Cardiovascular Risk with Gender‑Affirming Hormone Therapy
Gender incongruence refers to a persistent mismatch between an individual’s experienced gender and the sex assigned at birth. While modern terminology is recent, descriptions of gender variance date back to antiquity, including writings attributed to Hippocrates. By the 7th century, Paul of Aegina, in his Medical Compendium, described surgical procedures aimed at modifying sex characteristics. While these early interventions were not grounded in a modern understanding of gender identity, they reflect attempts to address distress related to discordance between physical characteristics and lived experience. For much of history, surgical intervention—most commonly orchiectomy—remained the primary medical approach. A more structured medical understanding began to emerge in the early 20th century, including the establishment of early centres dedicated to the study and care of gender‑diverse individuals. In modern practice, access to gender‑affirming hormone therapy (GAHT) and surgical interventions has improved. However, there remains a relative paucity of high-quality clinical research to guide management. Randomized controlled trials are lacking, and current recommendations are largely based on retrospective observational studies and extrapolation from cisgender populations. This limited evidence base makes it challenging to balance treatment goals with risk mitigation—particularly with respect to cardiovascular disease. This brief review aims to summarize the current evidence and provide a practical framework for clinicians.
Copyright (c) 2026 Canadian Diabetes & Endocrinology Today https://creativecommons.org/licenses/by-nc-nd/4.0
Perimenopause: Considerations for the Endocrinologist
Perimenopause is a clinically defined reproductive transition characterized by menstrual-cycle variability, fluctuating ovarian hormone secretion, and symptoms that often overlap with endocrine disease. Endocrinologists are well positioned to distinguish physiological reproductive aging from thyroid disease, hyperprolactinemia, pregnancy, premature ovarian insufficiency, and other causes of oligo-amenorrhea; to identify abnormal uterine bleeding requiring gynecologic evaluation; and to address the concurrent emergence of cardiometabolic and skeletal risk. Management should be symptom-directed and should explicitly separate the need for contraception and cycle control from the use of menopausal hormone therapy. This review presents a practical, evidence-based approach to diagnosis, risk assessment, and treatment for the endocrinology setting.
Low Risk for Recurrence of Differentiated Thyroid Cancer: A Paradigm Shift to De-Escalation and Simplifying Care for Long Term Follow-up
The incidence of thyroid cancer in Canada increased from 1984 to 2013, followed by a subsequent decline; the most recent projections estimate 6,100 cases in 2026. Low-risk differentiated thyroid cancer (DTC), with an excellent treatment response, is associated with a recurrence risk of less than 2% and a 20-year disease specific mortality of less than 1%. In alignment with the 2025 American Thyroid Association DTC Guidelines and the Follow-up and Transition of Care for Low Recurrence Risk Thyroid Cancer Patients in Canada, thyroid cancer care is undergoing a major evolution. This shift is centred around de-escalation of care, and for the first time, provides guidance on when to consider cessation of surveillance. For patients who have undergone hemithyroidectomy, recommended follow-up includes a one-time post-operative measurement of thyroglobulin (TG) with thyroglobulin antibodies (TGAB), annual thyroid-stimulating hormone (TSH) monitoring (targeted within the reference range), and ultrasound surveillance at 1–3 years. Consideration may then be given to cessation of all monitoring after 5–8-years. For patients undergoing total thyroidectomy (TT) without radioactive iodine (RAI), the new target for a biochemical excellent response is <2.5 ng/mL as well as a TSH level within the normal reference range. In this population, ultrasound is recommended at 1–3-year intervals following the initial assessment, with consideration of discontinuation between years 5–8 in patients demonstrating an excellent response; Canadian guidelines also recommend cessation of surveillance at year 5. Furthermore, for patients undergoing TT with or without RAI who maintain an excellent response, continued biochemical monitoring beyond 10–15 years is not required. Key elements of care for patients with low-risk thyroid cancer include reduced ultrasound surveillance, maintaining the TSH target within the normal reference range, annual TG/TGAB monitoring, and consideration of cessation of surveillance. Adoption of these principles will enhance patient care while maintaining excellent outcomes.
