Pharmaceutical compounding is the combining, mixing, or altering of ingredients to create a customized medication for an individual patient in response to a licensed practitioner's prescription. The quality of a finished compounded drug product can be affected by many factors, including the quality of the active pharmaceutical ingredient used and the compounding practices of the pharmacy in which the product is created. The FDA requires drug manufacturers to meet stringent quality-control standards for the contents of each product and to document how quickly the drug dissolves in the stomach. However, compounded capsules can vary significantly in dosage and absorption characteristics, with no independent check of quality or variation . In 2001, for example, the FDA analyzed a variety of 29 product samples from 12 compounding pharmacies and found that 34% of them failed one or more standard quality tests. In addition, 9 of the 10 failing products failed assay or potency tests, with all containing less of the active ingredient than expected. In contrast, the testing failure rate for FDA-approved drug therapies is less than 2% .
Compounded "bioidentical hormones" are plant-derived hormones that pharmacists prepare and label as drugs. The products are claimed to be biochemically similar or identical to those produced by the ovaries or body. However, the relevant chemicals (steroids) in plants are not identical to those in humans. To make products that work in humans, raw materials from the plants must be converted to human hormones synthetically. Thus, to the extent that they are potent, the "bioidentical" products would pose the same risks as those of standard hormonesâ€”plus whatever problems might be introduced during compounding.
Many promoters of bioidentical hormone products advocate saliva testing to determine who might benefit from them. In fact, some nonstandard labs encourage consumers to order tests based on whether they have various symptoms.
For many years, the scientific medical community believed that hormone replacement therapy (HRT) at any age would reduce the risk of heart attack and stroke. This hope was dashed by the Women's Health Initiative Study, which found that taking estrogen plus progestin for more than five years places postmenopausal women at risk for heart attacks, strokes, and several other serious problems . HRT is now mainly prescribed for the short-term treatment of postmenopausal symptoms using low doses of an estrogen such as estradiol.
The risk involved in prescribing a hormonal product depends on its chemical composition and biochemical properties, not on how it was made. However, many offbeat physicians are prescribing compounded "bioidentical" products as though they are safer than standard prescription drug products. On October 31, 2005, the American College of Obstetricians and Gynecologists (ACOG) warned against these products and the saliva tests typically used by those who prescribe them. In strongly worded documents [4,5], ACOG stated:
- There is no scientific evidence to support claims of increased efficacy or safety for individualized estrogen or progesterone regimens prepared by compounding pharmacies.
- Hormone therapy does not belong to a class of drugs with an indication for individualized dosing. Salivary hormone level testing used by proponents to "tailor" this therapy isn't meaningful because (a) salivary levels are not as accurate as blood levels and (b) they can vary within each woman depending on her diet, the time of day, the specific hormone being tested, and other variables.
- Most compounded products have not undergone rigorous clinical testing for either safety or efficacy. There are also concerns regarding their purity, potency, and quality.
- The FDA requires manufacturers of FDA-approved products that contain estrogen and progestins to include a black box warning that reflects the findings of the Women's Health Initiative. However, compounded products (including "bioidentical" hormones) are not approved by the FDA and have been exempt from having to provide patient package inserts that contain warnings and contraindications for estrogens and progestins.
- Given the lack of well-designed and well-conducted clinical trials of these compounded hormones, all of them should be considered to have the same safety issues as those hormone products that are approved by the FDA and may also have additional risks unique to the compounding process.
In 2007, Aetna announced that it would no longer cover about 25 types of"bioidentical hormones and compounded thyroid drugs. [Coverage policy changing for hormone, thyroid compounds .
|In January 2008, the FDA ordered seven compounding pharmacies listed to the right to stop making illegal claims about "bio-identical hormone replacement therapy (BHRT)" products. The companies were told that the FDA regards "bio-identical" as a marketing term that implies a benefit for which there is no medical or scientific basis . Some were also making unsupportable claims that their drugs are better than FDA-approved menopausal hormone therapy drugs and can be used to prevent and treat serious diseases such as Alzheimer's disease, stroke, and various forms of cancer.|
Some products contained estriol as well as progesterone and estrogen. No drug product containing estriol is FDA-approved, and its safety and effectiveness are unknown .
State Licensing Board Actions
Several physicians have been disciplined in cases that involved bioidentical hormones.
