An overlooked connection: serotonergic mediation of estrogen-related physiology and pathology

BACKGROUND: In humans, serotonin has typically been investigated as a neurotransmitter. However, serotonin also functions as a hormone across animal phyla, including those lacking an organized central nervous system. This hormonal action allows serotonin to have physiological consequences in systems outside the central nervous system. Fluctuations in estrogen levels over the lifespan and during ovarian cycles cause predictable changes in serotonin systems in female mammals. DISCUSSION: We hypothesize that some of the physiological effects attributed to estrogen may be a consequence of estrogen-related changes in serotonin efficacy and receptor distribution. Here, we integrate data from endocrinology, molecular biology, neuroscience, and epidemiology to propose that serotonin may mediate the effects of estrogen. In the central nervous system, estrogen influences pain transmission, headache, dizziness, nausea, and depression, all of which are known to be a consequence of serotonergic signaling. Outside of the central nervous system, estrogen produces changes in bone density, vascular function, and immune cell self-recognition and activation that are consistent with serotonin's effects. For breast cancer risk, our hypothesis predicts heretofore unexplained observations of the opposing effects of obesity pre- and post-menopause and the increase following treatment with hormone replacement therapy using medroxyprogesterone. SUMMARY: Serotonergic mediation of estrogen has important clinical implications and warrants further evaluation

A lifestyle intervention program for successfully addressing major cardiometabolic risks in persons with SCI: a three-subject case series

INTRODUCTION: This study is a prospective case series analyzing the effects of a comprehensive lifestyle intervention program in three patients with chronic paraplegia having major risks for the cardiometabolic syndrome (CMS). CASE PRESENTATION: Individuals underwent an intense 6-month program of circuit resistance exercise, nutrition using a Mediterranean diet and behavioral support, followed by a 6-month extension (maintenance) phase involving minimal support. The primary goal was a 7% reduction of body mass. Other outcomes analyzed insulin resistance using the HOMA-IR model, and plasma levels of fasting triglycerides and high-density lipoprotein cholesterol. All participants achieved the goal for 7% reduction of body mass and maintained the loss after the MP. Improvements were observed in 2/3 subjects for HOMA-IR and high-density lipoprotein cholesterol. All participants improved their risk for plasma triglycerides. DISCUSSION: We conclude, in a three-person case series of persons with chronic paraplegia, a lifestyle intervention program involving circuit resistance training, a calorie-restrictive Mediterranean-style diet and behavioral support, results in clinically significant loss of body mass and effectively reduced component risks for CMS and diabetes. These results were for the most part maintained after a 6-month MP involving minimal supervision