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Adult Male Hypogonadism: A Review

Author/s: 
Bradley D. Anawalt, Kim M. O’Connor, Mathis Grossmann

Importance Male hypogonadism is a clinical syndrome of signs and symptoms of testosterone deficiency and consistently low morning serum testosterone concentrations. The prevalence of hypogonadism due to hypothalamus, pituitary, or testes pathology is less than 1%, and the prevalence due to obesity (body mass index ≥30) is from 2% to 8%.

Observations The most common signs and symptoms of hypogonadism are decreased libido, decreased spontaneous erections, and small testes. Primary hypogonadism is characterized by deficient testicular production of testosterone despite elevated luteinizing hormone (LH) concentrations. The most common cause of primary hypogonadism is Klinefelter syndrome (≥2 X chromosomes and 1 Y chromosome), which affects 2 in 1000 men and is frequently undiagnosed. Secondary hypogonadism is caused by hypothalamic or pituitary dysfunction and is characterized by low testosterone concentrations and low or inappropriately normal LH and follicle-stimulating hormone (FSH) concentrations. The most common permanent causes of secondary hypogonadism are head and neck radiation and severe head trauma. The most common potentially reversible causes of secondary hypogonadism are obesity, severe illness, and medication use (opioids, corticosteroids, checkpoint inhibitors, and medications that cause hyperprolactinemia). Testing for hypogonadism is reserved for men with signs and symptoms of androgen deficiency. Hypogonadism is confirmed if an individual’s serum testosterone concentration is less than 264 to 300 ng/dL in at least 2 fasting samples collected between 7 and 10 am and measured with an accurate and external quality-controlled assay. Assessment of calculated free testosterone concentration derived using total testosterone and sex hormone–binding globulin (SHBG) concentrations is necessary for men with obesity, diabetes, and other conditions that cause low serum SHBG concentrations. Patients diagnosed with hypogonadism should have serum FSH and LH concentrations measured to distinguish primary from secondary hypogonadism. For men with obesity-induced hypogonadism, the recommended first-line management is weight loss. In men with obesity, weight loss of at least 5% typically increases serum total testosterone concentration significantly, and weight loss is associated with improved physical function, libido, and erectile function. Men with permanent hypogonadism, or those unable to discontinue medications that cause hypogonadism, may be treated with testosterone. The testosterone formulation (injection, gel, or pill) and dosage should be individualized with monitoring of serum testosterone concentration, hematocrit percentage, and possibly prostate-specific antigen concentration.

Conclusions and Relevance Primary hypogonadism affects less than 1% of men, whereas secondary hypogonadism due to obesity (body mass index ≥30) occurs in 2% to 8%. First-line treatment for obesity-induced hypogonadism is weight loss. Testosterone therapy should be initiated for men with permanent hypogonadism or those who are unable to discontinue medications that cause hypogonadism.

Keywords 
hypogonadism Androgens Erectile Dysfunction prostate-specific antigen Sex Hormone-Binding Globulin Testis testosterone

Hearing Aids for Adults With Mild to Moderate Hearing Loss

Author/s: 
Karina C. De Sousa, De Wet Swanepoel

Hearing loss is defined as an impaired ability to hear sounds at thresholds considered to be normal. Projections based on audiometric data from the National Health and Nutrition Examination Survey estimate that by 2030, approximately 55 million US adults will have hearing loss, including 35 million with mild loss (25-40 dB) and nearly 20 million with moderate or greater loss (>40 dB).1 The most common cause of hearing loss among hearing aid users is bilateral sensorineural hearing loss due to cochlear hair cell or auditory nerve degeneration. Functional effects of hearing loss differ with severity. Mild hearing loss may affect the ability to understand speech in noisy environments; moderate or greater hearing loss affects the ability to have individual conversations in a quiet room.

