Fact-checked by Grok 2 weeks ago

Prostate

The prostate gland is a small, walnut-sized organ that forms part of the , situated in the just below the urinary and surrounding the proximal portion of the . It consists of glandular and fibromuscular tissues organized into distinct zones, including zone (which comprises about 70% of the gland), the central zone, and the transition zone, all encased in a fibrous capsule. The gland's primary function is to secrete an alkaline fluid rich in enzymes, proteins, , , and other substances that neutralize the acidity of the female reproductive tract, nourish , enhance their motility, and contribute to the volume of for effective propulsion during . Anatomically, the prostate resembles an inverted cone with a base adjacent to the neck and an near the external , measuring approximately 3-4 centimeters in width, 3 centimeters in height, and weighing about 20-30 grams in adults. It is positioned anterior to the —separated by Denonvilliers' fascia—and lateral to the muscles, with the passing through its center and the ejaculatory ducts entering from the . Blood supply derives mainly from the inferior vesical and middle rectal arteries, while venous drainage occurs via the prostatic into the internal iliac veins; innervation comes from the autonomic , regulating secretion and smooth muscle contraction. During and , prostatic muscles contract to expel seminal fluid into the , while valves prevent retrograde flow into the and ensure separation from urinary function. The prostate develops embryonically from the around the 10th week of and enlarges significantly during under the influence of androgens, particularly testosterone, which it converts locally to the more potent (DHT) via the 5-alpha reductase. This hormone-dependent growth underscores its role in male reproductive physiology, but it also contributes to age-related changes, such as (BPH), which affects the transition zone and occurs in over half of men by age 60, leading to urinary symptoms without malignancy. Notably, the prostate is a common site for pathology in aging males, including () and (the second most frequent cancer in men worldwide), often originating in the peripheral zone, highlighting its clinical significance in and .

Anatomy

Gross anatomy

The prostate gland is situated in the male pelvic cavity, inferior to the urinary bladder and encircling the proximal urethra at the bladder neck, with its position anterior to the rectum and posterior to the pubic symphysis. In adult males, it typically weighs 20 to 25 grams and resembles the size and shape of a walnut, with approximate dimensions of 3 cm in transverse width, 3 cm in anteroposterior depth, and 5 cm in craniocaudal length. The gland is enclosed by a thin fibrous capsule and consists of approximately 50% glandular tissue and 50% fibromuscular stroma. The prostate assumes an inverted conical or pyramidal shape, featuring a broad base superiorly adjacent to the and a narrower inferiorly at the level of the external urethral . It is subdivided into distinct zones that reflect its internal architecture: the peripheral zone, comprising about 70% of the glandular volume and located posteriorly and laterally; the central zone, a smaller wedge-shaped at the base encircling the ejaculatory ducts; the transitional zone, which surrounds the mid-portion of the ; and the anterior fibromuscular zone, a non-glandular of dense muscle and anteriorly. Historically, the prostate has also been described in terms of five lobes—anterior, posterior, two lateral, and a —but the zonal model is more commonly used in modern anatomical and clinical contexts. Key relations include the anterior surface, which abuts the via the retropubic (preprostatic) space containing fat and the ; the posterior surface, closely apposed to the and separated by Denonvilliers' ; the inferolateral surfaces, which contact the muscles and are enveloped by the endopelvic ; and the superior aspect, which interfaces with the bladder neck and the inferior bases of the . Centrally, the gland envelops the , through which and pass. In imaging, transrectal ultrasound depicts the normal prostate as a symmetrical, crescent-shaped structure inferior to the base, exhibiting homogeneous echotexture and a thin hypoechoic peripheral capsule, with the central visible as an echogenic line. (MRI), particularly T2-weighted sequences, reveals the peripheral zone as uniformly hyperintense, the central zone as a low-signal wedge at the base, and the transitional zone as mildly heterogeneous; the capsule appears as a dark rim, and the overall volume is typically under 30 mL in healthy adults. These modalities aid in delineating the gland's contours and zonal for clinical assessment.