Use of Once-Weekly Insulin Icodec in the Perioperative and Inpatient Settings
Hyperglycemia in hospitalized patients is associated with increased morbidity, mortality, and healthcare utilization, and effective glycemic management remains a central component of inpatient care. Basal insulin therapy is a cornerstone of this management strategy, traditionally relying on once-daily long-acting insulin analogs that allow for flexible titration. Insulin icodec, a once-weekly basal insulin analog, represents a significant therapeutic advance by reducing injection burden and providing stable pharmacokinetics; however, it also introduces new challenges in acute care settings. Insulin icodec exhibits reversible albumin binding and a prolonged half-life of approximately 196 hours (~8 days). It reaches a steady state after 3–4 weekly injections and is associated with a relatively flat, sustained glucose-lowering profile. While these properties are advantageous in the outpatient setting, they limit the ability to rapidly titrate insulin dosing in response to acute illness, fasting, or surgical stress. This reduced flexibility raises concerns regarding its safety and practicality in hospitalized and perioperative patients, where insulin requirements may change abruptly. Diabetes Canada inpatient guidance emphasizes the importance of individualized insulin regimens and the ability to adjust therapy dynamically in response to changing clinical status, principles that may be more difficult to implement with once-weekly insulin formulations. This review focuses on adults with type 2 diabetes, in whom most clinical experience with insulin icodec has been accumulated.
Losing Weight, Losing Muscle? Muscle Health During GLP-1-Based Obesity Therapy
Glucagon-like peptide-1 receptor agonists (GLP-1RAs) and related nutrient-stimulated hormone (NuSH) therapies have transformed obesity pharmacotherapy, delivering weight loss approaching that seen with bariatric surgery. However, concerns have emerged regarding loss of fat‑free mass, skeletal muscle mass, and possible sarcopenia. Reductions in lean mass occur during treatment with semaglutide and tirzepatide, but these changes are generally proportional to total weight loss and occur alongside greater reductions in fat mass, visceral adiposity, and ectopic lipid deposition. The clinical interpretation of lean mass loss is further complicated by limitations of dual-energy X-ray absorptiometry, which cannot distinguish contractile muscle from body water, organs, and connective tissue. Importantly, available data suggest that muscle quality and metabolic function may improve despite reductions in absolute lean mass. Overall, current evidence does not support disproportionate skeletal muscle loss during GLP-1-based obesity therapy. This review summarizes current evidence on GLP-1RA and NuSH-associated changes in muscle mass, discusses mechanisms, identifies populations at risk, and outlines practical strategies to preserve muscle health during treatment.
Androgenetic Alopecia: Pathogenesis, Evaluation, and Management
Androgenetic alopecia (AGA) is a common, non-scarring, alopecia characterized by the progressive transformation of terminal hairs into miniaturized vellus hairs in a patterned distribution. Female AGA—often termed female‑pattern hair loss (FPHL)—and male AGA (often termed male‑pattern hair loss, MPHL) share similar underlying pathophysiologic, histopathologic, and trichoscopic features; however, they differ in their clinical presentation and patterns of scalp distribution. AGA represents the most prevalent cause of hair loss in both men and women and can have a significant impact on quality of life. Evidence from a large meta-analysis demonstrates a moderate impairment in health-related quality of life and emotional well-being, underscoring the meaningful psychosocial burden of AGA. Although patients are often referred for dermatologic evaluation, AGA may also have important endocrine implications. In selected cases—particularly in women or in atypical presentations—it may reflect underlying endocrinologic abnormalities, warranting targeted screening and management.
To Hold or Not to Hold? Periprocedural Management of Glucagon-like Peptide-1 Receptor‑based Agonists (GLP‑1ra) in Patients with Diabetes and Obesity
Glucagon-like peptide-1 receptor-based agonists have transformed the care of patients with diabetes and obesity. However, case reports that have associated their use with retained gastric contents and pulmonary aspiration have raised concerns regarding their safe use in patients undergoing procedures involving deep sedation, general anesthesia, or upper endoscopy. Here we present the evidence underlying these concerns and provide an evidence-informed framework for the periprocedural management of these agents. Further research is needed to better characterize these risks and provide mitigation strategies for individuals taking them in the perioperative period.
