Bioidentical hormone replacement therapy

From Wikipedia, the free encyclopedia

Bioidentical hormone replacement therapy (BHRT, also known as bioidentical hormone therapy^[1]) refers to the treatment of symptoms of menopause using hormones that are molecularly identical to endogenous hormones. Though "bioidentical" has been used in hormone packaging inserts to refer to molecularly identical hormones, the term bioidentical hormone replacement therapy is most often used to describe treatments that involve custom compounded hormone mixtures^[1] and adjusting the dosage of medication based on blood and saliva testing to ensure a specific hormone level in the body is reached.^[2][3][4] In contrast, conventional hormone replacement therapy adjusts dosing based on symtpom relief rather than attempting to reach a specific level of hormones in the body. Though advocates for compounded BHRT claim it offers health benefits beyond just symptom relief and lacks the risks of conventional hormone replacement therapy, there is no evidence to support these claims and bioidentical hormoens are expected to have the same risks and benefits as conventional hormones. In addition, since compounded products are not subject to FDA testing and quality control measures, their potency, purity and safety have been questioned. The Endocrine Society, American College of Obstetricians and Gynecologists, United States Food and Drug Administration, and Mayo Clinic have all released position statements stating that there is no research demonstrating bioidentical hormones, compounding or salivary testing offer superior results compared to conventional HRT. The term bioidentical has also been called a pseudoscientific neologism,^[5] and a clever marketing concept that lacks any scientific support.^[6]

Interest in bioidentical hormones increased when the Women's Health Initiative study examining conventional hormone replacement therapy reported previously unappreciated risks; the resulting negative publicity left many women seeking alternative treatments that were percieved as safer. Compounded BHRT has been endorsed and popularized by Suzanne Somers.^[7]

Contents 1 Terminology 2 Uses 3 Administration 4 Criticisms 4.1 Lack of evidence for claims 4.2 Safety 4.3 "Natural" claims 4.4 Salivary testing and compounding 5 Wiley Protocol 6 Regulatory status in the United States 7 Footnotes 8 External links

[edit] Terminology

"Bioidentical" describes hormones that exactly duplicate the molecular structure of those created by the human body^[8] and has been used in FDA packaging inserts since before 1998. Manufactured on an indiustrial scale, the hormones are available as commercial products available in standardized doses. Compounding pharmacies use bulk quantities to prepare individualized doses, prescriptions and delivery systems based on prescriptions. The lack of distinction between bioidentical hormones and BHRT has added to the confusion and lack of understanding.^[9]

Patients requesting "bioidentical" hormones may not be clear on what they are asking for. What is sought may be individual or tailored hormone replacements, and the marketing and advertising of BHRT has resulted in a significant increase in its popularity. Compounded BHRT has been promoted as a treatment that could improve the symptoms of menopause without the risks of conventional hormone replacement therapy.^{[6][10][11][12][13][14]}

There are a variety of FDA-approved bioidentical hormones used to treat symptoms of menopause: ^[15]

Hormone class	Type	Brand names	Preparations	Notes
Estrogens
	micronized 17 beta-estradiol
		Estrace and others	Pill and vaginal cream	Vaginal cream for vaginal symptoms only; sourced from plants; estradiol is bioidentical until ingested and converted in the liver to estrone
		Alora, Climara, Esclim, Estraderm, Vivelle and others	Patch	Sourced from plants
		Estrogel	Transdermal gel	Sourced from plants
		Estrasorb	Topical cream	Sourced from plants
		Estring	Vaginal ring	For vaginal symptoms only; sourced from plants
	Estradiol acetate	Femring	Vaginal ring
	Estradiol hemihydrate	Vagifem	Vaginal tablet	For vaginal symptoms only
Micronized progesterone
	Micronized progesterone USP	Prometrium	Pill
		Prochieve 4%	Vaginal gel
Combined preparations
	17 beta-estradiol and norethindrone acetate	Combipatch	Patch	Estradiol is bioidentical but the progestin is not
	17 beta-estradiol and norgestimate	Prefest	Pill
	17 beta-estradiol and levonorgestrel	Climara Pro	Patch