Microscopic anatomy

The prostate consists of glandular and fibromuscular as its primary components. The glandular forms compound tubuloalveolar structures, including acini lined by a single layer of cuboidal to columnar secretory cells with apical and basal nuclei, supported by a basal layer of flattened basal cells and occasional neuroendocrine cells. The fibromuscular , which constitutes about 50% of the 's volume, comprises bundles, fibroblasts, fibers, , blood vessels, and , providing structural support and aiding in the expulsion of secretions during . Histologically, the prostate is organized into distinct zones with varying glandular and stromal proportions. The peripheral zone, comprising approximately 70% of the glandular , is predominantly composed of closely packed acini with and minimal intervening stroma, making it the primary site for development. The central zone, forming a cone-shaped around the ejaculatory ducts and accounting for 25% of the gland, features more complex, undulating acini with papillary projections and a mixed glandular-stromal . The transitional zone, surrounding the proximal and representing about 5% in young adults, shows stromal predominance with fewer, more irregular glands, and it enlarges significantly in . The ductal system includes 15 to 30 main prostatic ducts that arise from the coalescence of smaller ductules draining the acini and open into the along the verumontanum. These ducts are lined by transitioning to near the urethral openings. The , a small blind-ending pouch in the midline of the verumontanum, represents a remnant of the Müllerian ducts. Prostatic fluid, secreted by the columnar epithelial cells, is a major component of , characterized by high concentrations of citrate (providing osmotic balance), polyamines such as (supporting ), and enzymes including (, a that liquefies ). The fluid maintains an alkaline of approximately 7.3 in healthy individuals, which helps neutralize vaginal acidity.57333-4) Normal prostate cells express androgen receptors () in both epithelial and stromal compartments, mediating dihydrotestosterone-dependent growth and differentiation. Epithelial is primarily in secretory and basal cells, while stromal predominates in fibroblasts and , facilitating essential for glandular maintenance.

Vascular and lymphatic supply

The arterial supply to the prostate gland originates primarily from branches of the , with the inferior vesical artery providing the major contribution, supplemented by the middle rectal and . These vessels give rise to the prostatic arteries, which are divided into anteromedial and posterolateral branches; the anteromedial branch supplies the central (transitional) zone, while the posterolateral branch perfuses the peripheral zone, ensuring zonal-specific nourishment for glandular and stromal tissues. Venous drainage from the prostate is mediated by the , commonly referred to as Santorini's plexus, a valveless network surrounding the prostate and . This primarily empties into the internal iliac veins via the vesical and prostatic veins, but it also communicates directly with the vertebral venous (Batson's ), facilitating potential flow under certain pressure conditions and contributing to metastatic dissemination in prostate . Lymphatic drainage follows a stepwise pattern, beginning with periprostatic vessels that converge on the internal and , as well as the obturator nodes—particularly those draining zone where many malignancies originate. From these pelvic nodes, lymph flows superiorly to the common iliac and para-aortic nodes, supporting immune surveillance and fluid in the pelvic region. Innervation of the prostate is autonomic, derived from the pelvic plexus (), which integrates sympathetic and parasympathetic inputs. Sympathetic fibers arise from spinal segments T10-L2 via the hypogastric nerves, promoting and glandular contraction, while parasympathetic fibers from S2-S4 travel through the to stimulate secretion and . Sensory afferents for pain and distension accompany both pathways, relaying signals to the . Physiologically, the prostate maintains robust through arterial s driven by the systemic circulation, with a dense network embedded in the facilitating delivery and waste removal essential for secretory activity. Venous outflow in the prostatic plexus is influenced by a modest pressure gradient of approximately 6 mm Hg toward the internal iliac veins, modulated by and intra-abdominal pressures to prevent stagnation.

Gene and protein expression

The (AR) gene, located on the , is a critical regulator of prostate development and function, with its expression maintained in normal prostate epithelial and stromal cells. The gene (KLK3/) encodes a predominantly expressed in prostate epithelial cells, contributing to seminal fluid liquefaction. TMPRSS2-ERG gene fusions, while characteristic of , occur rarely in normal prostate tissue and can be induced by androgens in nonmalignant epithelial cells under experimental conditions. Key proteins in the prostate include , a secreted by epithelial cells into seminal plasma and , with normal levels ranging from 0.5 to 5 ng/mL in healthy individuals. (ACPP), encoded by the ACPP gene, is another enzyme produced by prostate epithelium, functioning in processes and serving as a historical for prostate health. NKX3.1, a , acts as a highly specific marker for prostate tissue, with expression localized to the nucleoplasm and of prostatic cells. Expression patterns of prostate genes and proteins exhibit zonal variations, with higher levels observed in stromal cells compared to epithelial compartments across peripheral and transition zones. The Human Protein Atlas has profiled over 15,000 proteins, identifying 126 genes with elevated expression in the prostate, including 15 enriched genes such as KLK3 and ACPP, highlighting tissue-specific molecular signatures. Regulatory mechanisms involve androgen-responsive elements (AREs) in promoter regions, such as those upstream of the KLK3 gene, which drive AR-mediated transcription and secretion of prostate-specific proteins in response to testosterone or . Epigenetic modifications, including and alterations, maintain stable in normal prostate tissue, with an integrative epigenome map revealing zone-specific patterns that support epithelial differentiation. Recent studies from 2023 to 2025, utilizing single-cell sequencing, have elucidated stromal-epithelial interactions in the normal prostate, identifying distinct basal epithelial subpopulations with zone-specific signatures that influence signaling and . These analyses reveal heterogeneous expression profiles, such as elevated AR-related pathways in zone stroma, underscoring dynamic cellular crosstalk.