Anabolic Androgenic Steroids: No Longer on the Fringes of Endocrinology
In this review, “Anabolic Androgenic Steroids,” or “AAS” is used as the preferred term to indicate the use of exogenous androgens in supraphysiologic doses for the purpose of muscle growth or image enhancement. This definition does not include the use of physiologic doses of testosterone prescribed for the treatment of male hypogonadism. Although there is disagreement regarding the accuracy of this terminology, AAS continues to be one of the most common designations used in the literature today.
Safety of Estrogen-Based Feminizing Gender-Affirming Hormone Therapy: A Practical Endocrine Approach to Risk Stratification and Monitoring
Estrogen-based feminizing hormone therapy is a cornerstone of care for transfeminine and gender-diverse individuals. Its benefits are well established, including improvements in gender dysphoria, mental health, and overall quality of life, with meaningful downstream effects on social functioning and long-term well-being. Much of the historical concern regarding safety largely reflects earlier use of ethinyl estradiol, which was associated with substantially increased risks of venous thromboembolism (VTE) and cardiovascular events. Contemporary practice has shifted toward the use of 17β-estradiol delivered orally, transdermally, or by injection, alongside more individualized dosing, and attention to baseline risk. This transition has materially improved the safety profile of therapy. The primary safety concern remains VTE, alongside evolving considerations related to cardiovascular risk and malignancy screening. Contemporary data suggest that these risks are both predictable and modifiable, allowing clinicians to individualize therapy without compromising gender-affirming outcomes. This review provides a clinically focused framework for risk stratification, route selection, and monitoring of estrogen-based feminizing therapy.
Glucagon-like Peptide-1 Medicines for Peripheral Arterial Disease in Type 2 Diabetes: Are They Ready for Prime Time?
Comorbid peripheral arterial disease (PAD) affects approximately 12.5%–22% of individuals with type 2 diabetes (T2D), and is associated with an increased risk of major adverse limb events (MALE), such as revascularization procedures and lower extremity amputations, as well as heightened cardiovascular events and mortality. Despite this elevated risk, few therapies have been proven to reduce the risk of MALE. Although statins, proprotein convertase subtilisin/kexin type 9 (PCSK9) inhibitors, and low dose rivaroxaban plus aspirin have been shown to reduce the risk of MALE in individuals with PAD, there remains an unmet need for disease‑modifying agents to improve PAD outcomes in people with concomitant T2D and PAD. Current Diabetes Canada guidelines recommend glucagon-like peptide-1 (GLP-1) medicines for individuals with T2D and established cardiovascular disease (CVD), multiple risk factors, or chronic kidney disease (CKD) due to their proven cardiorenal benefits. Emerging data has shown that GLP-1 medicines reduce the incidence of MALE in individuals with T2D. This review summarizes the totality of evidence for GLP-1 medicines and their impact on MALE, drawing from randomized controlled trials (RCTs) and observational studies.
Addressing Metabolic Dysfunction‑Associated Steatotic Liver Disease (MASLD) in Endocrinology Settings in Canada: From Prevalence to Patient-Centered Management
Metabolic dysfunction-associated steatotic liver disease (MASLD) is highly prevalent in Canadian endocrinology, affecting up to 70% of those with type 2 diabetes and 75% with obesity. Despite this, routine screening is rare, leading to missed detection and intervention. Advanced fibrosis, observed in 15% of cases, increases the risk of liver and cardiovascular complications. This article addresses the burden of MASLD and the need for systemic screening and patient-centred care to improve outcomes and reduce Canada’s disease burden.
