Obesity is associated with heavy menstruation that may be due to delayed endometrial repair

Abstract

Heavy menstrual bleeding is common and debilitating but the causes remain ill defined. Rates of obesity in women are increasing and its impact on menstrual blood loss (MBL) is unknown. Therefore, we quantified BMI and MBL in women not taking hormones and with regular menstrual cycles and revealed a positive correlation. In a mouse model of simulated menstruation, diet-induced obesity also resulted in delayed endometrial repair, a surrogate marker for MBL. BrdU staining of mouse uterine tissue revealed decreased proliferation during menstruation in the luminal epithelium of mice on a high-fat diet. Menstruation is known to initiate local endometrial inflammation and endometrial hypoxia; hence, the impact of body weight on these processes was investigated. A panel of hypoxia-regulated genes (VEGF, ADM, LDHA, SLC2A1) showed consistently higher mean values in the endometrium of women with obesity and in uteri of mice with increased weight vs normal controls, although statistical significance was not reached. The inflammatory mediators, Tnf and Il6 were significantly increased in the uterus of mice on a high-fat diet, consistent with a pro-inflammatory local endometrial environment in these mice. In conclusion, obesity was associated with increased MBL in women. Mice given a high-fat diet had delayed endometrial repair at menstruation and provided a model in which to study the influence of obesity on menstrual physiology. Our results indicate that obesity results in a more pro-inflammatory local endometrial environment at menstruation, which may delay endometrial repair and increase menstrual blood loss.

Changes in abdominal subcutaneous adipose tissue phenotype following menopause is associated with increased visceral fat mass

“…The study was based on cross-sectional data and consequently, causal conclusions could not be drawn. Furthermore, we cannot exclude, that differential indications for the gynecological surgeries could be related to metabolic phenotype and thereby confound the results as both uterine fibroids and heavy menstrual bleedings are more frequent with obesity 53 , 54 . However, types of surgeries were evenly distributed between pre- and postmenopausal women suggesting that the confounding effect was limited.…”

VHL Ser65 mutations enhance HIF2α signaling and promote epithelial-mesenchymal transition of renal cancer cells

“…4 C, D, 5 B). Of the hypoxia signaling, known HIFα-regulated genes include ADM [ 28 ], VEGFA [ 12 , 29 ], PDK3 [ 30 ], LOX [ 31 ], MXI1 [ 32 ], PDK1 [ 33 ], XPNPEP1 [ 34 ], SLC2A1 [ 34 ], IRS2 [ 35 ], and PFKFB3 [ 36 ], which have been shown to promote tumor growth and progression in various types of cancers. Previous reports showed that tumorigenesis is promoted via upregulation of glycolysis by ENO2 [ 37 ], PGK1 [ 38 ], ERO1A [ 39 ], P4HA1 [ 40 ], and IRS2 [ 41 ].…”

Association of Anthropometric Indices with Menstrual Abnormality among Nursing Students of Nepal: A Cross-Sectional Study

“…In the study by Yunhui Tang, the odds of having heavy menstrual bleeding were less in underweight individuals as compared to those with normal BMI [ 30 ]. Increased menstrual blood loss in obese women is attributed to delayed endometrial repair secondary to a proinflammatory local endometrial environment in obese women [ 31 ]. Likewise, delayed endometrial repair in underweight females could be liked with the role of nutrition in healing.…”