madman
Super Moderator
Abstract
This review thoroughly explores the multifaceted roles of sexual hormones, emphasizing their impact beyond reproductive functions and underscoring their significant influence on cardiometabolic regulation. It analyzes the broader physiological implications of estrogen, testosterone, and progesterone, highlighting their effects on metabolic syndrome, lipid metabolism, glucose homeostasis, and cardiovascular health. Drawing from diverse molecular, clinical, and therapeutic studies, the paper delves into the intricate interplay between these hormones and cardiometabolic processes. By presenting a comprehensive analysis that goes beyond traditional perspectives, and recognizing sexual hormones as more than reproductive agents, the review sheds light on their broader significance in health and disease management, advocating for holistic and personalized medical approaches.
Sexual hormones: an overview
Sexual hormones, notably estrogens, progesterone, and androgens, play crucial roles beyond reproduction, being key regulators of metabolism and cardiovascular health.
Estrogens
In the female body, estrogen is predominantly produced in the ovaries, adrenal glands, and adipose tissues, playing a central role in regulating the menstrual cycle, reproductive system, and lipid metabolism[6]. Although in lower concentrations in men, estradiol is integral to male sexual health, harmonizing with testosterone to oversee libido, erectile function, and sperm development [7].
Progesterone
Progesterone mainly in females, acts via nuclear progesterone receptors (PGR) and a series of membrane receptors, mPRα through mPRε [8, 9] to regulate the menstrual cycle, prepare the endometrium for implantation, support fetal development, and enhance bone health by promoting osteoblast activity [10]. In males, it is also involved in spermiogenesis, sperm capacitation, and testosterone synthesis while modulating gonadotropin secretion and aiding sleep[11].
Androgens
Androgens including testosterone, dihydrotestosterone(DHT), and androstenedione, are synthesized in the gonads and adrenal glands and exert their biological effects through both genomic and non-genomic mechanisms. Testosterone is a principal androgen, a class of steroid hormones that plays an essential role in the development of male secondary sexual characteristics and reproductive function. The classical genomic mechanism involves nuclear androgen receptors (AR), which, upon binding testosterone, regulate gene expression that governs secondary sexual characteristics, muscle maintenance, and functions within the central nervous system. These changes are typically more gradual,with gene expression alterations unfolding over hours to days [17, 18]. Complementarily, androgens, particularly testosterone also engage non-genomic pathways through membrane receptors, rapidly altering cellular activity. These receptors, notably G Protein-Coupled Receptor class Cgroup 6 member A (GPRC6A) and the zinc transporter ZIP9(SLC39A9), are pivotal in initiating swift intra cellular signaling cascades. GPRC6A mediates rapid signaling responses including the activation of intracellular calcium release, while ZIP9 binds testosterone and triggers pathways involving calcium mobilization and MAPK activation [19].The molecular identity of membrane androgen receptors(mARs) is diverse, and although not fully characterized, they are known to modulate processes such as cell proliferation and apoptosis.
While nuclear receptors are classically associated with genomic effects and G Protein-Coupled Receptors (GPCRs) are classically associated with non-genomic effects, both types of receptors can mediate both genomic and non-genomic responses depending on the context and the specific signaling pathways involved [1–3].
This orchestration between nuclear and membrane receptors and their ligands represents an intricate network, which is crucial for the body homeostasis. Understanding this complex interplay is key to advancing therapeutic strategies in the realms of endocrine and metabolic health, where we can utilise dual signaling potential of these hormones through both genomic and non-genomic pathways.
Sexual hormones and metabolic regulation
Overview of metabolic syndrome (MetS), definition and diagnostic criteria
Sex hormones and fat mass
*In summary, sex hormones significantly influence body fat distribution and metabolic activity, contributing to sex specific cardiometabolic risks. While visceral fat is linked to higher MetS risk in males, subcutaneous fat in females offers some metabolic protection. The underlying mechanism may include that estrogen increases BAT activity, which influences energy expenditure and body fat distribution
Sex hormones and lipid metabolism
Estrogens
Progesterone
Androgens
*In summary, estrogens progesterone and androgens regulate lipid metabolism through complex interactions with enzymes, adipocyte differentiation, and adipogenesis. These hormones exert their effects in a sex-specific manner, contributing to the distinct patterns of fat distribution and metabolic profiles observed in men and women. The roles of estrogen, progesterone, and testosterone in lipid metabolism are summarized in Figure 2.
