Press Release
December 17, 2015

April 25, 2016 (Boca Raton, FL)

In April 2016, the Endocrine Society published a scientific statement regarding compounded bioidentical hormones and their use in clinical practice. The Endocrine Society stated some things we could all agree upon: [1] the hormone physiology and pharmacology, and [2] the need to use a quality compounding pharmacy to provide the compounded drugs. The remainder of their “scientific statement,” was a combination of opinion, inaccurate facts and a plea to try and convince the readers (physicians) to use “FDA” approved drugs. Below is a commentary on some of the misstatements.

[1] “Compounded hormone medications are meant to be an alternative when an individual does not have access to or has an adverse reaction to a medication approved by the U.S. Food & Drug Administration”

• Both the FDA and the United States Supreme Court agree that compounding is an important part of healthcare – not just as an alternative when FDA approved drugs are not available or tolerable, and there should be regulations and monitoring to assure patient safety. Thus, this statement: “compounded hormones are an alternative…” is an opinion not a true fact.
• The FDA takes a very broad view of what compounding is, defining it as "a practice in which a licensed pharmacist, a licensed physician, …combines, mixes, or alters ingredients of a drug to create a medication tailored to the needs of an individual patient.” Isn’t that what medicine should be about, individualized care?
• Additionally, in their raw form, ALL compounded hormones are FDA approved. Compounded hormones are individualized and not mass produced like FDA approved hormones, therefore, it is impractical if not impossible, to have every possible combination of compounded hormones go through the FDA approval process. The FDA and the United States Supreme Court agree!

[2] “Compounded hormone medications can be unsafe when inappropriate practices are used”

• This statement implies that compounded hormones are unsafe and FDA approved hormones are safe. Is “inappropriate practice” the teamwork that occurs between the patient, the physician and the compounding pharmacist to determine the right compound at the right dose for that particular patient? If so, then Hippocrates got it wrong when he said: “It is more important to know what sort of person has a disease, than to know what sort of disease a person has.” The Endocrine Society writing group (“writing group”) would define appropriate practice as regardless of the patient’s needs, just prescribe a mass-produced fixed dose drug, thereby treating the disease, not the patient!
• Further, all drugs, including compounded drugs, need to be prescribed and monitored by a well-trained physician and compounded by a reputable pharmacy.
• Physicians need to understand the risks and benefits of prescribing hormone therapy and be able to articulate these to the patient.
• Safety risks can be minimized through the pharmacist’s knowledge and skill.
• Under or over dosing is not unique to compounding pharmacies. Pharmaceutical companies, as opposed to compounding pharmacies, get to set their own potency windows. Compounding pharmacies have a 10% potency and reliability standard that must be met. However, reputable compounding pharmacies set their standards at ≤ 5%. We don’t know what the standards are for off the shelf, mass produced drugs including estrogens, progestins, testosterones, thyroid etc. Under or over dosing can occur with these drugs too. Since the Endocrine Society does not recommend monitoring, they would never know!
• Additionally, the Endocrine Society pointed out the 2010 fungal meningitis that occurred in New England. However, they neglected to state that more than 100,000 individuals die each year from FDA approved prescription drug adverse reactions. The latter is the fourth leading cause of death in the United States.
• Moreover, PremPro, an FDA approved drug, tested in the Women’s Health Initiative (WHI) increased cardiac events, strokes and breast cancer. Whereas, to date, there has never been a BHRT related death.

[3] “… widely available hormone treatments that are 100% chemically identical to the native hormones found in the body and FDA approved offer effective and safe options….etc.” I don’t think so!

