Group Tells the FDA to Restrict the Use of Compounded Hormones

[Nelson Vergel]

That is the message this group is using to convince the FDA to make prescribing compounded products a very restricted field.

The use of compounded bioidentical hormone therapies (cBHTs) — an increasingly popular approach to relieve symptoms of menopause and male hypogonadism — should be limited to the small number of patients who cannot benefit from an FDA-approved hormone therapy product, says a new report from the National Academies of Sciences, Engineering, and Medicine. It recommends that prescribers restrict the use of cBHTs to two circumstances: when a patient is allergic to an ingredient in an FDA-approved hormone product, and when a patient requires a specific dosage form not available for an FDA-approved product.

“Bioidentical” hormone therapies (BHTs) contain hormones that are chemically and structurally identical to those produced by the human body. They are available as FDA-approved products or non-FDA-approved compounded preparations. Unlike FDA-approved BHT products, compounded preparations have not been subjected to regulatory oversight or rigorous safety, efficacy, and quality control testing. Further, because cBHTs are custom-blended in different doses and forms — such as pills, creams, or pellets — the lack of standardization can increase the possibility of overdosing, underdosing, or contamination, says The Clinical Utility of Compounded Bioidentical Hormone Therapy: A Review of Safety, Effectiveness, and Use.

https://www.nationalacademies.org/news/2020/07/prescribers-should-restrict-the-use-of-non-fda-approved-compounded-bioidentical-hormones-except-for-specific-medical-circumstances

 

[Nelson Vergel]

On Wednesday July 1, 2020, the National Academies of Science, Engineering, and Medicine (NASEM) released a report titled “The Clinical Utility of Compounded Bioidentical Hormone Therapy: A Review of Safety, Effectiveness, and Use (2020).” First announced in September 2018, the report was commissioned and funded by the Food and Drug Administration (FDA), and the results align with FDA’s thinking that compounded hormone therapies pose a public health concern. Click here for a summary of NASEM’s recommendations: https://www.pccarx.com/pdf_files/PA_NASEM-cBHT-Recommendations_07-20.pdf

The report contains several deeply concerning recommendations, including that the use of compounded HRT be restricted and all reviewed hormone therapies be considered by FDA to be placed on the agency’s Difficult to Compound List. The report suggests this recommendation is included because compounds are not FDA-approved products and thus lack the population-based bioavailability data and labeling that FDA-approved products have. The recommendations also call for labeling requirements equivalent to FDA boxed warnings, which is counter to federal statute in the Drug Quality Security Act.

What are our primary concerns?

• PCCA is concerned that the report overstates the risks and minimizes the benefits of compounded therapies.
• We agree that more trials should be funded to assess the safety, efficacy and bioavailability of compounded hormone preparations, and that the entire scientific community will benefit.
• The committee seems to have ignored the many practitioners who testified about patient monitoring and titration of dosing which produces, in essence, patient-specific bioavailability data, simply because it was not done as part of a large-scale clinical trial. Individual patient bioavailability studies are unrealistic; rather, individual patients are evaluated by their doctors who monitor their lab values, symptoms, quality of life, and other parameters in assessing the value of the therapy.
• The report’s recommendations enter into the practice of medicine. The recommendations attempt to:
  1. Remove the ability of the physician to determine what is best for each individual patient
  2. Minimize the role of the physician in diagnosing, treating and following up with the patient
• The logic employed by NASEM would:
  1. Discourage patients from taking an active role in their own health care
  2. Lead to the end of off label prescribing or the use of any dosage of a drug that is not explicitly described in an approved product’s package insert

Womens Hormone Network | NASEM Report on the Clinical Utility of Compounded Bioidentical Hormones

News NASEM Report on the Clinical Utility of Compounded Bioidentical Hormones On Wednesday July 1, 2020, the National Academies of Science, Engineering, and Medicine (NASEM) ...

www.womenshormonenetwork.org

 

[Nelson Vergel]

Issue - cBHT and NASEM

a4pc.org

Home - SaveMyCompounds

Why Compounding is Important. Pharmacy compounding is a long-established tradition that allows a physician to prescribe a specific medication, prepared by a pharmacist, for a patient’s individual needs. Years ago, compounded medications provided the majority of prescription drug care. Today...

www.savemycompounds.com

The FDA, no fan of compounding, commissioned a study from the National Academies of Sciences, Engineering, and Medicine on "the safety, effectiveness, and use" of compounded bioidentical hormone [replacement] therapy (cBHT or cBHRT). The study concluded that there isn't much clinical evidence for or against cBHT. Strangely, though, the study recommended that cBHT be restricted.

