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Point/counterpoint: the case for bioidentical hormones.

"Drug think" is responsible for much of the current confusion about hormone supplementation. The public and physicians think about pharmacology rather than physiology. From a physiology textbook one would never get the impression that hormones are anything other than chemical messengers necessary for health. (1) Without hormones, we cannot live. Why then do we speak as though hormones are dangerous substances? And why do we assume that the harmful effects of non-hormones will be like those of our endogenous hormones?

The answer is suggested by the fact that medical students and doctors in training have minimal exposure to physiology and massive exposure to pharmacology. Exogenous chemicals, different from the actual hormone they are meant to replace, are used interchangeably in clinical practice, the popular press, and in prestigious medical journals, producing much of the controversy that surrounds hormone replacement.

Conflicts of Interest

A few billion dollars can purchase a lot of advertising to sway the public, hire hundreds of lobbyists, and buy influence with the FDA. According to Public Citizen's Congress Watch: (2) The drug industry spent $262 million on political influence in the 1999-2000 election cycle: $177 million on lobbying, $65 million on issue ads, and $20 million on campaign contributions. This was more than any other industry spent over the same period for political persuasion.

Additionally, a lot of money is spent to manipulate physicians--through sponsoring speakers, organizing symposia, and even conducting studies published as scholarly articles in prestigious journals. All these efforts are designed to give the impression that "evidence-based medicine" means the use of patented exogenous compounds. Physicians are dazzled with innumerable studies asking which is better--drug A or drug B? We seem to forget that sponsored studies have been shown to be biased, (3) and we fall into the trap of assuming the answer must involve using patentable exogenous chemicals.

In this discussion we are choosing neither drug A or B. We suggest the best solution is to work with the body and restore normal physiology--without introducing foreign compounds to the body's delicate web of interactions.

What Is a Bioidentical Hormone?

Supplementation with a compound of the exact molecular structure as a hormone produced by the body is often termed "bioidentical hormone therapy." The term does not indicate the source of the hormone, but rather refers to the chemical structure. Synonyms include biologically identical, bioidentical, or human hormones. For the sake of brevity, we will focus primarily on three commonly used hormones: progesterone, estriol, and estradiol.

Physicians who prescribe these hormones typically emphasize the importance of hormones for health, the significance of using compounds identical to the natural ones, the need for progesterone, the essential balance between progesterone and estrogen, the use of compounding pharmacies, and the importance of avoiding exogenous chemicals in chronic conditions.

Hormones Are Critical for Health

With the increase in life expectancy we enjoy in the 21st century, we can expect to live a substantial part of our lives in a state of hormonal deficiency. The age-related decline in hormones produces many of the diseases associated with midlife. We have several options: 1) do nothing and experience the adverse effects of hormonal deficiency; 2) take exogenous chemicals (drugs) to ameliorate the effects resulting from this decline; or 3) treat the root causes of disease by replacing exactly what is missing. Hormonal decline is associated with a loss of function as well as an increase in diseases such as heart disease. Effects include bone loss, cognitive decline, loss of muscle mass, and thinning of skin.

There are many specific benefits of hormonal supplementation. Testosterone reduces neuronal secretion of Alzheimer's [beta]-amyloid Peptides (4) and improves cognitive function. (5,6) Progesterone increases bone mass. (7-9) Mood is improved with testosterone and progesterone. (10-13) Hormones also improve sleep; (14,15) decrease inflammation; (16) ameliorate chronic fatigue; (17) improve sexual function, mood, muscle strength, and body composition;' normalize blood clotting; (18) improve spatial recognition; (19) and induce apoptosis of breast cancer cells. (20)

The Importance of the Identical Structure

Molecular structure determines activity. The smallest of changes can completely change the physiologic effect. Consider testosterone and estrone, whose structures are shown side by side in Figure 1.

