Current Opinion in Endocrinology & Diabetes and Obesity最新文献

Purpose of review: Rates of unintended pregnancy have remained relatively stagnant for many years, despite a broad array of female contraceptive options. Recent restrictions on access to abortion in some countries have increased the urgency for expanding contraceptive options. Increasing data suggest men are keen to utilize novel reversible male contraceptives.

Recent findings: Despite decades of clinical research in male contraception, no reversible hormonal product currently exists. Nestorone/testosterone, among other novel androgens, shows promise to finally move to pivotal Phase 3 studies and introduction to the marketplace.

Summary: Hormonal male contraception utilizes androgens or androgen-progestin combinations to exploit negative feedback that regulates the hypothalamic-pituitary-testicular axis. By suppressing release of gonadotropins, these agents markedly decrease endogenous testosterone production, lower intratesticular testosterone and suppress spermatogenesis. The addition of a progestin enhances the degree and speed of sperm suppression. The androgen component preserves a state of symptomatic eugonadism in the male. There is growing demand and acceptance of male contraceptive options in various forms. As these formulations progress through stages of drug development, regulatory oversight and communication with developers around safety and efficacy standards and garnering industry support for advancing the production of male contraceptives will be imperative.

Purpose of review: Adolescents often have irregular menstrual cycles after menarche until the reproductive axis fully matures. This review explores how menstrual regularity is established and the health risks associated with prolonged time to cycle regularity in adolescents.

Recent findings: Cross-sectional studies show an association between prolonged time to cycle regularity in adolescents and increased risks for ongoing menstrual dysfunction, cardiometabolic disorders, cancers, and overall mortality. Importantly, some of these cardiometabolic associations are independent of PCOS status.

Summary: The menstrual cycle can be used as a vital sign for assessing overall health. While further longitudinal studies are needed to establish causal relationships, these findings highlight a crucial window for early intervention in adolescents with prolonged time to cycle regularity to mitigate future risks.

Purpose of review: The increasing rate of obesity is having an adverse impact on male reproduction.

Recent findings: The negative effect of reactive oxygen species on male reproductive tissues and the age of onset of obesity are new areas of research on male infertility.

Summary: This review highlights how obesity impairs male reproduction through complex mechanisms, including metabolic syndrome, lipotoxicity, sexual dysfunction, hormonal and adipokine alterations as well as epigenetic changes, and how new management strategies may improve the reproductive health of men throughout life.

Purpose of review: Type 2 diabetes (T2D) is increasing to epidemic proportions and frequently associated with obesity and a low serum testosterone concentration in men. This review valuates recent randomized controlled trials (RCTs) investigating the effect of testosterone treatment on glycemic control and T2D prevention.

Recent findings: The 2-year Testosterone for the Prevention of Type 2 diabetes Trial (T4DM) study showed that in men aged 50 years and over with visceral obesity and impaired glucose tolerance, testosterone treatment on the background of a lifestyle intervention reduced T2D risk by 40%. The Testosterone Effects on Atherosclerosis Progression in Aging Men and Testosterone Trials demonstrated modest improvements in insulin sensitivity and body composition. However, the Testosterone Replacement Therapy for Assessment of Long-Term Vascular Events and Efficacy Response in Hypogonadal Men trial found no significant glycemic benefits over 2 years. Recent data from the Diabetes Prevention Program Outcome Study support the cost efficacy and durability of metformin.

Summary: In men at high risk of T2D, treatment with testosterone prevents the disease; however, there are caveats to its use and other approaches may be more applicable. Differences in trial designs, age groups, and outcome measures contribute to varying results. HbA1C is a suboptimal outcome measure. Future research should explore potential synergies between testosterone and GLP-1 receptor agonists in T2D management, while considering cost-effectiveness.

Purpose of review: Due to technical requirements and high cost, equilibrium dialysis-free testosterone (T) measurements are not commonly available in clinical practice. Clinicians rely on calculated free T (cFT) as a proxy. This review discusses using free T as a second-line assessment, highlighting its relevance in preventing misdiagnosis and overtreatment of male hypogonadism.

Recent findings: While there is consensus on measuring total T - comprising sex hormone-binding globulin (SHBG)-bound, albumin-bound, and free T - as a first step in diagnosing male hypogonadism, evidence confirms that aging and conditions like obesity influence both total T and SHBG levels. Furthermore, low free T has been associated with symptoms of androgen deficiency, even in men with normal total T. Clinicians should, however, be aware of limitations of free T calculations, particularly the lack of standardization. Recent developments include establishing age-stratified free T reference ranges measured by equilibrium dialysis.