- In 2008, the Medical Board of California charged Michael E. Platt, M.D., of negligence, incompetence, and inadequate record-keeping in connection with his care of three women, two of whom he diagnosed as hypothyroid even though their hormone levels tested normal. In 2009, the charges were settled with an agreement under which he was ordered enroll in the University of California's Physician Assessment and Clinical Education (PACE) program and serve 5 years on probation, during which his practice would be monitored or reviewed. Platt did enroll, but the PACE faculty concluded that he was deficient in clinical reasoning, judgment, and performance and that even a 3- to 6-month intensive study would not bring him to the level of a competent physician who is safe to practice medicine. In April 2011, the board filed an amended complaint that included concerns about additional patients plus reports of two undercover investigators who posed as patients . A few weeks later, Plat voluntarily surrendered his license [10}.
- In 2009, the Texas Medical Board reprimanded Steven Mays, D.O. and ordered him to pay an administrative penalty of $10,000. He is also required to hire a practice monitor for one year, pass an examination in jurisprudence, and take continuing education courses in ethics, recordkeeping, prescribing, and endocrinology (including thyroid disorders). The trouble arose during a 2-year period when he was medical director of a clinic that offered weight loss treatment, thyroid replacement therapy, and bio-identical hormone and/or human growth hormone (HGH) replacement therapy. The agreed order (shown below) states that during this period he (a) was responsible for false advertising statements, (b) failed to meet the standard of care for assessment, diagnosis, treatment, and documentation for twelve patients, and (c) delegated responsibility to unqualified and unlicensed staff members who administered inappropriate tests and treatments .
- In 2009, Robert M. Battle, M.D. signed a mediated agreed order under which he was disciplined by the Texas board. The complaint had accused him of using "junk science" to support his diagnosis and treatment of a woman who had consulted him for anxiety, depression, and hot flashes. The inappropriate methods included bio-identical hormone therapy .
- In 2011, the Texas board Board and Gary Steven Donovitz, M.D., entered into an Agreed Order requiring Donovitz to complete continuing education courses in medical recordkeeping sand risk management and pay an administrative penalty of $1,000. The Board found Donovitz failed to maintain adequate medical records and advertised in such a way as to create unjustified expectations about a treatment or procedure. The board charged that he had (a) advertised that bio-identical hormone delivery system r was superior to transdermal hormone administration and reduced the rick of breast cancer, (b) treated a woman for testosterone deficient without laboratory evidence that the patient had a hormone deficiency .
The Bottom Line
The bottom line for consumers is very simple: Steer clear of anyone who prescribes "bioidentical" hormones or recommends saliva testing as the basis for evaluating hormone status.
- Bouts BA. The misuse of compounding by pharmacists. Quackwatch, Oct 14, 2002.
- FDA Center for Drug Evaluation and Research. Report: Limited FDA survey of compounded drug products. FCER Web site, Jan 28, 2003.
- Writing Group for the Women's Health Initiative Investigators. Risks and benefits of estrogen plus progestin in healthy postmenopausal women: Principal results from the Women's Health Initiative randomized controlled trial. JAMA 288:321â€“333, 2002.
- No scientific evidence supporting effectiveness or safety of compounded bioidentical hormone therapy. ACOG news release, Oct 31, 2005.
- ACOG Committee on Gynecologic Practice. Compounded bioidentical hormones. Obstetrics and Gynecology 106:1139-1140, 2005.
- Coverage policy changing for hormone, thyroid compounds. Aetna Office Link Updates 4(3):6, 2007
- [../reg/bioidentical.shtml FDA takes action against compounded menopause hormone therapy drugs]. FDA News release, Jan 9, 2008.
- [bioidentical_myths.shtml Bio-Identicals: Sorting Myths from Facts]. FDA consumer update, Jan 9, 2008.
- Barrett S. Disciplinary action against Michael E. Platt, M.D. Casewatch Web site, Oct 14, 2011.
- First amended petition and application to revoke probation . In the matter of the accusation and petition to revoke probation against Robert E. Platt, M.D. Filed April 18, 2011.
- Stipulation of voluntary surrender of license and disciplinary order. In the matter of the accusation and petition to revoke probation against Robert E. Platt, M.D. Filed May 5, 2011.
- Agreed order. In the matter of the license of Steven Mays, D.O. Before the Texas Medical Board, Aug 3, 2009.
- Complaint. In the matter of the license of Robert M. Battle, M.D. Before the Texas Medical Board, Jan 21, 2009.
- Agreed order. In the matter of the license of Gary Donovitz, M.D. Before the Texas Medical Board, Aug 26, 2011.