Development

Embryological origins

The prostate gland develops from the endodermal lining of the , a structure that forms as a caudal extension of the during early embryogenesis. Around 10 to 12 weeks of , epithelial buds emerge from the epithelium at the base of the urethra, induced by paracrine signals from the adjacent mesenchyme, which is derived from Wolffian duct remnants. These buds represent the initial outgrowth of prostatic tissue and are patterned along the urethra in a manner that foreshadows the future zonal architecture of the gland. Prostate development is initially androgen-independent, with early specification of the occurring prior to significant hormonal influence; however, the outgrowth and branching of solid epithelial buds at approximately 12 weeks are driven by (DHT), the potent metabolite of testosterone produced locally in the via the 5-alpha reductase type 2. DHT binds to receptors in the , triggering paracrine factors such as fibroblast growth factors that induce epithelial and budding. By 16 weeks , these solid cords undergo canalization to form lumens, establishing a ductal network that continues to branch and elongate through the remainder of fetal life, with into distinct central, peripheral, and transition zones largely complete by birth. Genetic regulation plays a key role in bud formation and ductal morphogenesis, with the Sonic Hedgehog (SHH) signaling pathway essential for activating mesenchymal responses that support epithelial outgrowth; disruption of SHH in animal models leads to failure of prostate initiation and abnormal urogenital development. Transcription factors such as HOXB13 and FOXA1 are also critical, expressed in the developing to guide ductal and ; mutations in these genes in murine models result in reduced bud numbers, ductal dilation, and impaired epithelial maturation, though complete is not typically observed. Congenital prostate is exceedingly rare in humans and is frequently associated with broader urinary tract malformations, including or Wolffian duct anomalies, highlighting the interconnected embryological origins of these structures.

Postnatal changes

Following birth, the prostate gland remains relatively stable in size during infancy and childhood, with volumes typically ranging from 0.4 to 5.2 mL and an average of about 1.2 mL in boys aged 1 to 17 years.00563-6/fulltext) This quiescent phase persists until , when an surge, primarily driven by rising testosterone levels, initiates rapid glandular maturation and growth. During puberty, the prostate undergoes exponential expansion, increasing in volume approximately 10- to 20-fold from prepubertal levels (around 1-2 mL) to adult dimensions of 15-25 mL by ages 20 to 30 years, reaching a peak size during early adulthood. This growth is mediated by the conversion of testosterone to (DHT) via the enzyme , which binds to receptors in prostatic epithelial and stromal cells to promote and . The prostate achieves its mature structure by the end of the third decade, with balanced zonal contributions from the peripheral, central, and transition zones. In senescence, after age 50, prostate growth dynamics shift, with the overall rate of volume increase peaking around ages 56 to 65 at approximately 4.15 per year before gradually declining, reflecting stromal remodeling and accumulation of senescent cells that may predispose to in the transition zone. Prostate-specific antigen (PSA) levels, which rise steadily with glandular enlargement, have upper reference limits that increase with age (e.g., up to 6.5 ng/ after age 70) but can plateau or show attenuated increases in advanced age due to reduced secretory capacity. Hormonally, declining testosterone and DHT levels after age 50 are accompanied by a relative rise in influence, as increases the estrogen-to-androgen ratio, contributing to stromal predominance and altered glandular architecture. Environmental factors, such as , modulate these changes; higher (BMI) correlates positively with larger prostate volumes, with 2023 analyses showing obese men (BMI >30 kg/m²) exhibiting significantly greater volumes and symptom scores than normal-weight counterparts, potentially via and altered . Diet and metabolic status further influence size, though effects are more pronounced in midlife than . Magnetic resonance imaging (MRI) effectively tracks these postnatal alterations, revealing stable small volumes in (e.g., <5 mL), rapid zonal expansion during puberty, peak total volumes of 20-25 mL in young adulthood, and progressive transition zone enlargement in senescence, with overall growth slowing after age 65 as evidenced by serial T2-weighted scans. These imaging correlates aid in distinguishing physiological maturation from pathological states.

Physiology

Secretory functions

The prostate gland secretes a clear, slightly alkaline fluid that contributes approximately 20-30% of the total semen volume, typically amounting to 0.5-1.5 mL per ejaculation. This prostatic fluid has a pH range of 7.2-7.8, which helps neutralize the acidic environment of the vagina (pH around 4.0-5.0), thereby protecting sperm from inactivation and enhancing their viability during transit. Key components of the prostatic fluid include citrate, which serves as an energy source for sperm motility; zinc, which exhibits antibacterial properties to reduce infection risk in the reproductive tract; prostate-specific antigen (PSA), a serine protease that facilitates semen liquefaction; and prostaglandins, which promote uterine contractions and sperm transport. The secretion occurs primarily through an apocrine mechanism in the columnar epithelial cells lining the prostatic acini, where portions of the cell cytoplasm, including membrane-bound vesicles like prostasomes, are pinched off and released into the lumen. This process is regulated by the sympathetic nervous system via the hypogastric nerves, which stimulate glandular contraction and fluid expulsion during ejaculation. Enzymatic activities in the prostatic fluid are crucial for its function, with PSA playing a central role by cleaving high-molecular-weight proteins such as semenogelin I and II, which initially form a coagulum in ejaculated semen to prevent immediate sperm loss; this proteolysis leads to rapid liquefaction within 5-20 minutes post-ejaculation. Recent proteomic analyses of prostatic fluid, including expressed prostatic secretions collected from urine, have identified over 3,000 proteins, revealing a complex proteome that includes enzymes, antimicrobial agents, and signaling molecules, providing insights into prostate physiology and potential biomarkers for disease.