Now, despite the undisputed fact that millions of Americans use cBHT every day and rely on it, the FDA is using that study — yes, the one it paid for — as an excuse to consider limiting or even outright banning compounded hormone therapy.

This cannot be allowed to happen. The lives and health of too many people are at risk.

Have you benefited from Compounded Bioidentical Hormone Replacement Therapy (cBHRT)? If so, you won't be happy with what the FDA is planning.

The FDA has never been a fan of pharmacy compounding, but now it is making a move that could keep millions of people from using this critical therapy.

Here's the deal:

Last year, the agency commissioned the National Academies of Sciences, Engineering, and Medicine (NASEM) to conduct a study of cBHRT. The study ignored vast amounts of clinical evidence of its current effective use. But not surprising, NASEM recommended that cBHRT be severely restricted—which is exactly what the FDA paid it to say. The NASEM committee was composed of medical professionals with sterling credentials. However, none of the committee members has any clinical expertise or experience treating women or men with compounded hormones, and no experts on compounding were on the committee!

Never mind that tens of thousands of providers prescribe, and millions of Americans use cBHRT every day and rely on it. Never mind that the study didn't find any significant negative effects of cBHRT. Oh, and never mind that the NASEM study didn't even ask the basic question: Does cBHRT work for patients? (It does. Very well.)

And now:

The FDA is using that study—yes, the one it paid for—as an excuse to consider limiting compounded hormone therapy by adding the entire class of medication to its so-called “too-difficult-to-compound list. Under federal law, FDA does have the authority to place individual medications but not entire classes of drugs to this list. And there must be clear evidence of safety issues.

You read that right: If you use cBHRT, the medication may no longer be available to you.

In November 2020, 32 members of the House of Representatives sent a letter to the FDA commissioner, asking that the agency not limit cBHRT. That letter had a big impact but it’s not too late for individual members of Congress to add their voices to the chorus asking FDA to take action to protect hormone therapy.

We’ve made it easy for you. If you have not participated in one of these campaigns before, just enter your name and address in the box to the right. (If you have participated before, your information has already been entered for you.) We’ll match you with your House representative and Senators and provide pre-written messages that you can customize. (If your Representative is a sponsor of the letter, you’ll be thanking him or her for doing so!)

Take Action - SaveMyCompounds

Take Action!

www.savemycompounds.com

 

[Bryan_K77]

This is very frustrating to read,as we all know exactly what is a play here and public safety concerns as they suggest is surely not it.

 

[captain_j]

If they were somehow successful in banning the compounding of testosterone, I could see a large number of people turning to underground labs and "pharma" grade testosterone. It's incredibly easy to get. But who really loses here is us, since the quality control from underground labs is much worse than any US-based compounding pharmacy.

 

[HealthMan]

Sent a message to my state representatives. Please let us know if we can do anything else to stop this

 

[Bryan_K77]

If they were somehow successful in banning the compounding of testosterone, I could see a large number of people turning to underground labs and "pharma" grade testosterone. It's incredibly easy to get. But who really loses here is us, since the quality control from underground labs is much worse than any US-based compounding pharmacy.

This just seems so evil, not that I’m the least bit surprised as money always wins out

 

[Nelson Vergel]

Click here: cBHT Testimonials

 

[Bryan_K77]

Thank you Vergel! I just completed the form and please urge everyone else to as well, we must fight for our rights hard on this one!

 

[captain_j]

Just curious, where does this form submit your personal information to?

 

[Vin]

Any update on this potential Trt implications?

 

[JYD21]

Any update?

 

[Nelson Vergel]

Glad you asked! I was about to post a draft of the petition to get input from all of you. @madman @Cataceous @Vince @Jason Sypolt @Dr Justin Saya MD

TO BE SENT TO:

HEAD OF FDA

STATE REPRESENTATIVES AND SENATORS

PHARMACY BOARDS OF EVERY STATE



The undersigned women and men being treated with compounded hormones, their clinicians, hormone researchers and concerned citizens ask the FDA not to block patients' access to compounded hormones by not implementing most of the biased recommendations of the 2020 NASEM report. The recommendations from this FDA commissioned report, if implemented, will deprive millions of patients from getting the treatment they need to combat life-altering symptoms that are currently managed through compounded hormone therapy.

