Bioidentical hormone replacement therapy

"Bioidentical" hormone replacement therapy (BHRT) is the use of supplemental doses of steroid hormones with a chemical structure identical to endogenous human hormones (hormones naturally produced in the human body). On 1/10/2008 the US Food and Drug Administration sent [http://www.fda.gov/bbs/topics/NEWS/2008/NEW01772.html letters] warning seven pharmacy operations that the claims they make about the safety and effectiveness of their so-called "bio-identical hormone replacement therapy," or "BHRT" products are unsupported by medical evidence, and are considered false and misleading by the agency. The FDA is concerned that unfounded claims like these mislead women and health care professionals. Generally BHRT is prescribed to relieve the symptoms of menopause, though more recent therapies promise anti-aging effects and possible deferral of the diseases of aging. BHRT differs from conventional hormone replacement therapy, which by definition uses animal or synthetic hormones whose structures are similar or identical to those produced in the human body.

"Bioidentical"

The term "bioidentical" denotes hormones that are chemically synthesized so as to be identical to the endogenous hormones of the human body: estradiol, estrone, estriol, progesterone, and testosterone. The disadvantage of this strategy (and the subsequent necessity of synthetic hormones in medical practice) is that none of the endogenous hormones have sufficient bioavailability when administered by mouth. Only 17-hydroxylated steroids remain intact following the hepatic first pass effect when administered orally. The molecular structures of bioidentical hormones are not patentable (because patents can only be obtained for novel items, not pre-existing natural substances) but such hormones have been commercially profitable in some cases, particularly when it has been possible to patent some other aspect of their production. For example, in the case of bioidentical estrogen, the matrix delivery system of the estradiol patch has been patented; in the case of bioidentical prometrium, the delivery system of prometrium has been patented. Trials to conclusively establish the apparent advantages of bioidentical hormones have not been conducted. It is doubtful such trials will ever be conducted unless through governments or the proponents of this therapy.

Non-bioidentical synthetic progesterone analogues (called progestins) have actions similar or identical to the hormone progesterone, but progestins are a suspected human carcinogen. [cite web | url = http://www.inchem.org/documents/iarc/suppl7/progestins.html | title = Progestins as carcinogens | author = International Agency for Research on Cancer | accessdate = 2007-08-27 | date= 1998-03-03] Estrogens in general have been declared to be known carcinogens. [cite journal | last = Stephenson | first = J | year = 2001 | title = Estrogen as a carcinogen | journal = JAMA | volume = 285 | doi = 10.1001/jama.285.3.284-c | pages = 284-c ] Such declarations overlook the theoretical potential of estriol to reduce breast cancer risk.cite journal | last = Bardin | first = A | coauthors = Boulle N, Lazennec G, Vignon F, Pujol P | year = 2004 | title =Loss of ERbeta expression as a common step in estrogen-dependent tumor progression | journal = Endocrine-Related Cancer | volume = 11 | pages = 537–51 | pmid = 15369453 | doi =10.1677/erc.1.00800 ] , but this potential has not been shown in epidemiologic or double-blind randomized controlled studies.Bioidentical hormone replacement therapy has received attention since the results of the WHI studies were published. The Women's Health Initiative was a large hormone replacement therapy clinical trial which showed cancer and clot-inducing properties of Premarin and progestins. When these results were publicised, the use of Premarin and Progestins plummeted (epidemiologic studies have shown that in spite of fewer women receiving HRT, cancer rates have not subsided)Fact|date=January 2008. The apparent advantages of bioidentical hormones have been promoted by, among others, the actress Suzanne Somers. [cite book |last=Somers | first = Suzanne |year=2004 |title=The sexy years: discover the hormone connection: the secret to fabulous sex, great health, and vitality for women and men |location=New York |publisher=Crown Publishers |id=ISBN 0-609-60721-9]