The mere existence of an effect similar to that produced by a hormone does not make a compound a hormone. If it did, plastic would be a hormone. For example, bisphenol A (BPA) is an estrogen receptor agonist. When BPA binds with the estrogen receptor, the complex so formed interacts with DNA and can lower sperm counts and increase the risk of developmental problems, cancer, schizophrenia, neurologic disorders, and weight gain. The interaction with the hormone receptor does not make BPA a hormone--but rather the hormone mimicry interferes with normal physiologic processes, causing a wide variety of adverse effects. (21-26)

[FIGURE 1 OMITTED]

Typically, hormones initiate a cellular response by combining with either specific intracellular or cell membrane receptor proteins. The interaction of hormone and receptor will frequently produce both cytoplasmic and nuclear effects. The former include protein phosphorylation, increasing the concentration of intracellular secondary messengers (i.e. cyclic AMP), or changing ion channel permeability. In the nucleus, the hormone-receptor complex when bound to DNA stimulates or represses the expression of certain genes, thereby affecting protein synthesis. (27,28)

Since the hormone and hormone receptor complex often work together to mediate the hormonal activity, a complex made up of a receptor and a foreign compound is likely to result in an abnormal physiologic response. (29-32) Much of the confusion about bioidentical hormone replacement flows from the failure to distinguish hormones from non-hormones. Obtaining FDA approval for a hormone-mimicking compound, such as medroxyprogesterone (Provera) or conjugated equine estrogens (Premarin), does not turn it into a hormone. Unfortunately, many scholarly articles have even referred to Provera as "progesterone," and to conjugated equine estrogens as "estrogen." 33)

Before the release of the results of the Woman's Health Initiative (WHI), the medical community expected PremPro to help mitigate the postmenopausal increase in cardiovascular disease. While the extract of pregnant mares urine known as Premarin does contain one human estrogen, estrone, it also contains numerous equine estrogens foreign to human physiology. The WHI study demonstrated that the combination of Premarin with Provera produces the following adverse effects: (34) a 26% increase in risk of invasive breast cancer; a 29% increase in risk of myocardial infarction or death from CHD; a 41 % increase in risk of stroke; and a 200% increase in risk of thromboembolism.

The Importance and Safety of Progesterone Supplementation

Many of the adverse effects in the WHI apparently result from the failure to use the human hormone progesterone. We should not expect the exogenous chemical medroxyprogesterone to necessarily have the same physiologic effect. Physicians who prescribe bioidentical hormones emphasize the importance of balancing estrogens with progesterone, rather than progestins. There are critically important differences between the two.

Progesterone is a pregnancy class B drug. It is used in assisted reproductive technology as Crinone (35-38) and may be useful for pre-term labor. (39-43) Medroxyprogesterone is a pregnancy class X drug--a compound known to cause birth defects, and never to be used in pregnancy. Progesterone and physiologic levels of estrogens down-regulate inflammation. Medroxyprogesterone prevents the cardioprotective and anti-inflammatory effects of estradiol. (44)

In contrast to medroxyprogesterone, several lines of evidence suggest that progesterone reduces breast cancer risk. It is known to have an anti-proliferative effect. (45-47) A low endogenous progesterone level has been correlated with a five-fold increase in premenopausal breast cancer risk in women experiencing infertility when compared with women with normal hormone levels. (48) Contrariwise, a higher progesterone level in premenopausal women correlates with lower risk of breast cancer. Comparing the highest with the lowest tertile for progesterone in women with regular menses, the adjusted RR for breast cancer was 0.12 (95% CI, 0.03-0.52, P for trend= .005). (49)

A potential mechanism for the protective effect is suggested by an in vitro study that evaluated the effect of progesterone on the growth of T47-D breast cancer cells. It demonstrated increased apoptosis as mediated by regulation of the controlling genes. (50)

A cohort study involving 1,150 French women who received topical progesterone cream for mastalgia due to benign breast disease showed no increase in cancer (RR=0.8). Moreover, researchers noted a decrease in breast cancer risk among women using progesterone cream plus an oral progestogen (RR=0.5), compared with women using oral progestogens alone. (51)

