S42 Estrogen and memory in women

S42

s43 ESTROGEN

AND MEMORY

IN WOMEN

B B Sherwin, McGill University, 1205 Dr. Pentield Avenue, Montreal, QC, Canada,H3A 1Bl. It is well-established that specificreceptorsfor estrogenarefound in the hippocampus, a brain structureimportantfor memory. Estrogen alsomaintainsthe integrity of neuronalmorphologyin hippocampal tissue. Theseestrogenicinfluenceson brain functionprovidedthe rationale for investigating changes in cognitive functions in postmenopausal women. Perimenopausal womenfrequentlyreport memorydisturbances. In prospective studiesof p~menopausal women who underwentsurgical menopause, those treated with estrogen maintainedverbal memoryand had enhancedability to learn new material. In contrast,placebo-treated womenhad decreases in verbal memorypostoperatively.In anotherstudy,healthy65-year-oldestrogen usershadsignificantlyhigherscores on verbalmemorytasksthanhealthy 65-year-old womenwhonevertookestrogen.Recently,wefurthertested the e~ogen-memos ~lationship. Twen~-ei~t-ye~~ld women receivinga gon~o~opin-flying hormoneanalog(GnRH-a)to shrink uterinemyomashad significantlylower verbal memorytest scores. Moreover,the memorydeficit wasreversedin the groupthatrandomly receivedexogenous estrogenin additionto the G&II-a, while scores remaineddepressed in the womengiven placeboplusthe GnRH. In sag, researchfindingsfrom studieson spontaneously menopause women,surgicallymenopau~women,and younger,healthywomen provideconsistent supportfor thenotionthatjust asexogenous estrogen helps to maintain bone density and cardiovascularhealth in postmenopausal women, so too does it help to maintain and/or enhanceaspectsof brainfunction with aging.

A Morrison, C l&was, S Resnick,M Corrada, A Zonderman,R Brookm~er, Johns Hopkins University School of Medicine, 5501 Hopkins BayviewCircle,Baltimore,MD 21224,USA. This study investigates the relationship between estrogen replacement therapy (ERT) and Alzheimer’sdisease(AD). Recent reportsfrom a samplesuggested that womenwho receiveERT have a lowerrisk of AD comparedto womenwho neverusedERT. These investigationsrelied partially on retrospectiveascertainmentof dementiacases. We investigated ERT use in a prospective, longitudinal study; 472 post- or perimenopausal women were followedfor up to 16 yearsin the BaltimoreLongitudinalStudy of Aging (BLSVNIA). Thirty-eight incidentcasesof AD (NINCDS criteria) were diagnosedduring follow-up. ERT use was documentedprospectivelyat eachBLSA visit, and womenwho had ever usedoral and/ortransdermalestrogenswere consideredERT users. Cox proportionalhazardsmodelswere usedto estimatethe relativerisk of developingAD for ERT usersascomparedto women who never usedestrogenreplacement.The relative risk for AD in ERT users versus nonuserswas 0.46 (95% ~1-0.209-0.997). indicatinga reducedrisk for AD in ERT users,after adjustingfor educationallevel. ERT usershad a 54% reductionin risk for AD: converselyAD was 2.2 times more commonin womenwho had never used ERT. Our findings offer additional support for a protectiveinfluenceof ERT againsta subsequent diagnosisof AD.

s45

s44 ESTROGEN

PO6022 - A PROSPECT~E STUDY OF ESTROGEN REPLACEMENT THERAPY AND THE RISK OF DEVELOPING ALZHEIMER’S DISEASE IN THE BALTIMORE LONGITUDINAL STUDY OF AGING

REPLACEMENT DEPRESSION

IN WOMEN TREATED AND DEMENTIA

FOR

THE CAUSE OF PREMATURE

LX ~ckne~der,M.D., Departmentsof Psychiatry and Neurology and the School of Gerontology,University of SouthernCalifornia, Los Angeles,CA 90033. Estrogenreplacement therapy(ERT) hasbeenshownasa prophylaxis againstcardiovascular disease andosteoporosis. Its effects,however,are protean,includingboth nemo~opicand neuro~~smi~erm~ulating effects. In particular,it modulates choline@ andserotonergic fimction necessary for synthesisof choline acetyhransferase and for 5-HT2 binding. Incidences of dementiaincrease markedlywith agingandare higherin womencomparedwith men. A marked,relativeincrease in incidences of majordepression amongwomenin the60- to 70-yearage rangeexist,after a relativelylow incidenceperiodin the 50s. Results i?omtwo multicenter,placebo-controlled, randomized clinicaltrialsare presented in whichelderlywomenreceivingERTresponded muchbetter to treatments compared to womennot receivingERT. Thefirstwasa 30weektrial of tacrine(Cognexa),an acetylcholinesterase inhibitor,for Alzbeimer’sdisease;the secondwas a 6-week trial of ffuoxetine (Prozac@), a serotoninuptakeinhibitor,for majordepression. Patients who had beenreceivingBRT responded to tacrineby a subs~ti~ly greaterextent than patientsreceivingtacrinealone,improvingby 8.4 points on the Alzheimer’sDiseaseAssessment Scale. Similarly, depressed womenmaintained on ERT responded significantlybetterto fluoxetineovera (i-weekperiodthanthosenot receivingERT,with a 3timesgreaterdrugplacebodifferenceon the HamiltonRatingScalefor Depression.Theseob~~~ion~ studiessuggest a potential,clinically relevant cholinergic or serotonergicneuromodulatingrole for estrogens in old age.

36

MENOPAUSE

Dr I/A Godfree Deputy Director, The Am~ant Centre,80 LambethRoad,London UK* Prematuremenopause is ovarianfailure occurringafter puberty and beforethe ageof 40. It is characterised by amenorrhoea, elevated gonadotrophinlevelsandhypoestrogenaemia. The true incidenceof prematuremenopause is unwon and manycasesgo unrecognised; estimatesvary from l-3% of the femalepopulation. In morethan half of cases,the aetiology is unknown. The remaindercan be classifiedasfollows: A. latronenic a) Suraeq l bilateraloophorectomy * hysterectomyalonemayaccelerateovarianfailure l adnexalsurgery b) Radiotherany l dosesup to 500 radscauseovarianfailure in 60% of patients l dosesof 800 radsor moreleadto permanentovarian failure. c) Chemotherauv damageto ovariesis lesspredictable. Antimetabolites such as methotrexate may be more harmful to ovarian function than alkylating agents. Chemotherapy inducedovarianfailure is agerelated. Continued