Bioidentical Hormones - U.S. Senate Special Committee on Aging
Bioidentical Hormones - U.S. Senate Special Committee on Aging Bioidentical Hormones - U.S. Senate Special Committee on Aging
203 HORMONE THERAPY USE AND RISK OF CARDIOVASCULAR DISEASE with carotid intima-media thick- ofhormonetherapyinwomensoonaf- menopause. differ from the effects of ness."," Although age and years since ter menopause (who are likely to have therapy on CHD. Risk of stroke on hormenopausearehighlycorrelated,inour fewer complicated lesions), but pro- mone therapy was elevated by 77% in analyses years since menopause ap- gressively more unfavorable effects on women with 10 or less years since peared to influence hormone effects on CHD risk in later years. The trends menopause but by a nonsignificant 13% CHD somewhat more than chronologi- across categories of age and years since in women aged 50 to 59 years. The risk cal age. Estrogen may have dual and op- menopause appeared to be somewhat for stroke in women with less than 10 posing actions, retarding the earlier stronger in women wthout a history of yearssince menopause attenuated m a stages of atherosclerosis through ben- prior cardiovascular disease (al- nonsignificant increase of 23% when eficial effects on endothelial function though this trend was not signifi- those with prior cardiovascular disand blood lipids, bitt triggering acute canty different from women with prior ease and who were older than 60 years events in the presence of advanced le- cardiovascular discase, possibly due to were excluded. sions through procoagulant and in- small numbers). It is not known why This analysis of the WHI data proflammatory mechanisms.'" Our find- the effects of hormone therapy on videssomeconvergencewithinformaings are consistent with a neutral effect stroke overall, and in women close to tion from observational studies, ani- Table 5. Cardiovascular and Global Index Events by Years Since Menopause at Basehne Year 81ince Menopame vi0 10-la 120 No. ot Caes No. of Cases No. of Caesa CHD-t Stroke rota rtonsbty r|1 Hominote Hoorone Th-erpy Placebo HR Therapy Ptaelo, In . 3608) in . 35293 195% CQI- In . 4483) In - 4494) Conbinad Tiats 39 si 0.76 113 103 1039-1.16) 41 23 i77 100 79 (1.05 2.98) 53 67 0.76 142 149 (053-1.061 r---I I Hsrsomone MR Therapy Placebo (95% Cl)' (n -40e1) In * 4122) 1.i0 194 159 (0.84-.45) 1.23 142 113 (0.92-1.6) 0698 267 240 (0,78-1.241 P vtrtia HR ixn 195% Cir Trenat 1.28 .02 (1.03-1.58) 1.26 .36 0.98-1.62) 1.14 .51 (0.96-1.361 Global sdii§ 222 203 1.05 (0.86 l.27) 482 440 CEE Trno 1.12 0.98-1.27) 675 632 1.06 (109-t.22) .62 CHDt S1rolin Total mortny G0Ebalstdoa CCEE Plwaeto CEE Placebo CEE In=826) (n -8171 n = 14368 n1 sv15a0) (n.2231) 8 16 0(48 47 50 0.96 117 (0.20-1.17) 10.64-1.44) 17 8 2.24 43 30 1.47 86 10.92-5.44) (062-2.35) 14 , 21 0.60 63 70 0.93 169 10.33-1.29) (0.66-1.30) 60 62 0.94 179 177 1.05 39t 10.65-136) P0.85-1.29) Ptlacbo (n123181 111 72 152 381 1.12 .1 p.086-146) 1.20 .24 10.87-1.6S) 1.16 .42 0.93-'.45) 1.07 .63 1092-1.23 CEEC MPA TrW CEE+MPA In .2782 Placebo (n . 2712) CEE+MPA In .3047) Placebo n . 299 . CEE+MPA (In.18a01 Placebo In.118013) CHDI: Strke 31 24 35 15 0.08 10.54-I 43) 1.59 0.81-3.05) 86 57 53 49 1.23 77 10.6s-1.77) 1.12 56 10,76-1.64) 47 41 I 66 (114-2.41) t.35 (o.es2.03) .05 .87 rolal mrosraly 39 4e 0.81 79 79 1.03 98 88 1.11 .93 G1.52-1.24) 1.75 1.41) 2083-1 49) GlOWistard-§ 162 141 1.08 303 087-1.37) 263 1,17 pg99.1.38) 294 251 I.13 (o0951.351 .92 AbocWrarsi- GEE. mrn0oid s rns CHDe .c hrw dbo aCo, oders .rl. HRR.heaard st-IP -54 .resdroqpegriae 0064tM irCs 1 - o ws aoe.d .0 p- 1 ea 10-.0' cAtreo 04 a Ca. eo e 1o ns0 s0a1ei5 r1ng 100r 1691p ot eno. irrag 101115 tory55 00 n11060 rse eal 80015000 86oer triOS 01550 rSOC srttt 09968o t0).R0d as cHO d' -. 