Copyright (c) 2025 Canadian Diabetes & Endocrinology Today https://creativecommons.org/licenses/by-nc-nd/4.0
Optimizing the Use of Automated Insulin Delivery (AID) Systems in Routine Clinical Care of People with Type 1 Diabetes
With the updated Diabetes Canada Clinical Practice Guidelines recognizing automated insulin delivery (AID) as the standard of care for people with type 1 diabetes (PwT1D), clinicians play a vital role in supporting individuals to adopt and optimize use of this technology. AID systems integrate insulin pump therapy (IPT) and real-time continuous glucose monitors (rtCGM) in conjunction with a control algorithm to automate various aspects of insulin delivery. The recommendation to adopt AID is supported by robust evidence from both randomized-controlled trials and real-world studies across diverse populations, including all ages, previous experience with technology, baseline glycemia, and self-management behaviours. Glycemic benefits include consistent improvements in time in range (TIR) (often by >10%), and reductions in A1C, mean glucose levels, and hypoglycemia. Additionally, AID use has shown important improvements in person-reported outcomes, including reduced diabetes distress, reduced fear of hypoglycemia, improved quality of life, and improved sleep.
Type 2 diabetes (T2D) was once considered a disease of adults. However, the obesity pandemic has helped its transition to the pediatric population. While type 1 diabetes remains the most common type of pediatric diabetes in Canada, the incidence of youth-onset T2D has increased by 60% in recent years. Canada has one of the highest prevalences of youth-onset T2D in the world, with approximately 50% of new cases annually occurring in Indigenous children, with the remaining 50% of cases occurring in other ethnic groups, including Caucasians. As a relatively new disease in youth, there is a lack of natural history data for youth-onset T2D to predict long-term outcomes. However, its aggressive nature in youth suggests that these patients will likely have a significant burden of disease related to cardiometabolic risk, comorbidities, and complications. In this paper, we highlight current knowledge on the pathophysiology of youth-onset T2D, diagnostic criteria, the impact of obesity on diabetes risk, comorbidities and complications, and current treatments.
Running a Trans-Welcoming Clinical Practice
A wide range of terms are used to describe gender-diverse people, including transgender, gender-fluid, gender-queer, non-binary, and two‑spirit, reflecting the diversity of the community itself. Transgender and gender-diverse patients (TGDP) may experience gender dysphoria—the distress that arises when their gender identity does not align with the sex assigned at birth. TGDP are estimated to represent between 0.1% and 2% of the global population; in Canada, the 2019 census reported a prevalence of 0.35%. Access to gender-affirming care is strongly linked to improved health outcomes. One study found that suicidal ideation decreased from 67% prior to transition to just 3% afterward. Yet, despite the clear benefits, TGDP continue to face major barriers to care. According to the Trans PULSE survey, as of 2019, only 35% of respondents had completed their medical transition. Even in general healthcare, access remains inequitable: while 81% of respondents reported having a primary care provider (PCP), only 52% felt comfortable discussing trans‑related health issues with their PCP, and over 40% reported having an unmet healthcare need. These disparities reflect the ongoing impact of transphobia and prior trauma within healthcare systems, and as a result, TGDP face disproportionate health burdens compared to the general population, including lower rates of cancer screening, higher rates of mental health disorders, and sexually transmitted infections (Figure 1). Addressing these inequities requires urgent action to expand access to gender-affirming hormone therapy, surgery, and mental health care. Equally important, healthcare systems must adopt inclusive policies and practices that improve access to all forms of care for TGDP. This article outlines practical measures that any healthcare practice can implement to create a more welcoming and affirming environment.
Novel Treatment Options For Menopausal Symptoms
The world of menopause is undergoing a renaissance. In recent years, medical experts have taken to social media, igniting a long overdue surge of information on the subject that helps debunk the fear of menopausal hormone therapy (MHT), which stems from the 2002 Women’s Health Initiative (WHI) study.1 The devastating consequences on health and wellness were profound: an entire generation of women was suddenly deprived of symptom relief and quality of life (QOL) due to the marked decline in hormone prescriptions in North America. These effects continue to echo today. The near extinction of medical education on mature women’s health and wellness in our academic institutions since 2002 has left healthcare professionals ill-equipped to guide the next generation of menopausal women who seek contemporary medical advice and refuse to “live their mothers’ menopause.” The creation of the Menopause Foundation of Canada in 2022, recent sold-out menopause conferences, and renewed interest from pharmaceutical companies is convincing evidence that menopause is finally receiving the recognition and attention it deserves.
