Bioidentical Hormones for Menopausal Therapy

Cynthia K Sites

Women's Health. 2008;4(2):163-171.

Types & Formulations of Bioidentical Estrogens

Compounded estrogen formulations for menopause contain estradiol, estrone and/or estriol.^[5,16,17] Currently, products such as Biest (biestrogen) containing 20% estradiol and 80% estriol, and Triest (triestrogen) containing 10% estradiol, 10% estrone and 80% estriol, expressed on a mg per mg basis, are prepared by compounding pharmacies for patients. It appears that Biest, available as capsules, sublingual compounds and transdermal cream or gel is clearly the most common preparation used.^[5,16,17] It is important to understand that although the percentage of estrogens defines the compound, pharmacies vary in the total mg dose of Biest they dispense. For example, one pharmacy may prepare a 1.25 mg preparation of Biest (which contains 0.25 mg estradiol with 1.0 mg estriol), while another prepares a 2.5 mg preparation of Biest (which contains 0.5 mg estradiol and 2.0 mg estriol).^[16] Thus, the total weight in mg of the preparation dispensed by a particular pharmacy is the most important factor in understanding the doses of estrogens used by patients. In an informal telephone survey of four local US compounding pharmacies and three large national compounding pharmacies in Colorado, Texas and Wisconsin, identified through the internet, the 2.5 mg dose of Biest is the common transdermal estrogen preparation recognized by all seven compounding pharmacies at the time of writing.

The potency of estriol ranges from 1/10 to 1/100 that of estradiol, with 1/80 most often cited,^[18] leading one to believe that any benefits of Biest for menopausal symptoms may be more related to the estradiol component rather than to the estriol component. Estriol as the sole estrogen in any preparation is not commercially available in the USA, but is available commercially in Europe, mostly as vaginal preparations. Some practitioners in Europe may not consider vaginal estriol to be a bioidentical hormone, despite the fact that it has a structure like endogenous estriol. In a randomized, placebo-controlled trial of 88 women, 2 mg estriol alone as a daily dose vaginally in the absence of estradiol was reported to have beneficial effects on urogenital outcomes, including vaginal dryness, dysparunia, urogenital atrophy and in urodynamic testing variables, including maximum urethral pressure, mean maximum urethral closure and abdominal pressure transmission ratio.^[19] This study of estriol demonstrates that it may have beneficial effects as a single hormone for urogenital symptoms.

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Cite this: Bioidentical Hormones for Menopausal Therapy - Medscape - Mar 01, 2008.

Pharmacokinetics of US FDA-approved Transdermal Estradiol Gels
Pharmacokinetic parameter	Elestrin 0.87 g (estradiol 0.52 mg/day) mean	Estrogel 1.25 g (estradiol 0.75 mg/day) mean	Divigel 0.5 g (estradiol 0.5 mg/day) mean
AUC_0-24 (pg/h/ml)	335.2	679	504
C_max (pg/ml)	21.6	46.4	28.4
C_avg (pg/ml)	15.4	28.3	21
C_min (pg/ml)	9.4	Unknown	Unknown
T_max (h), range	18 (1-20)	Unknown	10 (0-72)
T_1/2 (h)	Unknown	36.5	Unknown
E2:E1 ratio	0.53	0.68	0.65

E2/E1: Estradiol/estrone.

Sidebar: Executive Summary

Relevance of Compounded Hormones in Medicine

Compounding is defined as the mixing of a drug or device consistent with a licensed practitioner"s prescription; it is distinguished from manufacturing because it is a compound made for one individual patient"s needs.
Compounded prescriptions may account for 1% of all prescriptions per year in the USA.
Compounded hormones have been defined as metabolites, therefore they are regulated as supplements rather than drugs. Because of this definition, they have not been subject to reports of efficacy and adverse events compared with US FDA-approved hormones.
The Endocrine Society, FDA and other organizations are now demanding greater scrutiny of compounded hormones, along with inclusion of package inserts stating similar risks as noncompounded hormones.

Foundation & Claims of Bioidentical Hormones

Bioidentical hormones are typically made from soy or yams.
Self-help books and the internet promote that bioidentical hormones allow menopausal women to get the exact dose they require.
Compounded bioidentical hormones in the USA typically contain a large quantity of estriol, a weak estrogen. The rationale for this is that rats pretreated with estriol developed less breast cancer; yet humans had more breast cancer when treated with estriol.

Patient Beliefs About Bioidentical Hormones for Menopause

Patients may believe that bioidentical hormones are safer because they are natural, without the risks of FDA-approved hormones.
Studies are needed since publication of the Women"s Health Initiative to determine current thinking about bioidentical hormones.

Types & Formulations of Bioidentical Estrogens

Biest, containing 80% estriol with 20% estradiol by weight, is one of the most popular bioidentical estrogen compounds in the USA.
Although estradiol in this compound is more potent and believed to offer the most benefit for menopausal symptoms, 2 mg of estriol alone administered vaginally has beneficial effects on urogenital symptoms in menopause.

Estrogen Receptor Subtypes & Bioidentical Estrogens

Estrogen-receptor subtypes may influence how various estrogens act in different tissues.
Estradiol binds equally to estrogen receptors α and ß; and with slightly greater affinity to estrogen receptor ß compared with α.

Evidence for Relief of Hot Flashes & Vaginal Dryness with Very Low-dose Estradiol

Skin patches (reservoir or imbedded types) deliver constant, low doses of estradiol that reduce hot flashes and vaginal dryness, although some women have skin sensitivity to the adhesive of the patch.
New transdermal gels that deliver estradiol are applied daily and reduce menopause symptoms with minimal skin reaction.
Low-dose transdermal patches and gels delivering estradiol may promote endometrial proliferation, so a progestin or progesterone should be considered if the patient has her uterus, to prevent endometrial hyperplasia.

Use of Bioidentical Progesterone

Prometrium® (oral estrogen, available in the USA) is effective in reducing endometrial hyperplasia when estrogens are also prescribed.
Prometrium improves sleep quality in menopause.
Compounded progesterone in transdermal creams does not reliably prevent endometrial hyperplasia.

Role of Testosterone in Menopausal Therapy

Oral testosterone must be methylated as part of hormone therapy for women with reduced sexual desire, and may have negative metabolic effects compared with transdermal bioidentical testosterone.
There are currently no FDA-approved testosterone patches for women in the USA, so patients use compounded products or lower doses of FDA-approved testosterone gels approved for men.
Long-term studies are needed to examine the safety of transdermal testosterone alone or in combination with estrogens.

Addition of DHEA to Menopausal Therapy

DHEA levels decrease with age in women and men; and although DHEA may be added to menopausal therapy to improve libido and the sense of well being, the data supporting this practice is inconsistent, and safety data are lacking.

Relevance of Salivary Hormone Measurements for Menopause Symptoms

Salivary hormone measurements are extremely variable, with no standards to indicate how hormone doses should be adjusted in menopausal women based on an improvement or lack of improvement in menopause symptoms.

Future Perspective

Compounded hormones are available for menopause symptoms and could be considered if the exact doses of hormones are not commercially available for a patient. A wide variety of FDA-approved bioidentical hormones are currently available.
New transdermal biodentical estradiol gels have been approved by the FDA for menopausal symptoms. In the future, new gels delivering small amounts of other hormones for menopause may reduce the need for compounded hormones for menopause symptoms without inducing endometrial hyperplasia.

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