In the United States, one in five prescriptions are written for off-label purposes.One This means that a doctor is prescribing a drug for a purpose for which it has not been officially approved by the U.S. Food and Drug Administration (FDA). The FDA approves a drug for a specific use, but doctors can legally prescribe the drug for other uses they deem medically appropriate.
These practices are common and are often based on new evidence, clinical experience, or guidelines from professional medical societies. Sometimes this can lead to abuse or misuse of the drug, but it also protects the doctor's ability to freely treat the patient and the patient's ability to use all available treatments after making an informed decision.
When it comes to progesterone (one of the four hormones from which most adults benefit), the route of administration is particularly important and influences its effectiveness.
Unfortunately, for transmucosal application, which is the preferred method, the FDA considers this to be converting the supplement into a drug. Therefore, because of this gray area, over-the-counter progesterone products cannot list transmucosal application on their labels, even though it is perfectly legal for doctors to prescribe it as such.
Legal technicalities block the best route to administer progesterone on the label.
In the complex landscape of modern medicine, off-label drug use represents a significant gray area that both empowers and challenges healthcare providers and patients. It is important to understand that the FDA regulates the approval and marketing of drugs but does not control the practice of medicine.
This regulatory framework gives doctors the freedom to prescribe drugs for off-label uses, known as off-label prescribing. Off-label use, providing alternative treatment options when standard treatments fail or are unavailable, can be critical to patient care.
For example, doctors may use hormones such as progesterone transmucosally despite primary approval for another route of administration. This flexibility is essential to tailor treatments to the needs of individual patients and to advance clinical practice based on new evidence and experience.
However, people who may benefit from transmucosal administration of drugs such as progesterone may not be provided this information due to FDA regulations. These regulations require that all over-the-counter (OTC) progesterone products be labeled for topical and cosmetic use only.
As a result, manufacturers cannot promote internal use of their products without reclassifying them as new drugs, which requires a lengthy and costly approval process.
Because of this regulatory environment, you may not be aware of the potential benefits and alternative applications of your drug. For example, someone seeking effective hormone therapy may not realize that transmucosal progesterone may be a viable option. This is because this information is not widely promoted or available due to regulatory constraints. As a result, patients may miss out on treatments that could significantly improve their quality of life.
Why it is recommended to apply progesterone to the gums and not the skin
Transdermal and transmucosal administration are two methods of delivering drugs through various types of body tissue. Transdermal administration involves applying the drug directly to the skin. The drug is then absorbed through the skin layers into the bloodstream over time.
Transmucosal administration involves applying a substance to mucous membranes, such as those found in the mouth. The compound is absorbed through mucosal tissues and enters directly into the bloodstream. The FDA considers the route of administration important in determining whether a progesterone product is considered a new drug. FDA believes that transmucosal applications are distinct from topical applications and are subject to different regulatory requirements.
However, I do not recommend transdermal progesterone. This is because the skin expresses high levels of the enzyme 5-alpha reductase. This causes a significant portion of the progesterone you are taking to be converted irreversibly, primarily to allopregnanolone, and cannot be converted back to progesterone.
This is why I recommend applying progesterone transmucosally to the gums. This is because progesterone is then absorbed directly into the bloodstream, rather than bypassing first-pass metabolism in the liver where it is converted to useless metabolites. As mentioned, if progesterone is used transmucosally on the gums as I advise, the FDA believes it converts it into a drug and prohibits any company from advising this on its label.
This is the case with Health Natura's Simply Progesterone, which comes pre-mixed with vitamin E and MCT oil. Health Natura says:2
“The FDA requires all OTC. Over-the-counter progesterone is indicated for topical and cosmetic use only. We cannot promote internal use of Simply Progesterone. Doing so would cause the FDA to reclassify Simply Progesterone as a drug, and we would have to stop selling this product.”
Some people have expressed concern that their products' labels say they are for skin use only, but please understand that this is most likely due to the reasons mentioned above. This is not for your protection. This is to protect the cash flow of pharmaceutical companies. Applying progesterone to the gums is the ideal route of administration and is a legal off-label use of progesterone.
In this case, progesterone is a natural hormone, not a drug, so it is very safe even when used in high doses. This is often mistakenly called progesterone, which is dangerous and no one should use it, unlike the synthetic progesterone called progestin used by pharmaceutical companies.
Tips for Proper Progesterone Dosing
Before considering using progesterone, it is important to understand that it is not a magic bullet, and that the greatest benefits will be gained by implementing a bioenergetic diet approach that backs up electrons in the mitochondria so they can effectively burn glucose as their primary fuel. It's important to understand the point. Energy production. My new upcoming book on cellular health covers this process in great detail.
