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 The problem with all these studies is that they commonly do not publish any data on albumin, prolactin, estradiol, LH, FSH or SHBG levels making interpretation very difficult.(1) In the following a general overview is given of how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.