Disclosure. Objectives 8/6/2015. Bio-Identical Hormone Replacement Therapy (BHRT): TO B-HRT OR NOT TO B-HRT. 49th Annual Meeting

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1 49th Annual Meeting Bio-Identical Hormone Replacement Therapy (BHRT): TO B-HRT OR NOT TO B-HRT Cassie Bozeman, Pharm. D. Personalized Medicine, Compounding, and Research Fellow Florida Society of Health-System Pharmacists (FSHP) Meeting August 8 th, 2015 Disclosure I do not have a vested interest in or affiliation with any corporate organization offering financial support or grant monies for this continuing education activity, or any affiliation with an organization whose philosophy could potentially bias my presentation OWNING CHANGE: Taking Charge of Your Profession Objectives Bioidentical Hormone Replacement Therapy Define BHRT, describe its role in compounding pharmacy, and understand the science and controversy surrounding BHRT Recognize the Wyeth Citizen Petition and the Food and Drug Administrations (FDA) stance on estriol and compounding This new approach to health gives you back your lean body, shining hair, and thick skin This new medication allows your brain to work perfectly and offers the greatest defense against cancer, heart attack, and Alzheimer s disease. Don t you want that? -Ageless: The Naked Truth about Bioidentical Hormones Create an opinion on the use of estriol and justify the decision on whether or not estriol should be used in compounding Stampfer MJ, Colditz GA. Preventive Medicine 1999;20:47-63 Haarbo J et al. Metabolism 1991;40(12): LeBlanc ES, et al. JAMA. 2001;285: HERS: NO benefit for secondary prevention of CHD Hersh AL, et al. JAMA. 2004;291(1):47-53 VTE and gallbladder disease Hulley SH, et al. JAMA. 1998;280(7):

2 Traditional HRT WHI Combination Product MPA + CEE Prempro Derived from a non-human source Conjugated Equine Estrogens (CEE) Premarin WHI: risk of breast cancer, MI, stroke, and VTE risk of hip fracture, colorectal cancer, and menopausal symptoms Hersh AL, et al. JAMA. 2004;291(1):47-53 Chemically Synthesized Medroxyprogesterone (MPA) Provera FDA-Approved Bioidentical Hormones Compounding & BHRT Oral (Estrace, Femtrace) Progesterone (Prometrium) Compounding The combining or altering of ingredients by a pharmacist, in response to a licensed practitioner s prescription, to produce a drug tailored to an individual patient s special needs Patch (Estraderm, Alora) Gel (Divigel, Estrogel, Elestrin) Emulsion (Estrasorb) Spray (Evamist) Topical Vaginal Ring (Estring, Femring) Tablet (Vagifem) Compounded Bioidentical Hormone Replacement Therapy 1. Are specifically compounded for an individual patient 2. Contain USP-grade hormones that have the same chemical and molecular structure as the estrogens and progesterone produced in the human body 1. Are not FDA-approved for treatment of menopausal symptoms US Food and Drug Administration (FDA). FDA Website. Compounded menopausal hormone therapy questions and answers. Files JA. Bioidentical Hormone Therapy. Mayo Clin Proc. 2011;86(7)673:680. What about our patients? Common Misconceptions of Patients Bioidentical hormones are natural Patient Responses BHRT restores a perfect balance of hormones based on lab test results BHRT is more effective than traditional HRT BHRT is safer than FDA-approved HRT Pinkerton JV, Santoro N. Menopause. 2015;22(9) Files JA, Ko MG, Pruthi S. Mayo Clin Proc. 2011; 86(7): Sood R, et al. J Am Board Fam Med. 2011;24(2):

3 Estrogen-Replacement Therapy Bioidentical Estrogens Produced in the ovaries Pregnenolone 17α-OH-Pregnenolone DHEA hydroxylation (E1) (E2) (E3) and : bioidentical hormones approved by the FDA,, and are available as compounded BHRT Weaker estrogen Strongest estrogen Weakest estrogen The estrogens do not share equivalent potency Kuiper GG. Endocrinology. 1997;138(3): Estrogen Receptors Bioidentical Estrogens Estrogen Receptor-α (ERα) Breast, Endometrium, Ovary ERα Binding Affinity Estrogen Receptor-β(ERβ) Bone, Kidney, Lung, Brain, Endothelial Cells, Intestinal Mucosa, Vaginal Tissue ERβ Binding Affinity Preparation Ingredients Dose Tri-est Bi-est (80%) (10%) (10%) (80 90%) (10 20%) mg/day mg/day Files JA, Ko MG, Pruthi S. Mayo Clin Proc. 2011;86(7): Proposed Benefits of Estrogen: What do we know? Lower risk of breast cancer? No endometrial proliferation? Protects against bone loss? Based on animal studies Not supported in clinical trials Oral estriol may cause endometrial hyperplasia, but evidence is conflicting Intravaginal estriol appears to be safer and may reduce urogenital symptoms may not have protective effects on bone, but the evidence is conflicting Cirigliano M. Journal of Women s Health. 2007; 16: Head KA. :Safety and Efficacy. Altern Med Rev 1998;3:101 Voojis GP, Geurts TBP.Eur J Obstet Gynecol Reprod Biol 1995;62: Estrogen is the most effective treatment for menopausal symptoms Estrogen increases the risk of VTE, stroke, endometrial hyperplasia and carcinoma and estrone are FDA-approved BHRT Compounded BHRT includes estradiol, estrone, estriol is not FDA-approved There is no evidence to support that bioidentical hormones are safer or more effective than traditional hormones 3