We based our demands on the following irregularities and facts described in an independent analysis of the NASEM report entitled: The Panel Put Policy-Making Before Patient Need.

In sum, NASEM's recommendations seek to severely restrict - or eliminate entirely- the ability of the physician to prescribe cBHT to his or her patients. In turn, the restriction on the physician's ability to prescribe cBHT would limit the patient 's choices for treatment. When a patient's choices are limited, so too is his or her path to wellness.

We therefore strongly urge the FDA to consider that patient need take priority over policymaking.

SIGNATURES HERE (Name, city, state)

BACKGROUND INFORMATION:​

After the FDA directed the National Academies of Sciences, Engineering, and Medicine ("NASEM") in 2018 to create a committee to assess the “clinical utility of treating patients with compounded bioidentical hormone therapy ("cBHT'')” , the committee published in July 2020 what is known as The Clinical Utility of Compounded Bioidentical Hormone Therapy: A Review of Safety, Efficacy, and Use (the "NASEM Report"). The committee was also asked to identify patient populations that might benefit from using cBHT and to "describe the physical and chemical characteristics of compounded BHRT drug products." The NASEM Report ultimately offered six recommendations which, if implemented, would severely restrict, or eliminate entirely the ability of the physician to prescribe cBHT to his or her patients. NASEM's recommendations, discussed in more detail below, go beyond an assessment of "clinical utility” as demonstrated in its off-scope recommendation to review 11 bioidentical hormones as candidates for the FDA Difficult to Compound List that should no longer be compounded.

​

Why are Compounded Hormone Formulations Important?​

Compounding has been a fundamental component of pharmacy practice and healthcare since ancient times. In fact, compounding is considered to be the "origin of the practice of pharmacy. Today, compounding is taught as part of the standard curriculum at most pharmacy schools, and more than 32,000 pharmacies nationwide offer compounding services.

Bioidentical hormones are hormones that are chemically similar or structurally identical in molecular structure to hormones people make in their bodies, which means these hormones bind to receptors and act in the body similarly to hormones produced by the body. This is a broad definition that includes FDA-approved hormone therapies and custom compounded products. Certain bioidentical hormones are commercially available by pharmaceutical manufacturers, such as micronized progesterone and estradiol. However, other bioidentical hormones are prescribed by physicians in unique strengths and combinations, and these bioidentical hormone formulations are prepared in compounding pharmacies and are often referred to as cBHT. Bioidentical hormones should not be confused with hormones that are referred to as "natural” such as Premarin, a conjugated estrogen made from horse urine, that is not structurally similar to human estrogen and has effects on the human body which are different than human estrogen, and which was used in the WHI study that caused great controversy in the hormone replacement world.

The customizable nature of cBHT can address these individual needs. Further, while FDA-approved BHT products are only available in limited dosing formulations and strengths, cBHT medications are available in an array of delivery methods (e.g., capsules, creams, sublinguals, lozenges, and vaginal suppositories) and dose strengths. For example, common compounded formulations include estriol alone, "bi-estrogen" or " bi-est" combinations (estradiol and estriol), or "tri-estrogen" or "tri-est" combinations (estrone, estradiol, and estriol), as well as progesterone, testosterone, and dehydroepiandrosterone("DHEA'').53 The ability to treat patients with a customized dose and /or formulation is in some cases the only way to successfully keep patients on therapy.

Without cBHT, these patients would be unable to receive the medications their physician determined they need to address their health conditions and improve their quality of life. Of note, an analysis of women's motivations for using cBHT found that women decide to use cBHT due to the "persistence of menopausal symptoms, the side effects of conventional [hormone treatments], and a personal preference for cBHT. These benefits and treatment options would not be available if unable to receive cBHT.

