Androgens

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.

Author/s:

Bradley D. Anawalt, Kim M. O’Connor, Mathis Grossmann

Prostate Cancer: A Review

Erin Blanchette — Wed, 12 Mar 2025 21:19:16 +0000

Date Added:

March 12, 2025

Journal/Publication:

JAMA

Publisher:

American Medical Association

Publication Date:

March 10, 2025

URL:

Prostate Cancer: A Review

Type:

Meta-analyses, Reviews, and Guidelines

Format:

Article

DOI (1):

10.1001/jama.2025.0228

Keywords

prostate

prostate cancer

adenocarcinoma

PMID (1):

40063046

MeSH

Prostate-Specific Antigen

An evidence-based review of our current understanding of prostate cancer. James W. Mold, MD, MPH

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Importance: Prostate cancer is the most common nonskin cancer in men in the US, with an estimated 299 010 new cases and 35 250 deaths in 2024. Prostate cancer is the second most common cancer in men worldwide, with 1 466 680 new cases and 396 792 deaths in 2022.

Observations: The most common type of prostate cancer is adenocarcinoma (≥99%), and the median age at diagnosis is 67 years. More than 50% of prostate cancer risk is attributable to genetic factors; older age and Black race (annual incidence rate, 173.0 cases per 100 000 Black men vs 97.1 cases per 100 000 White men) are also strong risk factors. Recent guidelines encourage shared decision-making for prostate-specific antigen (PSA) screening. At diagnosis, approximately 75% of patients have cancer localized to the prostate, which is associated with a 5-year survival rate of nearly 100%. Based on risk stratification that incorporates life expectancy, tumor grade (Gleason score), tumor size, and PSA level, one-third of patients with localized prostate cancer are appropriate for active surveillance with serial PSA measurements, prostate biopsies, or magnetic resonance imaging, and initiation of treatment if the Gleason score or tumor stage increases. For patients with higher-risk disease, radiation therapy or radical prostatectomy are reasonable options; treatment decision-making should include consideration of adverse events and comorbidities. Despite definitive therapy, 2% to 56% of men with localized disease develop distant metastases, depending on tumor risk factors. At presentation, approximately 14% of patients have metastases to regional lymph nodes. An additional 10% of men have distant metastases that are associated with a 5-year survival rate of 37%. Treatment of metastatic prostate cancer primarily relies on androgen deprivation therapy, most commonly through medical castration with gonadotropin-releasing hormone agonists. For patients with newly diagnosed metastatic prostate cancer, the addition of androgen receptor pathway inhibitors (eg, darolutamide, abiraterone) improves survival. Use of abiraterone improved the median overall survival from 36.5 months to 53.3 months (hazard ratio, 0.66 [95% CI, 0.56-0.78]) compared with medical castration alone. Chemotherapy (docetaxel) may be considered, especially for patients with more extensive disease.

Conclusions and relevance: Approximately 1.5 million new cases of prostate cancer are diagnosed annually worldwide. Approximately 75% of patients present with cancer localized to the prostate, which is associated with a 5-year survival rate of nearly 100%. Management includes active surveillance, prostatectomy, or radiation therapy, depending on risk of progression. Approximately 10% of patients present with metastatic prostate cancer, which has a 5-year survival rate of 37%. First-line therapies for metastatic prostate cancer include androgen deprivation and novel androgen receptor pathway inhibitors, and chemotherapy for appropriate patients.

Author/s:

Ruben Raychaudhuri, Daniel W Lin, R Bruce Montgomery

Diagnosis and management of polycystic ovarian syndrome

Erin Blanchette — Mon, 12 Feb 2024 16:38:09 +0000

Date Added:

February 12, 2024

Journal/Publication:

Canadian Medical Association Journal

Publisher:

Canadian Medical Association

Publication Date:

January 28, 2024

Issue:

Volume:

196

Pages:

E85-E94

URL:

Diagnosis and management of polycystic ovarian syndrome

Type:

Meta-analyses, Reviews, and Guidelines

Format:

Article

DOI (1):

10.1503/cmaj.231251

Keywords

diagnosis

diagnostic

polycystic ovarian syndrome

PCOS

menstruation

PMID (1):

38286488

MeSH

Polycystic Ovary Syndrome

A concise review of polycystic ovarian syndrome. James W. Mold, MD, MPH

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KEY POINTS

Polycystic ovarian syndrome (PCOS) is a chronic disorder associated with infertility; miscarriage; adverse pregnancy outcomes; and cardiovascular, metabolic, psychological and neoplastic risks.

DIagnosis of PCOS can be made based on the presence of any 2 of menstrual irregularities, clinical or biochemical hyperandrogenism or polycystic ovarian morphology on transvaginal ultrasonography.

Treatment of PCOS may target anovulation, androgen excess, hyperinsulinemia and weight management.

Patients with PCOS should have regular monitoring of their body mass index, blood pressure and metabolic parameters, and should be regularly screened for depression, anxiety and obstructive sleep apnea.

Author/s:

Ebernella Shirin Dason, Olexandra Koshkina, Crystal Chan, Mara Sobel