/8/09-040809/en/

[13] https://tuesdayshorse.wordpress.com/2014/07/23/pushing-premarin-big-pharma-big-bucks-part-1/

[14] http://www.collective-evolution.com/2016/05/14/pfizer-vp-comes-clean-tells-the-truth-about-pharmaceutical-companies-video/

© The Horse Fund

WHI — Women’s Health Initiative

The Women’s Health Initiative (WHI) was initiated by the U.S. National Institutes of Health (NIH) in 1991. The Women’s Health Initiative, which consisted of three clinical trials (CT) and an observational study (OS), was conducted to address major health issues causing morbidity and mortality in postmenopausal women.

Related Reading

Further reading on the use of “P values” and other sources of statistical error:

“Why Most Published Research Findings are False” http://journals.plos.org/plosmedicine/article?id=10.1371/journal.pmed.0020124

“A Dirty Dozen: Twelve P-Value Misinterpretations” http://exp-platform.com/Documents/2017-08%20KDDMetricInterpretationPitfalls.pdf

“Science’s Significant Stats Problem” http://nautil.us/issue/4/the-unlikely/sciences-significant-stats-problem

Don't sweat the latest report damning WHI report on Premarin. Take an alternative.
Don’t sweat the latest report damning WHI report on Premarin. Take an alternative.

Women — Don’t Sweat It

Don’t sweat it concerning these drugs and the confusion surrounding them. Work with a health care professional to find the right alternative for you. Here are some good alternative avenues for you to explore.

More at Tuesday’s Horse

• Horse pee reduces breast cancer. Say what? by Jane Allin
https://tuesdayshorse.wordpress.com/2013/06/13/horse-pee-reduces-breast-cancer-risk-say-what/

Premarin Horses

March for Premarin Horses featured image.
Pfizer’s Premarin family of HRT drugs is made from the urine of pregnant mares.

The Premarin family of drugs is made from the estrogen rich urine of pregnant mares. Hence the name Pregnant Mare’s Urine.

The conjugated equine estrogens produced from the urine of pregnant mares to make these drugs have been declared known carcinogens by the World Health Organization.

See all posts on Premarin Horses »

Learn how more about how these horses are used and what happens to cast off mares and byproduct foals at Premstoppers at http://horsefund.org/premstoppers-home.php.

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Please share far and wide, on behalf of women and horses.

 

 

 

Turn your back on Premarin type drugs and seek alternatives for symptoms of menopause

October is Breast Cancer Awareness Month and as it draws to a close we urge women to please turn your backs on Premarin type drugs — tablets and cream — and seek another treatment for menopausal symptoms.

There are alternatives.

Work with your doctor to find something to help you other than drugs made from pregnant mare’s urine — for your sake as well as the innocent mares and their byproduct foals.

Crazily I have had doctors argue with me that the Premarin family of drugs are not made with conjugated equine estrogens derived from the urine of pregnant mare. The absence of the word “equine” on the packaging is proof enough for them.

Of course “equine” was removed some years ago. Yes, we heard about it and we know how and why. I assure them that the key component of the drugs taken from the estrogen rich urine of pregnant mares remains the same. End of discussion.

I share this with you in case you encounter this argument yourself whether it be with a physician trying to prescribe it to you or when trying to warn someone who is taking it.

THE ALTERNATIVES

Jane Allin put together a list of alternatives to drugs such as Premarin, Prempro, Duavee and Duavive (See also pdf version at the end of this post).

Duavee by the way is the name given to Aprela when it was approved by the FDA during the last federal government shutdown and is being peddled in Europe under the name Duavive.

We asked Jane to review her report on alternatives and give us any updates. This is what led to Jane’s recent post on Tuesday’s Horse regarding the helpful properties of rhubarb. See Breast cancer, menopause and yes, rhubarb.

This in turn launched me on a vegan rhubarb recipe hunt which you can find here. See No need to sweat menopause when you can chill with some rhubarb.

