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

EFFECTS OF POSTMENOPAUSAL ESTROGEN
plus progestin study" o may provide additional
insight.
Itt preliminary subgroup analyses, the
estimated Hfs for CEE for several monitored
outcomes, including the global index,
were lower for wotnen aged 50 to
59 years, although differences in HRs
across age groups were not statistically
significant. While these results suggest
that CEE may be somewhat more favorable
in younger than in older women,
these subgroup analyses must he itoerpreted
with caution; wecannot exclude
the role of chance or linmited power.
Limitations
This trial was designed to test only one
unopposed estrogen preparation at a
single dose, administered orally We
cannot determine whether these results
wortld apply to other formulalions,
doses, or routes of administration.
Care is needed in making
comparisons of these estrogen-alone
trial results to those of the estrogen plus
progestin trial, even though this is of
considerable interest The differences
between these 2 study populations in
their baseline characteristics,""t' their
event rates, the length of intervention
and follow-up time, and the completeness
ofdata at this initial report are sufficient
to make simple contrasts potentially
misleading More detailed analyses
of these parallel trials are planned.
The high rates of discontintuation of
study medications and higher than expected
crossover from placebo to active
hormone use are further limitations.
The rate of'discontintation is less
than what is usually observed it clinical
practice" and svas similar in the 2
groups The somewhat higher drop-in
rate in the placebo group is not explained
by unblinding, which svas infrequent
(1.5%) and similar in the 2
groups Setsitivity analyses suggest that
the lack of adherence to assigned study
medication may have diluted the CEE
effects, both positive and negative, relative
to what might he observed with full
adherence, but it did not distort the
overall balance of effects.
Lower than anticipated event rates for
some outcomes, particularly CHD and
178
hip fractures, reduce the power relative
to what was originally projected but
reitforce the generally healthy status of
these participants. The fact that the trial
was stopped early lurther decreases the
precision of the estimated effects. A
longer intervention period may have
provided stronger statistical evidence of
CEE effects, particularly (or CHD, for
which some evidence of a trend with
time was observed, and for breast cancer,
for which the cumulauve effect of
long-term exposure remains uncertain.
Addtitonal data could have allowed
for more informattve subgroup
analyses. Extended follow-up of these
women without further intervention is
planned.
Clinical Implications
In women aged 50 to 79 years reporting
a prior hysterectomy, CEE did not affect
CHD rates but did increase the risk of
stroke, accounting for an excess risk of
12 cascs per 10000 person-years, andreduced
the risk of hip fractures, resulting
in 6 fewer cases per 10000 personyears
Unexpectedly, women taking CEE
also appeared to be diagnosed as having
breast cancer at a lower rate than
women taking placebo, but the estimated
7 fewer cases per 10000 personyears
did not reach statistical signiftcance.
The totality of monitored effects,
as summarized in the prespecified global
index, suggests an overall balance of risks
and benefits and importantly no effect on
total mortality
Eased on these findingc,women and
their health care professionals now have
usable risk esumates for the benefits and
harms of CEE alone. Women considering
taking CEE should be counseled
about an increased risk of stroke but can
be reassured about no excess risk of
heart disease or breast cancer for at least
6.8 years of use. At present, these data
demonstrate no overall benefit ofCEE
for chronic disease prevention in postmenopausal
sromeit and thus argue
against its use in this setting. Os'erall,
these data support the curretit US Food
and Drug Administration recommendations
for postmenopausal wometi to
use CEE only for menopausal symp-
toins at the smallest effective dose for
the shortest possible time."
Aid rJWHI Storins Commint- G..e L. Ardir.
sou. PhD itwintg Srup itro, Frid H.itni-on Cantot
R--rach Centkr ScnttL, Wh): Mar0n Lima
her. MD (woting lrop crd, Unne of f d,
Ca tiule rkronoii M oob o Alphabrtailodirt
A-odotL Aid, PhD (1ro Ukidy. Protdonre,
Ril. rIose; , rsford. MD tlu-otity of Au-
-oo.. litonPhooat); Shiiry A. A, Birft-oo. PhD
fFrid Huchin on Cf- R-h i Co r m Si. titi).
Hrnry Block, MD (Ruslh-Prilhbytin-St toLuWs MWd&
rt CNtiN, Chrago, i0t ODrnr# Bondh, MD (eWii For.ur
Unirsyify Sdroof rfMi .Wnton--aSrIr., NO:
Robert BrDDrrur P UrrenIty of N-erd, R-ro)t
Robirt Bnykl, MD (il.rourrty of Tiuoo Hoal&h inoIui
Ciontr. Stn Anto-i.) BftC..aa.. DrPH (ai-,
Purrta-hni Divsion of Ru-ht, Oatkl-d. Clifi):
norone Chlubawti, MD (Habor-UCLA RB.ur h aind
educaion tntuti. Tornrie, Coilf ): Ditdd Curb. MD
tUi i.t..yof Hau. Hondutu: Mailery Ga.. MD
lUni-y of Ci`nru tin, CioCirnaJ Oht) i otii
Hays, PhD tBayltCrkGoieiof i Mudoni, H-ostoo, Tie.:
Gr-ordo Hori. MD lUoorrnJIy of North C-otina.
