Melatonin and Prostate Health

Abstract

Melatonin, a neurohormone primarily secreted by the pineal gland, is widely recognized for regulating circadian rhythms. However, emerging studies reveal melatonin’s multifaceted role in cellular protection, antioxidative defense, and hormonal modulation—functions that may directly influence prostate health.

1. Introduction to Melatonin

Melatonin (N-acetyl-5-methoxytryptamine) is an indoleamine synthesized from tryptophan, primarily in the pineal gland. It is known for:

  • Regulating sleep-wake cycles
  • Modulating immune responses
  • Scavenging free radicals
  • Exerting anti-inflammatory and anti-proliferative effects

While most attention centers on its neurophysiological effects, melatonin’s endocrine and paracrine activity extends to various organs, including the prostate gland.

2. Melatonin Receptors in the Prostate

The human prostate expresses MT1 and MT2 melatonin receptors, primarily located in epithelial and stromal cells. These G-protein-coupled receptors mediate melatonin’s effects on:

  • Hormonal signaling
  • Cell proliferation
  • Apoptosis
  • Oxidative stress responses

Their expression is altered in aging men and in pathological conditions like prostate cancer, which suggests a possible regulatory role of melatonin in prostate physiology and pathology.

3. Melatonin and Benign Prostatic Hyperplasia (BPH)

BPH is a non-cancerous enlargement of the prostate, affecting over 50% of men above the age of 60.

Mechanisms of Action:

  • Anti-proliferative effect: Melatonin inhibits growth factors and reduces stromal hyperplasia.
  • Anti-androgenic effect: It reduces androgen receptor expression and inhibits dihydrotestosterone (DHT) pathways.
  • Modulation of inflammation: Melatonin suppresses pro-inflammatory cytokines such as IL-6 and TNF-α, which are upregulated in BPH.
  • Reduction of nocturia: Due to its effect on circadian rhythm and bladder function.

Supporting Evidence:

  • Animal studies show that melatonin supplementation reduces prostate weight and improves histological features of BPH.
  • A 2021 clinical pilot study reported significant improvement in nocturia and urinary flow rates among BPH patients supplemented with 2 mg of melatonin daily over 8 weeks.

4. Melatonin and Prostate Cancer

Prostate cancer (PCa) is one of the most common cancers in men worldwide. Several studies suggest melatonin has oncostatic properties via multiple mechanisms:

Key Anticancer Actions:

  • Anti-proliferative: Inhibits growth of PCa cells in vitro.
  • Pro-apoptotic: Induces cell death in malignant prostate cells.
  • Anti-angiogenic: Suppresses VEGF and tumor neovascularization.
  • Anti-androgenic: Reduces androgen production and receptor sensitivity.
  • Enhancement of radiotherapy and chemotherapy: Acts as a radiosensitizer and reduces side effects.

Notable Studies:

  • In LNCaP human prostate cancer cells, melatonin induced cell cycle arrest in the G1 phase.
  • Animal models show reduced tumor size when melatonin is co-administered with anti-cancer agents.
  • Epidemiological data suggest night shift workers with disrupted melatonin levels may have a higher risk of prostate cancer.

5. Melatonin and Urinary Benefits

Melatonin influences the lower urinary tract function both centrally and peripherally:

  • Improves nocturia: Enhances bladder storage capacity during nighttime.
  • Reduces overactive bladder symptoms: Through central nervous system modulation and anti-inflammatory effects.
  • Relieves lower urinary tract symptoms (LUTS): In BPH patients, melatonin improves urgency, frequency, and incomplete voiding.

A double-blind placebo-controlled trial (2018) showed that 3 mg melatonin nightly for 6 weeks improved urinary symptoms in aging men with mild to moderate LUTS.

6. Ingestion Methods and Dosage

Melatonin is typically ingested orally and is available in various forms:

  • Tablets / Capsules (immediate or extended-release)
  • Sublingual drops
  • Liquid sprays
  • Melatonin-rich foods (e.g., tart cherries, walnuts, grapes)

Common Dosage Ranges:

  • Sleep disorders: 0.3–5 mg, 30–60 minutes before bedtime.
  • Prostate and urinary health (off-label): 1–3 mg daily, generally taken at night.
  • Cancer adjunct therapy: Higher doses (10–20 mg) have been studied, but only under clinical supervision.

Bioavailability Considerations:

  • Oral melatonin has low bioavailability (~15%) due to first-pass hepatic metabolism.
  • Extended-release formulations or sublingual delivery may enhance efficacy in long-term treatment.

7. Safety and Contraindications

Melatonin is generally considered safe, even at higher doses. However, potential side effects include:

  • Daytime drowsiness
  • Headache
  • Dizziness
  • Hormonal effects (rare)

Contraindications:

  • Hormone-sensitive conditions (melatonin may act as a hormone modulator)
  • Concurrent use with sedatives or SSRIs should be monitored
  • Not recommended for chronic use without medical supervision in cancer patients unless part of a therapeutic plan

8. Conclusion

Melatonin, traditionally associated with sleep regulation, is gaining recognition for its broader systemic effects—particularly its protective and regulatory actions on the prostate gland. From reducing inflammation and prostate enlargement in BPH to inhibiting proliferation in prostate cancer models, melatonin emerges as a potential complementary agent in managing men’s prostate and urinary health. While current data is promising, more robust randomized controlled trials are essential to establish definitive clinical guidelines.

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