The prostate is the gland below the bladder that adds fluid to semen. It is one of the most hormone-sensitive tissues in the male body, and its growth pattern changes sharply with age: it develops under testosterone in youth, then often enlarges again in old age while testosterone falls. The old-age growth has a different cause from youthful growth. Estrogen rises with age, stress, disease, malnutrition and low thyroid, it is made in fat, and thyroid and progesterone are usually deficient when it rises.[1] Estrogen enlarges the prostate in experimental animals.[1]

Prostaglandins were first discovered in prostatic fluid, where they occur in significant concentrations.[1]

Conditions

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Enlargement (BPH)

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Prostate enlargement mainly affects older men, which sits oddly with the idea that testosterone drives growth and estrogen opposes it. The tissue growing in an old prostate differs from the tissue that grew in youth, and rising estrogen is the likely driver.[1]

Progesterone and pregnenolone also fall with age. Several studies with synthetic progestins found they shrink the enlarged prostate, and the saw palmetto remedy for prostate enlargement has been reported to contain pregnenolone or something similar. These substances would be expected to reduce the conversion of testosterone and other androgens to estrogen.[2]

Chronic inflammation is a second route. In enlarged prostate tissue, the endotoxin receptor TLR4 stained significantly more strongly where inflammation was present than where it was absent (mean score 5.13 vs 2.96). Men with inflammatory infiltrate were older and had higher BMI, larger prostates and worse urinary symptom scores.[3] Gut-derived endotoxin and histamine are a proposed source of that inflammation, discussed under Prostatitis.

Low androgen signaling can itself cause that inflammation. In human enlarged prostate specimens, lower androgen receptor expression in luminal cells went with more inflammation in the same region. In mice, disrupting androgen receptor signaling in those cells made them produce cytokines, weakened the epithelial barrier and drew in immune cells. The macrophages then released more Il-1 and Ccl2, which drove prostate cell proliferation. Blocking Il-1 signaling or depleting macrophages stopped the proliferation.[4] The authors suggest this may explain resistance to androgen-targeted therapy.

Prostate cancer

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Prostate cancer is usually framed as an androgen-driven disease, but incidence rises as men age and serum testosterone falls, and it essentially never appears in young men during peak testosterone years. High testosterone does not predispose to prostate cancer, and low testosterone is not protective; the saturation model separates androgen receptor occupancy from the old "more androgen, more cancer" story.[5]

Estrogen and dysplasia

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…simultaneous treatment of intact…rats with testosterone and estradiol-17beta for 16 weeks consistently induced a putative precancerous lesion, termed dysplasia, in the dorsolateral prostate of all animals. Since treatment of rats with androgen alone did not elicit the same response, we concluded that estrogen played a critical role in the genesis of this proliferative lesion.

— Shuk-mei Ho and M. Yu[7]

Estrogen enlarges the prostate in experimental animals. The old slogan that "estrogen grows female organs and testosterone grows male organs" led to estrogen therapy for prostate cancer on thin questionnaire-style evidence rather than solid physiology.[8]

Prolactin, which estrogen raises, stimulates growth of the rat lateral prostate and of human prostate epithelial cells in culture.[9] Aging often brings lower thyroid and progesterone tone with more conversion of testosterone toward estrogen in fat and other tissues.

Saturated model versus deprivation

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Castration shrinks the prostate, which historically licensed androgen deprivation, but cancer nests are found inside atrophic aging glands. Androgen deprivation and inflammation are discussed under Testosterone; the saturation model says once receptors are occupied, further serum testosterone does not keep raising risk.[5]

Fats and prostaglandins

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Polyunsaturated fatty acid-derived prostaglandins and related eicosanoids have been implicated in tumor metastasis, host immunoregulation, tumor promotion, and cell proliferation. Aspirin and other prostaglandin inhibitors belong in that practical set for cancers generally, including prostate contexts where estrogen, free fatty acids, and PUFA peroxidation interact.[10]

Prostatitis

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Prostatitis is inflammation of the prostate gland. The term covers acute and chronic bacterial infection, chronic pelvic pain syndrome, and inflammation without symptoms. Across five surveys of 10,617 men, 8.2% met criteria for prostatitis symptoms (range 2.2-9.7%), a rate comparable to ischaemic heart disease and diabetes. Men with a history of prostatitis symptoms had substantially higher rates of prostate enlargement, lower urinary tract symptoms and prostate cancer.[11]

Gut origin

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Much prostate inflammation starts in the intestine. Slow digestion lets the gut release serotonin, histamine, nitric oxide and endotoxin into the pelvic area, where they irritate the bladder and the nerves passing through.[12]

Inflammation in the intestine can raise systemic or regional histamine and [serotonin] enough to cause prostate swelling. Avoiding starchy vegetables, might help; supplementing vitamin D and thyroid can reduce inflammation. An antihistamine ([diphenhydramine] or cyproheptadine) and aspirin can reduce prostate swelling, and might help the intestine too.