Role in reproduction

The prostate gland contributes significantly to male reproduction by producing a substantial portion of seminal fluid, which constitutes approximately 20-30% of total semen volume and is essential for sperm transport, nourishment, and viability during fertilization. This fluid is released during ejaculation, integrating with spermatozoa from the testes and secretions from other accessory glands to form semen capable of surviving the vaginal environment and reaching the oocyte. The prostate's role ensures efficient sperm delivery, with disruptions potentially leading to infertility. In the ejaculation process, the emission phase is initiated by sympathetic nervous system activation via the hypogastric nerves, causing coordinated contractions of smooth muscle in the , , and ; these contractions propel prostatic fluid into the posterior urethra, mixing it with sperm to form the bulk of semen. Subsequent prostatic and periurethral muscle contractions during the expulsion phase, driven by somatic nerves, propel the semen through the urethra. This dual-phase mechanism, under autonomic control, is critical for reproductive success, as failure in emission can result in retrograde ejaculation or low semen volume. The prostate supports fertility by secreting nutrients such as zinc, citric acid, and enzymes that protect sperm from oxidative stress and enhance their survival and motility in the female tract; prostate-specific antigen (PSA), a key prostatic enzyme, facilitates semen liquefaction by proteolytically degrading the seminal coagulum formed by seminal vesicle proteins, thereby freeing sperm for progressive movement. Neural regulation involves the hypothalamic-pituitary-gonadal (HPG) axis, where gonadotropin-releasing hormone stimulates luteinizing hormone and follicle-stimulating hormone release, maintaining androgen levels that promote prostate secretory function and overall ejaculatory capacity; sensory input for orgasmic reflexes is mediated by the pudendal nerve, integrating afferent signals from the genitalia to trigger expulsion. Prostate disorders can profoundly impact fertility, with conditions like chronic prostatitis linked to reduced semen quality, including lower sperm concentration, motility, and viability due to inflammation-induced oxidative damage. Obstructive azoospermia has been associated with prostatic anomalies such as midline cysts, where cyst volume exceeding 0.117 ml correlates with severe oligo- or azoospermia by impeding fluid outflow. Studies highlight inverse relationships between enlarged prostate volume and semen parameters, suggesting that benign prostatic hyperplasia may compromise ejaculatory efficiency and sperm delivery. Evolutionarily, prostate secretions in seminal plasma play a key role in immune modulation, suppressing excessive female immune responses to foreign sperm antigens and protecting gametes from phagocytosis or antibody attack, thereby enhancing fertilization success and representing an adaptive trait in mammalian reproduction. Prostasomes, prostate-derived extracellular vesicles within seminal plasma, further contribute by transferring bioactive molecules that dampen inflammation and promote sperm-egg interaction.

Role in urination and micturition

The prostate gland encircles the prostatic urethra, a segment approximately 3–4 cm in length that passes through the central portion of the gland, facilitating the anatomical integration of urinary and reproductive pathways. This encirclement is primarily composed of smooth muscle fibers within the prostatic stroma, which contribute to the maintenance of urethral tone under normal conditions. The smooth muscle's contractile properties help regulate the passage of urine by providing structural support around the urethra. During micturition, the prostatic smooth muscle relaxes to permit unobstructed urine flow from the bladder. This relaxation is primarily mediated by a reduction in sympathetic nervous system activity and activation of parasympathetic pathways, which release nitric oxide to inhibit contraction in the urethral smooth muscle. Alpha-adrenergic receptors, particularly the α1A subtype, predominate in the prostate and maintain baseline tone; their blockade pharmacologically induces relaxation, underscoring their role in dynamic urethral resistance. The internal urethral sphincter, functionally supported by the prostate's smooth muscle at the bladder neck, aids in urinary continence by preventing involuntary leakage during bladder filling. Prostate size influences peak urinary flow rate (Qmax), with normal values ranging from 15–25 mL/s in healthy adult men; enlargement can compress the urethra, reducing flow and contributing to obstructive symptoms. Sensory innervation of the prostate arises from afferent fibers in the pelvic and hypogastric nerves, which detect urethral distension and glandular pressure changes, relaying signals to the spinal cord and brain for coordination of voiding reflexes. These afferents are linked to the perception of lower urinary tract symptoms (LUTS), such as urgency or incomplete emptying, particularly when prostatic changes alter sensory thresholds. After age 40, age-related alterations in prostatic smooth muscle, including increased stromal contractility and reduced compliance due to hormonal shifts, heighten the risk of bladder outlet obstruction and associated LUTS.