Two recent studies point to a difference in breast cancer risk when comparing synthetic progestins to bioidentical progesterone for hormone replacement therapy (HRT). A French cohort study involving 3,175 postmenopausal women predominantly using natural HRT (83% using transdermal estradiol and progesterone and non-medroxyprogesterone progestins) found no increased risk. (52) The French E3N-EPIC cohort study assessed the risk of breast cancer associated with HRT use in 54,548 postmenopausal women and found the risk was significantly greater (P<0.001) with HRT containing synthetic progestins (RR=1.4) than with HRT containing micronized progesterone, which actually reduced the risk (RR=0.9). (53)

While we await prospective trials to evaluate the safety of bioidentical progesterone with respect to the breast, these large cohort studies, along with the effects of progesterone on normal and cancerous breast cells, provide a large body of evidence supporting the safety of bioidentical progesterone. We know from prospective studies such as the Postmenopausal Estrogen/Progestin Interventions (PEPI) trial that progesterone is safer than medroxyprogesterone, yet many physicians continue to use the latter. (54)

The Essential Balance Between Progesterone and Estrogen

Physiologically, progesterone levels fall faster than estrogens; therefore, progesterone supplementation is typically needed years before estrogen declines. The physiologic role of progesterone goes far beyond the need to prevent unopposed estrogen stimulation of the endometrium. The E3N-EPIC cohort study showed that estrogen alone slightly increased the risk of breast cancer (RR=1.1), but the risk was actually reduced when estrogen was combined with progesterone (RR=0.9). Independent of the presence or absence of the uterus, progesterone (not progestins) should always be used to balance estrogen. (53)

Why Estriol?

Although estriol has been used in western Europe since the mid-1900s, most U.S. physicians are not familiar with it. In vivo, estriol is produced from estrone and directly from androstenedione. (55,56) It offers most of the benefits of estradiol, such as relief of vasomotor symptoms and vaginal atrophy, but appears safer.

One argument for the safety of estriol (as well as progesterone) is that human zygotes have been demonstrated to experience healthy embryogenesis and development in a milieu of high estriol and progesterone concentrations--levels present physiologically during pregnancy. If carcinogenesis does not occur with high levels of estriol during the most fragile phase of life, why should it be expected at much lower levels in mature adults? In animal models estriol has not shown carcinogenesis unless used in high doses, and it has even been shown to protect against carcinogen-induced breast cancer. Clinical studies have demonstrated that daily dosing results in minimal proliferation of breast and endometrial tissue. (57-60)

Studies on the ability of estriol to prevent bone loss have produced inconsistent results. For this reason many physicians use Bi-Est with 20% estradiol and 80% estriol. (61)

Currently the FDA is threatening to ban the use of estriol on the basis that it has not gone through new-drug FDA approval--even though the FDA has said that there is no safety issue with estriol and despite its inverse correlation with breast cancer (i.e. the more estriol, the lower the rate of cancer). (62) Under the Food and Drug Administration Modernization Act, Congress specifically recognized and approved the use of active ingredients that have a USP monograph as appropriate for use in compounding. Estriol has a USP monograph.

Compounding Pharmacies

The key issue is the use of human hormones at the appropriate dose--not the type of pharmacy. Most physicians using bioidentical hormones have a significant percentage of prescriptions filled at compounding pharmacies rather than non-compounding retail pharmacies. This is because compounding affords advantages such as customized dosing, so that the lowest effective dose can be used, and allows the prescribing of hormones such as estriol that are not available at non-compounding retail pharmacies.

