Testosterone and androgens in male health

Unfortunately effect of, or variation in, testosterone and other sex hormone levels has not been well studied in relation to CP/CPPS. A few studies indicate that levels are lower than normal relative to age and lifestyle. The problem with all these studies is that they commonly do not publish any data on albumin, prolactin, estradiol, LH, FSH or SHBG levels making interpretation very difficult.(1) In the following a general overview is given of how androgens and sex hormone affect male health.

"Sex hormones are implicated in the immune response, with estrogens as enhancers at least of the humoral immunity and androgens and progesterone (and glucocorticoids) as natural immune-suppressors."(2) Testosterone deficiency also leads to low levels of ATP, which causes tiredness, higher incidence of osteoporosis (especially with estradiol deficiency), worsen rheumatoid arthritis (both total and free testosterone and SHBG are lower than in healthy subjects), abdominal obesity, increased diabetes risk, low libido, erectile dysfunction, depression, coronary artery disease and other problems.

Coagulation factors are increased in low levels of (free?) testosterone, which may explain some of the features of CPPS and why some of the treatments (that have anti-thrombotic effect) lead to improvement.

Abdominal obesity is due to visceral fat building up. Visceral fat inhibits testicular function, secretes pro-inflammatory cytokines (TNF-alpha, IL-6, IL-8), but also IL-10. It also secretes leptin (affects GnRH and HPA axis regulation of LH/FSH, which in turn affects testo production), PAI-1 (simply explained: a "blood coagulant"), acute phase proteins and so on. A downward spiral.

There is also research (3) that indicate a possible hypothalamic testosterone lowering pathway independent of luteinizing hormone-releasing hormone, possibly mediated by pro-inflammatory cytokines released in the brain and by alcohol. "In addition, this pathway may play a role in androgen-dependent functions that are unrelated to fertility, such as cardiovascular, renal and immunological activity, muscle mass, behavior and cognitive abilities. These are usually considered genomic effects of androgens. In addition, testosterone exerts many very rapid, non-genomic effects as varied as airway smooth muscles reactivity, as well as reward, learning and analgesia."(4)

Additionally testosterone / gonadal function is affected by systemic disease. The following is summarised from Karagiannis and Harsoulis.(5) Acute disease and stress is associated with reversible impairment of gonadotropin and testosterone secretion. Severe starvation likewise (and can lead to hyperestrogenism and refeeding gynecomastia when relieved). In chronic disease gonadotropins are increased while testosterone is suppressed. In most cases of hypogonadism Leydig cell function is impaired.

Liver cirrhosis is associated with hypogonadism due to endocrine disruption. In alcoholics the symptoms are worsened by alcohol effects on the testes. Alcohol per se (without liver disease) can cause hypogonadism due to disruption of the HPA axis and other effects.

Hemochromatosis causes damage due to pituitary and testicular "poisoning" by accumulation of excess iron. Which leads to hypogonadism.

Chronic renal disease causes "major [negative] effects on the male reproductive system" due to its severe effects on the organism. The changes occur early in renal disease and do not improve by treatment or dialysis, rather worsen.

Metabolic syndrome cause decreased total testosterone and SHBG levels, gonadotropin secretion disturbances and aromatase production by fat cells that further depress testosterone etc.

Hypogonadism is also associated with rheumatic and autoimmune disease like RA and SLE. Some anti-rheumatic drugs can also irreversibly damage testicular function.