Clinical Significance

Inflammatory disorders

Inflammatory disorders of the prostate primarily encompass prostatitis, a condition characterized by inflammation of the prostate gland, which can be infectious or non-infectious in origin. Prostatitis affects men of all ages but is most common in those under 50, with varying prevalence estimates ranging from 2% to 10% depending on the population studied. The National Institutes of Health (NIH) classifies prostatitis into four categories to guide diagnosis and management: Category I (acute bacterial prostatitis), Category II (chronic bacterial prostatitis), Category III (chronic prostatitis/chronic pelvic pain syndrome, or CP/CPPS, further divided into IIIA inflammatory and IIIB non-inflammatory subtypes), and Category IV (asymptomatic inflammatory prostatitis). This classification, established in 1995 and widely adopted, emphasizes clinical presentation, infection status, and inflammatory markers rather than solely bacteriological findings. Acute bacterial prostatitis (NIH Category I) is typically caused by ascending urinary tract infections, with Escherichia coli being the most common pathogen, accounting for 50% to 90% of cases. Symptoms include sudden onset of dysuria, perineal pain, urinary frequency, and urgency, often accompanied by systemic signs such as high fever, chills, and malaise. Chronic bacterial prostatitis (NIH Category II) involves recurrent urinary tract infections due to persistent prostate infection, presenting with milder, intermittent symptoms like dysuria, pelvic discomfort, and lower back pain, without the acute systemic features. CP/CPPS (NIH Category III), the most prevalent form affecting up to 90% of prostatitis cases, manifests as chronic pelvic pain lasting at least three months, along with urinary symptoms and sexual dysfunction, but lacks evidence of bacterial infection; it is subdivided based on the presence of white blood cells in prostatic secretions. Asymptomatic inflammatory prostatitis (NIH Category IV) is incidentally discovered during evaluations for other conditions, such as elevated prostate-specific antigen, and requires no treatment unless associated with complications. The pathophysiology of bacterial prostatitis involves bacterial ascension from the urethra into prostatic ducts, facilitated by factors like urinary reflux or instrumentation, leading to acute inflammation and potential abscess formation. In chronic bacterial cases, biofilm formation by pathogens such as E. coli allows bacteria to evade antibiotics and host defenses, contributing to recurrence within prostatic acini and ducts. For CP/CPPS, neurogenic inflammation plays a key role, involving mast cell degranulation, release of neuropeptides like substance P, and central sensitization of pain pathways, which perpetuate pelvic pain without identifiable infection; this may be triggered by prior trauma, neuromuscular dysfunction, or autoimmune responses. Diagnosis of prostatitis relies on clinical history, physical examination including digital rectal exam, and targeted tests to differentiate categories. For bacterial forms, urine cultures from midstream, post-massage, and expressed prostatic secretions (EPS) are essential, with EPS obtained via prostate massage to assess leukocytes (>10 white blood cells per indicates ) and . In CP/CPPS, the UPOINT system evaluates six domains—urinary symptoms, factors, organ-specific findings, , neurologic/systemic symptoms, and tenderness—to guide individualized assessment and treatment, improving diagnostic precision over symptom-based approaches alone. Imaging like transrectal may be used if is suspected, but routine use is avoided to prevent . Treatment varies by category, focusing on symptom relief and infection eradication where applicable. Acute bacterial prostatitis requires hospitalization for severe cases, with intravenous antibiotics such as fluoroquinolones (e.g., ) or third-generation cephalosporins targeting E. coli and other , followed by oral therapy for 4-6 weeks to prevent chronicity. Chronic bacterial prostatitis is managed with prolonged oral antibiotics, again favoring fluoroquinolones due to their prostatic penetration, for 4-12 weeks, alongside alpha-blockers like tamsulosin to alleviate urinary symptoms by relaxing prostate . For /CPPS, antibiotics are not routinely recommended absent ; instead, 2024 guidelines emphasize , including alpha-blockers for voiding symptoms, agents, for , and psychological support, with evidence showing symptom improvement in 50-70% of patients through phenotype-guided approaches like UPOINT. cases warrant observation only, though monitoring for progression to symptomatic disease is advised.