04 riYo-ardal K.70I1n0 a, dnmrt, fte e o-cote .110021. ID.t C0., 1,4.. aera eri , bS-t -acr,. tcsawn,. enaca awr CEE ite MPA trels , hip Sau. a0 do0h l-, o01101004 1472 tAMA, Apil4,2007-Vat 297. N. .13 Repitsedl 02007 Aeriea MtditeatA.isodatioe. All rights rosoe-ed. Do-wdsCded from- i j jan-s cern at National Institute of Hiti, on April 5,2007
mal studies, and laboratory studies, which have focused mainly on the effects of estrogen on normal coronary arteries or women wvithout clinical cardiovascular disease.t-" However differences remain. One observational study examining this Issue predicted a reduced riskof CHDiis healthywomen who commenced hormone therapy within 4 years since menopause, and no effect in women with 10 or moreyears since menopause, while our combined trial data find a nonsigniftcani reduction in women starting hormone therapy during 10 or less years since menopause and increasing risks thereafter. Women's Health Initiative data suggest an advantage for CEE compared with CEE+MPA in regard to CHD, but the observational data would predict similar effects for these formulations (at least for CEE with the cyclical MPA more commonly used in observational studies).'- '^ 204 HORMONE THERAPY USE AND RISK OF CARDIOVASCULAR DISEASE There is also a divergence in regard to secondary prevention, with observational study but not trial data on women with existing disease suggesting CHD benefit for hormone users. 1 ' '7 The inclusion of a small proportion of women with prior disease in this analysis of trial data and in similar analyses of observational study data did not change the estimates of CHD risk ots hormone therapy by age or years since menopause appreciably, possibly because there were relatively few such women in younger age categories, and in the older age categories the presence of prior CHD is but one of many other factors contributing to risk.' Some observational and trial data agree in predicting early harm in women after initataon of hormone therapy. t tt '-" Confounding due to the healthier characteristics of hormone users, and failure to account for years since hormone therapy initiation, would lead to rPgwe 1. Estimated Absolute Excess Risk per 10000 Person-Years by Age Group at Baseline CH0 70-19 70-79 co-on AO. rG-p. Y 10-79 ftt tommy 70-79 room2 r too P r-0, 0.2n ra 090 072 03 027 0 70 Om6 30 0,34 o03 am 12t .It O.r7 r.ot t t3 3.s 306e Crentkron Trots i 1 * FFt i H -05 0 00 on t2o Eto..,.. Atit EmI PM oo 1os P10000bers- 0r7 sor 0.9s 0.15 01 0.70 overestimation of benefit for CHD in observational studies, even after adjusting for measurable factors.' Absolute risks may be more helpful than HRs to clinicians weighing the pros and cons of hormone therapy for particular patients. Because of low event rates in more recently menopausal women, the absolute excess risk will be very small, even in the presence of some increased relative risk due to hormone therapy. On the other hand the higher event rates in women more distant from menopause, together with their increased HRs, translate into large absolute excess risks. The low or absent cxcess risks of CHD in women with less than 10 years since menopause may be somewhat reassuring to women considering the use of hormones in the first few years after menopause. However, the incTeased absolute risk ofstroke in this subgroup (although not apparent us women aged 50-59 years in the CEE trial and at- CE TAtW CEE .?iPA TM 0eZo 5. 