​

Potential Unintended Consequence: Hormone Avoidance Will Cause Premature Deaths​

The NASEM report will not only stop compounded hormone manufacturing as we know it but it will also further increase hormone therapy avoidance that started after the faulty 2002 Women’s Health Initiative (WHI) study. A study funded by the Center for Disease Control and Prevention ("CDC") examined the effect of estrogen avoidance on mortality rates among hysterectomized women aged 50 to 59, following the 2002 WHI publication which was understood to show that hormone replacement therapy was harmful to women. Despite that both the WHI's methodology and substantive findings were later disputed, prescriptions for all forms of hormone therapy in hysterectomized women had declined by nearly 80% in the period from 2002 to 2011. Published in the American Journal of Health in 2013, the CDC study determined that the avoidance of estrogen therapy by prescribers and patients caused the premature death of anywhere between 50,000 and 91,000 post-menopausal women aged 50 to 59 since the WHI report was released in 2002. Similar to the WHI report, the NASEM Report appears to attempt to spread fear of cBHT, despite a lack of specific articulated risks. And just as the WHI report caused patients to shy away from estrogen to their detriment, the fear mongering by the Committee will cause harm to patients as well.

Conflict of Interest Cloud the Recommendations of the NASEM Report​

The NASEM report had a few strong biases:

• A lack of practicing cBHT medical prescribers, community health organizations, or pharmacists on the Study Committee.
• The Committee and its review team includes individuals who may be implicitly (or explicitly) biased against the use of cBHT by virtue of their participation in organizations that oppose compounding or their involvement with large pharmaceutical companies and the FDA itself. Moreover, that the Committee has little, if any, practical or clinical experience with cBHT may manifest as an aversion to compounding in light of popular misconceptions about the practice. most Committee members have close ties to large pharmaceutical companies (for which the cessation of compounding practices may be favorable), have served in organizations that have released position statements against cBHT, or are former employees of the FDA, whose position on cBHT is well-understood. most Committee members have close ties to large pharmaceutical companies (for which the cessation of compounding practices may be favorable), have served in organizations that have released position statements against cBHT, or are former employees of the FDA, whose position on cBHT is well-understood.

Only 1% of the Submitted Evidence was Considered​

The NASEM report committee ignored the body of evidence submitted by experienced prescribers and compounding pharmacists demonstrating that cBHT is both safe and effective- instead, it relied upon only thirteen of the hundreds of studies submitted by stakeholders in preparing its recommendations. In addition to its own searches, the Committee commissioned three additional literature searches by the National Academies Research Center. The commissioned searches yielded 410 articles related to position statements on hormone therapy; nearly 6,000 legal documents (e.g., federal and state cases, federal bills, law reviews) related to cBHT; and 62 dissertations / theses that could inform the Committee's understanding of the clinical use of cBHRT. The Committee also received hundreds of suggested articles and other references from study stakeholders, including the FDA, Professional Compounding Centers of America, representatives of select 503B outsourcing facilities, nonprofit professional organizations, and practicing medical prescribers of cBHT. Page 23 of the report also claimed that “the committee reviewed submitted testimonies from thousands of patients who use cBHT” without showing proof of this statement.

The Committee summarily concluded that the vast body of studies, articles, theses, and reference document s collected were not "of adequate methodologic rigor for inclusion in its review." Indeed, during its public briefing on the Report, Dr. Donald Mattison, NASEM's Committee Chairman for the Study, indicated that data submitted by top cBHT practitioners was not even considered.

In addition to the academic studies ignored by the Committee, the Committee also chose to disregard the testimony of various experts who presented their rationale, rooted in scientific research, for treating their patients with cBHT. Nearly 20 physicians submitted statements to NASEM regarding their regular practice of treating patients with cBHT for a variety of medical conditions, based on their experience and sound medical opinion. According to these physicians, cBHT has therapeutic effects in other areas including, among others, improving cognitive function, metabolic control of diabetes, and alleviating psychological disorders such as depression and anxiety.

Ultimately, the Committee relied upon a total of 13 studies as the basis for its recommendations on the safety and effectiveness of cBHT. In other words, out of the thousand s of studies on cBHT submitted to the Committee, the Committee only relied upon 13-or less than 1%. Most of these studies referred to only one hormone: DHEA. It also ignored the well-recognized and reasonable explanations as to why cBHT does not fit into the current regulatory framework for drug approvals- and instead seeks to hold compounded products to the same standards as FDA-approved drugs without consideration of the practical ramifications, or the applicable law and regulations that govern pharmaceutical compounding (e.g., Federal Food, Drug and Cosmetic Act and the 2013 Drug Quality and Security Act).