Type 1 diabetes (T1D) is an autoimmune disease characterized by progressive destruction of pancreatic β cells. This process is mediated by both cellular (T lymphocyte) and humoral (autoantibody) immune responses. Although T cells play a central pathogenic role, autoantibodies are the earliest detectable markers of β cell autoimmunity and are instrumental in diagnosing and predicting disease progression. Although T1D develops on a background of genetic risk, most individuals with genetic risk never develop type 1 diabetes. In contrast, virtually all individuals with 2 or more islet autoantibodies eventually develop type 1 diabetes.
Current and Emerging Treatments For the Management of Hypoparathyroidism
Chronic hypoparathyroidism is a rare endocrine disorder marked by parathyroid hormone (PTH) deficiency, leading to hypocalcemia and its associated complications. Conventional therapy with oral calcium and active vitamin D fails to address the hormonal deficit and poses risks such as hypercalciuria and nephrocalcinosis. Recent advances in PTH replacement therapy have shifted the treatment paradigm. Palopegteriparatide, a long-acting prodrug of PTH (1–34), is now U.S. Food and Drug Administration (FDA) and European Medicines Agency (EMA)-approved, demonstrating effective calcium homeostasis, reduced reliance on conventional therapy, and potential renal benefits. Discontinuation of rhPTH (1–84) has accelerated interest in emerging alternatives such as eneboparatide, calcilytics (e.g., encaleret), MBX2109, and oral PTH1 receptor agonists. These novel therapies target PTH signalling through diverse mechanisms—offering injectable and oral options with improved safety, efficacy, and quality-of-life outcomes. This review synthesizes current evidence on approved and investigational treatments, underscoring their mechanisms, clinical impacts, and roles in personalized care for chronic hypoparathyroidism.
Vaccinating Your Adult Diabetic Patient: What Vaccines Would You Recommend?
Adults with diabetes (type 1 or type 2) are at substantially higher risk of infections and complications from vaccine-preventable diseases. As a result, persons with diabetes experience higher rates of serious illnesses such as influenza, pneumonia, and other infections. Epidemiological studies show that during flu epidemics, persons with diabetes are hospitalized at much higher rates and are more likely to suffer serious complications (e.g., myocardial infarction, heart failure, stroke) than their non‐diabetic peers. Globally, diabetes is one of the most common comorbidities among patients with severe COVID-19. In short, diabetes—especially when poorly controlled or long-standing—is a risk factor for viral, bacterial, and fungal infections. People with diabetes are more likely to be hospitalized or die from illnesses such as influenza, pneumonia, and COVID-19. Clinicians should understand that diabetes itself impairs immunity, making timely immunization critical. Notably, the Canadian Immunization Guide confirms that there is no evidence suggesting that vaccines adversely affect blood glucose control.
Thyroid Nodules: Reducing Overdiagnosis and Investigations
Thyroid nodules (TN) are incredibly common, with approximately 5% of the population presenting with palpable TN. However, the widespread utilization of sensitive imaging techniques over the past few decades has led to a rapid increase in their prevalence. Notwithstanding the clinically palpable TN, the rate of incidental nodules picked up on imaging studies varies remarkably with the underlying imaging modality. For instance, the prevalence of TNs on computed tomography (CT) scans of the neck is reported to be 16.5%,3 FDG-PET to be 2% and on neck ultrasounds (US) well over 50%. The prevalence of TN is higher in females and increases with age, and while there has been little change in the overall reported incidence of palpable TNs, the rising prevalence can be almost exclusively attributed to the expanded use of imaging, particularly the widespread availability of sensitive US. It is estimated that over 60% of the population may have at least one TN.
Monogenic and Syndromic Obesity: Therapeutic Implications
Obesity is a complex, progressive and relapsing neuroendocrine condition, characterized by disordered communication between the gastrointestinal tract, adipocytes and the hypothalamus. It is a heterogeneous condition with unique etiologies, broadly classified as: polygenic obesity, monogenic obesity, syndromic obesity and secondary obesity.2 The most common form of obesity is polygenic, a highly hereditable condition that involves the clustering of genes that increase the risk for obesity. This inherited genetic risk is exploited by socio-biologic exposures. Monogenic and syndromic obesity result from rare genetic mutations and are characterized by early onset severe obesity and hyperphagia. Secondary obesity may occur as a result of medication exposures, hypothalamic damage or primary endocrine disorders. Accurate classification of obesity is critical to inform surveillance and management strategies, decrease health risk and improve quality of life through newly available targeted therapies.
