Биологиялық үйлесімді гормоналды терапия: тиімділігі күмәнді емдеу әдісі

Type of hormone replacement therapy with unclear efficacy

Bioidentical hormone replacement therapy (BHRT), also known as bioidentical hormone therapy (BHT) or natural hormone therapy, is the use of hormones that are identical on a molecular level with endogenous hormones in hormone replacement therapy. It may also be combined with blood and saliva testing of hormone levels, and the use of pharmacy compounding to obtain hormones in an effort to reach a targeted level of hormones in the body. A number of claims by some proponents of BHT have not been confirmed through scientific testing. Specific hormones used in BHT include estrone, estradiol, progesterone, testosterone, dehydroepiandrosterone (DHEA), and estriol. Custom compounded BHT is a practice almost wholly restricted to the United States It was supplanted on the market when its manufacturer, Ayerst (later Wyeth Pharmaceuticals), began producing the more easily manufactured equine estrogens in 1941 under the brand name Premarin; by 1992, Premarin was the most widely prescribed drug in the United States. In the 1970s, research and reports indicating risks from synthetic conjugated estrogens began to appear. Investigations determined that the addition of a progestogen to estrogen treatment reduced the risks. As early as 1980, the British Medical Journal (now The BMJ) recommended oral bioidentical progesterone as an option when side effects from synthetic progestogens otherwise mandated discontinuing treatment. In May 1998 the FDA approved Prometrium, an oral bioidentical progesterone product produced by Solvay Pharmaceutical. Physicians John R. Lee and Jonathan Wright were pioneers in the field of BHT. and promoted custom compounded BHT, with the goal of achieving what he called a "natural hormone balance". He based this goal on the clinical testing of saliva to establish where "deficiencies" existed, though agencies such as the FDA and the American Congress of Obstetricians and Gynecologists state that blood and saliva testing is unreliable and biologically meaningless.). The FDA considers BHT as currently used by BHT advocates to be a marketing term, not a scientific term, and does not recognize its use. and it may also mean that the hormones are "natural"; throughout the 1990s plant derived, compounded hormones were referred to as "natural hormone therapy". BHT is often used to refer to a set of diagnostic, prescribing, preparation and marketing practices including compounding, saliva testing, and an emphasis on countering the effects of aging rather than relieving the symptoms of menopause. This compounded BHT package has been promoted by Somers, Oprah Winfrey, and other proponents as safer and more effective than CHRT, though there is no evidence to support these claims. Compounded BHT has been marketed on the internet by pharmacies that make unfounded claims for its safety and its effectiveness for a variety of conditions. The hormone estriol, produced during pregnancy, is frequently compounded into bioidentical preparations in the United States. While some think it to be a weaker estrogen, with a more limited period of effectiveness than estradiol, it has been demonstrated to be a stronger estrogen in certain ways. Estriol is not found in any FDA approved drug, and its safety and effectiveness as a hormone supplement is unknown.

Progesterone is used both orally and transdermally. Oral progesterone is micronized (ground) to increase availability and is approved by the FDA to treat endometrial hyperplasia when used in opposition to estrogen. It has also been approved to relieve menopausal symptoms, either alone or in combination with estrogen. It is more reliable in treating menopausal sleep disorders than synthetic progestins. Transdermal progesterone is often used as a component of compounded BHT but has not been clinically proven to prevent endometrial hyperplasia, as oral progesterone has. A 2012 practice advisory published by Canadian Family Physician concluded "there is no convincing evidence that bioidentical hormones are safer or more effective than synthetic HRT".

Testosterone supplementation can improve libido in postmenopausal women, but can also reduce levels of high density lipoproteins. A testosterone patch has been approved for use in the United Kingdom and European Union, but in Canada and the United States there is no long term safety data on it. Dosages used in BHT can be as high as ten times the oral dose provided by comparable HRT regimens; the hormones used are known to adversely impact biological markers of cardiovascular disease and may produce a substantially higher risk of heart attack or stroke. There are potentially serious adverse effects and important safety information that is required to be given with FDA approved HRT as package inserts; however, they are typically not given (or required) with compounded bioidentical preparations, which has caused consumers to falsely assume that bioidenticals are safer than FDA approved hormones or lack any adverse effects—one of the concerns expressed about the hormones. BHT has also been associated with endometrial cancer. A review of clinical trials studying bioidentical progesterone use found that it was ineffective in managing vasomotor symptoms of menopause, but had mild and self limiting side effects.

