analyzed in experimental systems to determine their impact on Prognosis,Progression and Respronse to Therapy.

Materials/Methods: For gene expression profiling, frozen primary tissuefrom 20 patients is currently available in the clinic. In all patients, othercauses of POF are excluded. Follicles are isolated by microdissection andused for in-vitro transcription. High-density oligonucleotide Arrays are usedto determine the gene expression profile in the ovary of patients. Functionalsignificance of candidate gene will be addressed by a wide spectrum ofcurrent cell and molecular biological methods that are available in ourlaboratories.

Results: Our first results indicate, that sufficient material can be obtainedfrom one ovarian biopsy for gene expression profiling. Systematic geneexpression profiling in all our patient has already started. Preliminarilyresults indicate, that a gene, which is also involved in germcell aplasia inmale, is also expressed in fetal ovarian tissue and might be a candidate genefor POF. However, further investigations are necessary to elucidate theimportance of this gene for developing POF.

Conclusions: The disease in many patients with POF is likely to becaused by an alteration of gene expression involving one ore more geneticfactors leading to impaired oogenesis, accelerated apoptosis or disturbedrecruitment of follicles. However, traditional cloning stratagies did not leadto the identification of new candidate genes for this condition in the lastyears. Gene expression profiling using Array technology provides a pow-erful tool to determine new genetic factors for POF.

Supported by: Grant from MUL - Medizinische Universitat zu Lubeck.

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Transvaginal ultrasound assessment of the endometrium of postmeno-pausal women before using hormone replacement therapy. Ruben San-tiago, Josefina Romaguera. Univ of Puerto Rico Sch of Medicine, San Juan,PR, Puerto Rico.

Objective: Endometrial safety is mandatory when prescribing hormonereplacement therapy to women with an intact uterus. It is not knownhowever how many women already have pre-existing endometrial pathol-ogy prior to the initiation of treatment, especially in asymptomatic patients.Transvaginal ultrasound has been demonstrated to be accurate in diagnosingand evaluating endometrial abnormalities using �5.0 mm in a double-layerendometrial measurement as a threshold for screening patients at risk fordeveloping endometrial cancer. The objective of the study was to asses theefficacy of transvaginal ultrasound to exclude pre-existing endometrialpathology in asymptomatic post-menopausal women before starting hor-mone replacement therapy.

Design: In a cross-sectional study 33 healthy postmenopausal womenunderwent ultrasound evaluation of the endometrium before participation ina clinical trial in which the patients were treated with either raloxifene orPrempro. Findings of transvaginal ultrasound were defined as abnormal if adouble layer endometrial measurement of �5.0mm was obtained. Patientswith an abnormal lining had a hysteroscopy with dilatation and curettagedone to rule out any malignancy.

Materials/Methods: Postmenopausal women �60 years old with an intactuterus, having either osteopenia or osteoporosis and who had menopause atleast 5 years before beginning the study were included. Women with historyof postmenopausal bleeding, contraindications for therapy, known or sus-pected history of breast cancer, an estrogen dependent neoplasia, and anyclinically significant endometrial or ovarian pathology, were excluded fromthe study. Also patients who had therapy for more than one month durationmore recently than 6 months with estrogens, antiestrogens, progestins,androgens, tamoxifen, tibolone, or SERMs (including raloxifene) could notparticipate.

Results: The mean measurement for the endometrial lining was 5.46 mm(range of 2.0 mm-16.1 mm). Of these, 39.39% (13 of 33) had an abnormalresult. One of the patients with an increased endometrial lining (16.1mm)had a pathology report of adenocarcinoma. This represents 3.03% (1 of 33)of the studied population and 7.69% (1 of 13) of the patients with anabnormal endometrial lining result. The rest of the patients with an abnor-mal result (12) had benign pathology reports.

Conclusions: Postmenopausal females �60 years old will benefit fromroutine transvaginal sonogram to exclude endometrial pathology beforestarting hormonal replacement therapy.

Supported by: Eli Lilly and Company, University of Puerto Rico Schoolof Medicine.

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Clinical response as an endpoint in studies of estrogen replacementtherapy in postmenopausal women. James A. Simon, Marvin Heuer.Women’s Health Research Ctr, Laurel, MD; Novavax, Columbia, MD.

Objective: The primary efficacy variable in phase III trials of estrogenreplacement therapy (ERT) is the change from baseline in the mean dailycount of moderate and severe hot flushes and vasomotor symptoms. In ourrecent phase III trial of EstrasorbTM, we also evaluated clinical response asan endpoint.

Design: A randomized, multicenter, double-blind, placebo-controlled,parallel-group study was conducted in postmenopausal women with �7moderate to severe hot flushes per day.

Materials/Methods: Two hundred postmenopausal women were random-ized to receive 7.5 mg estradiol in a 3.0-g daily dose of Estrasorb topicalemulsion (Novavax, Inc., Columbia, Md) or matching placebo applied toeach thigh and calf for 12 weeks after a 1-week placebo run-in. Clinicalresponse was defined as the complete absence of moderate and severe hotflushes during each 7-day period. The percentage of clinical responders wasassessed for each week of active treatment, as was the change from screen-ing of the mean daily count of moderate and severe hot flushes.

Results: Clinical response was greater with Estrasorb topical emulsionthan with placebo at Weeks 3 to 12. Clinical response ranged from 15%(Week 3) to 40% (Week 12) for subjects receiving Estrasorb versus 3%(Week 3) to 16% (Week 12) for placebo. During Weeks 8 to 12, 36% to40% of subjects receiving Estrasorb had a clinical response compared withjust 10% to 16% of subjects receiving placebo. Correspondingly, Estrasorbwas significantly (P �.001) more effective than placebo at Weeks 3 to 12for the primary efficacy variable.

Conclusions: Clinical response represents another possible way to assessefficacy in ERT trials, differentiating active treatment from placebo andcorroborating the results from the primary efficacy analysis.

Supported by: Novavax, Inc.

NURSES IN REPRODUCTIVE MEDICINE

P-140

hMG given subcutaneously may be associated with serum sickness-likereactions. S. Thoma, J. Hudelson, B. Guth, S. Thomas, W. L. Gentry.Advanced Fertility Group, Indianapolis, IN.

Objective: To determine prevalence of systemic side effects related tosubcutaneous (SQ) administration of human menopausal gonadotropins(hMG).

Design: Retrospective review of charts in patients who had complaints offlu-like symptoms while receiving SQ hMG.

Materials/Methods: Records were reviewed of 10 patients undergoingovulation induction with SQ hMG between April 2000 and April 2002.Patients complaining of flu-like symptoms (fever, myalgia, nausea) wereevaluated with CBC, sed rate, and liver function tests.

Results: Approximately 2000 patients were exposed to SQ hMG duringthis review period. Ten (10) patients recorded systemic flu- like symptomssuspected to be drug related. Five (5) of these patients had at least 1abnormal lab value. All symptoms rapidly abated after discontinuing hMG.

Patient Lab Values

Patient WBC Sed. Rate ALT Diagnosis

S.S. 14,900 62 Tubal FactorJ.M. 13,800 16 EndometriosisD.S. 15,400 73 89 Male FactorR.L. 13,800 11 EndometriosisS.L. 11,200 80 19 Tubal/Male Factor

Conclusions: Local reactions to SQ hMG are well recognized and quitecommon. However, little has been reported concerning systemic reactions.Although quite rare, we report 5 cases of serum sickness-like reactions thatpromptly abated after discontinuing hMG.

Supported by: None.

S162 Abstracts Vol. 78, No. 3, Suppl. 1, September 2002