Sex hormone in glucose homeostasis
Estrogens
Progesterone
Androgens
*In conclusion, testosterone, estradiol, and progesterone all play specific and significant roles in regulating β-cell function, glucose levels, and insulin sensitivity. However, the relationships between these hormones and various metabolic processes are complex and influenced by various factors.
The role of sexual hormones in cardiovascular diseases
The role of sex hormones in hypertension and vascular aging
Estrogens
Androgens
The role of sex hormones in coronary artery disease
The role of sex hormone-binding globulin (SHBG) in metabolic syndrome and CVD
Summary and perspective
Sex hormones, encompassing androgen, estrogen, and progesterone, play vital roles in regulating energy metabolism and cardiovascular function. This review elucidates the extensive impact of sexual hormones beyond their conventional reproductive functions, providing a detailed analysis of how testosterone, estrogen, and progesterone uniquely contribute to cardiometabolic health. It becomes clear that testosterone influences muscle mass, body fat, insulin sensitivity, and metabolic rate. Estrogen exhibits favorable effects on lipid metabolism, contributing to vascular health and cardio protection. Progesterone, frequently examined alongside estrogen, exhibits unique effects on glucose metabolism and may also exert an influence on vascular response. Acknowledging the dual role of sexual hormones in both metabolic and cardiovascular systems underscore the need for a more integrated approach in research and medical treatment. This provides novel perspectives for managing these conditions medically.
The insights into the roles of estrogen, testosterone, and progesterone in cardiometabolic health could lead to novel diagnostic markers for metabolic syndrome or cardiovascular diseases. For example, considering SHBG levels as a predictor for cardiovascular events could shift how we evaluate risk and manage patient care. Moreover, the distinction understanding of how these hormones influence inflammation and lipid metabolism might help the development of personalized hormone replacement therapies, which could be tailored to mitigate the risk of metabolic syndrome, diabetes, or atherosclerosis in patients with hormone deficiencies. Furthermore, the significant roles of sex hormones in metabolic processes and cardiovascular health could lead to the development of personalized treatment strategies based on an individual’s sex hormone profile. For instance, individuals with certain hormonal imbalances could be treated with specific hormone therapies to improve their metabolic health.
Collaborative efforts between endocrinologists, cardiologists, and researchers could foster new interdisciplinary treatment protocols and potentially lead to the development of new pharmaceutical treatments that modulate hormone levels or their activity to improve cardiometabolic health outcomes.
This review thoroughly explores the multifaceted roles of sexual hormones, emphasizing their impact beyond reproductive functions and underscoring their significant influence on cardiometabolic regulation. It analyzes the broader physiological implications of estrogen, testosterone, and progesterone, highlighting their effects on metabolic syndrome, lipid metabolism, glucose homeostasis, and cardiovascular health. Drawing from diverse molecular, clinical, and therapeutic studies, the paper delves into the intricate interplay between these hormones and cardiometabolic processes. By presenting a comprehensive analysis that goes beyond traditional perspectives, and recognizing sexual hormones as more than reproductive agents, the review sheds light on their broader significance in health and disease management, advocating for holistic and personalized medical approaches.
Sexual hormones: an overview
Sexual hormones, notably estrogens, progesterone, and androgens, play crucial roles beyond reproduction, being key regulators of metabolism and cardiovascular health.
Estrogens
In the female body, estrogen is predominantly produced in the ovaries, adrenal glands, and adipose tissues, playing a central role in regulating the menstrual cycle, reproductive system, and lipid metabolism[6]. Although in lower concentrations in men, estradiol is integral to male sexual health, harmonizing with testosterone to oversee libido, erectile function, and sperm development [7].
Progesterone
Progesterone mainly in females, acts via nuclear progesterone receptors (PGR) and a series of membrane receptors, mPRα through mPRε [8, 9] to regulate the menstrual cycle, prepare the endometrium for implantation, support fetal development, and enhance bone health by promoting osteoblast activity [10]. In males, it is also involved in spermiogenesis, sperm capacitation, and testosterone synthesis while modulating gonadotropin secretion and aiding sleep[11].