Hormones can be administered in a variety of ways, including percutaneous skin and vaginal creams, oral pills, topical gels, vaginal rings and tablets, and transdermal patches. Although all preparations of a given type of estrogen may be molecularly identical before their introduction into the human body, estrogens administered orally are modified by the liver before entering the bloodstream and most of it is converted to estrone; estrogen bypassing the digestive tract and liver via the skin is not converted to a new form before entering the bloodstream. Creams and gels applied to the skin also enter the blood directly and without modification but absorption of the gels, creams, and patches can vary from application to application, depending on the temperature and condition of the skin. Some advocates of compounding have also claimed that customized compounding provides customized results, but the claim is weak since compounding is aimed at producing a single hormone profile with absolute blood or saliva levels—which has not been demonstrated to be better than CHRT—and does not consider the rate at which individuals will differ in the activity, metabolism and excretion of the hormones. There have been no clinical trials directly comparing the effectiveness or efficacy of bioidentical versus non bioidentical compounds. BHT skeptics have also pointed out that there is no certainty regarding hormone levels in the body. The warnings are supported by the Society of Obstetricians and Gynaecologists of Canada. Although promoted as a way of customizing treatment, hormone therapy does not require customization; Literature reviews by private practitioners who sell bioidentical preparations suggest benefits and advantages of BHT over its conventional counterpart, but there is skepticism over claims made about BHT; there is no peer reviewed evidence that compounded bioidentical hormones are safer or more effective than FDA approved formulations or that they carry less risk. the chief medical editor of Endocrine Today called compounded BHT a "marketing concept" with no scientific backing, The following specific claims have been made for the efficacy of bioidentical hormones and compounded BHT, with varying evidence to support or contradict them: Somers' book may have increased awareness of the existence of BHT for a growing number of menopausal women, but also may have caused confusion by making unsubstantiated claims for BHT and referring to bioidentical hormones as non drug products with fewer risks. Michael Cirigliano and Judi Chervenak have stated in reviews of the literature on BHT that large scale, peer reviewed studies should be used to establish the safety, efficacy and beliefs about the use of bioidentical hormones. Endogeny: this meaning of natural implies that the hormones are molecularly identical to those found within the body. However, BHT is unnatural as it opposes the biologically determined declining levels of fertility hormones in aging women and medicalizes a stage of human life that is probably normal. Plant derived: Women who purchase compounded BHT are more likely to associate natural with the idea that the hormones are derived from plant sources. However, both bioidentical and non bioidentical hormones are sourced from the same plants, generally soy beans or yams.

Compounded BHT is used almost exclusively in the United States, and pharmacists are permitted to adjust dose and delivery method according to the prescription. However, the FDA does have authority over the compounded product. The FDA's concerns over the marketing and use of bioidentical hormones were supported by the American Association of Clinical Endocrinologists. In response to the FDA's actions, the International Academy of Compounding Pharmacists began a letter writing campaign to the FDA to reverse this action, citing Wyeth's attempt as a "self serving, and at times duplicitous, campaign to restrict patients' access to alternatives to its own products". In November 2006, the American Medical Association adopted a policy urging the FDA to survey compounded BHT products for purity and dosage; to maintain a registry and require mandatory adverse event reporting by manufacturers and compounding pharmacies related to bioidentical hormones; to mandate the inclusion of uniform patient information, including warnings and precautions regarding bioidentical products; and to prohibit the use of the term bioidentical hormones unless the agency has approved the preparation. On July 18, 2008, a US Appeals Court issued a ruling stating that new drug approval processes should not be applied to compounded drugs that complied with established guidelines, and also that provisions of the regulations relevant to the use of estriol were still in effect, preventing the FDA from taking action against pharmacies using estriol in compounded products.

The Wiley Protocol is a version of compounded BHT endorsed by T. S. Wiley. Its goal is to produce serum levels of estradiol and progesterone that are identical to those of a young woman with a normal menstrual cycle. It has been criticized for a variety of reasons.