[edit] Uses

BHRT is used like conventional hormone replacement therapy to reduce the symptoms and side effects of menopause. In 2002, the Women's Health Initiative study (WHI) revealed an increase in breast cancer, heart attacks and stroke in older women given conventional hormone replacement therapy (HRT),^[16] which led to a decline in prescriptions for HRT.^[17] Pfizer has been ordered to pay over $100 million in punitive damages to just two women who used their hormone replacement thereapy: more than 10,00 additional product liability lawsuits have been filed throughout the US related to conventional hormone therapy.^[18] BHRT has since been strongly promoted as a natural alternative with fewer risks than conventional HRT, though there is no evidence to support this claim. Estimates from sales of bulk hormones for compounding suggest that more than 1 million women may be using compounded BHRT.^[6]

Bioidentical hormones are often compounded to individualize the dose and delivery vehicle for each patient.^[19] While non-bioidentical hormones are not likely to be tracked in the blood because standard testing does not measure their byproducts, bioidentical hormones can be tracked with conventional blood tests, which proponents argue is an advantage. Skeptics of BHRT argue that it is uncertain if there is an ideal blood level of hormones, and that symptom control, not a specific blood level, is the primary goal of treatment.^[15]

[edit] Administration

Hormones can be administered in a variety of ways, including skin and vaginal creams, pills, topical gels, vaginal rings and tablets, and transdermal patches. Though all preparations are molecularly identical before their use, estrogens administered orally are modified by the liver before entering the blood, while those entering through the skin are not. Creams and gels applied to the skin also enter the blood directly and unmodified, but it is not clear how much is actually absorbed.^[15]

[edit] Criticisms

Bioidentical hormone replacement therapy has been criticized in many peer-reviewed sources for making unsubstantiated claims about being effective against a variety of health conditions, for lacking evidence of safety of the compounds, for claiming to be more "natural" than conventional HRT and for the frequently-associated practices of compounding and saliva testing.

Advocates for BHRT have claimed that commonly compounded BHRT preparations are not commercially available, which is not true. Customized compounding does not actually provide customized results since it is aimed at producing a single hormone profile, which has not been demonstrated to be better than conventional hormone replacement therapy and does not consider rate at which individuals will differ in the activity, metabolism and excretion of the hormones.^[8]

[edit] Lack of evidence for claims

There is little peer reviewed evidence for or against BHRT and a lack of consensus regarding its appropriateness, effectiveness and adverse effects. Some literature reviews suggest benefits and advantages in the use of BHRT over conventional counterparts^[20][21] while others state that there is still insufficient evidence to support the claims made about BHRT with a lack of randomized controlled trials needed to form firm conclusions.^{[3][8][22][5]} The United States Food and Drug Association warned that claims about compounded BHRT products are unsupported by medical evidence, unlike claims made by manufacturers of FDA-approved products.^[12] BHRT has been called a "marketing concept" with no scientific backing by the chief medical editor of Endocrine Today.^[15][6]

Bioidentical hormones and compounded BHRT are expected to have the same risks and benefits as conventional HRT, though the latter has the benefit of being heavily studied and regulated while BHRT has no scientific data to support claims of safety or efficacy.^{[5][15][3][13][23][8]} Despite this a variety of specific claims have been made for the effectiveness of bioidentical hormones and BHRT, with varying evidence to support or contradict them.^[3]