Compounding pharmacies are regulated by state governments. Usually, the board of pharmacy is the responsible agency. Compounding pharmacies follow regulations set by the U.S. Pharmacopeia. We agree that there are concerns about variable potency, impurities, and contamination. Thus, we encourage the use of pharmacies accredited by the Pharmacy Compounding Accreditation Board (PCAB). Most compounding pharmacies do not perform "sterile compounding." State regulations require consistency in purity and dosage. U.S. Pharmacopeia potency regulations require that the active ingredient in all compounded preparations be between 90.0% and 110.0% of the amount stated 63,64

Wyeth, the maker of Prempro, has been a leader in opposing the use of compounding pharmacies and has effectively petitioned the FDA to assist in eliminating competition. Could this be related to the fact that Wyeth made more than $1 billion annually from the sale of Premarin and Prempro before the WHI study? These drugs are still on the market although they are known to increase cancer risk.

Exogenous Chemicals (Patentable Drugs) and Chronic Conditions

It is stated that allopathic drugs are the fourth to sixth leading cause of death in the U.S. In hospitalized patients, fatal adverse drug reactions (excluding errors in drug administration, noncompliance, overdose, drug abuse, therapeutic failures, and possible adverse drug reactions) numbered about 106,000. (65) Modern pharmacologically based medicine is dangerous. These deaths result from properly prescribed, FDA-approved drugs. (66)

Conclusions

The use of exogenous chemicals as hormone substitutes has been shown to be unsafe and should be stopped. Hormone supplementation should be done with compounds identical to the natural molecules. Although more research is needed, there is already evidence of the benefits of hormone supplementation in the proper doses and in proper balance. The future of medicine is in physiology rather than pharmacology.

REFERENCES

(1) Kronenberg HM, Melmed S, Polonsky KS, Larsen PR, eds. Williams Textbook of Endocrinology. 11th ed. Philadelphia, Pa.: WB Saunders; 2008:3.

(2) Public Citizen. The other drug war: Big Pharma's 625 Washington lobbyists. Congress Watch, July 2001. Available at: http://www.citizen.org/publications/release.cfm?ID=7077. Accessed Apr 27, 2008.

(3) Turner EH, Matthews AM, Lindaratos E, Tell RA, Rosenthal R. Selective publication of antidepressant trials and its influence on apparent efficacy. N Eng/J Med 2008;358:252-260.

(4) Gouras GK, Xu H, Gross RS, Testosterone reduces neuronal secretion of Alzheimer's [beta]-amyloid peptides. Proc Natl Acad Sci USA 2000;97:1202-1205.

(5) Tan RS. Memory loss as a reported symptom of andropause. Arch Androl 2001;47:185-189.

(6) Snyder PJ, Peachey H, Berlin JA. Effects of testosterone replacement in hypogonadal men. J Clin Endocrinol Metab 2000;85:2670-2677.

(7) Prior JC. Progesterone as a bone-trophic hormone. Endocr Rev 1990;11:386-398.

(8) Lee JR. Is natural progesterone the missing link in osteoporosis prevention and treatment? Med Hypotheses 1991;35:316-318.

(9) Khosla S, Melton LJ III, Atkinson EJ, et al. Relationship of serum sex steroid levels and bone turnover markers with bone mineral density in men and women: a key role for bioavailable estrogen. J Clin Endocrinol Metab 1998;83:2266-2274.

(10) Morita K, Her S. Progesterone pretreatment enhances serotonin-stimulated BDNF gene expression in rat c6 glioma cells through production of 5alpha-reduced neurosteroids. J Mol Neurosci 2008;34:193-200.

(11) Wang C, Swerdloff RS, Iranmanesh A, et al. Transdermal testosterone gel improves sexual function, mood, muscle strength, and body composition parameters in hypogonadal men. J Clin Endocrinol Metab 2000;85:2839-2853.

(12) Wang C, Alexander G, Berman N, et al. Testosterone replacement therapy improves mood in hypogonadal men--a clinical research center study. J Clin Endocrinol Metab 1996;81:3578-3583.

(13) Van Wingen GA. Progesterone selectively increases amygdala reactivity in women. Mol Psychiatry 2008;13:325-333.