Andra bloggar om CPPS, kroniskt bäckenbottensmärtsyndrom, testosteron, androgener
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(1) If FSH and LH are elevated the testicular production of testosterone is impaired. If low then it may be caused by pituitary adenoma (elevated prolactin) or Cushings (aberrant cortisol) or hemochromatosis (elevated transferrin).
(2) Cutolo M, Capellino S, Sulli A, Serioli B, Secchi ME, Villaggio B, Straub RH. Estrogens and autoimmune diseases. Ann N Y Acad Sci 1089:538-547, 2006.
(3) James, P.J., Rivier, C., Lee, S. Presence of corticotropin-releasing factor and/or tyrosine hydroxylase in cells of a neural brain-testicular pathway that are labelled by a transganglionic tracer. J. Neuroendocrinol. 20:173-181, 2008 (and research by Riviers et al referenced therein.)
(4) http://pblcr.salk.edu/08_testosterone.html accessed 2009-03-08 at 1613 GMT.
(5) Karagiannis A, Harsoulis F. Gonadal dysfunction in systemic disease. Eur J Endocrin 152:501-513, 2005.

Sexual health-concluding remark

Erectile dysfunction (ED) and ejaculatory dyssynergia (EDS) strongly affect quality of life in some CPPS sufferers. Why these occur and how many men that are affected is not clear. Research in ED and EDS is in my opinion lacking in standardized procedures and useful measurables (the 2-minute limit is not a good parameter-it is in fact ridiculous). The fact that circumcised and normal men are not distinguished is also a confounding factor. Lack of detailed information on thyroid and gonadal function (prolactin, SHBG, DHEA etc) is yet another.

Infertility in CPPS

Prostatitis is an indicator of infertility risk (e.g. if epidydimial infection / inflammation or zinc or magnesium abnormalities are present). It has been estimated that somewhere between 35-90% of men seeking for help with infertility has had or has some prostatitis-like disease or symptoms (including STD’s)(1). Notice that inflammation or abnormalities in any of the: testicles, prostate, epididymis, seminal vescicles, vas deferens, ampollae, Cowper’s gland and the glands of Littre affect fertility! (There are of course other causes, but the above are prostatitis-related.)

Andra bloggar om CPPS, kroniskt bäckenbottensmärtsyndrom, prostata, infertilitet
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(1) Colpi GM (ed.). Male infertility today, nr 4, 2004. Imprimatur: fotolito e stampa grafiche gelmini, Milano.

Ejaculate (semen) abnormalities in CPPS

Ejaculate is comprised of sperm, prostatic fluid (watery, 15-30%), urethral (Littre’s) and bulbourethral (Cowper’s) gland fluids (viscous, clear) and seminal vesicle fluid (gelatinous, 50-70% of volume). About 1.5-5 milliliters is the average. Anecdotal evidence indicates that semen gets yellowish and thicker or too watery and having a non-homogenous appearance in CPPS, especially during flares. Is this because of abnormal proportions of the various fluids or other causes ?

Ejaculate is slightly alkaline: pH 7.3-8.5 (variation is due to methodology and values as low as about 6.5 can be found in the literature). Higher pH is indicative of infection and too low pH impairs sperm motility. Some CPPS sufferers have high pH.

A small study has found that ejaculate citrate levels are depressed in NIH-II, IIIa and IIIb patients compared to controls. Interestingly NIH-II and IIIa sufferers had very similar levels 3.32 +/- 0.79 mg/ml and 3.41 +/- 0.88 (controls 8.55 +/- 1.20) indicating commonality. IIIb sufferers have intermediate values (4.37 +/- 0.77).(1)

Analyses have also shown decreased levels of magnesium, zinc, fructose(2), spermine, prostate anti-microbial factor (PAF) and other substances. There are also conflicting studies on seminal microflora. There is a case report of CPPS in conjunction with the presence of uric acid in the ejaculate.(3)

Ejaculate main composition: Zinc 0.352 ± 0.048 g/liter; Magnesium 0.120 ± 0.060 g/liter; Calcium 1.200 ± 0.080 g/liter; Citric acid 4.80 ± 26.9 g/liter; Cholesterol 0.078 ± 0.013 g/liter; Spermine 0.243 ± 0.025 g/liter; Lysozyme 0.021 ± 0.006 g/liter; Acid phosphatase 2.56 million IU per liter.(4)