Claim	Evidence
Bioidentical hormones fit precisely in receptors while conventional HRT fit 'cockeyed'; this mismatch causes serious side effects	Synthetic progestins and endogenous progesterones have different binding affinities for different receptors depending on the model and animal used; the differing pharmacodynamics have not been associated with specific side effects
The body is unable to metabolize synthetic hormones	The biological half-life for synthetic hormones is between five minutes and two days
Lack of progesterone causes 'estrogen dominance', resulting in irregular or painful, heavy menses	Oral progesterone is no more effective than placebo at alleviating symptoms of premenstrual syndrome
Progesterone can counter-act stress, increases metabolism and decreases abdominal fat	There is no evidence to support weight loss due to progesterone
'Normal' levels of progesterone maintained with BHRT protects against breast cancer	The claim is based on a single study of infertile patients during child-bearing years; there is some evidence to support a link between hormonal treatment for infertility and a reduced risk of breast cancer, but these benefits are not expected to translate to women seeking relief from the symptoms of menopause
Progesterone therapy can prevent cardiovascular disease, atherosclerosis and raise good cholesterol	Hormone replacement therapy shows no benefits to cardiovascular risk factors or cardiovascular outcomes but is associated with increased risks of thromboses and embolisms
The side effects reported in the Women's Health Initiative study were due to the synthetic nature of the hormones used	Comparison of cardiovascular risks in postmenopausal women taking either different types of synthetic progestins versus various bioidentical hormones demonstrated no differences in outcomes; increased risks of thrombosis or embolism were associated with derivatives of norpregnane, a non-bioidentical progestin
Proponents claim bioidentical hormones provide noticeable benefits including protecting the eyes and skin from drying out, regulating the menstrual cycle, improving mental function, improving blood cholesterol and reduce hot flashes and night sweats associated with menopause as well as providing the recognized benefit of improved bone mineral density	No evidence exists comparing bioidentical with conventional hormone therapy, but BHRT has been associated with three cases of endometrial cancer; a Cochrane review of the risks and benefits of hormone replacement therapy concluded that hormone replacement therapy should not be used to treat manage any chronic disease
Estriol can decrease the risk of breast cancer	Estriol has been shown to cause breast cancer cell growth
Testosterone supplementation can protect the cardiovascular system and preserve mental function	Testosterone supplementation can improve the libido of postmenopausal women but reduces good cholesterol and shows no indication of protecting mental functioning
Pharmacists use their expertise regarding bioidentical hormones to meet the needs of their clients and improve health outcomes	Compounding is a legitemate practice but there is no evidence that clearly delineates the benefits and risks of BHRT

In 2006 actress Suzanne Somers released the book Ageless: The Naked Truth About Bioidentical Hormones, which endorsed the use of bioidentical hormones. Ageless mentioned one approach, the Wiley Protocol, specifically. The book was criticized by a group of doctors who, though generally supportive of the use of bioidentical hormones, state that more research is required and object to the Wiley Protocol in particular for its potential danger and its creator being unqualified.^[24]

[edit] Safety

Since bioidentical hormones are in fact used in many FDA-approved, standard hormone replacement therapy preparations, the relative advantages and differences between bioidentical and nonbioidentical hormones has been questioned. The primary differences between conventional and bioidentical hormone replacement therapy as popularly promoted mainly involves the testing of blood or saliva-bound estrogen levels and the use of individualized compounding rather than a standard dose, mixture and application of hormones. Saliva testing has not been shown to accurately measure blood-bound hormone levels, and neither approach has any research to support a relationship to symptom relief. The FDA recommends the lowest dose of hormone that effectively relieves symptoms and does not recommend custom-compounding, blood or saliva testing.

Many of the claims made about estriol, a hormone that is frequently compounded into bioidentical preparations, are based on research that is several decades old, using animal models rather than humans. These claims often misrepresent the implications and overstate the benefits of the studies, as well as overlooking the risks. The custom-compounded preparations promoted by BHRT advocates are not FDA-approved. The FDA has acknowledged that they are unaware of any adverse events connected to the use of estriol but ordered pharmacies to discontinue its use.^[25] Estriol's safety and effectiveness is unknown; the agency's Assistant Director of the Office of Compliance has stated that use of the hormone would require a permit for research and application for a new drug.^[26]