(14) Paredes SD, Barriga C, Rodriguez AB. Melatonin and tryptophan as therapeutic agents against the impairment of the sleep-wake cycle and immunosenescence due to aging in Streptopelia risoria. Neuro Endocrinol Lett 2007;28:757-760.

(15) Lemoine P, Nir T, Laudon M, Zisapel N. Prolonged-release melatonin improves sleep quality and morning alertness in insomnia patients aged 55 years and older and has no withdrawal effects. J Sleep Res 2007;16:372-380.

(16) Iwasaki Y, Asai M, Yoshida M, et al. Dehydroepiandrosterone-sulfate inhibits nuclear factor-kappa B-dependent transcription in hepatocytes, possibly through antioxidant effect. J Clin Endocrinol Metab 2004;89:3449-3454.

(17) Cleare AJ, Heape E, Malhi GS, et al. Low-dose hydrocortisone in chronic fatigue syndrome: a randomised crossover trial. Lancet 1999;353:455-458.

(18) Jesse RL, Loesser K, Eich DM, et al. Dehydroepiandrosterone inhibits human platelet aggregation in vitro and in vivo. Ann N Y Acad Sci 1995;774:281-290.

(19) Darnaudery M, Koehl M, Piazza PV, et al Pregnenolone sulfate increases hippocampal acetylcholine release and spatial recognition. Brain Res 2000;852:173-179.

(20) Formby B, Wiley TS. Bcl-2, survivin and variant CD44 v7-v10 are downregulated and p53 is upregulated in breast cancer cells by progesterone: inhibition of cell growth and induction of apoptosis. Mol Cell Biochem 1999;202:53-61.

(21) Cagen SZ, Waechter JM Jr, Dimond SS, et al. Normal reproductive organ development in CF-1 mice following prenatal exposure to bisphenol A. Toxicol Sci 1999;50:36-44. Available at: http://.toxsci.oxfordjournals.org/cgi/content/abstract/50/1/36. Accessed Apr 27, 2008.

(22) Le HH, Carlson EM, Chua JP, Belcher SM. Bisphenol A is released from polycarbonate drinking bottles and mimics the neurotoxic actions of estrogen in developing cerebellar neurons. Toxicol Lett 2008;176:149-156.

(23) Vom Saal FS, Hughes C. An extensive new literature concerning low-dose effects of bisphenol A shows the need for a new risk assessment. Environ Health Perspect 2005;113:926-933.

(24) Okada H, Tokunaga T, Liu X, et al. Direct evidence revealing structural elements essential for the high binding ability of bisphenol A to human estrogen-related receptor-gamma. Environ Health Perspect 2008;116:32-38.

(25) Brown JS Jr. Effects of bisphenol-A and other endocrine disruptors compared with abnormalities of schizophrenia: an endocrine-disruption theory of schizophrenia. Schizophr Bull, Advance Access, Jan 31, 2008. doi:10.1093/schbul/sbml47.

(26) Morrissey RE, George JD, Price CJ, et al. The developmental toxicity of bisphenol A in rats and mice. Fundam App Toxicol 1987;8:571-582.

(27) Beato M, Chavez S, Truss M. Transcriptional regulation by steroid hormones. Steroids 1996;61:240-251.

(28) Nelson DL, Cox MM, eds. Lehninger Principles of Biochemistry. 4th ed. New York, N.Y: WH Freeman; 2004:884-892.

(29) Alexander IE, Clarke CL, Shine J, Sutherland RL. Progestin inhibition of progesterone receptor gene expression in human breast cancer cells. Mol Endocrinol 1989;3:1377-1386.

(30) Haas D, White SN, Lutz LB, Rasar M, Hammes SR. The modulator of nongenomic actions of the estrogen receptor (MNAR) regulates transcription-independent androgen receptor-mediated signaling: evidence that MNAR participates in G protein-regulated meiosis in Xenopus laevis oocytes. Mol Endocrinol 2005;19:2035-2046.

(31) McDonnell DP, Nawaz Z, O'Malley BW. In situ distinction between steroid receptor binding and transactivation at a target gene. Mol Cell Biol 1991;11:4350-4355.