Other than that there are no notable changes.

Please keep reporting those Premarin television and magazine ads!

Thank you.

PDF
Alternatives to Drugs Made with Conjugated Equine Estrogens by Jane Allin (pdf, 7 pp)

FURTHER READING
Premstoppers Home »
Reports Regarding Premarin Horses »
Images of PMU Horses; Images from PMU Farm in China »

PMU Horses win two awesome new friends

Jane Allin and I, together with you, have been championing the cause of PMU horses for over a decade.

PMU horses are mares kept continually pregnant in order to collect their estrogen rich urine to make drugs like Prempro, Premarin and Duavee for the easing of menopausal symptoms. A tragic offshoot of this process are of course the mares’ byproduct foals. As Allin points out:

    Sadly, foals born to these mares are usually worth less than the urine their mothers produce. They are considered to be nothing more than a living byproduct of Premarin. To the PMU farmers, they are often worth more dead than alive.

NEW FRIENDS

Joining us in the battle to save PMU horses are two awesome new friends.

Rebecca

First, there’s a lovely lady called Rebecca who has gone to live in China with her husband sent to work there by his company.

Rebecca has been looking for a way to help PMU horses in a really big way and now she has it. Not only is Rebecca a professional photographer used to covering very difficult assignments, but also very well versed on the issue.

Inspired by the work of Jane Allin who uncovered that there are PMU horses in China, Rebecca is determined to locate some of these farms and document them. She is donating 100% of her time and we are helping her with her expenses. We are moved by her generosity and courage.

We couldn’t be more delighted and grateful.

Dr. Greene

An eminent women’s health care physician contacted us and offered to help in any way he can.

In particular, he likes the way we are alerting doctors to the true potential and significant dangers to patients treated with Premarin, Prempro and Duavee. He is for educating them more than ever.

We pointed out that we still have doctors responding to our Dear Physician Letter arguing that conjugated estrogens (how they are listed on the label) are not necessarily dangerous.

We responded that the estrogens in question are conjugated equine estrogens, a known carcinogen as declared by the World Health Organization.

Some doctors are shocked. Some doctors continue to argue that we are wrong because the the word equine is nowhere on the label.

Indeed it is not.

We point out that the word “equine” was omitted from packaging years ago and the FDA has done nothing about it.

Dr. Greene concurs with our plan to press the FDA to make the labeling of drugs reflect the true nature of these drugs — that they are made with conjugated equine estrogens. But will they listen to us, or anybody else for that matter?

He has a plan.

Dr. Green is writing a paper on the dangers of conjugated equine estrogens and drugs associated with them. He will use his paper to rally doctors on his side to make a strong case to outlaw the use of this ingredient. Full stop.

He justly observes that drugs made with conjugated equine estrogens are outmoded, outdated, totally unnecessary and most importantly of all a great potential danger to the health, safety and welfare of women and horses.

As his own work on this issue unfolds, Dr. Greene supports our work – especially this golden opportunity to expose PMU farms in China.

He is therefore guaranteeing to match your donations dollar for dollar to our Premstoppers Campaign from now through Friday, May 13, 2016.

THANK YOU

To all of you who have followed and supported our activities to keep this issue alive, thank you. You have helped make sure these horses are not forgotten.

FROM OUR WEBSITE

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TUESDAY’S HORSE

Side effects of raising awareness about the Premarin family of drugs and PMU horses »

FDA approved alternatives to Premarin derivatives. Are they safer? »

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FDA-Approved Alternatives to Premarin Derivatives – are they safer ?

by JANE ALLIN

Contrary to popular belief, the FDA has yet to approve any generic as a substitute for Premarin and its daughter products (i.e. Prempro, Premphase, Duavee).

Accordingly no prescription drugs used to treat menopausal symptoms, other than the Premarin family, contain pregnant mare’s urine.