Once you have your diet under control, an effective strategy that can help prevent estrogen excess is to take transmucosal progesterone (not oral or transdermal), a natural estrogen antagonist. As mentioned earlier, progesterone is one of the four hormones that many adults believe they can benefit from. (The other three are thyroid hormones T3, DHEA, and pregnenolone.)
A general recommendation is to take 25 to 50 mg of bioidentical progesterone each evening one hour before bed to promote sleep. Progesterone should be mixed with natural vitamin E for optimal bioavailability. The bioavailability difference between taking progesterone orally without vitamin E and with vitamin E is 45 minutes versus 48 hours.
Health Natura's Simply Progesterone contains a pre-blend of vitamin E and MCT oil. You can also make your own by dissolving pure USP progesterone powder in one high-quality vitamin E capsule and rubbing it on your gums. 50 mg of powdered progesterone is approximately 1/32 teaspoon.
Do not use synthetic vitamin E (alpha tocopherol acetate – acetate indicates it is synthetic). Natural vitamin E is denoted as “d alpha tocopherol”. This is the pure D isomer that the body can use.
There are other vitamin E isomers as well, and the D isomer to be effective requires the full spectrum of tocopherols and tocotrienols, especially the beta, gamma, and delta types. For examples of ideal vitamin E, refer to your store's vitamin E label. You can use brands with similar labels.
For menstruating women, progesterone should be taken during the luteal phase, or last half of the cycle, which may be decided to begin 10 days after the first day of menstruation and to stop progesterone once menstruation begins.
If you are a man or a woman who is not menstruating, you can take progesterone daily for 4 to 6 months and then stop for a week. The best time to take progesterone is 30 minutes before bed. This is because progesterone has anti-cortisol properties and can help you sleep better by increasing GABA levels.
Does the FDA want the power to regulate medical practice?
The 2023 omnibus budget bill (4,155 pages containing $1.7 trillion in spending) includes 19 lines giving the FDA the authority to ban off-label uses of approved drugs. In a Wall Street Journal commentary, Joel Zinberg wrote:three
“Doctors routinely prescribe medications and use medical devices approved and labeled by the Food and Drug Administration (FDA) for specific uses. However, sometimes doctors identify other beneficial uses for these techniques and prescribe them to their patients without special official approval.
The new law amends the Food, Drug, and Cosmetic Act (FDCA) to give the FDA the authority to prohibit off-label uses of approved products. “This unwarranted infringement on the doctor-patient relationship risks undermining medical innovation and patient care.”
“The new provisions were enacted at the urging of the FDA,” says Zinberg.4 It's a response to a 2021 legal ruling that limited the FDA's authority to intervene in medical practices. In March 2020, the FDA banned the use of electroshock devices for one specific purpose: to treat patients who have engaged in self-harm or aggressive behavior that could cause harm to others.
The device is FDA approved, and the FDA has banned its use in certain situations but allows its use for smoking addiction and other purposes.5 This led to a lawsuit (Rotenberg Education Center v. FDA Judge) in which Judge Rotenberg Education Center, a school for people with severe behavioral and intellectual disabilities, sued the FDA over the ban.
The court ruled in favor of the schools, saying the FDA's ban violated federal law because it violated practitioners' rights to practice medicine. Currently, the FDA does not have the authority to ban medical devices for specific uses.
Currently, Section 360f of the FDCA gives the FDA the authority to ban medical devices only if they pose an “unreasonable and substantial risk of disease or injury.” You can ban a device outright, but you can't pick and choose when it can and cannot be used.
“Prohibiting doctors from prescribing or using approved devices for specific off-label indications would violate another FDCA provision that prohibits the FDA from regulating the ‘practice of medicine,’” says Zinberg.6 Additionally, according to the proposed rule published in the Federal Register on March 26, 2024:7
“The Food and Drug Administration (FDA, FDA, or us) is proposing to ban electrical stimulation devices (ESDs) intended for self-injurious behavior (SIB) or aggressive behavior (AB). The FDA has determined that these devices present an unreasonable and substantial risk of illness or injury that cannot be corrected or eliminated by labeling.
This proposal follows court decisions invalidating prior bans and amendments to the federal Food, Drug, and Cosmetic Act that clarified the authority to ban devices for more than one intended use. If finalized, this measure will mean that ESDs for SIB and AB will be adulterated and cannot be legally sold.”
Health care decisions are up to you and your doctor
As the FDA and Big Pharma move beyond regulatory boundaries, the FDA takes the lead on powerful healthcare decisions that must be made at an individual, personalized level between patients and their healthcare providers. During the pandemic, it became clear how patients suffered when health agencies were able to dictate which medications doctors could prescribe to patients.
The FDA's refusal to allow transmucosal applications on OTC progesterone labels is another example of industry interfering with the practice of medicine. Rubbing progesterone into the gums is safe and the preferred method of application.