(32) Thomas P, Pang Y, Dong J, et al. Steroid and G protein binding characteristics of the seatrout and human progestin membrane receptor alpha subtypes and their evolutionary origins. Endocrinology 2007;148:705-718.

(33) Recker RR, Davies KM, Dowd RM, Heaney RP The effect of low-dose continuous estrogen and progesterone therapy with calcium and vitamin D on bone in elderly women: a randomized controlled trial. Ann Intern Med 1999;130:897-904.

(34) Rossouw JE, Anderson GL, Prentice RL, et al. Risks and benefits of estrogen plus progestin in healthy postmenopausal women: principal results From the Women's Health Initiative randomized controlled trial. JAMA 2002;288:321-33.

(35) Kleinstein J, Luteal Phase Study Group. Efficacy and tolerability of vaginal progesterone capsules (Utrogest 200) compared with progesterone gel (Crinone 8%) for luteal phase support during assisted reproduction. Fertil Steril 2005;83:1641-1649.

(36) Daya S, Ward S, Burrows E. Progesterone profiles in luteal phase defect cycles and outcome of progesterone treatment in patients with recurrent spontaneous abortion. Am J Obstet Gynecol 1988;158:225-232.

(37) Check JH, Chase JS, Nowroozi K, Wu C. Spontaneous abortion rate in patients with endometriosis treated with progesterone Int J Fertil 1987;32:366-368.

(38) Hensleigh PA, Fainstat T Corpus luteum dysfunction: serum progesterone levels in diagnosis and assessment of therapy for recurrent and threatened abortion. Fertil Steril 1979;32:396-400.

(39) Di Renzo GC, Rosati A, Mattei A, Gojnic M, Gerli S. The changing role of progesterone in preterm labour. Br J Obstet Gynecol 2005;112 (Mar Suppl 1):57-60.

(40) Spong CY, Meis PJ, Thom EA, et al. Progesterone for prevention of recurrent preterm birth: impact of gestational age at previous delivery. Am J Obstet Gynecol 2005 Sep;193 (3 Pt 2):1127-1131.

(41) Meis PJ, Klebanoff M, Thom E, et al. Prevention of recurrent preterm delivery by 17 alpha-hydroxyprogesterone caproate. N Engl J Med 2003;348:2379-2385.

(42) Doggrell SA. Recurrent hope for the treatment of preterm delivery. Expert Opin Pharmacother 2003; 4:2363-2366.

(43) Lim AC, Bioemenkamp KW, Boer K, et al. Progesterone for the prevention of preterm birth in women with multiple pregnancies: the AMPHIA trial. BMC Pregnancy Childbirth 2007;7(Jun 19):7.

(44) Booth EA, Lucchesi BR. Medroxyprogesterone acetate prevents the cardioprotective and anti-inflammatory effects of 17-beta estradiol in an in ivvo model of myocardial ischemia and reperfusion. Am J Physiol Heart Circ Physiol 2007; 293: H 1408-H 1415.

(45) Mauvais-Jarvis P, Kuttenn F, Gompel A. Estradiol/progesterone interaction in normal and pathologic breast cells. Ann NY Acad Sci 1986;464:152-167.

(46) Inoh A, Kamiya K, Fujii Y, Yokoro K. Protective effects of progesterone and tamoxifen in estrogen-induced mammary carcinogenesis in ovariectomized W/Fu rats. Jpn J Cancer Res 1985;76:699-704.

(47) Wren BG, Eden JA. Do progestogens reduce the risk of breast cancer? A review of the evidence. Menopause J North Am Menopause Soc 1996; 3:4-12.

(48) Cowan LD, Gordis L, Tonascia JA, Jones GS. Breast cancer incidence in women with a history of progesterone deficiency. Am J Epidemiol 1981;114:209-217.