Image from PMU farm in Manitoba showing the collection bag used to collect the urine from pregnant mares used in the making of the Premarin family of drugs.
Image from PMU farm in Manitoba showing the collection bag used to collect the urine from pregnant mares used in the making of the Premarin family of drugs.

However much confusion arises when the subject of HRT is broached, particularly in terms of the safety aspect of FDA-approved versions that are not derived from pregnant mare’s urine.

The vast majority of FDA-approved HRT prescription drugs are synthetic bioidenticals — hormones identical on a molecular level to endogenous hormones that are synthesized in the lab from natural plant sources.

These are not to be confused with the compounded bioidenticals, none of which are approved by the FDA.

Premarin and its derivatives are also synthetics but, of course, sourced from an animal by-product.

Apart from Brisdelle, the only non-hormonal FDA-approved HRT, the rest fall into three categories of hormone combinations as follows:

• Estrogen combinations (e.g. Estrace, Cenestin, Enjuvia, Menest)
• Estrogen/Progestin combinations (e.g. Activella)
• Estrogen/Androgen combinations (e.g. Menogen, Covaryx)

The estrogen combinations are intended as substitutes for Premarin and Duavee while the estrogen/progestin versions are proposed alternatives to Prempro and Premphase.

Estrogen/androgen replacement therapy primarily represents mainstay therapy for young women who have undergone a hysterectomy. See http://www.medscape.com/viewarticle/438357.

A good proportion of these drugs contain estradiol or esterified estrogens (non-equine) as the estrogen component (e.g. Estrace, Femtrace, Activella, Femhrt, Angeliq). However several have identical equine estrogens that are derived from plant-based sources versus pregnant mare’s urine.

That said, these drugs are not entirely identical nor are they exactly equivalent in constituents. Cenestin, Enjuvia, and Menest are three such HRTs included in this group.

Cenestin was originally developed as a generic for Premarin by Duramed/Barr but in 1997, the FDA refused to approve the abbreviated new drug applications from Duramed and Barr Laboratories for a generic version of Premarin.

The FDA’s rationale was quite straightforward. A synthetic generic version of Premarin could not be approved because the exact chemical composition of Premarin could not be fully identified. This has been a controversial topic for years, a topic The Horse Fund has visited in the past. See https://tuesdayshorse.wordpress.com/2014/11/14/the-quest-for-a-generic-premarin-a-bitter-pill-to-swallow/.

In any case, all three of these drugs – Cenestin, Enjuvia, and Menest – contain similar estrogen components that are found in Premarin and its derivatives.

Premarin however is a complex mixture of numerous hormonal components, of which only some of the estrogenic components are found in the plant-based synthetics.

The table below compares the ingredients of Premarin, Cenestin and Enjuvia. I was unable to locate the same information for Menest.

However the pharmacology is similar to the others and contains a mixture of esterified estrogenic substances, principally estrone, that are of the type excreted by pregnant mares (e.g. sodium estrone sulfate, sodium equilin sulfate).

ESTROGEN PREMARIN CENESTIN ENJUVIA
sodium estrone sulfate Yes Yes Yes
sodium equilin sulfate Yes Yes Yes
sodium 17 alpha-dihydroequilin sulfate Yes Yes Yes
sodium 17 beta-dihydroequilin sulfate Yes Yes Yes
sodium 17 alpha-betahydroequilenin sulfate Yes Yes Yes
sodium 17 beta-betahydroequilenin sulfate Yes Yes Yes
sodium 17 alpha-estradiol sulfate Yes Yes Yes
sodium equilenin sulfate Yes Yes Yes
sodium 17 beta-estradiol sulfate Yes Yes Yes
sodium D8,9-dehydroestrone sulfate Yes No Yes
5,7,9 (10) estratrien-3beta, 17 beta-diol Yes No No
17 alpha-dihydro-delta, 8,9-dehydroestrone Yes No No
17 beta-dihydro-delta, 8,9-dehydroestrone Yes No No
5,7,9 (10) estratrien-3betal-ol-17-one Yes No No
2-hydroxy-estrone Yes No No
2-methoxy-estrone Yes No No

In addition to the extra estrogens contained in Premarin, it also contains six progestin and four androgen equine hormones. See http://surmeno.blogspot.com/2006/03/comparison-of-ingredients-premarin-and.html.

