Decreased efficacy of twice-weekly intravaginal dehydroepiandrosterone on vulvovaginal atrophy.

OBJECTIVE: While daily intravaginal administration of 0.50% (6.5 mg) dehydroepiandrosterone (DHEA, prasterone) for 12 weeks has shown clinically and statistically significant effects on moderate to severe (MS) dyspareunia as the most bothersome symptom (MBS), the present study analyzes the effect of a reduced dosing regimen on MBS vaginal dryness. METHOD: Daily intravaginal 0.50% prasterone for 2 weeks followed by twice weekly for 10 weeks versus placebo. RESULTS: Maximal beneficial changes in vaginal parabasal and superficial cells and pH were observed at 2 weeks as observed for intravaginal 10 µg estradiol (E2). This was followed by a decrease or lack of efficacy improvement after switching to twice-weekly dosing. The decrease in percentage of parabasal cells, increase in percentage of superficial cells and decrease in vaginal pH were all highly significant (p < 0.0001 to 0.0002 over placebo) at 12 weeks. In parallel, the statistical significance over placebo (p value) on MBS vaginal dryness at 6 weeks was 0.09 followed by an increase to 0.198 at 12 weeks. For MBS dyspareunia, the p value of 0.008 at 6 weeks was followed by a p value of 0.077 at 12 weeks, thus illustrating a decrease of efficacy at the lower dosing regimen. The improvements of vaginal secretions, color, epithelial integrity and epithelial surface thickness were observed at a p value < 0.01 or 0.05 over placebo at 2 weeks, with a similar or loss of statistical difference compared to placebo at later time intervals. No significant adverse event was observed. Vaginal discharge related to the melting of Witepsol was reported in 1.8% of subjects. CONCLUSION: The present data show that daily dosing with 0.50% DHEA for 2 weeks followed by twice-weekly dosing is a suboptimal treatment of the symptoms/signs of vulvovaginal atrophy resulting from a substantial loss of the efficacy achieved at daily dosing.

Glutamine does not increase ammonia in systemically drained small bowel transplants.

Glutamine (Gln) enhances small bowel function and ameliorates acute injury, but its metabolism generates portal ammonia (NH4), which normally is detoxified by the liver. Its beneficial use in small bowel transplantation (SBTx) therefore, may be offset by hyperammonemia, since such grafts may be systemically drained. We tested the hypothesis that oral glutamine supplementation increases plasma NH4 in rats with systemically drained SBTx. Lewis rats with isologous SBTx had plasma NH4 and Gln assayed during isonitrogenous, isocaloric Gln dietary supplementation and were compared to controls. Plasma NH4 levels were higher in the SBTx group during all dietary manipulations, consistent with previous studies. A Gln-deficient diet (0%) caused plasma Gln levels to fall in both experimental and control animals, but had no consistent effect on NH4 levels. With Gln supplementation (12.5 and 25% of total protein) Gln levels returned to baseline but again, plasma NH4 levels did not significantly change. We conclude that oral glutamine supplementation given in an isonitrogenous manner does not increase ammonia beyond that which is usually seen in animals with systemically drained SBTx. This suggests that Gln-enriched diets are not specifically contraindicated in patients with systemically drained SBTx and may be beneficial.