Untreated hearing loss is associated with social isolation that can reduce quality of life.2 A meta-analysis of 5 randomized trials (825 adults with mild to moderate hearing loss) that compared those not receiving hearing aids with those who received hearing aids that amplified sounds via air conduction had improved ability to discriminate sound and speech and hearing-related quality of life based on Hearing Handicap Inventory for the Elderly,2 which quantifies self-perceived functional and emotional hearing handicap (such as negative feelings and psychological distress from communication problems). The Hearing Handicap Inventory for the Elderly scores (lower scores indicate less handicap; scale, 0-100) improved by −26.5 (95% CI, −42.2 to −10.8) points with hearing aids, exceeding the minimal clinically important difference of 18.7 points.2

Amplification with hearing aids is the primary treatment for hearing loss, but use is limited. Traditional Medicare does not cover hearing aids, and coverage for associated services remains limited. In a nationally representative cohort using data from the National Health and Aging Trends Study, hearing aid use among US adults aged 71 years and older with hearing loss was 29.2% in 2021, including 14.4% among those with mild loss and 45.3% among those with moderate hearing loss.3 Although reasons for nonuse were not directly assessed, lower-income individuals, along with those who have milder degrees of hearing loss, are less likely to use hearing aids.3 Until recently, hearing aids in the US could only be obtained through licensed hearing care professionals such as audiologists. However, since October 2022, the US Food and Drug Administration has allowed adults to buy hearing aid devices without a medical examination, prescription, or professional fitting. This regulatory change has enabled over-the-counter (OTC) direct-to-consumer hearing aids, with potential to broaden access.

Keywords 
hearing loss hearing aids Audiologists quality of life

Prepregnancy Care and Counseling: A Review

Author/s: 
Kylie M. Cooper, Linda M. Szymanski, Paru S. David

Importance Prepregnancy care and counseling optimize maternal health before conception to improve outcomes for mothers and infants. In the US, 66.4% of reproductive-aged women have at least 1 modifiable risk factor for adverse pregnancy outcomes.

Observations For all individuals desiring pregnancy, recommended interventions include folic acid supplementation; cessation of tobacco, alcohol, cannabis, and opioids; immunizations against hepatitis B virus, varicella, and rubella; and screening for syphilis and HIV. Folic acid use before pregnancy is associated with reduced fetal neural tube defects (relative risk [RR], 0.67; 95% CI, 0.52-0.87). Maternal tobacco smoking is associated with increased risks of stillbirth (summary RR [sRR], 1.46; 95% CI, 1.38-1.54), neonatal death (sRR, 1.22; 95% CI, 1.14-1.30), and perinatal death (sRR, 1.33; 95% CI, 1.25-1.41). Screening for and treatment of syphilis and HIV prior to and during pregnancy decrease rates of fetal and neonatal infection. Prepregnancy immunizations against hepatitis B virus, varicella, and rubella decrease neonatal infection and mortality. Individuals using tobacco, alcohol, cannabis, and opioids should receive counseling and treatment prior to pregnancy (eg, buprenorphine or methadone for opioid use disorder). For individuals with chronic disease, routine health examinations and contraceptive care in the year before conception can optimize pregnancy timing and are associated with decreased risk of severe maternal morbidity. Compared with planned pregnancies, unintended pregnancies are associated with increased risk of postpartum depression (15.7% vs 9.6%; adjusted odds ratio [aOR], 1.51; 95% CI, 1.40-1.70), preterm birth (9.4% vs 7.7%; aOR, 1.21; 95% CI, 1.12-1.31), and low infant birth weight (7.3% vs 5.2%; aOR, 1.09; 95% CI, 1.02-1.21). Weight loss prior to conception is recommended for individuals with a body mass index of 25 or greater because overweight and obesity are associated with increased risk of gestational diabetes, gestational hypertension, and cesarean delivery. Among patients with pregestational diabetes (type 1 or 2), hemoglobin A1c of less than 6.5% is associated with a decreased risk of fetal anomaly compared with hemoglobin A1c of 6.5% or greater. Cardiovascular complications such as hypertension and heart failure occur in 15% of pregnancies and are more common among those with preexisting cardiovascular disease. These patients should receive counseling on maternal and neonatal risk, monitoring, and medication management by specialists in cardiology and maternal fetal medicine.

Conclusions and Relevance Prepregnancy counseling and care reduce maternal morbidity and neonatal morbidity and mortality. Primary care–based discussion of reproductive goals, immunizations, screening for infections and substance use, and risk-reducing interventions such as folate supplementation can optimize outcomes in individuals contemplating pregnancy.

