Impact of Menstrual Phases on Stress Markers: A Pilot Study

PURPOSE: Previous research has shown that different phases of the menstrual cycle may impact biometrics such as markers of stress and inflammation [e.g., cortisol (CORT), interleukin-6] as well as body composition. However, there is scarce literature regarding markers of stress and oxidative stress such as salivary a-amylase (sAA), immunoglobin-A (SIgA) and uric acid (UA), in relation to the four different menstrual phases. The purpose of this study was to examine the impact of menstrual phases on sAA, CORT, UA and SIgA. METHODS: 21 pre-menopausal women with regular menstrual cycles (n=9) oral contraceptive users (OC) and (n=12) non-oral contraceptive users (non-OC) recorded baseline cycle dates using the Flo Period Tracker appä. Participants began experimental testing after recording baseline dates, consisting of four total sessions with one session occurring during the 1) menses, 2) late follicular, 3) ovulatory and 4) late luteal phase. Salivary markers: CORT, sAA, UA, and SIgA, along with diastolic and systolic blood pressure (BP), total body water (TBW) and body fat percentage (BF%) were recorded during each phase. BF% and TBW were determined via InBody bioelectric-impedance analyzerä. 500uL of saliva was collected, with samples immediately frozen at -80°C until analysis. Saliva samples were centrifuged at 4°C for a duration of 15 minutes at 1500g prior to analysis and duplicated for CORT, sAA, UA and SIgA concentrations. Statistical procedures were conducted via SAS v 9.4 (Cary, NC). One way repeated measures analysis of variance was used to evaluate outcome measures as well as changes in salivary markers and body composition measurements across different menstrual cycle phases. Fisher’s Least Significant Difference test was used to compare means in the instance of a significant main effect (p \u3c 0.05). Partial eta squared (hp2) was run to determine effect size. RESULTS: sAA concentrations were significantly lower during the follicular phase compared menstruation phase (p = 0.006, ηp2 = 0.14). The main effect for SIgA approached significance (p = 0.05). There were no changes in CORT, UA, BF%, TBW or diastolic and systolic blood pressure. CONCLUSION: These findings suggest the menstrual cycle influences sAA concentrations in both OC users and non-OC users. More research needs to be conducted with a larger sample size in order to determine significance of SIgA in relation to menstrual phases

Efficacy and safety of lampalizumab for geographic atrophy due to age-related macular degeneration: Chroma and Spectri phase 3 randomized clinical trials

IMPORTANCE: Geographic atrophy (GA) secondary to age-related macular degeneration is a leading cause of visual disability in older individuals. A phase 2 trial suggested that lampalizumab, a selective complement factor D inhibitor, reduced the rate of GA enlargement, warranting phase 3 trials.OBJECTIVE: To assess the safety and efficacy of lampalizumab vs sham procedure on enlargement of GA.DESIGN, SETTING, AND PARTICIPANTS: Two identically designed phase 3 double-masked, randomized, sham-controlled clinical trials, Chroma and Spectri, enrolled participants from August 28, 2014, to October 6, 2016, at 275 sites in 23 countries. Participants were aged 50 years or older, with bilateral GA and no prior or active choroidal neovascularization in either eye and GA lesions in the study eye measuring 2.54 to 17.78 mm(2) with diffuse or banded fundus autofluorescence patterns.INTERVENTIONS: Participants were randomized 2:1:2:1 to receive 10 mg of intravitreous lampalizumab every 4 weeks, sham procedure every 4 weeks, 10 mg of lampalizumab every 6 weeks, or sham procedure every 6 weeks, through 96 weeks.MAIN OUTCOMES AND MEASURES: Safety and efficacy assessed as mean change from baseline in GA lesion area at week 48 from centrally read fundus autofluorescence images of the lampalizumab arms vs pooled sham arms, in the intent-to-treat population and by complement factor I-profile genetic biomarker.RESULTS: A total of 906 participants (553 women and 353 men; mean [SD] age, 78.1 [8.1] years) were enrolled in Chroma and 975 participants (578 women and 397 men; mean [SD] age, 77.9 [8.1] years) were enrolled in Spectri; 1733 of the 1881 participants (92.1%) completed the studies through 48 weeks. The adjusted mean increases in GA lesion area from baseline at week 48 were 1.93 to 2.09 mm(2) across all groups in both studies. Differences in adjusted mean change in GA lesion area (lampalizumab minus sham) were -0.02 mm(2) (95% CI, -0.21 to 0.16 mm(2); P = .80) for lampalizumab every 4 weeks in Chroma, 0.16 mm(2) (95% CI, 0.00-0.31 mm(2); P = .048) for lampalizumab every 4 weeks in Spectri, 0.05 mm2 (95% CI, -0.13 to 0.24 mm(2); P = .59) for lampalizumab every 6 weeks in Chroma, and 0.09 mm(2) (95% CI, -0.07 to 0.24 mm(2); P = .27) for lampalizumab every 6 weeks in Spectri. No benefit of lampalizumab was observed across prespecified subgroups, including by complement factor I-profile biomarker. Endophthalmitis occurred after 5 of 12 447 injections (0.04%) or in 5 of 1252 treated participants (0.4%) through week 48.CONCLUSIONS AND RELEVANCE: In Chroma and Spectri, the largest studies of GA conducted to date, lampalizumab did not reduce GA enlargement vs sham during 48 weeks of treatment. Results highlight the substantial and consistent enlargement of GA, at a mean of approximately 2 mm(2) per year