Andra bloggar om CPPS, kroniskt bäckenbottensmärtsyndrom, prostata, ejakulat, sperma
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(1) Chen J, Xu Z, Zhao H, Jiang X. Citrate in expressed prostatic secretions has the feasibility to be used as a useful indicator of category IIIB prostatitis. Urol Int 78(3):230-234, 2007. The essentially same article was also published as Chen J, Zhao HF, Xu ZS, The prostate has secretory dysfunction for category IIIA and IIIB prostatitis in J Urol 177(6):2166-2169, 2007.
(2) Engeler DS, Hauri D, John H. Impact of prostatitis NIH IIIB (prostatodynia) on ejaculate parameters. Eur Urol 44(5):546-548, 2003.
(3) Motrich RD, Olmedo JJ, Molina R, Tissera A, Minuzzi G, Rivero VE. Fertility and Sterility 85(3):751, 2006.
(4) Sexually transmitted diseases, Holmes KK, Mårdh P-A, Sparling PF, Weisner PJ, Cates W Jr, Lemon SM, et al., eds.

Magnesium and zinc in the prostate

CP/CPPS is currently not connected with magnesium or zinc insufficiency, but the prostate is the most zinc and magnesium-rich organ in the body (up to 20 times higher concentration than in other organs). Magnesium is essential for seminal fluid quality and sperm "survival" and uro-genital health. A study (1) has shown that magnesium levels were significantly decreased in the seminal plasma of normozoospermic chronic prostatitis sufferers. But other studies have shown no such correlation(2). Zinc is essential for sperm quality, prostate and uro-genital health in general (3,4) and also for health in general.

Plasma zinc levels are below normal in patients with malignancies (decreased about 60-70%), but above normal in patients with benign hyperplasia and chronic prostatitis(5). Levels in controls is 94.5±10.38 µg/100 ml; with benign diseases of the prostate between 145 and 173 µg/100 ml (highest in BPH) and patients with malignancy 59.6±3.08 µg/100 ml(6).

It is unclear if the raised zinc levels are causing the illness or are an effect thereof(7). Anecdotal data suggest zinc supplementation may improve semen abnormalities.
Both minerals are tightly regulated in the body and not stored (if one does not include the skeleton).

(Curiously MgCl was suggested in France before WWII as an effective diuretic and uro-prostatic function "corrector" [J. Favier, "Equilibre mineral et sante", Librairie Le François, 1951]. Which is popular to mention on self-help and altmed sites.)

Andra bloggar om CPPS, kroniskt bäckenbottensmärtsyndrom, prostata
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(1) Edorh AP, Tachev K, Hadou T, Gbeassor M, Sanni A, Creppy EE, Le Faou A, Rihn BH. Magnesium content in seminal fluid as an indicator of chronic prostatitis. Cell Mol Biol (Noisy-le-grand). 2003;49 Online Pub:OL419-23.
(2) Colleen S, Mårdh PA, Schytz A. Magnesium and zinc in seminal fluid of healthy males and patients with non-acute prostatitis with and without gonorrhoea. Scand J Urol Nephrol 9:192-197, 1975.
(3) "Zinc: a key urological element" by IM Bush et al., presentation at the 1974 AMA annual meeting, Chicago, USA
(4) Yan M, Song Y, Wong CP, Hardin K, Ho E. Zinc deficiency alters DNA damage response genes in normal human prostate epithelial cells. J Nutr 138:667-673, 2008.
(5) Goel and Sankwhar, Comparative study of zinc levels in benign and malignant lesions of the prostate, Scand J Urol Nephrol, 108-12, 2006
(6) Goel T, Sankhwar S. Comparative study of zinc levels in benign and malignant lesions of the prostate. Scand J of Urology and Nephrology, 40(2):108-112, 2006.
(7) Antibacterial effect of intraprostatic zinc injection in a rat model of chronic bacterial prostatitis by YH Cho et al., Int J Antimicrob Agents 19:576-582, 2002