Benign enlargement

Benign prostatic hyperplasia (BPH) is a non-cancerous condition characterized by the proliferation of stromal and epithelial cells in the prostate gland, primarily affecting the transitional zone that surrounds the . This enlargement can lead to compression of the , resulting in (LUTS) and potential complications if untreated. BPH is distinct from , as it does not involve , though both can coexist in older men. Epidemiologically, BPH becomes increasingly prevalent with age, affecting approximately 50% of men between 51 and 60 years old, rising to 70% in those aged 60 to 69, and reaching up to 80% in men over 70, with histological evidence present in up to 90% by age 85. The condition predominantly involves the transitional zone of the prostate, where nodular develops and contributes to urethral obstruction. Globally, the of symptomatic BPH cases among men aged 40 and older was estimated at 94 million in 2019, with rates continuing to rise due to aging populations. The of BPH centers on the hormone (DHT), which drives the of stromal and epithelial cells in the prostate. DHT is produced locally in the prostate through the action of the 5-alpha reductase, which converts testosterone to DHT; this process is essential for normal prostate development but becomes dysregulated in BPH, leading to excessive glandular and stromal growth. Inhibition of 5-alpha reductase has been shown to reduce prostate volume and alleviate symptoms by lowering DHT levels. Symptoms of BPH primarily manifest as LUTS, including urinary hesitancy, weak or interrupted urine stream, incomplete bladder emptying, , and urgency. These symptoms are quantified using the International Prostate Symptom Score (IPSS), a validated comprising seven questions on urinary frequency, urgency, and stream quality, with scores ranging from 0 (asymptomatic) to 35 (severely symptomatic); scores of 0-7 indicate mild symptoms, 8-19 moderate, and 20-35 severe. Key risk factors for BPH include advancing age, which is the strongest predictor due to cumulative hormonal and cellular changes, and a family history, with genetic factors accounting for 39-72% of heritability based on twin and family studies. , encompassing , , and , is associated with increased BPH risk through mechanisms like chronic inflammation and hormonal imbalances. Recent research has linked to larger prostate volumes and higher BPH incidence, suggesting it as a modifiable contributor via metabolic pathways. Complications of untreated BPH include acute urinary retention (AUR), occurring at an annual rate of approximately 2% in men with moderate to severe symptoms, as observed in long-term studies like the Medical Therapy of Prostatic Symptoms (MTOPS) trial where the placebo group experienced a 7.1% cumulative risk over four years. Other complications encompass bladder stones, with an overall incidence of about 10% in BPH patients due to urinary stasis and incomplete emptying.

Prostate cancer

Prostate cancer is a malignant neoplasm originating from the glandular epithelial cells of the prostate, representing a significant global health burden. In the United States, an estimated 313,780 new cases are projected for 2025, accounting for approximately 30% of all male cancer diagnoses and making it the second leading cause of cancer death among men, with about 35,770 fatalities expected that year. Recent trends indicate a resurgence in incidence, with rates increasing by 3% annually since 2014 after a prior decline, alongside a notable rise in late-stage diagnoses, including distant-stage disease advancing by nearly 3% per year in men under 55 and up to 6% in those aged 55-69. This uptick is attributed to evolving screening practices and potential delays in diagnosis, exacerbating the disease's impact on public health. Pathologically, prostate cancer is characterized by adenocarcinoma in over 95% of cases, predominantly arising in the peripheral zone, which accounts for about 70% of glandular tissue and the majority of tumors. The assesses tumor aggressiveness by evaluating glandular architecture under , with scores ranging from 6 (least aggressive, Grade Group 1) to 10 (most aggressive, Grade Group 5), guiding and . A key molecular hallmark is the TMPRSS2-ERG fusion, present in approximately 50% of cases, resulting from chromosomal rearrangements that drive oncogenesis and are more prevalent in populations. Major risk factors include advancing age, with over 80% of diagnoses occurring in men over 65; ancestry, conferring a 1.7-fold higher incidence and 2.1-fold increased mortality risk compared to other groups; and germline mutations such as , which elevate lifetime risk by up to 20%. (PSA) screening remains controversial due to its association with and of indolent cancers, prompting guidelines to recommend shared decision-making rather than routine use in all men. Staging employs the TNM system, integrating tumor extent (T1-T4), nodal involvement (N0-N1), and metastasis (M0-M1), alongside PSA levels and Gleason score to classify disease as localized, regional, or distant. Advanced imaging like prostate-specific membrane antigen (PSMA)-PET enhances detection accuracy, identifying occult metastases with sensitivity exceeding 80% in high-risk cases and improving staging precision over conventional methods. Recent advances from 2023 to 2025 highlight targeted therapies transforming management. The 2025-presented LUNAR demonstrated that neoadjuvant 177Lu-PSMA-617 radioligand combined with stereotactic body radiation doubled in oligometastatic hormone-sensitive compared to radiation alone. Water vapor ablation, via systems like Vanquish, has emerged as a focal option; the VAPOR 2 (initiated 2023) enrolled over 200 intermediate-risk patients, showing safety and efficacy in ablating targeted lesions while preserving surrounding tissue, with no serious adverse events reported. A 2025 study identified tumor-supportive macrophages expressing SPP1 and TREM2 as drivers of treatment resistance, revealing that dual blockade with anti-SPP1 antibodies and significantly enhanced anti-tumor responses in preclinical models. Updated NCCN and EAU guidelines for 2025 further emphasize active surveillance for low- and select intermediate-risk cases, incorporating multiparametric MRI and genomic testing to minimize while monitoring progression.