Copyright (c) 2024 Canadian Diabetes & Endocrinology Today https://creativecommons.org/licenses/by-nc-nd/4.0
Addressing Inositol Use in PCOS Management
Polycystic ovary syndrome (PCOS) is a heterogeneous complex endocrine disorder characterized by oligo-ovulation, insulin resistance, and hyperandrogenism. Treatment should be individualized based on each patient’s symptoms and reproductive goals. Unfortunately, there is no pharmacologic medication that simultaneously promotes ovulation, improves metabolic health, and reduces clinical hyperandrogenism. Metformin is a well accepted, evidence-based pharmacologic therapy that targets the insulin resistance pathway and improves ovulatory frequency, but it has limited effects on clinical hyperandrogenism as well as poor tolerability for some patients. The growing interest in complementary therapies has highlighted the need for more tolerable and ‘non-pharmacologic’ treatment options. Inositol, a naturally occurring compound, has gained attention as a promising therapeutic agent for managing PCOS. This review aims to support shared decision-making between clinicians and patients by exploring the roll of inositol as a complementary therapy for PCOS management.
Type 2 diabetes (T2D) poses a substantial global health burden. In 2023, we published an overview on the remission of T2D. Since then, additional long-term data has emerged regarding the outcomes associated with T2D remission, highlighting the importance of revisiting this topic. This article synthesizes findings from the landmark Diabetes Remission Clinical Trial (DiRECT), its 5-year follow-up, and recent studies exploring the enduring benefits of both short-term and sustained remission.
Glucagon-like Peptide-1 Receptor Agonists and Thyroid Cancer: Myth or Reality?
Glucagon-like peptide-1 receptor agonists (GLP-1RAs) are being used increasingly for the management of type 2 diabetes mellitus (T2DM) or obesity because of their association with robust glucose lowering, weight loss, and cardiorenal benefits. The association between GLP-1RA treatments and thyroid cancer has been a topic of discussion since their early development with the understanding that GLP-1 receptors are present on rodent thyroid parafollicular cells (C-cells), and that GLP-1RAs can cause an increase in calcitonin, and both C-cell hyperplasia and medullary thyroid carcinoma (MTC). This data from rodent studies has led to GLP-1RAs being contraindicated in patients with a personal or family history of MTC or with multiple endocrine neoplasia syndrome type 2. Despite this contraindication, the human relevance of GLP-1RA induced MTC in rodents has not been proven. Normal or hyperplastic C-cells in humans may not express the GLP-1 receptor, and studies of human MTCs have shown variable expression of the GLP-1 receptor. Studies have shown conflicting evidence regarding the expression of the GLP-1 receptor in human papillary thyroid cancer (PTC) cell lines: however, GLP-1RAs did not have significant effects on the proliferation of PTC cells. Because of the data that potentially links GLP-1RAs to an increased risk of thyroid cancer, clinical studies in humans are important in addressing this issue. I will review the relevant data from human studies that have analyzed the potential link between GLP-1RA treatment and thyroid cancer, including pharmacovigilance and observational studies as well as randomized controlled trials (RCTs).
The Role of GLP-1R and GIPR Agonism in Heart Failure
Heart failure (HF) is a clinical syndrome characterized by signs and symptoms of structural and functional cardiac abnormalities. It is corroborated by elevated N-terminal pro‑B‑type natriuretic peptide (NT-proBNP) levels and objective evidence of pulmonary or systemic congestion. More than 100,000 Canadians are diagnosed with HF annually. For years, HF has been classified based on left ventricular ejection fraction (LVEF). HF with reduced ejection fraction (HFrEF) refers to symptomatic HF with an LVEF <40%. However, if the LVEF is >50%, this is known as HF with preserved ejection fraction (HFpEF). In HFpEF, obesity is commonly implicated in the disease pathophysiology, and is present in up to 80% of people with this condition. Obesity contributes to concentric heart remodelling through mechanisms such as insulin resistance, diabetes, hyperlipidemia, visceral adipose tissue expansion, and myocardial steatosis. Additionally, obesity leads to a pro-inflammatory state which affects the vasculature and visceral organs.2 Glucagon‑like peptide-1 receptor agonists (GLP‑1RAs), such as semaglutide, have shown promise in weight reduction across multiple Phase 3 clinical trials. Agents combining GLP-1RA and glucose-dependent insulinotropic peptide receptor (GIPR) agonism, such as tirzepatide, have also contributed to clinically significant weight loss. As such, their impact in addressing obesity‑related HFpEF is under investigation. This paper reviews the data on GLP-1RAs and tirzepatide in patients with HF across the LVEF spectrum, with a particular focus on those with HFpEF.