Summary: Free T remains a subject of longstanding controversy. Factors such as age and obesity can alter total T and SHBG levels. Free T serves as a second-line indicator of androgen exposure, taking SHBG fluctuations into account. Given that commonly used free T calculators only provide approximations of free T, there is a need to further standardize free T calculators.

Purpose of review: Physical activity (PA) is acknowledged as an important component of lifestyle therapy in the management of polycystic ovary syndrome (PCOS). The purpose of this current systematic review is to analyze recent literature assessing the role of PA and exercise interventions as potential treatment for PCOS.

Recent findings: The recent literature published since 2022 has focused on understanding the specific benefits of different PA modalities on PCOS pathophysiology, suggesting that high intensity exercise may relay greater metabolic improvements, although results are still inconclusive; expanding our understanding of the impact PA has on a wider range of outcomes, including sleep, quality of life, inflammation, and DNA methylation; and recognizing barriers and limitations of implementing efficacious PA interventions for individuals with PCOS.

Summary: Current literature supports a role for PA in improving PCOS-related cardiometabolic and reproductive outcomes; however, there is still a significant evidence gap of high-quality studies assessing optimal exercise regimens as well as strategies for implementing PA interventions in real-world settings for individuals with PCOS.

Purpose of review: This review highlights emerging evidence supporting the premise of precision diabetes care including but not limited to monogenic diabetes and discuss potential opportunities, challenges, and limitations for clinical adoption.

Recent findings: Driven by a single gene mutation, monogenic diabetes remains the best use-case for precision diabetes care. However, the increasing prevalence of diabetes among adolescents and young adults in an obesogenic environment makes triaging potential patients for genetic screening clinically challenging. High-dimensional molecular biomarkers (i.e., multiomics) can improve the risk prediction for incident type 2 diabetes (T2D), over and above a well established prediction model based on clinical variables alone. Machine learning approaches using clinical variable-based clustering methods have generated novel and reproducible T2D subgroups with distinct phenotypic and omics characteristics that are associated with differential long-term outcomes. This stratification-strategy may inform clinical decisions. However, on-going discussion and research will be needed to understand the clinical utility of sub-phenotyping T2D for precision care.

Summary: Precision diabetes care has extended from uncommon monogenic diabetes to T2D which will need more complex approaches like multiomics and machine-learning methods. The successful clinical translation will require cumulative evidence and close collaboration among the stake holders.

Purpose of review: Evolving understanding of thyroid eye disease (TED) has led to rapidly advancing therapeutic options. Most new treatments under development or recently available to patients are predicated on insights into disease mechanism.

Recent findings: TED, a disfiguring process, involves inflammation and remodeling of the connective tissues around the eye. TED most frequently presents as a component of Graves' disease. Advances in our understanding of cells involved in TED and their molecular interactions have led to novel therapeutic targets. Among these cell types are orbital fibroblasts and a subset comprising monocyte progenitor cells, known as CD34 + CXCR4 + fibrocytes. Among the attributes of fibrocytes is their expression of several autoantigens associated with Graves' disease, including TSHR, thyroglobulin and thyroperoxidase. Fibrocytes also express high levels of the insulin-like growth factor-I (IGF-I) receptor, thought to mediate fibroblast activation. Therapeutically targeting the TSHR/IGF-IR receptor complex using an IGF-I receptor antagonist, teprotumumab, has resulted in substantial clinical benefit for patients with TED. The neural axon repellent, Slit2, and its cognate receptor, ROBO1, appear to modulate the inflammatory phenotype of these orbit-infiltrating fibrocytes.

Summary: More detailed understanding of orbital fibroblasts and the distinctions between cell subsets comprising them should lead to more effective therapies with fewer side effects.

Purpose of review: To analyze the evolving epidemiologic trends in thyroid disease, focusing on risk factors, underlying drivers of these changes, and their implications on clinical practice and research priorities.

Recent findings: Thyroid disease remains one of the most prevalent groups of disorders globally, and the shift in its frequency and distribution is multifactorial. The prevalence of hypothyroidism increases with age, although normal thyrotropin ranges appear to be age-dependent, raising concern for potentially inappropriate levothyroxine use. Hyperthyroidism and Graves' disease continue to be predominant in reproductive-age women but exhibit a milder phenotype at diagnosis. Thyroid nodules are increasingly found in asymptomatic patients, likely from more widespread use of neck and chest imaging. Thyroid cancer incidence has risen exponentially over the years, mostly driven by overdiagnosis of low-risk tumors; however, a small rise in incidence of higher risk tumors has been noted. Obesity appears to be a risk factor for thyroid cancer occurrence and more aggressive forms of the disease.

Summary: Understanding epidemiologic trends in thyroid disease is crucial for guiding clinical practice and research efforts, aiming to optimize patient outcomes while preventing unnecessary and potentially harmful interventions.