Eleven Hormones Currently Being Easily Compounded May be Added to the Difficult to Compound List​

And despite its primary focus on DHEA-and its failure to consider any studies on estrone, estradiol cypionate, pregnenolone, testosterone cypionate, or testosterone propionate at all-the Committee nevertheless recommended that estradiol, estrone, estradiol cypionate, estriol, pregnenolone, progesterone, testosterone, testosterone cypionate, and testosterone propionate and all pellet cBHT therapies be considered candidates for the FDA "Difficult to Compound List." Assessment of these compounds and formulations for inclusion on FDA's list of Difficult to Compound Drugs was outside of NASEM's commission scope- indeed, FDA was still working on a rule to address Difficult to Compound Drugs. Yet, NASEM took it upon itself to recommend that these 11 cBHT ingredients be included on the list.

The NASEM Report Negates a Prior Supreme Court Ruling and Congress’ Prior Decision​

The NASEM report seem to ignore the U.S. Supreme Court’s ruling in THOMPSON V. WESTERN STATES MEDICAL CENTER, wherein the majority stated that:

"Preserving the effectiveness and integrity of the FDCA's new drug approval process is clearly an important governmental interest, and the Government has every reason to want as many drugs as possible to be subject to that approval process. The Government also has an important interest, however, in permitting the continuation of the practice of compounding so that patients with particular needs may obtain medications suited to those needs. And it would not make sense to require compounded drugs created to meet the unique needs of individual patients to undergo the testing required for the new drug approval process. Pharmacists do not make enough money from small-scale compounding to make safety and efficacy testing of their compounded drugs economically feasible, so requiring such testing would force pharmacists to stop providing compounded drugs. Given this, the Government needs to be able to draw a line between small-scale compounding and large-scale drug manufacturing."

Furthermore, the NASEM Report seems to ignore that Congress specifically and intentionally exempted compounded medications from FDA approval via Section 503A of the Federal Food, Drug, and Cosmetic Act.

The NASEM Report Erases the Line Between Pharmaceutical Drug Manufacturing and Compounding​

In asserting that the evidence in support of BHT compounding should be evaluated against the same standards as FDA-approved medication, the Committee seeks to erase the line between compounding and drug manufacturing.

cBHT is used for a variety of medically necessary reasons by patients across the U.S., and continued access to cBHT is critical to patient health and well-being. Given the strong potential bias influencing the Committee's recommendations and the omission from the final report of key data supporting the safety and efficacy of cBHT, we recommend that FDA not rely on or consider the NASEM Report. It is further recommended that FDA not take steps to limit access to cBHT to millions of children, women, and men without adequate evidence to support a risk to patients, which should be considered on a drug product and/or formulation basis.

​

Potential Positive Outcome​

Instead of resolving concerns with appropriate cBHT use by eliminating or severely restricting use of cBHT drug products, FDA should work collaboratively with the medical and pharmacy compounding industries to improve upon and develop systems to address the perceived shortcomings in adverse event reporting and prescription labeling. Developing improved systems to provide patients information on use of ingredients commonly used in compounded therapies as well as improved systems for collecting adverse event information and safety reports will not only benefit the use of cBHT but will improve overall monitoring of compounded therapies.

 

[JYD21]

Awesome. I'm still trying to understand this and what it means for our collective health. Thanks for all your help staying on top of this.

 

[JD-CO]

First post. Thanks for this work that all of you do. You have changed my life and my family’s.

It is striking that one of the causes of action was “Whether available evidence of safety and effectiveness supports their use.” In other words, there is no information sufficient to claim there is a public health risk, so prove the negative….does the Act require this criteria during review? Is review even required under the Act?

If this NASEM report review was not mandated by the Act, then it might it be worth making a FOIA request to get the intra-agency communications that led up to the inception of the NASEM report (including texts)? From the outside, it appears this report does indeed blur the line on the Act, legislative intent, and the existing jurisprudence. And to the benefit of massively resourced companies that can meet the FDA requirements, at the expense of public (my) health. This may further undermine the report if a specific big-Pharma tie can be made. And may aid in follow on litigation…preserve the record…

Who are the attorneys fighting against this? Non-profit or have the compounding pharmacies taken a stand collectively? I mean, their market could be annihilated….

 

[Nelson Vergel]

Great comment. I forwarded it to APC- the Alliance for Pharmacy Compounding, and other stakeholders

 

[Nelson Vergel]

@JD-CO

This is what they said:

"This was done by APC in August of 2020 when the NASEM report was first released. That’s how we (APC) discovered that the FDA was directly involved and overseeing the creation of the study."