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Bioidentical hormone therapy: Clarifying the misconceptions

Cleveland Clinic Journal of Medicine. 2011 December;78(12):829-836 | 10.3949/ccjm.78a.10114
December 1, 2011|Cleveland Clinic Journal of Medicine
Lynn Pattimakiel, MD, NCMP;Holly L. Thacker, MD, FACP, NCMP, CCD
Author and Disclosure Information

Lynn Pattimakiel, MD, NCMP
Department of Internal Medicine, Center for Specialized Women’s Health, Cleveland Clinic

Holly L. Thacker, MD, FACP, NCMP, CCD
Director, Center for Specialized Women’s Health, Department of Obstetrics and Gynecology, Cleveland Clinic

Address: Lynn Pattimakiel, MD, Department of Internal Medicine, G10, Cleveland Clinic, 9500 Euclid Avenue, Cleveland, OH 44195; e-mail pattiml@ccf.org

Dr. Thacker has disclosed that she has taught and spoken for Bayer and Novogyne Pharmaceuticals, makers of menopausal hormone therapies.

ABSTRACTMany women are turning to bioidentical hormone therapy on the basis of misconceptions and unfounded claims, eg, that this therapy can reverse the aging process and that it is more natural and safe than approved hormone therapy. The aim of this article is to clarify some of the misconceptions.

KEY POINTS

  • Hormone therapy is indicated for relief of menopausal symptoms; claims of reversal of the aging process are unsubstantiated.
  • Products that are custom-compounded are not regulated by the US Food and Drug Administration and therefore carry no assurance of purity, safety, or efficacy.
  • Transdermal progesterone creams do not achieve high enough serum levels to protect the endometrium.
  • Hormone therapy is titrated on the basis of symptom response. Measuring hormone levels in saliva is not called for and is probably not reliable.

WHAT IS CUSTOMIZED COMPOUNDED HORMONAL THERAPY?

There is often confusion between the terms “bioidentical hormones” and “customized compounded therapy,” which are often used interchangeably. Compounded therapy combines ratios of bioidentical hormones into a particular recipe or mixture. Customized compounding can be done by local compounding pharmacies.2

These customized compounds are often promoted as more “natural” and “individualized” therapy for postmenopausal women. These formulations, in fact, may have ingredients similar to those in FDA-approved products, but they are not regulated for safety, efficacy, and dosing consistency. There is no proof that compounded hormones have fewer side effects or are more effective than FDA-approved hormone preparations (Table 2).12

Compounded bioidentical estrogen products

There are several commonly marketed compounded products.

Tri-estrogen (tri-est) is a compounded hormone preparation made up of a mixture of 80% estriol, 10% estrone, and 10% estradiol.12

Bi-estrogen (bi-est) contains estriol and estradiol in a ratio of 8:1 or 9:1.

Although both tri-est and bi-est are largely composed of estriol, given the low potency of estriol, the effects of these products may be solely mediated by their major bioactive component, estradiol.10,12 No large prospective, well-controlled clinical trial has investigated the compounded ratios of these mixtures of estrogens.10

Tri-est and bi-est are frequently promoted as posing less risk of breast or endometrial cancer than FDA-approved agents, although there is no research to back up this claim.12 In fact, estriol may have a stimulatory effect on the breast and endometrium.9

In addition to these “standard” compounded preparations, women can receive more customized compounds.

Valid uses for customized compounded formulations

Some clinical providers use customized compounded formulations when prescribing hormone therapy to women who have allergies to certain ingredients, such as peanut oil (found in the FDA-regulated oral product Prometrium). Customized compounded formulations have also been used when prescribing hormones currently not FDA-approved for women, such as testosterone and DHEA.12 Before oral micronized progesterone was marketed in the United States as Prometrium, it was frequently prescribed as a compounded hormone.

HORMONE THERAPY COMES IN VARIOUS FORMS

Both FDA-regulated hormone therapy and unregulated compounded hormone therapy come in various doses and dosage forms administered by different routes, allowing for individualization for each woman’s specific characteristics.

Estrogens: Oral, transdermal, others

Estrogen therapy can be given orally, transvaginally (as creams, tablets, and rings), transdermally (as patches, gels, and creams), subcutaneously in pellets, intranasally (in Europe), and by injection.11

Most oral contraceptives contain the synthetic estrogen ethinyl estradiol. Ethinyl estradiol is more potent than human estrogens,11 specifically in increasing the production of hepatic proteins (sex-hormone-binding globulin, renin substrate, corticosteroid-binding globulin, and thyroid-binding globulin).11

Bioidentical estradiol, taken orally in tablet form, is first processed through the liver and converted into estrone.12 This stimulates proteins such as C-reactive protein, activated protein C, and clotting factors, which may increase the risk of clotting.12 Estradiol given transdermally by patch or gel or vaginally bypasses the liver and enters the bloodstream as 17-beta estradiol, therefore avoiding stimulation of these proteins.12 Case-control data have shown an associated lower risk of deep venous thromboembolism with transdermal therapy.3

Subcutaneous pellet therapy is a less common, non-FDA-approved method of hormone therapy to relieve postmenopausal symptoms.10 In an outpatient procedure, the pellet is inserted into the subcutaneous fat of the abdomen.10 The crystalline pellet is biodegradable and contains a mixture of testosterone and 17-beta estradiol.10 It is important to remember that endometrial stimulation may be prolonged with this form of therapy and levels may be supraphysiologic.

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