Chapdl Hill) Susim H-odri. DO tWoyno Shtt Unirventy
School of Meidun/Huzd Hospitil. Dtroit,
Mich): arbrab V H-uard. PhD tMedShtr Rea-rsh
tnrtiut,/Huward UnituenDty. ton, Kl Of ; todith
Hi. MD (G-oge Woshngton Utrcirty Medr-
Col Criter. Wdohintt DQ: Alan ubHbiL MD turi
unlty of Califoria rt tior, Ora-ge)l Robhca
hrkson, MD iThu Ohio Sito U--oty, CobourWOl.
KRo C. iuhnou.- MD (tionitrty ofTr= essue, Mophi,),
Hurand Judd, MD (UtNenity o1 Chof-a at
Los Aoeuls)r: thr Madoy Kotchun, MD tMbdiQI Cutru
of W.osOi.. Miwoauhik tL-.t KulIt, MDO trtr-nty
of Ptib burgh. Pitibbugh. Pat) Andra Z. to-
Croai. PhD iFrd Hutironroo c- RiruueahC-nWr.
Sfboakt, Dorothe tane. MD (Stole UlnrMy of Now
Yotk ot Stony Book): Robit D. LanEor. MD lUnhernSy
of Cofomt t ao Dwigo. Ltota/chula Vi1t1:
Norontau ton MD (Uuru iy of Medkidnu nd Dubkby
of N-wionoy. Ne-ro o. E. tiotr. MD tUmvr-riy
of Alabtua at Ou mingha.): JoAnn Mauton,
MD luegho- oud Wontons HospFit iHorord Mod.r.
School. Burton-, Md: Keon Magi, MD (Urroit
M ui ruta, MKnorAliots ludith Odck-i. PhD
tU.Noetitty of Mamidch-sMt/Folbn Chnic Worcutrt
, aMy ioOSulSn.n, MD (U.oivty of M.ma Mi.
ari, FM. iLa--nc Phltip. MD (Eotry u tirty,
Atont. Gal) R.s$ L. ProNtic, PhD (Frid Huutchinon
Cootor Birirh Coot-r. S-uttl.). Chiryl Ritfbogh.
PhDiK)rilt P-r r -ta Corte, fur WishRPt-th.
PoitAUd. Ord: t.h. Robbins. MD tUnirv-
My of Cffdotisa at D.aro. Sareoiri o). hcqus E.
Ro-sow. MD tiontrnait H-1t Lung dnd Blood Institute,
Bfithed. Md); Gboh Sitrt. MD (UaIrir-i
of Wisonsin, Mod-o). Masroa L. Stfiikk. PhD
OStrord Privobn Research cntor, Stford Um.
rrity S. tautord, CaidI Loda yVu Hot. PhD ltrihwestern
Un-eTty, Chuago, ll. Ioan J... ad ki-
W-.ndu PhD ftinrurity at Ouftalo. Bufalo. NY);
Robit Wal.t,. MD (iUnvio- y 1owa. Iowa City/
Daounoprt): Sylvi WSy rth ittm PhD Ab-rt
E rskin CoUtgo of Meid-on. BroWr, NY).
Flnhuolal DOlm.oso..s: Dr And-rron has ri-ei-d
speakong honoraria troo acdea i and othe nonproft
_tinitioith bat nay r-CwroO topput tot thks
act-t fhe roo arhut phaonar-uhat cootinuu.Hn
duding Wyoth. Dr, kuf is s epy of Pot e, Inc
Dr Chdbno banki h.u otd as a -oRulant lor Aita-
Zirt-t. Lilly. NOVtlh, oud Pf-rr Dr Ga. hat tfoi,,d
risuareh granit andW .o ar ro Ouro-tid.
Lilly. GlanuSrithKlyi-, Mirtk. Plua. Proftir nd
GC-nWe. AM Wyth, ho-o caaru nrdLuit ntfr ftro
A-ontni, Lilly, GlaroioithKflin. Mir-k. Ortho-
Mcifed. nd Prodtr aid GC hblr. and senrit on tho
1710 JAMA. Apnl 14, 2q4-Vd 29), i o. 1 4 (Reptrnted) t21y1t4 A.r..ctr ..i-Mcdbal tusuniartn. All righi' ro-oril.
Doarooded fron, r imn eurom ai Nationl inntifte of Hh. uon Apil 16, 2007