• The only “chemically identical” FDA approved hormone options that are available are Prometrium and the Estradiol patch. All other preparations are non-bioidentical ethinyl estradiol (found in OCP’s), synthetic progestins found in birth control pills, the Mirena IUD, and medroxyprogesterone acetate (found in PMP HRT). Premarin is a non-human bioidentical hormone that is chemically identical to hormones found in horses.
• Comparing and contrasting oral estrogens (typically not bioidentical) and bioidentical estrogens NOT orally administered:
• Significantly different effects are seen between oral and transdermal/ subcutaneous (TD/SQ) administered estrogens. These differences may in part be related to route of administration, avoiding first-pass metabolism, thereby decreasing the amount of potentially toxic estrogen metabolites. TD/SQ estrogen doesn’t adversely affect inflammatory markers such as CRP, coagulation factors, and the fibrinolytic pathway, while oral estrogen can adversely alter these markers.
• Also, oral estrogen therapy, as opposed to TD/SQ estrogen, is associated with increased risk of stroke, venous thromboembolism, pulmonary embolism, hypertension, gallbladder disease, metabolic syndrome, insulin resistance, liver cancer, and weight gain. Oral estrogens increase sex hormone binding globulin (SHBG), which can result in decreased testosterone bioavailability and can elevate liver enzymes, estrone, CRP, triglycerides, and matrix metalloproteinases. Oral estrogen decreases IGF-1 and growth hormone levels, and may impair conversion of T4 to T3.
• Synthetic Progestins versus bioidentical Progesterone:
• Synthetic progestins and bioidentical progesterone both exhibit endometrial protection when used in combination with estrogen, however, they differ in their chemical structures, metabolism, potency, steroid receptor affinity, intracellular mechanisms of action, and biological and clinical effects.
• Synthetic progestins increase breast cell proliferation rates and are associated with increased rates of breast cancer. As opposed to micronized Progesterone which causes coronary vasodilation, synthetic progesterone increases coronary artery reactivity, endothelial damage and plaque formation, while worsening insulin resistance and decreasing HDL. Thus, synthetic progestins are associated with an increased risk of cardiovascular disease and acute MI.
• As opposed to progestins, progesterone, acting as a neurosteroid, has neuroprotective effects on the brain and nervous system, while progestins (MPA) does not.
• Allopregnanolone, the oral progesterone metabolite, modulates neuronal excitability, and potentiates GABA, thereby exhibiting anxiolytic, sedative, and anti-epileptic properties. Conversely, synthetic progestins are associated with increased depression and anxiety, and do not seem to improve quality of life in postmenopausal women as much as micronized progesterone.
• Bioidentical progesterone is associated with a decreased risk of breast cancer, as compared to synthetic progestins, via various mechanisms. It inhibits estrogen stimulated breast cells; downregulates estrogen receptor alpha (ER-⍺ - the receptor associated with breast cell proliferation); increases the conversion of more potent estrogens into less potent estrogens, etc.
• Regarding boosting testosterone levels in women, it is true that there are no FDA approved therapies using testosterone, however, observational studies mostly show an inverse relation between testosterone levels in women and cardiovascular risk, cardiovascular events, and all-cause mortality.
• A 2014 study (Davis S, et al.) using physiologic exogenous transdermal testosterone replacement in postmenopausal women was associated with improved verbal learning and memory.
• Low levels of testosterone in women are associated with lower bone mineral density, and a small study found estradiol and testosterone replacement in women significantly increased bone mineral density.
• There is no obvious association with bioidentical testosterone replacement in females and the risk of ovarian or endometrial cancer, however, high androstenedione levels may be associated with some types of ovarian cancer, perhaps due to its conversion to estrone, thus emphasizing the need for monitoring, which the writing group does not support.
• Compared to the use of methyltestosterone (oral – synthetic), bioidentical testosterone has not been shown to increase the risk of breast cancer.

[4] “LT4 is bioidentical and a highly effective and safe therapy and is the treatment of choice for hypothyroidism. The complex tissue-specific deiodinase system converts T4 to T3 and supplies the proper amount of T3 to each of thebody’s tissues according to its requirements.”

• This statement contradicts their previous statement regarding “the preferable ratio of 14:1.” LT4 alone, typically does not obtain this desired ratio. However, the combination of LT4 and LT3 may obtain this ratio, if the patient’s required thyroid dosing fits within the mass produced available doses. However, most patients want, and need individualized dosing to assure “their” thyroid function is optimum. This typically can only be achieved by compounding.
• Since the writing group uses TSH +/ T4 as its measuring stick, it is unclear how they would know whether or not a patient needs T3 as well as how much they need. They should heed their own advice: measure and monitor – complete thyroid hormones, not just select ones.

Conclusion

You have to know who you are dancing with before you get on the dance floor! This 2016 Endocrine Society statement was authored by six individuals, 4 of whom have financial relationships with large pharmaceutical companies. Thus, it’s easy to conclude they could have a conflict of interest and should not be the group writing a scientific statement comparing the use of bioidentical hormones and synthetic hormones in clinical practice. It is unfortunate that they are using this medium, writing as if they are the last and final word on the subject, when they are not, (see the recent Wall Street Journal Article – quoting a well-respected endocrinologist re: compounded thyroid) to try and convince physicians to use synthetic hormones, without appropriate monitoring, that increase morbidity and possibly mortality. As functional medicine physicians we know better. Thus, it is our responsibility to educate our peers and healthcare clients.