An understanding of human responses to hypoxia is important for the health of millions of people worldwide who visit, live, or work in the hypoxic environment encountered at high altitudes. In spite of dozens of studies over the last 100 years, the basic mechanisms controlling acclimatization to hypoxia remain largely unknown. The AltitudeOmics project aimed to bridge this gap. Our goals were 1) to describe a phenotype for successful acclimatization and assess its retention and 2) use these findings as a foundation for companion mechanistic studies. Our approach was to characterize acclimatization by measuring changes in arterial oxygenation and hemoglobin concentration [Hb], acute mountain sickness (AMS), cognitive function, and exercise performance in 21 subjects as they acclimatized to 5260 m over 16 days. We then focused on the retention of acclimatization by having subjects reascend to 5260 m after either 7 (n = 14) or 21 (n = 7) days at 1525 m. At 16 days at 5260 m we observed: 1) increases in arterial oxygenation and [Hb] (compared to acute hypoxia: PaO2 rose 9±4 mmHg to 45±4 while PaCO2 dropped a further 6±3 mmHg to 21±3, and [Hb] rose 1.8±0.7 g/dL to 16±2 g/dL; 2) no AMS; 3) improved cognitive function; and 4) improved exercise performance by 8±8% (all changes p<0.01). Upon reascent, we observed retention of arterial oxygenation but not [Hb], protection from AMS, retention of exercise performance, less retention of cognitive function; and noted that some of these effects lasted for 21 days. Taken together, these findings reveal new information about retention of acclimatization, and can be used as a physiological foundation to explore the molecular mechanisms of acclimatization and its retention.

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10105 Background: Gynecologic symptoms and sexual dysfunction from endocrine therapy are troublesome side effects for a significant number of patients. This study explored amelioration of vaginal dryness and dyspareunia with fluocinonide cream, a strong topical corticosteroid. Methods: A single-arm, open-label phase II trial of topical fluocinonide 0.05% cream to improve vaginal symptoms in women on endocrine therapy in the adjuvant setting for early stage breast cancer was performed. Patients with vaginal symptoms applied topical vaginal fluocinonide 0.05% cream twice a day for two weeks then once daily for two weeks. Patients were assessed for symptoms by weekly completion of the Mayo/North Central Cancer Treatment Group Patient Pretreatment Questionnaire. The primary outcome was a change from baseline in patient-reported effects of vaginal dryness and dyspareunia on a scale from 0 (no symptoms) to 4 (very severe symptoms) from time of enrollment and at 4 weeks. Secondary outcomes were decrease in vaginal itching and total vaginal index score. Comparisons were made with Wilcoxon sign rank test with 2.5% significance level. Results: Thirty-four women were accrued. At 4 weeks compared with baseline, vaginal dryness improved from a median score of 2 (moderate symptoms) to 0 (no symptoms) ( P < .001) and dyspareunia from 3 (severe symptoms) compared with 1 (mild symptoms) ( P = .002). Percentage of patients who had > 2 point improvement in vaginal dryness and dyspareunia was 69.0% and 75% respectively. Secondary analysis showed decrease in vaginal itching score from 1 to 0 ( P = .001) and vaginal index score of 6 to 1 ( P = .002). Twenty-one patients experienced low-grade toxicities which were mostly limited to skin irritation. Conclusions: Fluocinonide 0.05% cream improves vaginal dryness and dyspareunia experienced by women receiving endocrine therapy and has the potential to improve quality of life of cancer survivors and compliance of endocrine therapy. Clinical trial information: NCT00297011.