4 Progesterone Progestogens Pregnenolone 17α-OH-Pregnenolone Progesterone is FDA-approved for the prevention of endometrial hyperplasia and carcinoma for women taking estrogen-replacement with an intact uterus DHEA Medroxyprogesterone (MPA) Synthetic, non-bioidentical, progestin Most-studied progestin; used in WHI Progesterone (Prometrium) FDA-approved bioidentical hormone Micronized in peanut oil Compounded Progesterone Non-FDA approved bioidentical hormone Proposed Benefits of Progesterone Safety of Progesterone vs MPA Improvement in sleep Vasomotor symptoms Little to no adverse effects on lipids compared to MPA? Risk of breast cancer compared to MPA? Lipids PEPI Trial: Oral micronized progesterone seems to have little or no adverse effect on HDL compared to MPA Breast Cancer WHI: adding a progestin to estrogen therapy increases risk of breast cancer compared to estrogen therapy alone. Prospective cohort: estrogen + MPA was associated with excess breast cancer risk, while estrogen + progesterone was not The evidence is conflicting Barret-Connor E, et al. JAMA 1995;273(3):199 Fournier A, Berrino F, Clavel-Chapelon F. Breast Cancer Res Treat. 2008;107(1):103 Miller VT, et al. JAMA. 1995; 273(3): FournierA, Berrino F, Clavel-Chapelon F. Breast Cancer Res Treat. 2008; 107: Beral V Million Women Study Collaborators. Lancet. 2003;362:419 Androgens Testosterone Pregnenolone 17α-OH-Pregnenolone DHEA Addition of testosterone to estrogen therapy in postmenopausal women has been shown to improve sexual function Insufficient evidence to support use for well-being, composition, bone preservation, or cognition Prescribed for sexual function Not FDA-approved for use in women Topical compounded 1% (0.5 g daily) Oral micronized testosterone (adverse changes in lipids) Somboonporn W, et al. Cochrane Database Syst Rev Sood R, et al. JABFM. 2011; 24(2):

5 Dehydroepiandrosterone (DHEA) Salivary Testing Oral DHEA improved sexual interest and satisfaction in some studies of women with adrenal insufficiency, but not in postmenopausal women Vaginally administered DHEA (1%) improved sexual desire and arousal in postmenopausal women with moderate to severe vaginal atrophy. Salivary assessments of hormone levels are inaccurate and do not correlate with levels determined from serum Women who received progesterone patch had widely varied salivary levels of progesterone compared with those who received placebo patch, and these varying levels did not correspond to serum levels Salivary levels of all hormones seem to vary greatly on the basis of foods, herbs, and spices consumed prior to sampling Davis SR, Panjari M, Stanczyk FZ. J Clin Endocrinol Metab. 2011;96(6): Labri F, et al. Menopause. 2009;16(5): Lewis JG. Maturitas. 2002;41(1):1-6. Zava DT. Proc Soc Exp Biol Med. 1998;217(3): Symptom Assessment & the FDA Titrations of HRT are based on symptoms rather than corresponding laboratory values Manufacturing vs. Compounding New Drugs Unapproved Drug False & Misleading Advertising Select pharmacies are engaged in manufacturing, not compounding Compounded BHRT prescription drugs are really new drugs is not currently an FDA approved drug Select pharmacies are engaged in false and misleading safety and efficacy claims 2008 Stance on No drug containing estriol has ever been approved by the FDA therefore the safety and efficacy of estriol is unknown Pharmacies may not compound estriol-containing drugs unless they have an FDA-sanctioned Investigational New Drug application Publication Date: April 8, 2008 Conaway E. J Am Osteopath Assoc. 2011;111(3): FDA Consumer Health Information. U.S. Food and Drug Administration. April, Summary 49th Annual Meeting Results from the WHI and a trend for natural alternatives peaked interest in BHRT, which many believe to be a safer option to traditional hormone replacement therapy BHRT is effective for the treatment of menopausal symptoms, but there is no evidence that bioidentical hormones have any advantage over conventional hormone therapies Compounding pharmacies play a crucial role in bio-identical hormone replacement therapy, as they have the ability to tailor therapies to each patient s needs Bio-Identical Hormone Replacement Therapy (BHRT): TO B-HRT OR NOT TO B-HRT Cassie Bozeman, Pharm. D. Personalized Medicine, Compounding, and Research Fellow Florida Society of Health-System Pharmacists (FSHP) Meeting August 8 th, 2015 OWNING CHANGE: Taking Charge of Your Profession 5