Estrogens and Gastroparesis: A Clinical Relevance

Abstract

Normal gastric emptying requires coordinated function of upper stomach fundus, lower body, antrum, and pylorus. Gastric motility is controlled by a very complex set of neuornal and hormonal signals. Several cell types, including the extrinsic innervation to the stomach, enteric nerves, glia, smooth muscle cells, interstitial cell of Cajal (ICC), and immune cells are known to be responsible for normal gastric motility functions. It has been shown that, in diabetic as well as idiopathic patients, the lack of functional coordination between these cell types may have been lost; therefore, the motility of the stomach is impaired and thus leads to abnormal gastric emptying [1]. Gastroparesis is a chronic motility disorder defined as delayed gastric emptying of solids and liquids in the absence of obstruction. The most common forms include idiopathic, diabetic, and post-surgical complications [1–3]. The majority of idiopathic patients are either obese or overweight [3]. A significant limitation to developing targeted therapy for gastroparesis is a lack of understanding of the pathological and cellular etiology. Women, in particular the younger population with a mean age of 33–44 years, are more susceptible for gastroparesis than age-matched men [1–3]. Ovarian hormonal influence has been proposed as a major contributor to changes observed in gastric emptying in both health and disease states [4]. Most of our understanding for gastroparesis has come from animal studies focused on diabetic, hyperlipidemia, and oxidative stress-induced gastroparesis (reviewed in detail in [4]). Most recently, Ravella et al. [5] demonstrated that lack of sex hormones can lead to impaired nitrergic function leading to delayed gastric emptying. Studies published in experimental diabetic rats have demonstrated that serum estrogens are elevated, and this may be somewhat harmful for altered gastric emptying [6]. In contrast, Mankhey et al. [7] demonstrated that diabetes induction reduced serum estrogen levels and that supplementation of this hormone improved renal function. It is important to note that the type of methodologies that were utilized in measuring hormone concentrations, diabetes duration, dietary conditions (animal chow contains phytoestrogens), and cellular changes occurring due to chronic hyperglycemia versus estrogen treatment, may negatively influence the actual levels of hormones and/or their gastric receptors localized in enteric neurons. Finally, this may provide a misleading interpretation of the beneficial effects of these hormones on regulating gastric motility. In contrast, other studies have shown that, in general, gastric emptying is slower in young female rodents than age-matched male counterparts, and that estrogen may be the contributor for observed slower gastric emptying in both pregnant and non-pregnant rodents (reviewed in detail in [4]). Nevertheless, the above studies undoubtedly suggest that endogenous sex hormones may play an important role in gastric motility functions in females, and that a change in hormone levels and/or their receptor concentrations may drastically affect the stomach motility function that is seen in a diabetic or idiopathic setting [4]. However, as noticed with animal experiments, conflicting findings exist with regards to hormones and gut function in human studies. Estrogen and progesterone have inhibitory effects on smooth muscle of the lower esophageal sphincter, pylorus, and small bowel muscle strips, J. N. Rao Department of Surgery, University of Maryland School of Medicine, Baltimore, MD 21201, USA