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A Case for Bioidentical Hormones

Posted Nov 30 2012 12:18pm

 

by Dr. Roger Garcia

hormone therapy There is a lot of confusion and myths propagated about bioidentical hormones and whether they are safer than traditional hormone replacement therapies (HRT).  Bioidentical hormones have been maligned as medications that are unregulated, non-FDA approved and not supported by science.   Perhaps a closer look concerning their use is now in order.

We know that science has demonstrated that the replacement of our hormones brought about by age-related decline will significantly improve the quality of ones life.  The question then becomes whether bioidentical hormones or synthetic hormones should be used to replace our declining levels.

The process of deriving bioidentical hormones from the lab is by definition, a synthetic process but whose final chemical structure is a molecularly exact replica of that found in the human body.  Hence, the term bioidentical.  Traditional hormone medications in contrast are also made through a synthetic process in the lab but with an all-important difference-they are structurally and functionally different from the natural hormones they are attempting to replace.  These hormones are chemically altered to secure patents to protect profits for the pharmaceutical industry as naturally occurring bio-identical hormones by law cannot be patented.

The problem, however, is that the molecular structure determines activity so that even the smallest of changes can completely change the physiologic effect.  This was clearly demonstrated by the Women’s Health Initiative (WHI) study of 2002, which tested the effects of Premarin (conjugated equine estrogens) and Provera (medroxyprogesterone acetate (MPA)), the most prescribed drug combination hormone replacement therapy for menopausal women at that time.   These drugs while helping with symptoms of menopause through their hormonal mimicry, also interfered with normal physiologic processes, causing a wide variety of adverse effects.  The WHI study was halted because the use of the study drugs, Premarin and Provera (also in PremPro), increased the risk of breast cancer, heart attack, blood clots, and stroke.

The result of this study was not entirely unexpected as this combination has been shown to have precisely these problems.  Studies have consistently shown a decreased risk of breast cancer with natural prescribed progesterone and increased risk with synthetic progestins. (progestins generally refers to synthetic progestogens and a progestogen is the category of hormone molecules, natural and synthetic, that act like progesterone in the uterus).   There are many reasons for this.  Progesterone down-regulates estrogen receptor-1 (ER-1) in the breast, induces breast cancer cell apoptosis (cell death), diminishes breast cell mitotic activity (anti-proliferative and anti-breast cancer effect), and arrests human cancer cells in the GI phase by upregulating cyclin-dependent kinase inhibitors and downregulating cyclin D1.

The French E3N-EPIC cohort study assessed the risk of breast cancer associated with HRT in 54,548 postmenopausal women and found the risk was significantly greater with HRT containing synthetic progestins than with HRT containing progesterone. This is one reason why progesterone should always be used to balance estrogen independent of the presence or absence of the uterus.

As well, progesterone maintains and augments the cardioprotective effects of estrogen through various mechanisms while MPA does not.  The PEPI trial demonstrated progesterone augments estrogen’s positive effects on lipids while progestins negated these positive effects.  Progestins are also shown to significantly increase the amount of insulin resistance (Type II diabetes) when compared to estrogen alone or estrogen and progesterone. Coronary artery spasm, which increases the risk of heart attack and stroke, can be reduced with estrogen and progesterone but the addition of MPA to estrogen has the opposite effect and results in vasoconstriction. Progesterone was shown to decrease the formation of a protein that initiates athrogenic plaques (coronary artery disease), vascular cell adhesion molecule-1, while MPA did not. This is consistent with other studies that showed progesterone by itself or in combination with estrogen, inhibited atherosclerotic plaque formation.  Progestins promoted atherosclerotic plaque formation and prevent the plaque-inhibiting and lipid-lowering actions of estrogen.   MPA was also shown to increase the amount of collagen in vascular plaques, which promotes clot formation increasing the risk of heart attack, stroke and blood clots.

MPA has also been associated with increased fatigue, weight gain, and decrease exercise tolerance, while natural progesterone demonstrates none of these problems.  Progesterone also has numerous beneficial effects on the brain and nervous system, including supporting myelin formation and activating GABA receptors.  Synthetic progestins do not share these physiological effects.  In fact, the Women’s Health Initiative Memory Study (WHIMS) found PremPro doubled the risk of developing dementia in women age 65 and older.

