A PROTON PUMP INHIBITOR ALTERS THE pH OF THE HUMAN UTERINE CAVITY

Abstract

To present two cases of increased pH of the uterine cavity after taking lansoprazole, an oral proton pump inhibitor (PPI). Case study. We examined infertile women to see whether chronic endometritis (CE) existed, through assessment of endometrial plasma cells (CD138 immunostained cells) and uterine microbiota by sequencing the 16S ribosomal RNA gene (Varinos Inc., Japan). CE was diagnosed applying the criteria (>5.15/10xmm2) reported by Liu et al. (1). We also examined the intrauterine pH directly on the endometrial surface using a Portal pH Meter (Japan Asch Inc., Japan) that has been utilized for the esophageal mucosa of esophagitis (2). We have reported in ESHRE annual meeting 2020 that intrauterine pH is weakly acidic (5.58±0.59) and it increases in the case of CE (6.67±0.39). Patient 1: A 44-year-old infertile woman noticed changes of her vaginal discharge after taking orally lansoprazole 30 mg for reflux esophagitis. Her initial intrauterine condition had been normal with pH: 6.3, Lactobacillus: 97%, and CD138-positive cells: 1.7/10xmm2. After PPI intake for a month, her intrauterine pH rose to 7.0, which suggested existence of CE. Therefore, we collected the endometrial tissue again and performed microbiota and pathological tests: Lactobacillus was 99% and CD138-positive cells were 1.6/10xmm2, which did not indicate CE histologically and bacterially. After discontinuing PPI, her intrauterine pH dropped to 6.7 with Lactobacillus: 97% and CD138-positive cells: 2.0/10xmm2. Patient 2: A 47-year-old woman, whose initial uterine pH had been 6.4, noticed a change of odor of vaginal discharge after taking PPI (lansoprazole 30 mg daily) for gastric ulcer. Her intrauterine pH rose to 7.1 with Lactobacillus :9.1% and CD138-positive cells: 0.7/10xmm2. After discontinuation of PPI, her intrauterine pH dropped to 6.2 with no CD138-positive cells, but Lactobacillus was 2.60%. We experienced two cases in which the pH of uterine cavity increased while taking oral PPI. We have reported that the uterine luminal pH in human is weakly acidic (around 6.0) and that the pH increases in the presence of CE or abnormal endometrial microbiota. In animals, such as mice (3) and mares (4), the uterine luminal pH is acidic at the time of implantation, and the acidic environment in the uterus is considered to be important for embryo implantation, and the vacuolar H + -ATPase pump, which is a type of proton pump, is expressed in the endometrium at the time of implantation in bovine (5) and mice (2), but there have been no reports in humans. These 2 cases which we presented here suggest that some proton pumps are also expressed in the endometrium and acidify the uterine cavity in humans, which could control the intrauterine environment independently of inflammation or microbiota.