Bioidentical Hormones - U.S. Senate Special Committee on Aging

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155 11. The c~urrent mechanism(s) related to single patient INDs, orphan-drugs, and compassionate use are not feasible for physicians to initiate, as many patients are "one of a kind" and the time required .for the current mechanism(s) are unrealistic. Loyd V. Allen, Jr., Ph.D., Editor-in-Chief, International Journal of Pharmaceutical Compounding, www!UPC.comi, .: _ 4... . .. . -. .. '' ?, ' .r;" X7: ,..... ~~~~ . . - .0 a C ! * . ii ,i ; .4 . . L . ... ,. ''r C . .ViO
156 ORIIGINAL CONTrMIBTION JANMA-EXPRESS Risks and Benefits of Estrogen Plus Progestin in Healthy Postmenopausal Women . Principal Results From the Women's Health Initiative Randomized Controlled Trial Writing T Group for the Women's Health Initiative Investigators E WOMEN 's HEALTH INfITAttve (WHI) focuses on defining the risks and ben efits of Tstrategies that could poten-' tially reduce the incidence of heart disease, breast and colorectal cancer. and fractures in postmenopausal women, Between 1993 and 1998. the W-HI enrolled 161809 postmoenopausal women in the age range of 50 to 79 years into a set of clinical trials (trials of low-fat dietary pattern, calcium and vitamin D supplementatiun. and 2 trials of postmenopausal hormone use) and an observational study at 40 clinical centers in the United States. This article reports principal results for the trial of combined estrogen and progestin in women with a uterus. The trial was stopped early based on health risks that exceeded health benefits over an average folloiw-up of 5.2 yeats. A parallel trial of estrogen alone in women who have had a hysterectomy is being continued, and the planned end of this trial is March 2005, by which time the average follow-up will be about 8.5 years. The WHI- clinical trials were designed in 1991-1992 using the accumulated evidence at that time. The primary outcome for the trial of estrogen plus progestin was designated as coronary heart disease (CHD). Potential cardioprotection was based on generally Foe editorial comment wee p 366. 02002 Ai-enin MtdiMs Ansriairx AUt ri Context Despite decadmsof accumulated obserational evidence, the balantce ofrinks and benefits for hormone owe in healthy postrnenopausal women remains uncertain. Objective To assess the major health benefits and risks of the most commonly used combined hormone preparation in the United States. Design Estrogen plus progestin component of the Woumer'siHealth Initiative, arandomized controlled primary prevention trial (planned duration, 8.5 yeaes) inwhich16608 postmenopausal women aged 50-79 years with an intact uterus at baseline were recruited by 40 US dlinical centers In 1993-1998. Interventions Participants received conjugated equine estrogens, 0.625 mg/d. plus medroxyprogesterone acetate, 2.5 mg/ri. in I tablet (n=8506) or placebo (n -8102). Main Outcomes Mleasures The primary outcome was coronary heart disease (CHD) (nonfatal myocardial infarction and CHD death), with invasive breast cancer as the pnimary adverse outcome. A global index summarizing the balance of risks and benefits indluded the 2 primaiy outcomes plus stroke, pulmonary embotism (PE), e~ndometrial cancer, colorectal cancer, hip fracture, and death due to other causes.. Results On May 31,2002. after amean of 5.2years offollow-u~p, the data and safety monitoring board recommended stopping the trial of estrogeh plus progestin Vs placebo because the test statistic for inivasive breast cancer exceeded the stopping boundary for this adverse effect and the global index statistic supported risks exceeding benefits. This report includes data on the major dhsnical outcomes through April 30, 2002. Estimated hazard ratios (HRs) (nominal 95% confidence intervals ICis]) were as follows: Cl-D, 1.29 (1.02-1.631 with 286 cases; breast cancer, 1.26 (1.00- 1.59) witli 290 cases: stroke, 1,41 (1.07-1.85) with 212 cases, PE, 2.13 (1.39-3125) with 1 01 cases; colorectal cancer, 0.63 (0.43-0.92) with 11 2 cases; reidometrial cancer. 0.83 (0.47-1.47) with 47 cases; trip fracture. 