(49) Micheli A, Muti P, Secreto G, et al. Endogenous sex hormones and subsequent breast cancer in premenopausal women Int J Cancer 2004;112:312-318.

(50) Formby B, Wiley TS. Progesterone inhibits growth and induces apoptosis in breast cancer cells: inverse effects on Bcl-2 and p53. Ann Clin Lab Sci 1998;28:360-369.

(51) Plu-Bureau G, Lee MG, Thalabard JC, Sitruk-Ware R, Mauvais-Jarvis P. Percutaneous progesterone use and risk of breast cancer: results from a French cohort study of premenopausal women with benign breast disease. Cancer Detect Prev 1999;23:290-296.

(52) De Lignieres B, de Vathaire F, Fournier S, et al. Combined hormone replacement therapy and risk of breast cancer in a French cohort study of 3175 women. Climacteric 2002;5:332-340.

(53) Fournier A, Berrino F, Riboli E, Avenel E, Clavel-Chapelson F Breast cancer risk in relation to different types of hormone replacement therapy in the E3N-EPIC cohort. Int J Cancer 2005;114:448-454.

(54) The Writing Group for the PEPI Trial. Effects of estrogen or estrogen/progestin regimens on heart disease risk factors in postmenopausal women. The Postmenopausal Estrogen/Progestin Interventions (PEPI) Trial. JAMA 1995;273:199-208.

(55) Grodin JM, Suteri PK, MacDonald PC. Source of estrogen production in postmenopausal women. J Clin Endocr Metab 1973; 36:207-214.

(56) Longcope C. Estriol production and metabolism in normal women. J Steroid Biochem 1984; 20;959-692.

(57) Lemon HM. Pathophysiological consideration in the treatment of menopausal patients with oestrogens; the role of oestriol in the prevention of mammary carcinoma. Acta Endocrinol 1980; 233:S17-S27.

(58) Lauritzen C. Results of a 5 years prospective study of estriol succinate treatment in patients with climacteric complaints. Horm Metab Res 1987;19:579-584.

(59) Pratt JH, Longcope C. Estriol production rates and breast cancer. J Clin Endocrin Metab 1978; 46:44-47.

(60) Lippman M, Monaco ME, Bolan G. Effects of estrone, estradiol, and estriol on hormone responsive human breast cancer in long-term tissue culture. CancerRes 1977:37:1901-1907.

(61) Head KA, Estriol: safety and efficacy. Alt Med Rev 1998;3(2):101-113.

(62) Lyytinen H Pukkala E, Ylikorkala O. Breast cancer risk in postmenopausal women using estrogen-only therapy. Obstet Gynecol 2006;108:1354-1160.

(63) U.S. Pharmacopeia 29 (795). Available at: http://pharmacopeia.cn/v29240/usp29nf24s0_c795.html. Accessed Apr 27, 2008.

(64) U.S. Pharmacopeia Revision Bulletin 797. Available at: http://www.usp.org/pdf/EN/USPNF/generalChapter797.pdf. Accessed Apr 27, 2008.

(65) Lazarou J, Pomeranz BH, Corey PN. Incidence of adverse drug reactions in hospitalized patients: a meta-analysis of prospective studies. JAMA 1998;279:1200-1205.

(66) Starfield B. Is U.S. health really the best in the world? JAMA 2000;284:483-485.

Steven F Hotze, M.D., is vice president of the Pan American Allergy Society and founder and CEO of the Hotze Health and Wellness Center and Hotze Pharmacy, 20214 Braidwood Dr., Suite 215, Katy, TX 77450. Dr. Hotze uses bioidentical hormones in the treatment of his patients. Donald

P Ellsworth, M.D., is a director of the Pan American Allergy Society. He has treated more than 6,000 patients with bioidentical hormones. Contact: drdonellsworth@gmail.com.
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Author:Hotze, Steven F.; Ellsworth, Donald P.
Publication:Journal of American Physicians and Surgeons
Article Type:Clinical report
Geographic Code:1USA
Date:Jun 22, 2008
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