0. so 31 27 H et o. 02t D.: 775 0.77 0.: 1.r3 1.27 t .ro IE~s otto. MMg tsw 000 0. 0 35 0. 070 i2 t 02 0.ts 0'a r1oe It. i7 I f Sso ~ 2,07 3.O7 2C 31 3 -. 10 0 009 Ot W t 035 r t F l ~~~~~~0 so t O -00 0 00 95 t2O tnn9OAio^2esetssssrho mer ioomPeoiri-tha totsoamd Ariroto roams otiti mertoooo Peconyna st. Thees ifated abstote caress r- s kray dfter stightnyon tr abfolate erb s riskdehd isti from thedlterer,-i inc-aes per 100 p--na-sears bten adiste hiarene ar-d pia-eba grarps. Esirr.etdt esueht- tisk- , pe. t0tmo peIon-years iluted as toana.toed prr-etage n the pia..bo groap x (had rato mtor ptaoeho gmup-1)1t 1000. Ertenars bidlsate 95% wtnkdltsu tisiemats. estnated sing boots2trp meftods. CEE mdtrorrygatedespanre estrogens: CHD. io0naty heoart d se: SMPA. medro ryprogesterox acette. *P..03 conpaed MsMth the age groap of 50 to s yeas. tP=.02 compared rht the age group of 50 to 59 ypas OP= .01 mOrparcd roth at g gro up of so to s years. 02007 Amerie Itislteatl Asoiaution AU rights enexred. (Ftprnted) IAMA, Apl 4. 2OO7-VYI 297. N. 13 1473 fotloeded hrom mm.jo 0mm at Natioaal estitate of Hlth. rot April 5, 2007
- Page 155 and 156: 152 compounding standards can be en
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- Page 165 and 166: year). These 'drop-in" rates were a
- Page 167 and 168: years of prior use, 11 vs 2; HR, 4.
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- Page 185 and 186: 10000 isoor i I ea '° a wan 20-24
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- Page 199 and 200: _ ORWIGNAL CONTIuBUTION 196 Postmen
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203<br />
HORMONE THERAPY USE AND RISK OF CARDIOVASCULAR DISEASE<br />
with carotid intima-media thick- ofhorm<strong>on</strong>etherapyinwomenso<strong>on</strong>af- menopause. differ from the effects of<br />
ness."," Although age and years since ter menopause (who are likely to have therapy <strong>on</strong> CHD. Risk of stroke <strong>on</strong> hormenopausearehighlycorrelated,inour<br />
fewer complicated lesi<strong>on</strong>s), but pro- m<strong>on</strong>e therapy was elevated by 77% in<br />
analyses years since menopause ap- gressively more unfavorable effects <strong>on</strong> women with 10 or less years since<br />
peared to influence horm<strong>on</strong>e effects <strong>on</strong> CHD risk in later years. The trends menopause but by a n<strong>on</strong>significant 13%<br />
CHD somewhat more than chr<strong>on</strong>ologi- across categories of age and years since in women aged 50 to 59 years. The risk<br />
cal age. Estrogen may have dual and op- menopause appeared to be somewhat for stroke in women with less than 10<br />
posing acti<strong>on</strong>s, retarding the earlier str<strong>on</strong>ger in women wthout a history of yearssince menopause attenuated m a<br />
stages of atherosclerosis through ben- prior cardiovascular disease (al- n<strong>on</strong>significant increase of 23% when<br />
eficial effects <strong>on</strong> endothelial functi<strong>on</strong> though this trend was not signifi- those with prior cardiovascular disand<br />
blood lipids, bitt triggering acute canty different from women with prior ease and who were older than 60 years<br />
events in the presence of advanced le- cardiovascular discase, possibly due to were excluded.<br />
si<strong>on</strong>s through procoagulant and in- small numbers). It is not known why This analysis of the WHI data proflammatory<br />