Androgens
Androgens including testosterone, dihydrotestosterone(DHT), and androstenedione, are synthesized in the gonads and adrenal glands and exert their biological effects through both genomic and non-genomic mechanisms. Testosterone is a principal androgen, a class of steroid hormones that plays an essential role in the development of male secondary sexual characteristics and reproductive function. The classical genomic mechanism involves nuclear androgen receptors (AR), which, upon binding testosterone, regulate gene expression that governs secondary sexual characteristics, muscle maintenance, and functions within the central nervous system. These changes are typically more gradual,with gene expression alterations unfolding over hours to days [17, 18]. Complementarily, androgens, particularly testosterone also engage non-genomic pathways through membrane receptors, rapidly altering cellular activity. These receptors, notably G Protein-Coupled Receptor class Cgroup 6 member A (GPRC6A) and the zinc transporter ZIP9(SLC39A9), are pivotal in initiating swift intra cellular signaling cascades. GPRC6A mediates rapid signaling responses including the activation of intracellular calcium release, while ZIP9 binds testosterone and triggers pathways involving calcium mobilization and MAPK activation [19].The molecular identity of membrane androgen receptors(mARs) is diverse, and although not fully characterized, they are known to modulate processes such as cell proliferation and apoptosis.
While nuclear receptors are classically associated with genomic effects and G Protein-Coupled Receptors (GPCRs) are classically associated with non-genomic effects, both types of receptors can mediate both genomic and non-genomic responses depending on the context and the specific signaling pathways involved [1–3].
This orchestration between nuclear and membrane receptors and their ligands represents an intricate network, which is crucial for the body homeostasis. Understanding this complex interplay is key to advancing therapeutic strategies in the realms of endocrine and metabolic health, where we can utilise dual signaling potential of these hormones through both genomic and non-genomic pathways.
Sexual hormones and metabolic regulation
Overview of metabolic syndrome (MetS), definition and diagnostic criteria
Sex hormones and fat mass
*In summary, sex hormones significantly influence body fat distribution and metabolic activity, contributing to sex specific cardiometabolic risks. While visceral fat is linked to higher MetS risk in males, subcutaneous fat in females offers some metabolic protection. The underlying mechanism may include that estrogen increases BAT activity, which influences energy expenditure and body fat distribution
Sex hormones and lipid metabolism
Estrogens
Progesterone
Androgens
*In summary, estrogens progesterone and androgens regulate lipid metabolism through complex interactions with enzymes, adipocyte differentiation, and adipogenesis. These hormones exert their effects in a sex-specific manner, contributing to the distinct patterns of fat distribution and metabolic profiles observed in men and women. The roles of estrogen, progesterone, and testosterone in lipid metabolism are summarized in Figure 2.
Sex hormone in glucose homeostasis
Estrogens
Progesterone
Androgens
*In conclusion, testosterone, estradiol, and progesterone all play specific and significant roles in regulating β-cell function, glucose levels, and insulin sensitivity. However, the relationships between these hormones and various metabolic processes are complex and influenced by various factors.
The role of sexual hormones in cardiovascular diseases
The role of sex hormones in hypertension and vascular aging
Estrogens
Androgens
The role of sex hormones in coronary artery disease
The role of sex hormone-binding globulin (SHBG) in metabolic syndrome and CVD
Summary and perspective
Sex hormones, encompassing androgen, estrogen, and progesterone, play vital roles in regulating energy metabolism and cardiovascular function. This review elucidates the extensive impact of sexual hormones beyond their conventional reproductive functions, providing a detailed analysis of how testosterone, estrogen, and progesterone uniquely contribute to cardiometabolic health. It becomes clear that testosterone influences muscle mass, body fat, insulin sensitivity, and metabolic rate. Estrogen exhibits favorable effects on lipid metabolism, contributing to vascular health and cardio protection. Progesterone, frequently examined alongside estrogen, exhibits unique effects on glucose metabolism and may also exert an influence on vascular response. Acknowledging the dual role of sexual hormones in both metabolic and cardiovascular systems underscore the need for a more integrated approach in research and medical treatment. This provides novel perspectives for managing these conditions medically.
The insights into the roles of estrogen, testosterone, and progesterone in cardiometabolic health could lead to novel diagnostic markers for metabolic syndrome or cardiovascular diseases. For example, considering SHBG levels as a predictor for cardiovascular events could shift how we evaluate risk and manage patient care. Moreover, the distinction understanding of how these hormones influence inflammation and lipid metabolism might help the development of personalized hormone replacement therapies, which could be tailored to mitigate the risk of metabolic syndrome, diabetes, or atherosclerosis in patients with hormone deficiencies. Furthermore, the significant roles of sex hormones in metabolic processes and cardiovascular health could lead to the development of personalized treatment strategies based on an individual’s sex hormone profile. For instance, individuals with certain hormonal imbalances could be treated with specific hormone therapies to improve their metabolic health.
Collaborative efforts between endocrinologists, cardiologists, and researchers could foster new interdisciplinary treatment protocols and potentially lead to the development of new pharmaceutical treatments that modulate hormone levels or their activity to improve cardiometabolic health outcomes.