0.66 (0.45-0.98) with 106 cases; and death due to other causes, 0.92 (0.74-1.14) with 331 cases. Corresponding HRs (nominal 95% Cis) for composite outcomes were 1.22 (1 .09-i.36) for tortal cardiovascular disease (arterial and venous disease), 1-03 (0.90- 1.17) fortotal cancer, 0 76 (069-0.85) for combined tractures, 0.98 (0.82-1.18) for total mortallty, and 1.15(1.03-1 28) for the global index. Absolute excess rinks per 10000 personyears attributable to estrogen plus progestin were 7 more CHD events, 8 more strokes, 8 more PEs, and 8 more invasive breast cancers. while absolute nisk reductions per 1 0000 person-years were 6 fewer colorectal cancers and 5 fewer hip fractures. The absolute exoess risk of events ixdluded in the global index was 19 per 10000 person-years. ConclusIons Overall health risks exceeded benefits from use of combined estrogen plus progestin for an average 5.2 -year follow-up among healthy postinenopausal US women. All-cause mortality was not affected during the tnial. The risk-benefit proftle found in this trial is not consistent with the requirements for a viable intervention for primary prevention of chronic diseases. and the resuffs indicate that this regimen should not be initiated or continued for primary prevention of CHD. JAMA. 2002Z28&321 3333s ~ e s r s AetMia in-mu0e ud FieaxxiWaI. pipxxre.am at ith. ed fi ii silde. his terv-d, (Rete~awdlJAMsA,juiyi7,es-vi2002 5.12 N.3 sa1 Dxs-ilxadwd Fle aserjaxan at National Institute of SItht, .. April 16, 2007
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S. HRG. 110-129 Bioidentica
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CONTENTS Page Opening Statement of
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2 The sale of bioidentical hormone
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4 ever, as Dr. Wartofsky points out
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6 with every stage of the disease:
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8 I am pleased to appear before thi
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10 When the trials began, many rese
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Women who began treatment more than
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14 One small trial using oral estra
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16 FDA is aware that a growing numb
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18 DEPARTMENT OF HEALTH & HUMAN SER
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20 safety and efficacy. However, as
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22 adulteration and misbranding pro
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24 The 2002 CPG reflects FDA's curr
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26 Equally concerning are claims by
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28 concerned about the use and mark
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30 Part I: Materials and Partnershi
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32 drugs, when the compounding of t
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34 Our staff identified 34 Web site
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1. Introduction 36 Chairman Kohl, R
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diet and fitness products. 5 For ex
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include "natural" progesterone crea
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42 unique to the computer age, such
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computer users to spam(ftuce.0ov -
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46 accuracy of advertising for heal
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48 Now, you have identified in your
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50 claim." Therefore, since the ter
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52 Such quality control problems ha
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54 Statement Before the U.S. <stron
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in the U.S., whereas WHI participan
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58 between science and hearsay and
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60 How can we determine whether bio
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62 doctors-are not getting the obje
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64 27. Writing Group for the PEPI T
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66 Dr. MANSON. Well, I think that m
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68 Statement of Leonard Wartofsky,
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70 in the WHI. In fact, no study as
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In summary, the Endocrine Society i
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74 The FDA also regulates aspects o
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Statement of Loyd V. Allen, Jr., Ph
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82 Senator SMITH. Dr. Allen, as I h
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84 Now, when you are talking about
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86 The only thing the WHI proved wa
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88 Testimony Of T.S. Wiley before t