As of 2018 data, 30–60% of reproductive‑aged women in Canada were affected by overweight (body mass index [BMI] 25.9–29.9) and obesity (BMI >30.0), and these rates are increasing. Obesity during pregnancy is associated with higher rates of preeclampsia, gestational diabetes, macrosomia, stillbirth, post‑term pregnancy, and increased caesarean delivery rates. Obesity is also associated with higher rates of diabetes, which has well‑known consequences for pregnancy, and ovulatory dysfunction, which impacts fertility, such as in polycystic ovarian syndrome (PCOS). Addressing obesity and its associated metabolic impacts could have a profound effect on reproductive and fetal health. Since the 2000s, incretin-based therapies for diabetes and obesity have become the focus of research and clinical practice. Glucagon‑like‑peptide 1 (GLP-1), an endogenous incretin hormone secreted by intestinal L-cells in response to food intake, and its agonists, have been available for clinical use in Canada since the introduction of liraglutide in 2011. Recently, pharmacologic agonists of glucose-dependent insulinotropic polypeptide (GIP), an incretin synthesized in the K-cells of the duodenum and jejunum, have also become available. Dual agonism of these hormones is associated with more significant reductions in blood glucose and weight. The currently available incretin-based therapies are listed in Table 1, and their physiologic effects are summarized in Figure 1. Active research is underway on new molecules, for example agonists of amylin and glucagon, in various combinations with GLP‑1 and GIP, to maximize clinical benefits. These combinations have shown weight loss effects rivalling those of metabolic surgery. Considering their potential, this medication class has taken the world by storm. Canada's Drug Agency (CDA) found that expenditure on injectable semaglutide, under the brand-name Ozempic™, increased from $13.5 million in 2019 to $227 million in 2021, with 20% of the claims being for non-type 2 diabetes use. The metabolic improvements and weight loss achieved with incretin-based therapies are associated with improved fertility. While product monographs warn against use in pregnancy and lactation, conception while on these treatments is becoming more common. Considering this increasing reality, this review aims to summarize what is currently known about GLP-1 and GIP agonists and their effects during pregnancy.
A Practical Approach to the Incidental Adrenal Mass
With modern use of abdominal imaging, incidental detection of adrenal masses is increasingly common. These lesions are estimated to be present in 4% of all patients and in up to 10% of the elderly population. Fortunately, most adrenal masses are benign non‑functioning adenomas. However, some of these lesions are hyperfunctioning or harbour malignancy. A familiarity with the evaluation and management of incidental adrenal masses is of interest to endocrinologists as well as surgeons and primary care providers who order abdominal imaging tests. In 2023 a multidisciplinary working group of Canadian radiologists, endocrinologists, and radiologists published an updated guideline on the diagnosis, management, and follow‑up of the incidentally discovered adrenal mass.4 This publication has helped clarify the necessary imaging and biochemical testing required prior to creating a management plan for a patient with an incidental adrenal lesion. When faced with an adrenal mass, the clinician must answer 3 essential questions: 1) Is the mass benign or malignant? 2) Is the mass hormonally functional or non-functional? 3) How should the mass be managed?
