The FDA May Soon Block Your Access to Compounded Hormones: Seeking Comments

Nelson Vergel

Founder, ExcelMale.com
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.
 

Nelson Vergel

Founder, ExcelMale.com

Via another ruling, the FDA already blocked access to compounded hCG. Some states are now mimicking the FDA:

 

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