Despite the fact that these alternatives contain several of the Premarin estrogenic components, a study comparing the pharmacokinetics and relative bioavailabilities of key estrogen components of Premarin with those of synthetic plant-based equivalents concluded that these are not in fact bioequivalent to Premarin and therefore cannot be assumed to be therapeutically equivalent. See http://www.ncbi.nlm.nih.gov/pubmed/10865186.

But does this mean that these and other FDA-approved synthetics are safe?

Unfortunately these alternative synthetics carry with them the same or similar warnings associated with their use.

However it is often cited in scientific literature that estrogens derived from pregnant mares urine pose a greater risk due to the complexity and concentrations of the combined hormones together with the unmistakable fact that equine estrogens are foreign to humans.

Given that alternatives such as Cenestin and Enjuvia assimilate the equine equivalents in Premarin, despite the fact they are derived from plants, it is perplexing why anyone would elect to choose these to alleviate menopausal symptoms – purely from the aspect of being equine-related and extrinsic to the human endocrine system. More likely it is a case where they are unaware of what they contain.

And what about the rest that contain estradiol (e.g. Estrace) and other esterified non-equine estrogens, or those that contain progestins and androgens extracted from plant sources?

Here are some examples of the risks associated with these so-called “safer” alternatives compared to the Premarin derivatives. Source: http://www.rxlist.com/script/main/hp.asp.

Estrogen-only HRT

Premarin (Conjugated Equine Estrogens – CEEs) http://www.rxlist.com/premarin-drug.htm
• Endometrial cancer, cardiovascular disorders, breast cancer and probable dementia (> 65 yrs).

Enjuvia (plant –derived equine estrogens) http://www.rxlist.com/enjuvia-drug.htm
• Endometrial cancer, cardiovascular disorders, breast cancer and probable dementia (> 65 yrs).

Estrace (estradiol – plant based) http://www.rxlist.com/estrace-drug.htm
• Endometrial cancer, cardiovascular disorders, breast cancer and probable dementia (> 65 yrs).

Estrogen –Progestin HRT

Prempro/Premphase (CEEs/progestin) http://www.rxlist.com/prempro-drug.htm
• Invasive breast cancer, cardiovascular disorders, and probable dementia (> 65 yrs).

Activella (estradiol/progesterone – plant based) http://www.rxlist.com/activella-drug.htm
• Invasive breast cancer, cardiovascular disorders, and probable dementia (> 65 yrs).

And let’s not forget the newest addition to the Premarin family.

Duavee (CEES/bazedozifene(SERM) http://www.rxlist.com/duavee-drug.htm
• Endometrial cancer, cardiovascular disorders, and probable dementia (> 65 yrs).
• The SERM bazedoxifene is believed to inhibit the formation of breast cancer cells by binding to the estrogen receptor thus interfering with its activity.

Premstoppers Campaign. Warning, Premarin Contains Horse Urine.

The picture is clear.

In effect the FDA-approved hormone-containing alternatives carry with them the same risks and warnings associated with drugs derived from conjugate estrogen estrogens, whether that be estrogen alone or combinations. Albeit the risks may not be of the same significance as those associated with drugs manufactured from pregnant mare’s urine.

Nonetheless they still exist, and potentially more so for susceptible individuals.

Although the hormonal ingredients are similar or equivalent, they may or may not function identically for any single given woman. This applies to the Premarin derivatives as well.

And so, as much as it may seem that these hormones are safer than the Premarin family of drugs, there is no solid evidence to prove this.

