ABSTRACT
As aging proceeds, fertility problems arise, and the success rate of in vitro fertilization declines. During reproductive aging, rat ovaries present spontaneous formation of cysts, followed by a concomitant increase in sympathetic nerve activity, causing infertility and cessation of ovarian function. ß2-Adrenergic receptors, which are activated by noradrenaline (NA), modify follicular development and steroid secretions; thus, increased nerve activity has been associated with the development and maintenance of cystic structures. The purpose of this work was to block the effect of this sympathetic activity through in vivo administration of propranolol (a ß-adrenergic receptor antagonist) to determine whether it delays cyst formation and cessation of the ovarian function in rats that had reached the subfertile period. Propranolol was administrated daily to 8- and 10-month-old rats for 2 months. Estrous cycling activity was monitored by vaginal smear, serum concentration of the steroidal hormones was determined by enzyme-immune assay and morphological analysis of the ovaries was performed using 6 µm tissue slices stained with hematoxylin-eosin. Propranolol increased the number of healthy follicles, the ovulation rate, and levels of serum sexual steroids (androstenedione, testosterone, and estradiol) and recovered estrous cycling activity. It also decreased the number of follicular cysts. These results suggest that the blockade of ß-adrenergic receptors recovered ovarian function during reproductive aging. It is suggested that propranolol induces a time-dependent extension of the subfertile window, and it could be used to increase the success rate of fertility programs in aging woman.
Subject(s)
Adrenergic beta-2 Receptor Antagonists/administration & dosage , Fertile Period/drug effects , Ovarian Cysts/drug therapy , Propranolol/administration & dosage , Animals , Down-Regulation/drug effects , Female , Humans , Menstrual Cycle/drug effects , Ovarian Cysts/genetics , Ovarian Cysts/metabolism , Ovarian Cysts/physiopathology , Ovarian Follicle/drug effects , Ovarian Follicle/metabolism , Ovarian Follicle/physiopathology , Rats , Rats, Sprague-Dawley , Receptors, Adrenergic, beta-2/genetics , Receptors, Adrenergic, beta-2/metabolismABSTRACT
OBJECTIVE: To assess the impact of omalizumab as an add-on therapy to standard treatment with inhaled corticosteroids (ICS) and long-acting beta-2 agonists (LABA) on asthma-related quality of life (QoL) in patients with severe allergic asthma. METHODS: This was a 20-week, randomized, open-label, study involving Brazilian patients (>12 years) with severe persistent allergic asthma inadequately controlled despite regular treatment with, at least, ICS (≥500 µg/day fluticasone or equivalent) + LABA. The primary objective was to assess the mean change from baseline in overall Asthma-related Quality of Life Questionnaire (AQLQ) score in omalizumab-treated patients compared with the control group. Secondary outcome measures included rescue medication use, incidence of asthma exacerbations, perception of treatment efficacy among patients, mean change from baseline in AQLQ score, and >1.5-point increase in overall AQLQ score. RESULTS: In the omalizumab group, overall AQLQ score was 3.2 (0.9) (mean [SD]) at baseline and 4.4 (1.3) at week 20 versus 3.0 (1.0) at baseline and 3.0 (1.1) at week 20 in the control group. Mean change from baseline on overall AQLQ score at week 20 in the omalizumab group was 1.2 (0.2) versus 0 (0.1) in the control group, showing a significant increase in scores from baseline in the omalizumab group (p < .001). There was also a statistically significant difference (p < .001) in the number of patients who showed a >1.5-point increase from baseline in overall AQLQ score after 20 weeks, thus indicating a better QoL in the omalizumab group. There was no significant difference with respect to the use of rescue medication, incidence of asthma exacerbation, and adverse events between treatment groups. The global evaluation of treatment effectiveness was significantly better for omalizumab (p < .001). CONCLUSION: Omalizumab was well tolerated and significantly improved the overall AQLQ score. Hence, it is a potential add-on therapy for severe persistent allergic asthma not controlled by standard prescribed treatment in Brazilian patients.