mechanisms.'" Our find- the effects of horm<strong>on</strong>e therapy <strong>on</strong> videssomec<strong>on</strong>vergencewithinformaings<br />
are c<strong>on</strong>sistent with a neutral effect stroke overall, and in women close to ti<strong>on</strong> from observati<strong>on</strong>al studies, ani-<br />
Table 5. Cardiovascular and Global Index Events by Years Since Menopause at Basehne<br />
Year 81ince Menopame<br />
vi0 10-la 120<br />
No. ot Caes No. of Cases No. of Caesa<br />
CHD-t<br />
Stroke<br />
rota rt<strong>on</strong>sbty<br />
r|1<br />
Hominote Hoor<strong>on</strong>e<br />
Th-erpy Placebo HR Therapy Ptaelo,<br />
In . 3608) in . 35293 195% CQI- In . 4483) In - 4494)<br />
C<strong>on</strong>binad Tiats<br />
39 si 0.76 113 103<br />
1039-1.16)<br />
41 23 i77 100 79<br />
(1.05 2.98)<br />
53 67 0.76 142 149<br />
(053-1.061<br />
r---I I<br />
Hsrsom<strong>on</strong>e<br />
MR Therapy Placebo<br />
(95% Cl)' (n -40e1) In * 4122)<br />
1.i0 194 159<br />
(0.84-.45)<br />
1.23 142 113<br />
(0.92-1.6)<br />
0698 267 240<br />
(0,78-1.241<br />
P<br />
vtrtia<br />
HR ixn<br />
195% Cir Trenat<br />
1.28 .02<br />
(1.03-1.58)<br />
1.26 .36<br />
0.98-1.62)<br />
1.14 .51<br />
(0.96-1.361<br />
Global sdii§ 222 203 1.05<br />
(0.86 l.27)<br />
482 440<br />
CEE Trno<br />
1.12<br />
0.98-1.27)<br />
675 632 1.06<br />
(109-t.22)<br />
.62<br />
CHDt<br />
S1rolin<br />
Total mortny<br />
G0Ebalstdoa<br />
CCEE Plwaeto CEE Placebo CEE<br />
In=826) (n -8171 n = 14368 n1 sv15a0) (n.2231)<br />
8 16 0(48 47 50 0.96 117<br />
(0.20-1.17) 10.64-1.44)<br />
17 8 2.24 43 30 1.47 86<br />
10.92-5.44) (062-2.35)<br />
14 , 21 0.60 63 70 0.93 169<br />
10.33-1.29) (0.66-1.30)<br />
60 62 0.94 179 177 1.05 39t<br />
10.65-136) P0.85-1.29)<br />
Ptlacbo<br />
(n123181<br />
111<br />
72<br />
152<br />
381<br />
1.12 .1<br />
p.086-146)<br />
1.20 .24<br />
10.87-1.6S)<br />
1.16 .42<br />
0.93-'.45)<br />
1.07 .63<br />
1092-1.23<br />
CEEC MPA TrW<br />
CEE+MPA<br />
In .2782<br />
Placebo<br />
(n . 2712)<br />
CEE+MPA<br />
In .3047)<br />
Placebo<br />
n . 299 .<br />
CEE+MPA<br />
(In.18a01<br />
Placebo<br />
In.118013)<br />
CHDI:<br />
Strke<br />
31<br />
24<br />
35<br />
15<br />
0.08<br />
10.54-I 43)<br />
1.59<br />
0.81-3.05)<br />
86<br />
57<br />
53<br />
49<br />
1.23 77<br />
10.6s-1.77)<br />
1.12 56<br />
10,76-1.64)<br />
47<br />
41<br />
I 66<br />
(114-2.41)<br />
t.35<br />
(o.es2.03)<br />
.05<br />
.87<br />
rolal mrosraly 39 4e 0.81 79 79 1.03 98 88 1.11 .93<br />
G1.52-1.24) 1.75 1.41) 2083-1 49)<br />
GlOWistard-§ 162 141 1.08 303<br />
087-1.37)<br />
263 1,17<br />
pg99.1.38)<br />
294 251 I.13<br />
(o0951.351<br />
.92<br />
AbocWrarsi- GEE. mrn0oid s rns CHDe .c hrw dbo aCo, oders .rl. HRR.heaard st-IP -54 .resdroqpegriae 0064tM<br />
irCs 1 - o ws aoe.d .0 p- 1 ea 10-.0' cAtreo 04 a Ca. eo e 1o ns0 s0a1ei5 r1ng 100r 1691p ot eno. irrag<br />
101115 tory55 00 n11060 rse eal 80015000 86oer triOS 01550 rSOC srttt 09968o<br />
t0).R0d as cHO d' -. 04 riYo-ardal K.70I1n0 a, dnmrt, fte e o-cote .110021.<br />
ID.t C0., 1,4.. aera eri , bS-t -acr,. tcsawn,. enaca awr CEE ite MPA trels , hip Sau. a0 do0h l-, o01101004<br />
1472 tAMA, Apil4,2007-Vat 297. N. .13 Repitsedl 02007 Aeriea MtditeatA.isodatioe. All rights rosoe-ed.<br />
Do-wdsCded from- i j jan-s cern at Nati<strong>on</strong>al Institute of Hiti, <strong>on</strong> April 5,2007
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