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Confusion and Media Hype 90 Instead
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92 see a doctor tell a diabetic nea
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94 the only compelling reason to ta
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96 identical hormones synthesized f
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98 The world as we know it, from ba
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100 thereby experienced long period
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102 Bio-identical progesterone repl
Page 107 and 108: 104 had reached optimum theoretical
Page 109 and 110: 106 and the patient can be can reas
Page 111 and 112: 108 Estradiol and Analytical Resear
Page 113 and 114: 110 A controlled systematic pilot c
Page 115 and 116: 112 of set doses. The Wiley Protoco
Page 117 and 118: 114 I'd advocate for either Accredi
Page 119 and 120: 116 D.C., and established a goal to
Page 121 and 122: 118 If this legislation passes, fed
Page 123 and 124: first and second finger on the barr
Page 125 and 126: 122 These products that have been s
Page 127 and 128: 124 Bcl-2, survivin and variant CD4
Page 129 and 130: 126 These are experiments by other
Page 131 and 132: 128 cerebro-cellular inflammation c
Page 133 and 134: 130 Years # women *1>0.5 8 *1+ 9 *2
Page 135 and 136: *Breast cancer 132 -57 y.o. recurre
Page 137 and 138: 134 *Labor intense for patient and
Page 139 and 140: 136 Senator SMITH. Thank you very m
Page 141 and 142: 138 makes these hormones uniquely s
Page 143 and 144: 140 tomize the Wiley Protocol by ra
Page 145 and 146: 142 "natural," because all lead to
Page 147 and 148: 144 maceutical commerce, often with
Page 149 and 150: 146 WHITE PAPER #1 DID YOU KNOW THA
Page 151 and 152: 148 WHITE PAPER #2 Pharmacy Compoun
Page 153 and 154: 150 bleeding of the bowel, locate t
Page 155 and 156: 152 compounding standards can be en
Page 157: 154 I. The FDA's definition of a "N
Page 161 and 162: Initially, the design allowed women
Page 163 and 164: ards analyses," stratified by clini
Page 165 and 166: year). These 'drop-in" rates were a
Page 167 and 168: years of prior use, 11 vs 2; HR, 4.
Page 169 and 170: trogen plus progestin exposure. Clo
Page 171 and 172: 168 RISKS AND BENEFITS OF ESTROGEN
Page 173 and 174: EFFECTS OF POSTMENOPAUSAL ESTIROGEN
Page 175 and 176: EFFECTS OF POSTMENOPAUSAL ESTROGEN
Page 179 and 180: pEyECTS OF POSTMENOPAUSAL ESTROGEN
Page 185 and 186: 10000 isoor i I ea '° a wan 20-24
Page 187 and 188: ~SDt~rpa g~2~Q ~ !~fm~. b~e ~ ng jh
Page 189 and 190: Is associated with an Increased ris
Page 191 and 192: 188 Postmenopausal hormone therapy
Page 193 and 194: group (P= 04001), and In this subgr
Page 195 and 196: Treatmnent recommendations Based on
Page 197 and 198: 21.Grodsteln F. Manson JE, Colditz
Page 199 and 200: _ ORWIGNAL CONTIuBUTION 196 Postmen
Page 201 and 202: showed no striking differences in H
Page 203 and 204: (214 cases; P for trend=.72): howev
Page 205 and 206: 202 HORMONE THERAPY USE AND RISK OF
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206 HORMONE THERAPY USE AND RISK OF
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208 HORMONE THERAPY USE AND RISK OF
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210 ,lmcCII na: CLI I tr: tarty ver
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212 ,mucmai rimi &ronos farty bstro
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214 LntIucwu miau: rronos nary estr
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XVI. PNharmacy Licensure Requiremen
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XVI. Pharmacy Licensure Requirement
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220 Roster of Board of Pharmacy Ece
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050. 0l7404405400 Al-h. PeVbU 03283
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Conclusions * Age is a powerful ris
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Women's Health Initiative Trials of
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Hormone Therapy after WHI * Change
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Statement of the American Pharmacis
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232 APhA Statement to the S
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240 Written Testimony of Steven F.
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242 STATEMENT OF DAVID G. ADAMS On
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244 Report on State Laws and Regula
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246 Only one state, Utah, requires
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248 5. Compounding Copies of FDA-Ap
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