Premarin, the most popular estrogen replacement therapy, is derived from pregnant horses’ urine, hence its name, Pre (pregnant)-mar (horse)-in (urine).  It consists of a combination of conjugated equine (horse) estrogens that are more potent and more carcinogenic than other natural estrogens such as estradiol and especially estriol.  4-hydroxyequilenin, is especially potent, 100 times the potency of natural estrogen, and carcinogenic. Many of these foreign estrogens bind very tightly to the human estrogen receptors, making them highly stimulating and carcinogenic. Natural estrogens have no such carcinogenic metabolites. A combination of the natural estrogens, estriol and estradiol have been shown to actually protect against breast cancer and result in a reduction of breast cancer risk. When this is added to natural progesterone’s powerful breast cancer risk reduction, one would expect a significant reduction in breast cancer in women on natural hormone replacement than in women on no therapy.

Finally, all oral estrogens, including Premarin, will increase clotting factors and inflammatory proteins, increasing the risk of clotting, stroke and heart attack. This does not occur with transdermal (topical) estrogens.  Transdermal estradiol, when given with or without oral progesterone, has no detrimental effects on coagulation and no increased risk of thromboembolism (traveling clots).  This is in contrast to an increased risk of thromboembolism with Premarin, with or without synthetic progestin, whether both are given orally (eg, oral estrogen and oral progestin),or whether given as transdermal estrogen and oral synthetic progestin, or whether both estrogen and progestin are given transdermally.

Compounding pharmacies have equally gotten a bum rap.  The argument goes that because they are not overseen by the FDA and their compounded bioidentical formulations are not FDA approved, they are presumed to be unsafe compared to traditional HRT.  The reality is that the federal case, Western States, held that compound pharmacies are not under FDA jurisdiction.Instead, they ARE regulated by the state and local government, usually the board of pharmacy who adopt the standards set by the U.S. Pharmacopeia (USP). The 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. Despite this regulation, to avoid questions of potency and/or content uniformity, it is best to use the large national pharmacies that specialize in compounded hormones and are accredited by the Pharmacy Compounding Accreditation Board (PCAB).  Even with these assurances, if one then wishes to avoid compounding, a better choice is to use FDA approved bioidenticals than the use of synthetics.

In addition, bioidentical hormones, like all compounded medications, are made from FDA and USP-registered materials, the same as those used by pharmaceutical manufacturers. The ingredients and their suppliers are regulated by the FDA, with additional oversight by the USP.  Also, compounded medications are in a similar position as manufactured products prescribed for off-label use.  That is, off-label use of manufactured products, which represents a fifth of all prescriptions, although not approved by the FDA for such use, is still commonly prescribed at the discretion of the physician based on experience and clinical results. The same discretion is used for the prescription of compounded bioidentical hormones.

It is beyond the scope of this article to address all the research that has been done on bioidentical hormones.  However, in citing just a few research studies here, it should be obvious that contrary to the claim that bioidenticals are not supported by science, there is substantial scientific and medical evidence that bioidentical hormones are safer and have more efficacious forms of HRT than the commonly used synthetic versions.  More research will be needed to clarify this proposition further and is now presently being conducted.  However, given the state of the art today, the question that must be answered by boomers seeking to improve their quality of life is: Which form of HRT would you rather be treated with?


References:

1. Rossouw JE, Anderson GL, Prentice RL, LaCroix AZ, Kooperberg C, Stefanick ML, Jackson RD, Beresford SA, Howard BV, Johnson KC, Kotchen JM, Ockene J; Writing

Group for the Women’s Health Initiative Investigators. Risks and benefits of estrogen plus progestin in healthy postmenopausal women: principal results From

the Women’s Health Initiative randomized controlled trial. JAMA. 2002 Jul 17;288(3):321-33.

 

2. Malet C, Spritzer P, Guillaumin D, Kuttenn F. Progesterone effect on cellgrowth, ultrastructural aspect and estradiol receptors of normal human breast

epithelial (HBE) cells in culture. J Steroid Biochem Mol Biol. 2000Jun;73(3-4):171-81.

 

3. Mauvais-Jarvis P, Kuttenn F, Gompel A. Antiestrogen action of progesterone in breast tissue. Breast Cancer Res Treat. 1986;8(3):179-88.

 

4. Söderqvist G, von Schoultz B, Tani E, Skoog L. Estrogen and progesteronereceptor content in breast epithelial cells from healthy women during the

menstrual cycle. Am J Obstet Gynecol. 1993 Mar;168(3 Pt 1):874-9.