It is important to note that some of these drugs have been approved by the FDA because data collected from trials has proven their effectiveness in relieving menopausal symptoms and reducing the risk of osteoporosis.

However there have been no long-term studies like the WHI performed to assess their safety profile.

In the absence of comparable data, the risks are generally assumed to be similar to CEEs and other forms of estrogens.

Moreover, regardless of the source and type of hormones, it is always recommended that estrogens, with or without progestins, should be prescribed at the lowest effective doses and for the shortest duration consistent with treatment.

Brisdelle as an alternative?

Brisdelle approved.
Brisdelle becomes first non-hormonal replacement therapy drug for the treatment of menopausal symptoms in NA.

As mentioned there is only one FDA-approved non-hormonal HRT. In early June of 2013 the U.S. Food and Drug Administration approved the drug “Brisdelle” (paroxetine – Paxil) manufactured by Noven Pharmaceuticals for the treatment of hot flashes due to menopause.
 
Brisdelle contains the selective serotonin reuptake inhibitor paroxetine mesylate, making it unique from all other FDA-approved treatment for hot flashes which contain the hormones estrogen or progestin. 

Brisdelle poses none of the risks associated with estrogens or estrogen combination therapies.

However it is a selective serotonin reuptake inhibitor (SSRIs) (antidepressant), which has been shown to increase the risk of suicidal thoughts and behavior in pediatric and young adult patients when used to treat major depressive disorder and other psychiatric disorders. See http://www.rxlist.com/brisdelle-drug.htm.

Whether this risk applies to menopausal women is unclear.

As with any drugs and medications there are inherent risks, the nature of which can range from mild to life-threatening. Always consult your doctor to help decide what is best for your particular situation.

Please visit our Alternatives to Premarin page to learn more about options other than drugs containing conjugated equine estrogens. See http://www.horsefund.org/pmu-alternatives-to-cee-drugs.php.

Comparing the cost of FDA-approved HRT

Pharmaceutical Industry: A prescription for money.
Pharmaceutical Industry: A prescription for making huge profits.

As an aside and for interest’s sake here is a list of some of the more common HRTs available and the costs associated with them. The list is by no means comprehensive and includes the tablet form of the drug only.

This information was taken from http://www.goodrx.com and pertains only to the U.S. Prices are per tablet and converted to monthly costs based on a 30-day interval.

For consistency, all of the costs were taken from Walgreen’s with the discount coupons applied. Obviously prices will vary depending on store, geographic location, available coupons, etc. and are only intended to provide a relative comparison using the same base source.

DRUG NAME TYPE GENERIC
AVAILABLE?
PATENT
EXPIRATION
DATE
PRICE
PER
TABLET
MONTHLY
COSTS
(APPROX)
Prempro / Premphase CEEs / Progestin No Expired $5.77 $173
Brisdelle SSRI (paroxetine) No Apr 2029 $5.74 $172
Duavee CEEs / SERM (bazedoxifene) No Oct 2016 $4.77 $143
Premarin CEEs No Expired $4.33 $130
Angeliq Estrogen / Progestin No Oct 2017 $4.31 $129
Cenestin CEEs — plant based No Expired $3.97 $119
Prefest Estradiol / Progestin No March 2020 $3.37 $112
Enjuvia CEEs — plant based No Feb 2021 $2.75 $83
Femtrace Estradiol acetate No Dec 2021 $2.68 $80
Activella Estradiol / Progestin Yes Expired $2.06 $78
Menest CEEs — plant based No Expired $1.77 $53
Femhrt Estrogen / Progestin Yes Expired $1.32 $40
Ogen Estrogen (estrone) Yes Expired $0.28 $8
Estrace Estradiol Yes Expired $0.13 $4

Clearly, Pfizer is laughing all the way to the bank at the expense of women and horses alike.

END.

© The Horse Fund

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