Keywords 
Pregnancy Prepregnancy Family Planning Services Maternal Health Gestational Diabetes maternity

Diagnosis and management of bronchiectasis

Author/s: 
Maeve P. Smith

Bronchiectasis is a chronic, debilitating respiratory condition that affects people of all ages. It is most prevalent in women and those older than 60 years, and prevalence is increasing. Patients have daily excessive sputum and associated symptoms, recurrent chest infections and impaired health-related quality of life. In North America, management guidelines are lacking. This review discusses best evidence to guide the long-term management of non–cystic fibrosis bronchiectasis in adults, focusing on the two most common single-entity types of bronchiectasis in adults: idiopathic and postinfectious bronchiectasis (Box 1). Table 1 lists all the types of bronchiectasis by cause.

Keywords 
Bronchiectasis sputum diagnosis management fibrosis

2026 ACC/AHA/AACVPR/ABC/ACPM/ADA/AGS/APhA/ASPC/NLA/PCNA Guideline on the Management of Dyslipidemia: A Report of the American College of Cardiology/American Heart Association Joint Committee on Clinical Practice Guidelines

Author/s: 
Roger S. Blumenthal, Pamela B. Morris, Mario Gaudino, Heather M. Johnson, Timothy S. Anderson, Vera A. Bittner, Ron Blankstein, LaPrincess C. Brewer, Leslie Cho, Sarah D. de Ferranti, Eugenia Gianos, Ty J. Gluckman, Kristen F. Gradney, Ijeoma Isiadinso, Donald M. Lloyd-Jones, Joel C. Marrs, Seth S. Martin, Kellie H. McLain, Laxmi S. Mehta, Samia Mora, Wudeneh M. Mulugeta, Pradeep Natarajan, Ann Marie Navar, Carl E. Orringer, Tamar S. Polonsky, Harmony R. Reynolds, Joseph J. Saseen, Michael D. Shapiro, Daniel E. Soffer, Sheila A. Tynes, Chloé D. Villavaso, Salim S. Virani, John T. Wilkins

Aim: The "2026 ACC/AHA/AACVPR/ABC/ACPM/ADA/AGS/APhA/ASPC/NLA/PCNA Guideline on the Management of Dyslipidemia" retires and replaces the "2018 AHA/ACC/AACVPR/AAPA/ABC/ACPM/ADA/AGS/APhA/ASPC/NLA/PCNA Guideline on the Management of Blood Cholesterol."

Methods: A comprehensive literature search was conducted from October 2024 to December 2024 to identify clinical studies, systematic reviews and meta-analyses, and other evidence conducted on human participants that were published in English from MEDLINE (through PubMed), EMBASE, the Cochrane Library, Agency for Healthcare Research and Quality, and other selected databases relevant to this guideline.

Structure: The focus of this clinical practice guideline is to address the evaluation, management, and monitoring of individuals with dyslipidemias, including high blood cholesterol, hypertriglyceridemia, and elevated lipoprotein(a).

Keywords: ACC/AHA clinical practice guideline; HDL; LDL; anticholesteremic agents; atherosclerosis; atherosclerotic disease; cardiovascular disease; cardiovascular diseases; cholesterol; drug interactions; dyslipidemia(s); hydroxymethylglutaryl-CoA reductase inhibitors; hypercholesterolemia; hyperlipid(a)emia/s; hyperlipoproteinemia type II; hypertriglyceridemia; hypolipidemic agents; lipids; lipoprotein(a); primary prevention; risk adjustment; risk assessment; risk factors; simvastatin; statin(s); triglycerides.

Keywords 
Proliferating Cell Nuclear Antigen cholesterol Hypertriglyceridemia Lipoprotein(a) primary prevention

Female pattern hair loss

Author/s: 
Eric McMullen, Ammar Saed Aldien, Cathryn Sibbald, Jeffrey Donovan

Female pattern hair loss (FPHL) is a common, nonscarring hair-loss disorder. Prevalence of FPHL increases with age; 12% of females will have symptoms by age 29 years, 25% by age 50 years, and 41% to 50% at age 70 years and older. Risk factors include genetics and endocrinological diseases (e.g., polycystic ovarian syndrome, adrenal hyperplasia, ovarian or adrenal tumours).