 

5. Greendale GA, Reboussin BA, Hogan P, Barnabei VM, Shumaker S, Johnson S,Barrett-Connor E. Symptom relief and side effects of postmenopausal hormones:results from the Postmenopausal Estrogen/Progestin Interventions Trial. Obstet Gynecol. 1998 Dec;92(6):982-8.

 

6. Hargrove JT, Maxson WS, Wentz AC, Burnett LS. Menopausal hormone replacement therapy with continuous daily oral micronized estradiol and progesterone. Obstet Gynecol. 1989 Apr;73(4):606-12.

 

7. de Lignières B. Effects of progestogens on the postmenopausal breast. Climacteric. 2002;5(3):229–235.

 

8. Wood CE, Register TC, Lees CJ, Chen H, Kimrey S, Cline JM. Effects of estradiol with micronized progesterone or medroxyprogesterone acetate on risk markers for breast cancer in postmenopausal monkeys. Breast Cancer Res Treat. 2007;101(2):125–134.

 

9. Foidart JM, Colin C, Denoo X, et al. Estradiol and progesterone regulate the proliferation of human breast epithelial cells. Fertil Steril. 1998;69(5):963–969.

 

10. Groshong SD, Owen GI, Grimison B, et al. Biphasic regulation of breast cancer cell growth by progesterone: role of the cyclin- dependent kinase inhibitors, p21 and p27(Kip1). Mol Endocrinol. 1997;11(11):1593–1607.

 

11. Fournier A, Berrino F, Riboli E, Avenel V, Clavel-Chapelon 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.

 

12. Effects of estrogen or estrogen/progestin regimens on heart disease risk factors in postmenopausal women. The Postmenopausal Estrogen/ Progestin Interventions (PEPI) Trial. The Writing Group for the PEPI Trial. JAMA. 1995;273(3):199–208.

 

13. Wagner JD; Martino MA; Jayo MJ; Anthony MS; Clarkson TB; Cefalu WT. The effects of hormone replacement therapy on carbohydrate metabolism and cardiovascular risk factors in surgically post- menopausal cynomolgus monkeys. Metabolism 1996 Oct;45(10):1254-62.

 

14. Elkind-Hirsch KE; Sherman LD; Malinak R. Hor- mone replacement therapy alters insulin sensitivity in young women with premature ovarian failure. J Clin Endocrinol Metab 1993 Feb;76(2):472-5.

 

15. de Lignieres B. Oral micronized progesterone. Clin Ther 1999. jan;21(1):41-60.

 

16. Godsland IF; Gangar K; Walton C; Cust MP; Whitehead MI; Wynn V; Stevenson JC. Insulin resis- tance, secretion, and elimination in postmenopausal women receiving oral or transdermal hormone re- placement therapy. Metabolism 1993 Jul;42(7):846-53.

 

17. Minshall RD, Stanczyk FZ, Miyagawa K, et al. Ovarian steroid protec- tion against coronary artery hyperreactivity in rhesus monkeys. J Clin Endocrinol Metab. 1998;83(2):649–659.

 

18. Mishra RG, Hermsmeyer RK, Miyagawas K, et al. Medroxy- progesterone acetate and dihydrotestosterone induce coronary hyperreactivity in intact male rhesus monkeys. J Clin Endocrinol Metab. 2005;90(6):3706–3714.

 

19. Miyagawa K, Roöch J, Stanczyk F, Hermsmeyer K. Medroxypro- gesterone interferes with ovarian steroid protection against coronary vasospasm. Nat Med. 1997;3(3):324–327.

 

20. Otsuki M; Saito H; Xu X; Sumitani S; Kouhara H; Kishimoto T; Kasayama S. Progesterone, but not medroxyprogesterone, inhibits vascular cell adhesion molecule-1 expression in human vascular endothelial cells. Arterioscler Thromb Vasc Biol 2001 Feb;21(2):243-8.

 

21. Wagner JD, Martino MA, Jayo MJ, Anthony MS, Clarkson TB, Cefalu WT. The effects of hormone replacement therapy on carbohy- drate metabolism and cardiovascular risk factors in surgically postmeno- pausal cynomolgus monkeys. Metabolism. 1996;45(10):1254–1262.