Potential advantages

* Emphasis on topical administration; avoids problems such as blood clotting that are caused by the hepatic metabolism of orally administered hormones [cite journal | last = Scarabin | first = PY | coauthors = Oger E, Plu-Bureau G | year = 2003 | title = Differential association of oral and transdermal oestrogen-replacement therapy with venous thromboembolism risk | journal = Lancet | volume = 362 | pages = 428–32 | pmid = 12927428 | doi = 10.1016/S0140-6736(03)14066-4 ]
* Progesterone may work differently in the body than medroxyprogesterone acetate [cite journal | last = Simoncini | first = T | coauthors = Mannella P, Fornari L, Caruso A, Willis MY, Garibaldi S, Baldacci C, Genazzani AR. | year = 2004 | title = Differential signal transduction of progesterone and medroxyprogesterone acetate in human endothelial cells | journal = Endocrinology | volume = 145 | issue = 12 | pages = 5745–56 | url = http://endo.endojournals.org/cgi/content/full/145/12/5745 | doi = 10.1210/en.2004-0510 | pmid = 15358673 ]
* Individualized compounded doses may be prescribed, rather than "one dose fits all" approach of conventional hormone replacement therapy [cite journal | last = Romero | first = M | year = 2002 | title = Bioidentical hormone replacement therapy. Customizing care for perimenopausal and menopausal women | journal = Advance for Nurse Practitioners | volume = 10 | issue = 11 | pages = 51–2 | pmid = 12478948] Conventional hormone replacement therapy is also available in a wide range of dosages and dosage forms.
* Theoretically, inclusion of estriol may be protective against hormone-induced cancer. Unlike estradiol, estriol binds preferentially to the second estrogen receptor (ERbeta). ERbeta may function as a tumor suppressor. Estriol is not approved for human use by the FDA, who considers the term "bio-identical" to be non-scientific. [{cite web |last=Peck |first=Peggy |title=FDA Cracks Down on Bio-Identical Hormones from Compounding Pharmacies |publisher=MedPageToday |url=http://www.medpagestoday.com/ProductAlert/Prescriptions/dh/7908 |format=web article |accessdate=2008-01-11}]

Patentable drugs are extensively tested. In the absence of similar testing, the potential benefits of BHRT remain unconfirmed. BHRT may present risks for breast cancer similar to those posed by conventional HRT. A pilot study conducted by the U.S. National Institutes of Health indicated that the risks of blood clotting and strokes that arise with Premarin and PremPro are lower with bioidentical esterified estrogens, in women with variations of their clotting systems which make them prone to clots. [cite journal | last = Smith | first = N. | coauthors = Heckbert, S.R., Lemaitre, R.N., Reiner, A.P., Lumley, T., Weiss N.S., Larson, E.B., Rosendaal, F.R. & Psaty, B.M. | title = Esterified estrogens and conjugated equine estrogens and the risk of venous thrombosis | journal = JAMA | year = 2004 | volume = 292 | pages = 1581–1587 | issue = 13 | pmid = 16973976 | accessdate = | doi = 10.1001/jama.292.13.1581] Oral conjugated equine estrogens (Premarin) were found to be associated with increased venous thrombotic risk. The study found that users of esterified estrogen had a lower venous thrombotic risk than those using conjugated estrogens.

Basics

Bioidentical hormone replacement therapy is used to help treat the symptoms of menopause, perimenopause, and post-menopause. Treatment with bioidentical hormones is theoretically based on creating a unique cocktail of hormones for the individual patient, based on hormone deficiencies identified via saliva samples,an approach that is "in direct contradiction to evidence-based guidelines which support tailoring hormonal therapy individually, according to symptoms". [Cirigliano, M. Bioidentical hormone therapy: A review of the evidence PMID 17627398] These are often referred to as "custom-compounded" hormone products. The doses are individualized, and the mixture of products may not be commercially available.Fact|date=January 2008 However, although some of the estrogen and/or progestogen components are FDA approved, the mixtures themselves are not, as they have not been studied to confirm that they are absorbed appropriately or provide predictable levels in blood and tissue. [cite web | url = http://www.menopause.org/expertadvice.htm#cchormones | title = Custom-compounded hormone products | accessdate = 2007-08-27 | author = North American Menopause Society] The entire concept has been criticised as a marketing scheme with no scientific basis. [cite web |last=Kalvaitis |first=Katie |title=Compounded hormone therapies: unproven, untested - and popular.(Endocrine Today 6(5) March 25, 2008) |url=http://www.endocrinetoday.com/view.aspx?rid=27231 |format=web reprint |accessdate=2008-03-25]

Bioidentical hormones, sometimes referred to as natural hormones, are those that are molecularly identical to the hormones that are produced in the body. Hormones and steroids are taken from plants and animals and altered to be identical in molecular structure, then put into a form that can be absorbed by the body: cream, oral, suppository or injections. The plants that the hormones are extracted from are soyFact|date=January 2008 and yams, while the animals are pigs or horses. The plant hormones are chemically altered to become molecularly identical to the ones humans produce, as plants do not produce estrone, estriol, estradiol, progesterone, or testosterone..