The Endocrine Society issued a position statement that bioidentical hormones carry essentially the same risks and benefits as non-bioidentical molecules.^[13] The American College of Obstetricians and Gynecologists in February 2009 re-iterated its position from November, 2005 that there was no proven benefits to safety or efficacy of compounded bioidentical hormones, nor is there any benefit to salivary testing of hormone levels or customized dosing of hormones.^[23] The Mayo Clinic states that there is no evidence that pharmacy-compounded BRHT is safer or more effective than conventional hormone replacement, and that some bioidentical hormones are already available in certain FDA-approved products.^[2] The U.S. Food and Drug Administration has warned several pharmacies about making unsubstantiated claims about the safety and effectiveness of compounded hormone products.^[12] The North American Menopause Association has stated that compounded bioidentical hormones have not been approved by the FDA, so there is no guarantee of purity, potency, efficacy or safety, and they may contain unknown contaminants,^[2] and the Australian Menopause Society has similarly stated that there is no evidence that bioidentical hormones administered using lozenges are any safer than conventional hormones.^[27][28]

BHRT has been linked to three cases of endometrial cancer in Australia, in which it was suggested that the ratio of estrogen to progesterone was inadequate, leading to endometrial hyperplasia. The authors of the case reports emphasized that unlike hormones used for conventional therapy, which are well-studied and the risks are understood, BHRT are unregulated and little is known about their production, quality control, pharmacokinetics, safety or efficacy.^[4] Bioidentical hormones found in the body can also cause proliferation of cells in the breast, leading to breast cancer.^[29]

[edit] "Natural" claims

Bioidentical hormones are frequently marketed as being "natural", or more natural than conventional HRT. The term "natural" has been used several different ways - two alternatives are that the source of the molecules is a plant, and that the molecules are identical to endogenous hormones.

Women who purchase compounded BHRT are more likely to associate the term "natural" with the former meaning.^[8] Most forms of compounded bioidentical hormones are produced through conversion of diosgenin (extracted from soy or yam plants) into progesterone which is used as a chemical precursor to create bioidentical and non-bioidentical hormones (the source and extraction processes used are the same for both types). The Harvard Women's Health Watch, published by Harvard Medical School, states that the "natural' part of the marketing of BHRT may be a euphemism for "unregulated" rather than safe.^[15]

However, the term "natural" can technically be used to indicate any product with an animal, plant, or mineral source, and as such applies to hormones that are not bioidentical, including Premarin (a non-bioidentical hormone extracted from the urine of pregnant horses), as well as to the molecules extracted from soybean and yam sources.^[15]

[edit] Salivary testing and compounding

BHRT is frequently associated with testing of saliva to establish a baseline hormone level, and the compounding of the substances by pharmacists. Neither of these processes are supported by research demonstrating either is beneficial.^{[3][30][31][2][4]}

[edit] Wiley Protocol

The Wiley Protocol is a controversial type of compounded BHRT endorsed by T. S. Wiley. It attempts to produce serum levels of estradiol and progesterone that are identical to those of a young woman at the various times throughout the menstrual cycle. In contrast, most bioidentical hormone practitioners instead seek to produce consistent estradiol and progesterone levels that are less than the average levels of a normal menstrual cycle. It has been shown that using serum levels to judge the effects of transdermal progesterone can be misleading.^[32] Others have sharply criticized the Wiley Protocol.^{[33][34][35][36][11]}

[edit] Regulatory status in the United States

Pharmacy-compounded BHRT is not regulated by the FDA, but is regulated by the boards of pharmacies for each state. Pharmacists can adjust the doses and delivery methods of compounded BHRT according to the doctor's prescription.^[37]

Compounding pharmacies were warned by the FDA to stop using the non-scientific term bioidentical in 2008, a warning supported by The Endocrine Society and the American Association of Clinical Endocrinologists.^[38] The FDA also sent letters to seven pharmacies warning them that the claims they were making about the safety and effectiveness of the compounded BHRT products they were selling were unsupported by medical evidence, and were considered false and misleading by the agency.^[12]

The FDA has also expressed concern that unfounded claims made about BHRT mislead women and health care professionals, but allows compounding of products when a licensed practitioner decides that an approved drug does not meet the patient's needs.^[39]

[edit] Footnotes

[edit] External links

• Senate Hearings on Bioidentical Hormones: Sound Science or Bad Medicine? by the United States Senate Special Committee on Aging