 

22. Adams MR, Kaplan JR, Manuck SB, et al. Inhibition of coronary artery atherosclerosis by 17-beta estradiol in ovariectomized mon- keys. Lack of an effect of added progesterone. Arteriosclerosis. 1990;10(6):1051–1057.

 

23. Register TC, Adams MR, Golden DL, Clarkson TB. Conjugated equine estrogens alone, but not in combination with medroxyprogesterone acetate, inhibit aortic connective tissue remodeling after plasma lipid lowering in female monkeys. Arterioscler Thromb Vasc Biol. 1998;18(7):1164–1171.

 

24. Clarkson TB. Progestogens and cardiovascu-

lar disease. A critical review. J Reprod Med 1999 Feb;44(2 Suppl):180-4.

 

25. Fitzpatrick LA, Pace C, Witta B. Comparison of regimens containingoral micronized progesterone of medroxyprogesterone acetate on quality of life in postmenopausal women: a cross-sectional survey. J Womens Health Gend Based Med. 2000;9(4):381–387.

 

26. Baulieu E, Schumacher M. Progesterone as a neuroactive neurosteroid, withspecial reference to the effect of progesterone on myelination. Steroids. 2000

Oct-Nov;65(10-11):605-12.

 

27. Shumaker SA, Legault C, Rapp SR, Thal L, Wallace RB, Ockene JK, Hendrix SL,Jones BN 3rd, Assaf AR, Jackson RD, Kotchen JM, Wassertheil-Smoller S,

Wactawski-Wende J; WHIMS Investigators. Estrogen plus progestin and the incidence of dementia and mild cognitive impairment in postmenopausal women: the Women’s Health Initiative Memory Study: a randomized controlled trial. JAMA. 2003 May 28;289(20):2651-62.

 

28. Zhang F; Chen Y; Pisha E; Shen L; Xiong Y; van Breemen RB; Bolton JL. The major metabolite of eq- uilin, 4-hydroxyequilin, autoxidizes to an o-quinone which isomerizes to the potent cytotoxin 4-hy- droxyequilenin-o-quinone. Chem Res Toxicol 1999 Feb;12(2):204-13.

 

29. Pisha E; Lui X; Constantinou AI; Bolton JL Evidence that a metabolite of equine estrogens, 4- hydroxyequilenin, induces cellular transformation in vitro. Chem Res Toxicol 2001 Jan;14(1):82-90.

 

30. Melamed M, Castaño E, Notides AC, Sasson S. Molecular and kinetic basis for the mixed agonist/antagonist activity of estriol. Mol Endocrinol. 1997;11(12):1868–1878.

 

31. Scarabin PY; Alhenc-Gelas M; Plu-Bureau G; Taisne P; Agher R; Aiach M. Effects of oral and transdermal estrogen/progesterone regimens on blood coagulation and fibrinolysis in postmenopausal women. A randomized controlled trial Arterioscler Thromb Vasc Biol 1997 Nov;17(11):3071-8.

 

32. Canonico M, Oger E, Plu-Bureau G, et al. Hormone therapy and venous thromboembolism among postmenopausal women: impact of the route of estrogen administration and progestogens: the ESTHER study. Circulation. 2007;115(7):840–845.

 

33. Cushman M, Kuller LH, Prentice R, et al. Estrogen plus progestin and risk of venous thrombosis. JAMA. 2004;292(13):1573–1580.

 

34. Feeman WE Jr. Thrombotic stroke in an otherwise healthy middle- aged female related to the use of continuous-combined conjugated equine estrogens and medroxyprogesterone acetate. J Gend Specif Med. 2000;3(8):62–64.

 

35. Canonico M, Oger E, Plu-Bureau G, et al. Hormone therapy and venous thromboembolism among postmenopausal women: impact of the route of estrogen administration and progestogens: the ESTHER study. Circulation. 2007;115(7):840–845.

 

36. Jick SS, Kaye JA, Russmann S, Jick H. Risk of nonfatal venous thromboembolism in women using a contraceptive transdermal patch and oral contraceptives contain norgestimate and 35 ìg of ethinyl estradiol. Contraception. 2006;73(3):223–228.

 

37.  Thompson v Western States, 122 S C5 1497, 1505 (2002).

 

38. Radley DC, Finkelstein SN, Stafford RS. Off-label prescribing among office-based physicians. Arch Intern Med. 2006 May 8;166(9):1021-6.

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