Keywords 
Female Pattern Hair Loss Hair Loss Alopecia

The association between medication use and vitamin B12 deficiency in the elderly population: a cross- sectional study

Author/s: 
Monique P H Tillemans, Thijs J Giezen, Toine C G Egberts, Kees J Kalisvaart

Background
Vitamin B12 deficiency is common in the elderly population and can cause severe complications. The use of certain medication has in previous studies been associated with vitamin B12 deficiency in the general population. To identify elderly patients at risk for vitamin B12 deficiency due to medication use, we evaluated the association between medication use and vitamin B12 deficiency in the elderly population.

Methods
Hospitalized geriatric patients 65 years of age or over with a serum vitamin B12 measurement within one week of the admittance date were included. Patients were classified as either B12 normal (258–635 pmol/L) or B12 deficient (< 148 pmol/L). Upon hospital admission patients’ medication use was verified. The association between vitamin B12 deficiency and the use of antacid, antiepileptic, antidiabetic, lipid lowering and other medication was evaluated by univariate and multivariate analyses.

Results
Of the 7132 patients included in the study, 532 (7.5%) had vitamin B12 deficiency and 3433 (48.1%) patients had normal vitamin B12 concentrations. Metformin use was significantly and independently (adjusted OR 2.5; 95% CI 1.7–3.6) associated with a dose-dependent higher risk of vitamin B12 deficiency. The use of other medication evaluated in this study was not associated with vitamin B12 deficiency.

Conclusions
Metformin use is significantly associated with vitamin B12 deficiency in the elderly, and this risk rises with higher metformin doses. Monitoring and timely start of vitamin B12 supplementation along with the lowest possible metformin dose are essential to prevent complications.

Keywords 
metformin Metformin Treatment anticonvulsants Antacids Vitamin B 12 Deficiency

Management of Premenstrual Disorders

Author/s: 
Rebeca Ortiz Worthington, Lindsey M Eastman, Jason T Alexander

Premenstrual disorders encompass a spectrum of cyclic affective and physical symptoms that interfere with daily functioning, occurring during the luteal phase and resolving with or immediately following menstruation. Premenstrual disorders may be caused by fluctuations of estrogen in the luteal phase, leading to dysregulation of serotonin, increased sensitivity to changes in the progesterone metabolite allopregnanolone, or both. Diagnosis can be made based on symptom assessment with daily ratings for at least 2 consecutive menstrual cycles, such as the Daily Record of Severity of Problems.1,2 Affective symptoms include lability (mood swings, sudden sadness or tearfulness, sensitivity to rejection), irritability or anger, depressed mood, and anxiety or tension. Physical symptoms include difficulty concentrating, lethargy or fatigue, appetite changes, sleep disturbances, breast tenderness, joint pain, and abdominal bloating.

Premenstrual syndrome (PMS) is characterized by the cyclic occurrence of any of these affective or physical findings during the premenstrual period and affects approximately one-quarter of menstruating individuals. Premenstrual dysphoric disorder (PMDD) is more severe than PMS and less common (affecting 2%-5% of females). Based on the Diagnostic and Statistical Manual of Mental Disorders (Fifth Edition) (DSM-5), the diagnosis of PMDD requires at least 5 symptoms, including at least 1 affective symptom and 1 physical symptom, the week before menses. Symptoms of PMDD substantially decrease or resolve the week after menses.1,2 Treatment choices are based on the timing and severity of symptoms and patient goals such as desire for contraception.

Keywords 
Premenstrual Dysphoric Disorder Luteal Phase menstruation Affective Symptoms

Exacerbation risk in patients with bronchiectasis receiving DPP-1 inhibitors vs placebo: A meta-analysis of RCTs

Author/s: 
Giulia Carvalhal, Júlia Moreira Diniz, Larissa Calixto Hespanhol, David Curi Barbosa Izoton Cabral, Jafar Aljazeeri

Background: No therapies have been approved to alter bronchiectasis progression. Dipeptidyl peptidase-1 (DPP-1) inhibitors, which target neutrophil serine protease activation, are under investigation as potential disease-modifying agents.

Methods: We conducted a systematic review and meta-analysis of randomized controlled trials (RCTs) comparing DPP-1 inhibitors versus placebo in patients with non-cystic fibrosis bronchiectasis. PubMed, Cochrane, EMBASE, Web of Science, Scopus, ClinicalTrials.gov, and ICTRP were searched from inception until April 26, 2025. Primary outcomes included time to first exacerbation and proportion of patients remaining exacerbation-free. Secondary outcomes included post-bronchodilator % Forced Expiratory Volume in 1 s (FEV1), Quality of Life-Bronchiectasis (QoL-B) questionnaire scores, and rate of adverse events. Time-to-event outcome was analyzed using Kaplan-Meier (KM)-estimated individual patient data (IPD), whereas random-effects meta-analyses were performed for remaining outcomes.