— Ray Peat[13]

SIBO turns up in most chronic prostatitis patients. In a pilot study, 14 of 16 (88%) tested positive on a lactulose breath test, and rifaximin (550 mg three times daily for 10 days) significantly lowered their prostatitis symptom scores, abdominal pain and bloating by day 28.[14] A separate study of 42 patients found a positive breath test in 33 (78.6%), and 73% of those also had lactose malabsorption.[15]

Sexual function

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Of 296 men treated for chronic prostatitis or chronic pelvic pain syndrome, 214 (72.3%) reported sexual dysfunction: 25% erectile dysfunction only, 33.4% ejaculatory problems only and 41.6% both. Men with both had worse symptoms and quality of life.[16]

Chronic bacterial prostatitis is a common, treatable cause of premature ejaculation. It was found in 52% of 153 men with premature ejaculation, significantly more often than in 100 healthy controls.[17] After one month of antibiotics matched to culture results, 62 of 74 treated men (83.9%) gained longer ejaculatory latency and good control through a 4-month follow-up, and none of the 20 untreated men improved.[18] Standard cultures can miss fungal causes: one case of Candida prostatitis went undiagnosed for 20 years.[19]

Practice

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Get a clinical evaluation first, since other conditions produce the same symptoms and bacterial cases respond to culture-matched antibiotics.[11] For chronic inflammation, work on the gut: fewer starchy vegetables, vitamin D, thyroid, an antihistamine such as diphenhydramine or cyproheptadine, and aspirin. Test for SIBO when bloating or abdominal pain comes with the prostate symptoms. See SIBO, Premature ejaculation and Erectile dysfunction.

See also

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References

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  1. ↑ 1.0 1.1 1.2 1.3 Ray Peat, "Prostate Cancer," raypeat.com.
  2. ↑ Ray Peat, "Prostate Cancer," raypeat.com.
  3. ↑ He Y, Ou Z, Chen X, Zu X, et al. "LPS/TLR4 Signaling Enhances TGF-β Response Through Downregulating BAMBI During Prostatic Hyperplasia," Sci Rep. 2016;6:27051. doi:10.1038/srep27051. PMID 27243216.
  4. ↑ Zhang B, Kwon OJ, Henry G, Malewska A, et al. "Non-Cell-Autonomous Regulation of Prostate Epithelial Homeostasis by Androgen Receptor," Mol Cell. 2016;63(6):976-89. doi:10.1016/j.molcel.2016.07.025. PMID 27594448.
  5. ↑ 5.0 5.1 Morgentaler A. "Goodbye androgen hypothesis, hello saturation model," Eur Urol. 2012;62(5):791-793. PMID 22728116.
  6. ↑ Ho SM, Yu M. "Selective increase in type II estrogen-binding sites in the dysplastic dorsolateral prostates of noble rats," Cancer Res. 1993;53(3):528-532. PMID 7678774.
  7. ↑ Cancer Research 53:528-532, 1993[6]
  8. ↑ Ray Peat, "estrogen causes the prostate," "Prostate Cancer," raypeat.com.
  9. ↑ Ray Peat, "Prolactin--which is increased," "Prostate Cancer," raypeat.com.
  10. ↑ Ray Peat, "aspirin and other prostaglandin," "Prostate Cancer," raypeat.com.
  11. ↑ 11.0 11.1 Krieger JN, Lee SW, Jeon J, Cheah PY, Liong ML, Riley DE. "Epidemiology of prostatitis," Int J Antimicrob Agents. 2008;31 Suppl 1:S85-90. doi:10.1016/j.ijantimicag.2007.08.028. PMID 18164907.
  12. ↑ Ray Peat, "Milk", One Radio Network
  13. ↑ Ray Peat Forum Q&A, "Prostate Swelling Treatment," collected in Ephemera: Ray's Email Exchanges
  14. ↑ Weinstock LB, Geng B, Brandes SB. "Chronic prostatitis and small intestinal bacterial overgrowth: effect of rifaximin," Can J Urol. 2011;18(4):5826-5830. PMID 21854715.
  15. ↑ Mancini A, Bruno C, Vergani E, et al. "Chronic prostatitis and small intestinal bacterial overgrowth: is there a correlation?," Ann Infect. 2018;2:6.
  16. ↑ Lee SW, Liong ML, Yuen KH, Leong WS, Cheah PY, Khan NA, Krieger JN. "Adverse impact of sexual dysfunction in chronic prostatitis/chronic pelvic pain syndrome," Urology. 2008;71(1):79-84. doi:10.1016/j.urology.2007.08.043. PMID 18242370.
  17. ↑ Shamloul R, el-Nashaar A. "Chronic prostatitis in premature ejaculation: a cohort study in 153 men," J Sex Med. 2006;3(1):150-154. PMID 16409229.
  18. ↑ El-Nashaar A, Shamloul R. "Antibiotic treatment can delay ejaculation in patients with premature ejaculation and chronic bacterial prostatitis," J Sex Med. 2007;4(2):491-496. PMID 17367444.
  19. ↑ Demirci A, Bozlak N, Turkel S. "Chronic prostatitis developing due to candida infection: A case diagnosed 20 years later and review of up-to-date literature," Urol Case Rep. 2018;20:88-89. PMID 30105207.