Diabetic kidney disease (DKD) affects 40% of individuals with diabetes mellitus (T2DM) and is associated with an increased risk of cardiovascular events, hospitalization for heart failure, and premature death. Existing treatments focus on lifestyle measures, glycemic control, blood pressure and lipid management, inhibition of the renin‑angiotensin‑aldosterone system (RAAS), and the use of sodium glucose cotransporter 2 inhibitors (SGLT2-i). However, substantial residual risk of progression to end-stage kidney disease (ESKD) or cardiovascular complications remain despite optimal therapy. Finerenone, a non-steroidal mineralocorticoid antagonist (MRA), has been shown to reduce important outcomes when added to evidence-based therapies, and is approved by Health Canada as an adjunct to standard of care therapy in adults with chronic kidney disease (CKD) and T2DM to reduce the risk of ESKD and a sustained decrease in estimated glomerular filtration rate (eGFR), cardiovascular death, non-fatal myocardial infarction, and hospitalization for heart failure.
Cardiovascular Safety of Testosterone Replacement Therapy in Hypogonadal Men
Testosterone replacement therapy (TRT) aims to restore serum testosterone levels in men with hypogonadism. Symptoms associated with hypogonadism include reduced libido, erectile dysfunction, fatigue, depression, and loss of muscle mass and bone density. The primary purpose of TRT is to alleviate these symptoms and improve quality of life by restoring serum testosterone levels to the physiological range. The prevalence of hypogonadism in men increases with age, affecting approximately 2–5% of middle-aged and older men and up to 20% of elderly men. Despite its therapeutic benefits, the cardiovascular safety of TRT remains a topic of debate and investigation. Cardiovascular disease is a leading cause of morbidity and mortality among men, and any therapy that might influence cardiovascular risk requires careful evaluation. Early observational studies raised concerns about potential adverse cardiovascular outcomes associated with TRT. These findings prompted regulatory agencies to issue warnings and recommend further research. In response, more recent trials, including the TRAVERSE Study, have provided new insights into the relationship between TRT and cardiovascular health. This article aims to provide a review of recent evidence on the cardiovascular safety of TRT.
The Role of Bisphosphonate Drug Holidays in the Management of Osteoporosis
Osteoporosis is a chronic skeletal disorder of compromised bone strength leading to an increased risk of fragility fractures, particularly with advancing age. More than 2 million Canadians are living with osteoporosis, and osteoporotic fractures are associated with considerable morbidity, increased mortality, and high economic burden to the healthcare system. The ultimate goal of osteoporosis pharmacotherapy is to reduce the risk of fragility fractures. Bisphosphonates are the most widely used first-line medications for osteoporosis due to their robust anti-fracture efficacy and favourable safety profile, as demonstrated in short-term randomized placebo-controlled trials of 3-years duration with fracture outcome assessed as the primary endpoint. However, the optimal duration of bisphosphonate therapy has been questioned regarding their long‑term efficacy and safety given their long half‑life in bone. Prolonged use is associated with very rare but serious adverse complications such as atypical femoral fracture (AFF) and osteonecrosis of the jaw (ONJ). Moreover, while extension trials indicate that long‑term bisphosphonate therapy helps maintain bone density, the evidence supporting further fracture risk reduction with prolonged treatment is less convincing. Regarding concerns about rare adverse effects and the attenuated benefit-to-risk ratio with long‑term use, several professional organizations have issued guidelines suggesting bisphosphonate drug holidays. This approach aims to minimize prolonged exposure and mitigate rare risks while preserving some residual anti-fracture benefits from the persistent drug in the skeleton. Here, we review the role of bisphosphonate drug holidays in the long-term management of osteoporosis, the supporting evidence, recommended guidelines on treatment duration, along with key considerations for implementing a bisphosphonate drug holiday.
Treatment of Obesity in Individuals with Type 1 Diabetes
The prevalence of obesity (OB) is increasing among individuals with type 1 diabetes (T1D), posing unique challenges for managing their blood sugar levels and long-term health. Unlike type 2 diabetes (T2D), which is closely linked to OB and insulin resistance (IR), addressing OB in T1D requires careful consideration, because patients rely on external insulin, which can contribute to weight gain. In this review, we will discuss the causes and complications of OB in individuals with T1D, current approaches to treatment, potential lifestyle, and medical, and surgical interventions to manage weight while effectively maintaining optimal blood sugar control.