The FDA recognizes pharmacy compounding of BHRT products when the product conforms to a licensed practitioner’s decision that an FDA-approved drug does not meet the patient's needs, but the FDA is concerned that claims about BHRT products are false and misleading. [cite web|url=http://www.fda.gov/ola/2007/hormone041907.html|publisher=FDA|title=Statement of Steven K. Galson, M.D., M.P.H., Director, Center for Drug Evaluation and Research, U.S. Food and Drug Administration before Senate Special committee on Aging, "Bio-Identical Hormones: Sound Science or Bad Medicine"|date=April 19, 2007|accessdate=2007-12-01] Some bioidentical hormones are FDA approved. [cite web|url=http://www.health.harvard.edu/newsweek/What-are-bioidentical-hormones.htm|title=What are bioidentical hormones?|publisher=Harvard Health Publication, Harvard Medical School|month=August | year=2006|accessdate=2007-12-01] Others, such as Estriol, are not approved for human use by the FDA. [cite web |last=Peck |first=Peggy |title=FDA Cracks Down on Bio-Identical Hormones from Compounding Pharmacies |publisher=MedPageToday |url=http://www.medpagestoday.com/ProductAlert/Prescriptions/dh/7908 |format=Web article |accessdate=2008-01-10] . Compounding pharmacies were warned by the FDA to stop using the "non-scientific" term "bio-identical" in 2008, a warning supported by The Endocrine Society and the American Association of Clinical Endocrinologists. [cite web |last=Frieden |first=Joyce |title=FDA Cracks Down on Bioidentical Hormones |url=http://www.clinicalendocrinologynews.com/article/PIIS1558016408700440/fulltext |format=web reprint |accessdate=2008-03-05]

Individually-compounded mixtures have not been approved by the FDA, and by their very nature are not susceptible to FDA approval. Consequently, they are untested for purity, potency, efficacy or safety, and some may contain unknown contaminants. Estrogen and progesterone are available in FDA-approved forms - estradiol derived from soy or yam sources is found in some approved medications. [cite web | url = http://www.mayoclinic.com/health/bioidentical-hormones/AN01133 | title = Bioidentical hormones: Are they safer? | author = Mayo Clinic | date= 2007-08-21 | accessdate = 2007-08-27]

Wiley Protocol

The Wiley Protocol is a controversial type of compounded BHRT that is endorsed by T. S. Wiley and actress Suzanne Somers. Others have sharply criticized it. [cite news|url=http://www.nytimes.com/2006/10/15/fashion/15suzanne.html?pagewanted=all|title=A Battle Over ‘Juice of Youth’|publisher=New York Times|author=Ellin, Abby|date=October 15, 2006|accessdate=2007-12-01] [cite web|url=http://www.abcnews.go.com/print?id=2874767|publisher=ABC News, 20/20|title=Suzanne Somers: Super Saleswoman: Has Somers Found the Fountain of Youth?|author=Sherr, Lynn and Glenn Ruppel|date= February 16, 2007|accessdate=2007-12-01] [cite news|url=http://www.newsweek.com/id/44568|title=A Real Somers Storm: At war over Suzanne Somers's book on 'bioidenticals'|publisher=Newsweek|date=November 13, 2006|accessdate=2007-12-01] [cite web| url = http://www.womensvoicesforchange.org/2007/01/ask_dr_pat_bioi.html |author = Patricia Yarberry Allen | accessdate=2007-05-04 |date= 2007-01-12 |title = Ask Dr. Pat: Bioidentical Hormones]

References

* [http://www.inchem.org/documents/iarc/suppl7/progestins.html Progestin carcinogenicity] - 1987 meta-analysis regarding the carcinogenicity of medroxyprogesterone acetate
*cite journal|last =Francisco|first =L|authorlink =|coauthors =|title =Is bio-identical hormone therapy fact or fairy tale?|journal =The Nurse practitioner|volume=28|issue=7|pages=39–44|publisher =Vernon Publications|year=2003|url =http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?CMD=DisplayFiltered&DB=pubmed|doi=|pmid =12861094|accessdate =2007-02-20
* [http://www.fda.gov/bbs/topics/NEWS/2008/NEW01772.html FDA Takes Action Against Compund Menopause Hormone Therapy Drugs]

External links

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