Acog committee opinion, number 322, november 2005

This document reflects emergingclinical and scientific advances as ABSTRACT: Compounded bioidentical hormones are plant-derived hor- mones that are prepared, mixed, assembled, packaged, or labeled as a drug by a pharmacist and can be custom made for a patient according to a physi- cian’s specifications. Most compounded products have not undergone rigor- ous clinical testing for safety or efficacy, and issues regarding purity, potency, and quality are a concern. Compounded hormone products have thesame safety issues as those associated with hormone therapy agents that are Copyright November 2005 by the American College of approved by the U.S. Food and Drug Administration and may have addi- tional risks intrinsic to compounding. There is no scientific evidence to sup- port claims of increased efficacy or safety for individualized estrogen or stored in a retrieval system, ortransmitted, in any form or by any Compounded drugs are agents that are prepared, mixed, assembled, pack- aged, or labeled as a drug by a pharmacist. Unlike drugs that are approved by the U.S. Food and Drug Administration (FDA) to be manufactured and sold in standardized dosages, compounded medications often are custom made for a patient according to a physician’s specifications. One category of compounded products is referred to as “bioidentical hormones”; however, there is confusion over what this term implies. Bioidentical hormones are plant-derived hormones that are biochemically similar or identical to those The steroid hormones most commonly compounded include dehy- droepiandrosterone, pregnenolone, testosterone, progesterone, estrone, estradiol, and estriol (1). Bioidentical hormones made by a compounding pharmacist from a health care provider’s prescription are available in various The American College of
routes of administration, including oral, sublingual, and percutaneous or as Obstetricians and Gynecologists
implants, injectables, and suppositories. Examples of compounded hor- mones include Biest and Triest preparations. The name Biest (biestrogen) commonly refers to an estrogen preparation based on a ratio of 20% estra- diol and 80% estriol on a milligram-per-milligram basis. A similar prepara- tion, Triest (triestrogen), usually contains a ratio of 10% estradiol, 10% estrone, and 80% estriol. It is important to note that these ratios are not based on each agent’s estrogenic potency but on the milligram quantity of the Gynecologists. Obstet Gynecol 2005;106:1139–40.
different agents added together (2). Purchases of compounded hormones arenot typically reimbursed by insurance companies.
Most compounded products have not undergone Health Initiative. However, because compounded any rigorous clinical testing for either safety or effica- products are not approved by the FDA and have no cy, and issues of quality assurance regarding the puri- official labeling (ie, a package insert), they are exempt ty, potency, and quality of compounded products are from including the contraindications and warnings a concern. From June 2001 to December 2001, the required by the FDA in class labeling for hormone FDA analyzed 29 product samples from 12 com- therapy. Given the lack of well-designed and well- pounding pharmacies (3). The types of products var- conducted clinical trials of these alternative therapies, ied, but examples include oral, injectable, pellet compounded hormone products should be considered implants, and inhalation compounds such as hormon- to have the same safety issues as those associated with al products, steroids, and antibiotics. Although none hormone therapy agents that are approved by the of the compounded products failed identity testing, 10 FDA. They also may have additional risks intrinsic to of the 29 products (34%) failed one or more standard compounding. There is no scientific evidence to sup- quality tests performed. Nine of the 10 failing prod- port claims of increased efficacy or safety for individ- ucts failed assay or potency tests, with all products ualized estrogen or progesterone regimens.
failing potency testing demonstrating subpotentresults; that is, the products analyzed contained less of References
the active ingredient than expected. In comparisonwith these results, the analytical testing failure rate for 1. Drisko JA. Natural isomolecular hormone replacement: an evidence-based medicine approach. Int J Pharmaceut drug therapies approved by the FDA is less than 2%.
Although many advocates and compounders of 2. Boothby LA, Doering PL, Kipersztok S. Bioidentical hor- bioidentical hormones recommend the use of sali- mone therapy: a review. Menopause 2004;11:356–67.
vary hormone level testing as a means of offering 3. Food and Drug Administration, Center for Drug Evaluation individualized therapy, hormone therapy does not and Research. Report: limited FDA survey of com- belong to a class of drugs with an indication for indi- pounded drug products. Available at: http://www.fda.gov/cder/pharmcomp/survey.htm. Retrieved June 15, 2005.
vidualized dosing. Individualized dosing is indi- 4. Marder MZ, Joshi U, Mandel ID. Estrogen concentration cated when a narrow therapeutic window exists for a in human parotid and submaxillary saliva. J Dent Res drug or a drug class. Such drugs include those with nonlinear pharmacokinetics, those that are renally 5. Hardiman P, Thomas M, Osgood V, Vlassopoulou V, eliminated as the active drug, some that are not Ginsburg J. Are estrogen assays essential for monitoring metabolized during first pass through the liver, gonadotropin stimulant therapy? Gynecol Endocrinol and those with clearly defined therapeutic and toxic 6. Klee GG, Heser DW. Techniques to measure testosterone concentrations based on large population pharmaco- in the elderly. Mayo Clin Proc 2000;75 Suppl:S19–25.
kinetic studies of serum concentrations. Steroid hor- 7. Lewis JG, McGill H, Patton VM, Elder PA. Caution on the mones such as estrogen and progesterone do not use of saliva measurements to monitor absorption of prog- meet these criteria and, thus, do not require individ- esterone form transdermal creams in postmenopausal There is no evidence that hormonal levels in sali- 8. Meulenberg PM, Ross HA, Swinkels LM, Benraad TJ.
The effect of oral contraceptives on plasma-free and sali- va are biologically meaningful. Whereas saliva is an vary cortisol and cortisone. Clin Chim Acta 1987;165: ultrafiltrate of the blood and in theory should be amenable to testing for “free” (unbound) concentra- 9. Wren BG, McFarland K, Edwards L, O’Shea P, Sufi S, tions of hormones, this has not proved to be the case Gross B, et al. Effect of sequential transdermal proges- (4). The problem with salivary testing and monitoring terone cream on endometrium, bleeding pattern, and plas- of free hormone levels is twofold: 1) there is no bio- ma progesterone and salivary progesterone levels in logically meaningful relationship between salivary postmenopausal women. Climacteric 2000;3:155–60.
10. Bolaji II, Tallon DF, O’Dwyer E, Fottrell PF. Assessment sex steroidal hormone concentrations and free serum of bioavailability of oral micronized progesterone using a hormone concentrations and 2) there is large within- salivary progesterone enzymeimmunoassay. Gynecol patient variability in salivary hormone concentrations (5–9). Salivary hormone levels vary depending on 11. Raff H, Raff JL, Duthie EH, Wilson CR, Sasse EA, diet, time of day of testing, the specific hormone Rudman I, et al. Elevated salivary cortisol in the evening being tested, and other variables (6, 7, 10–12).
in healthy elderly men and women: correlation with bonemineral density. J Gerentol A Biol Sci Med Sci 1999; Currently, the FDA requires manufacturers of products approved by the FDA that contain estrogen 12. Zava DT, Dollbaum CM, Blen M. Estrogen and progestin and progestogen to use class labeling (the black box bioactivity of foods, herbs, and spices. Proc Soc Exp Biol warning) reflective of the findings of the Women’s

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