Diagnostic and therapeutic approaches

Diagnosis of prostate conditions typically begins with clinical evaluation and screening tools tailored to the suspected . The digital rectal examination (DRE) allows of the prostate through the rectal wall to assess for nodules, asymmetry, or enlargement, serving as an initial step in evaluating or screening for cancer in high-risk individuals. (PSA) testing measures serum levels of this prostate-derived protein, with a of 4 ng/ often prompting further investigation, though decisions incorporate age, race, and family history for personalized . Multiparametric (mpMRI) enhances detection by visualizing suspicious lesions, scored via the Prostate Imaging-Reporting and Data System (PI-RADS), where scores of 4 or 5 indicate high likelihood of clinically significant cancer, guiding targeted biopsies. Confirmatory diagnosis frequently involves prostate , with transrectal (TRUS)-guided systematic sampling as the standard approach, typically involving 12 cores from predefined zones to detect cancer or . For (BPH), diagnostics emphasize symptom scoring via tools like the International Prostate Symptom Score alongside DRE and to rule out malignancy, with uroflowmetry assessing voiding dysfunction. Therapeutic strategies vary by condition severity and patient factors. For low-risk prostate cancer, watchful waiting or active surveillance monitors disease progression without immediate intervention, reserving treatment for symptomatic advancement or rapid PSA rise. In BPH management, 5-alpha reductase inhibitors (5-ARIs) such as reduce prostate volume by inhibiting conversion, alleviating symptoms in men with enlarged prostates greater than 30 grams. Radiation therapies include (EBRT) delivering precise doses to the prostate and implanting radioactive seeds for localized control in intermediate-risk cases. , particularly (ADT) using luteinizing hormone-releasing hormone agonists or antagonists, suppresses testosterone to slow cancer growth in advanced stages. Surgical options address both BPH and cancer. (TURP) removes obstructing tissue endoscopically for BPH, improving urinary flow in moderate-to-severe cases. Radical prostatectomy, often robotic-assisted for enhanced precision and reduced recovery time, excises the entire gland in localized cancer, achieving cure rates over 90% for organ-confined disease. Focal therapies like , which freezes targeted areas, and high-intensity focused ultrasound (HIFU), using sound waves to ablate tissue, offer minimally invasive alternatives for low-to-intermediate risk tumors, preserving surrounding structures. Emerging approaches as of 2024-2025 emphasize targeted . PSMA-targeted , including lutetium-177-PSMA-617 radioligand , bind prostate-specific on cancer cells to deliver , extending in metastatic castration-resistant cases by over 4 months in pivotal trials. Neoadjuvant expansions, highlighted at the AACR 2025 annual meeting, explore checkpoint inhibitors like prior to to enhance in high-risk localized . The Canadian Urological Association (CUA) 2025 guidelines for metastatic castration-naive recommend intensified ADT combined with novel hormonal agents like abiraterone, improving radiographic . Treatment outcomes reflect disease stage, with 5-year relative survival exceeding 99% for localized but dropping to approximately 30-37% for metastatic disease, per data. Common side effects include , affecting up to 50-80% post-prostatectomy or depending on nerve-sparing techniques, and , occurring in 5-20% of surgical patients but often resolving within a year. These impacts underscore the need for multidisciplinary care to mitigate quality-of-life burdens.

Historical and Comparative Perspectives

Historical discovery and research

The earliest references to prostate-related conditions appear in , where (c. 460–370 BCE) described and other symptoms in older men, attributing them to obstructions in the urinary tract that modern interpretations link to prostatic enlargement. Herophilus of (c. 335–280 BCE), often called the father of for his pioneering human dissections in , provided the first detailed description and naming of the prostate gland as a distinct structure surrounding the , distinguishing it from surrounding tissues. These ancient observations laid foundational insights into prostatic , though limited by the era's anatomical methods and ethical constraints on dissection. During the , anatomical study advanced significantly with direct human dissections, culminating in Andreas Vesalius's seminal work De Humani Corporis Fabrica (1543), which included the first accurate illustrations of the prostate as a glandular structure encircling the , correcting earlier Galenic misconceptions derived from animal dissections. In the , Giovanni Morgagni's De Sedibus et Causis Morborum per Anatomen Indagatis (1761) further correlated prostatic with clinical symptoms through findings, notably linking prostate stones to urinary disorders and , establishing pathology as a bridge between and disease. Concurrently, Scottish surgeon John Hunter (1728–1793) advanced understanding of prostatic by describing the enlarged median lobe's role in urinary obstruction, based on his extensive observations and experiments, which emphasized the gland's dynamic changes in disease states like . The 20th century marked transformative milestones in prostate research and treatment. In 1904, American urologist Hugh Hampton Young performed the first radical perineal prostatectomy for cancer at , pioneering a surgical approach that removed the while preserving continence, though with high initial risks, setting for modern oncologic interventions. Decades later, Brenton Huggins's 1941 experiments demonstrated that prostate cancer growth depends on androgens, showing tumor regression via or therapy, a discovery that revolutionized endocrine management and earned him the in or in 1966. Advancements in diagnostics accelerated in the late with the identification of (PSA) in the 1970s by researchers including Richard J. Ablin, who isolated it from prostatic tissue as a potential . The development of a sensitive PSA in the 1980s enabled widespread screening, dramatically increasing early detection rates and reducing mortality, though it also sparked debates on . Imaging evolved from rudimentary X-rays to sophisticated modalities, including transrectal ultrasound developed in the 1970s. A 2019 review traces the progression of MRI from the early 1980s to multiparametric MRI by the 2010s, highlighting how these tools improved localization and accuracy.

