Prostate-Specific Antigen

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

What Is Prostate Cancer?

Megan George — Fri, 25 Jul 2025 13:49:16 +0000

Date Added:

July 25, 2025

Journal/Publication:

JAMA Patient Page

Publication Date:

July 24, 2025

URL:

What Is Prostate Cancer?

Type:

Patient Education Materials

DOI (1):

10.1001/jama.2025.10177

Keywords

Patient Information

jama Patient Information

MeSH

Prostate-Specific Antigen

Digital Rectal Examination

early detection of cancer

Early Detection of Cancer* / methods

Information for patients about prostate cancer. James W. Mold, MD, MPH

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Prostate cancer is a common malignancy in older men. Prostate cancer typically affects older men (average age at diagnosis is 67 years) and is more common among Black men than White men.1 More than half of prostate cancer risk is due to genetic factors. Prostate cancer is the second most common cause of cancer in men worldwide, with about 1.5 million cases diagnosed in 2021. In the US, 3.4 million men were living with prostate cancer in 2021.

Author/s:

Rebecca Voelker, MSJ

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

Fifteen-Year Outcomes after Monitoring, Surgery, or Radiotherapy for Prostate Cancer

Rowan Hutchins — Sun, 19 Mar 2023 05:00:00 +0000

Date Added:

March 19, 2023

Journal/Publication:

NEJM

Publisher:

Massachusetts Medical Society

Publication Date:

March 11, 2023

URL:

Fifteen-Year Outcomes after Monitoring, Surgery, or Radiotherapy for Prostate Cancer

Type:

Clinical Research Results

Format:

Article

DOI (1):

10.1056/NEJMoa2214122

Keywords

PMID (1):

36912538

MeSH

Disease Progression

Prostate-Specific Antigen

prostatectomy

Androgen Antagonists

prostatic neoplasms

This is the best evidence we have to date regarding the benefits of, or lack thereof, of treatment of localized prostate cancer. James W. Mold, MD, MPH

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Background

Between 1999 and 2009 in the United Kingdom, 82,429 men between 50 and 69 years of age received a prostate-specific antigen (PSA) test. Localized prostate cancer was diagnosed in 2664 men. Of these men, 1643 were enrolled in a trial to evaluate the effectiveness of treatments, with 545 randomly assigned to receive active monitoring, 553 to undergo prostatectomy, and 545 to undergo radiotherapy.
Methods

At a median follow-up of 15 years (range, 11 to 21), we compared the results in this population with respect to death from prostate cancer (the primary outcome) and death from any cause, metastases, disease progression, and initiation of long-term androgen-deprivation therapy (secondary outcomes).
Results

Follow-up was complete for 1610 patients (98%). A risk-stratification analysis showed that more than one third of the men had intermediate or high-risk disease at diagnosis. Death from prostate cancer occurred in 45 men (2.7%): 17 (3.1%) in the active-monitoring group, 12 (2.2%) in the prostatectomy group, and 16 (2.9%) in the radiotherapy group (P=0.53 for the overall comparison). Death from any cause occurred in 356 men (21.7%), with similar numbers in all three groups. Metastases developed in 51 men (9.4%) in the active-monitoring group, in 26 (4.7%) in the prostatectomy group, and in 27 (5.0%) in the radiotherapy group. Long-term androgen-deprivation therapy was initiated in 69 men (12.7%), 40 (7.2%), and 42 (7.7%), respectively; clinical progression occurred in 141 men (25.9%), 58 (10.5%), and 60 (11.0%), respectively. In the active-monitoring group, 133 men (24.4%) were alive without any prostate cancer treatment at the end of follow-up. No differential effects on cancer-specific mortality were noted in relation to the baseline PSA level, tumor stage or grade, or risk-stratification score. No treatment complications were reported after the 10-year analysis.
Conclusions

After 15 years of follow-up, prostate cancer–specific mortality was low regardless of the treatment assigned. Thus, the choice of therapy involves weighing trade-offs between benefits and harms associated with treatments for localized prostate cancer. (Funded by the National Institute for Health and Care Research; ProtecT Current Controlled Trials number, ISRCTN20141297. opens in new tab; ClinicalTrials.gov number, NCT02044172. opens in new tab.)

Author/s:

Hamdy, Freddie, Donovan, Jenny, Lane, Athene, Metcalfe, Chris, Davis, Michael, Turner, Emma, Martin, Richard, Young, Grace, Walsh, Eleanor, Bryant, Bollina, Prasad, Doble, Andrew

Association of Treatment With 5α-Reductase Inhibitors and Prostate Cancer Mortality Among Older Adults

John Bayhi — Sat, 19 Oct 2019 15:06:17 +0000

Date Added:

October 19, 2019

Journal/Publication:

JAMA Network Open

Publisher:

American Medical Association

Publication Date:

October 18, 2019

URL:

Association of Treatment With 5α-Reductase Inhibitors and Prostate Cancer Mortality Among Older Adults

Type:

Clinical Research Results

Format:

Article

DOI (1):

10.1001/jamanetworkopen.2019.13612

Keywords

prostate cancer

5-alpha-reductase inhibitors

5α-Reductase Inhibitors

5-ARIs

prostate-specific antigen

PSA

PMID (1):

31626312

MeSH

Humans

male

Prostate-Specific Antigen

Prostactic Hyperplasia

5-alpha-reductase inhibitors reduce PSA levels, even in patients with prostate cancer, so beware. James W. Mold, MD, MPH

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5α-reductase inhibitors (5-ARIs) are used to treat benign prostatic enlargement, a common condition causing urinary outflow obstruction. They also reduce prostate-specific antigen (PSA) by approximately 50%. Our group has recently published that among US military veterans, 5-ARIs are associated with delays in prostate cancer (PC) diagnoses, higher grade and stage at presentation, and worse PC-specific mortality (PCSM), presumably because of misinterpreted PSA values. We hypothesized that these results are generalizable to the broader US population.

Author/s:

Kumar, A, Nalawade, V, Riviere, P, Sarkar, RR, Parsons, JK, Murphy, JD, Rose, BS