Results: 2523 patients from four RCTs were included, of whom 1689 (66.9 %) received DPP-1 inhibitors. Compared with placebo, DPP-1 inhibitors prolonged the time to first exacerbation (HR 0.79; 95 % CI: 0.71 to 0.88) and increased the proportion of patients remaining exacerbation-free (RR 1.33; 95 % CI 1.12 to 1.58). A slower decline in post-bronchodilator % FEV1 was observed (MD 1.1 %; 95 % CI 0.05 to 2.15), but no difference in QoL-B scores (MD 1.35; 95 % CI -0.72 to 3.42). The safety profile of DPP-1 inhibitors was acceptable and comparable to placebo. Moderate certainty was found across endpoints.

Conclusions: DPP-1 inhibitors prolong time to first exacerbation and reduce exacerbation rates in patients with bronchiectasis, with an acceptable safety profile. These findings support their potential as a disease-modifying strategy.

Registration: PROSPERO (CRD420251042542).

Keywords: Bronchiectasis; DPP-1 inhibitor; Dipeptidyl-peptidases and tripeptidyl-peptidases; Meta-analysis; Randomized controlled trials; Systematic review.

Keywords 
Bronchiectasis DPP-1 inhibitor Dipeptidyl-peptidases and tripeptidyl-peptidases meta-analysis

Ann Arbor Guide to Triaging Adults With Suspected Urinary Tract Infection for In-Person and Telehealth Settings

Author/s: 
Jennifer Meddings, Kristin Chrouser, Karen E. Fowler

Importance: Urinary tract infection (UTI) is common in ambulatory care settings and the primary reason for antibiotic prescribing. Despite several guidelines focused on the type and duration of antibiotics prescribed for treating UTI, there is limited outpatient guidance on how to best triage patients with presumed UTI.

Objective: To assess the appropriateness of different triage and management recommendations involving empiric antibiotics, urine testing strategies, and visit types and how these recommendations vary by patient sex, age, presenting symptoms, and clinical history.

Evidence review: Using the RAND/UCLA Appropriateness Method, a 13-member multidisciplinary panel (physicians, advanced practice providers, and nurses) performed a scoping review of the literature publications from 2009 to June 2024 and rated the appropriateness of 136 clinical scenarios (48 for women, 49 for men, and 39 scenarios not specific to sex) with up to 9 management strategies per scenario for a total of 1094 scenarios. For each scenario, experts rated the appropriateness of empiric treatment, types of urine testing, and triage to visit type (in-person, virtual, or none) as appropriate (ie, benefits outweigh risks), inappropriate, or of uncertain appropriateness. Appropriateness ratings were summarized into 2 groups: nonpregnant adult women and adult men.

Findings: Major recommendations based on symptoms included (1) same-day in-person evaluation if symptoms were concerning for pyelonephritis, complicated cystitis, or urinary obstruction; (2) a visit if additional nonurinary symptoms were present (ie, diarrhea, genital discharge, or cough); (3) neither urine testing nor empiric treatment solely due to a change in urine color or appearance without other bladder (cystitis) symptoms; (4) empiric treatment without testing or a visit, for women, if there were new classic cystitis symptoms of dysuria, urinary frequency, urgency, or suprapubic pain without risks for antibiotic resistance; (5) urinalysis with culture (ideally reflexed to culture) before taking first antibiotic dose for women at risk of antibiotic resistance (eg, recent antibiotic treatment for UTI or recurrent UTIs) and all men; and (6) empiric treatment considered for patients with barriers to obtaining timely urine testing or visits.

Conclusions and relevance: The appropriateness of empiric antibiotics, urine testing, and different clinical evaluation options were defined for adults presenting with concerns for UTI in common ambulatory triage settings, including telehealth. These criteria for ambulatory triage of suspected UTI symptoms in adults are anticipated to help standardize and improve the appropriateness of empiric antibiotic prescribing, urine testing, and visit type triage.

Keywords 
urinary tract infections Triage Urinalysis telemedicine
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