Prostate in other animals

The prostate gland exhibits significant anatomical variations across mammalian species, reflecting evolutionary adaptations in reproductive . In monotremes such as the and , the prostate is absent or represented only by rudimentary glandular tissue surrounding the , lacking the well-defined structure seen in mammals. In like mice and rats, the prostate is multilobular, typically comprising four distinct lobes—ventral, dorsal, lateral, and cranial—that surround the and contribute variably to seminal fluid production. By contrast, in , the prostate forms a single, diffuse, bilobed structure that encircles the proximal to the , serving as the primary accessory sex gland without distinct lobes or accompanying . Functional differences in the prostate also vary by , particularly in secretion volume and with other glands. In herbivorous mammals such as ruminants, the prostate produces a larger volume of alkaline fluid rich in enzymes and nutrients, comprising a substantial portion of the to support survival in the extended female reproductive tract. In some species, including macaques and baboons, the prostate shows partial fusion or close anatomical with the , leading to combined secretory contributions that enhance ejaculate coagulation and motility. Animal models derived from non-human prostates have been instrumental in studying prostate diseases. The transgenic of the prostate (TRAMP) model, utilizing rodents with their lobular prostate anatomy, recapitulates progressive development, including neuroendocrine differentiation and , driven by SV40 T-antigen expression under the probasin promoter, making it a key tool for evaluating therapeutic interventions. Similarly, the prostate, with its diffuse structure and spontaneous age-related (BPH), serves as a valuable analog for BPH due to shared hormonal drivers like and histopathological similarities, facilitating preclinical testing of minimally invasive treatments. Evolutionary conservation underscores the prostate's fundamental role in male reproduction across mammals. Androgen dependence, mediated by the (AR), is highly preserved, ensuring prostate development and secretory function in response to testosterone signaling from puberty onward. Recent comparative transcriptomic analyses in 2024 revealed strong conservation of AR expression patterns between canine and human prostates, with lower AR transcripts in neoplastic tissues, highlighting shared molecular pathways that drive pathogenesis despite anatomical differences. In , prostatic disorders pose significant clinical challenges in companion animals. In , prostatic cysts often arise secondary to BPH or bacterial , leading to urethral obstruction, , and discomfort, requiring surgical drainage or for management. In ferrets, prostate neoplasia, though less common than or cystic disease linked to adrenocortical tumors, can manifest as aggressive causing urinary obstruction and requires multimodal therapy including hormone suppression and .

Homologous structures in females

In females, the Skene's glands, also known as paraurethral glands, serve as the homologous structure to the male prostate. These are paired glands located along the distal portion of the , with their ducts opening near the urethral meatus. Typically small, measuring less than 1 cm in diameter in their normal state but capable of enlargement to 1-2 cm in pathological conditions, the glands are embedded in the anterior vaginal wall. Embryologically, they arise from the , the same origin as the male prostate, and exhibit similar histological features, including expression of (PSA) and . The primary functions of the Skene's glands involve fluid secretion that contributes to lubrication of the and during . This secretion, a milk-like ultrafiltrate of , may also play a role in , where a viscous is expelled from the urethral openings during . Additionally, the glands produce substances with antibacterial properties, potentially including , which could help prevent urinary tract infections (UTIs) by coating the . Their location adjacent to the anterior vaginal wall links them to the , a sensitive thought to involve glandular tissue stimulation during sexual activity. Pathological conditions affecting the Skene's glands include cysts, often resulting from duct obstruction, which can lead to urethral compression and urinary symptoms. Abscesses may arise from , presenting as painful periurethral masses requiring . Rare adenocarcinomas originating from these glands have been documented, typically presenting as urethral masses with PSA expression, and are treated with surgical excision or radiation. Recent histological studies have examined interactions between Skene's glands and midurethral slings used in incontinence , revealing potential glandular incorporation or at sling sites that may influence postoperative outcomes. A 2024 study highlighted enhanced orgasmic activity linked to glandular function, noting increased fluid expulsion and pleasure in women with active involvement during sexual response. Additionally, a 2022 investigation found prostatic metaplasia in 100% of vaginal specimens from transmasculine individuals on testosterone therapy, suggesting hormonal induction of glandular changes resembling male prostate tissue.