Hormone treatment is designed to reduce the production of testosterone; it has a temporary effect on decreasing PSA and of weakening the cancer. Side effects are erectile dysfunction 100%, increase in weight, development of “man boobs”, loss of energy, increase in depression. Research done in the last ten years on 600 dead men revealed a much higher level of PCa in men from 20 up – see attachment “Prostate Graph.tif”, than anyone had imagined. Clearly PCa is extraordinarily slow-growing form of cancer. Many think it should not be called “cancer” as it does not behave like any other form of cancer (except for some breast cancers).

The very use of the word “cancer” so terrifies men that they can’t wait to have a radical prostatectomy to get rid of the perceived horrors of the word. Urologists gain many more patients because of this fright, rushing them into making life-changing decisions they will regret for the rest of their lives, when in fact, waiting another year to carefully research the alternatives will probably produce no discernable change.

TESTOSTERONE and PROSTATE CANCER

TESTOSTERONE

Dr John Hart, Medical Director, Sydney Medical Longevity Clinic, www.MedicalLongevity.com.au. Phone +612 8060 5143

         In a healthy male, the hypothalamus at the base of the brain, releases GnRH to the pituitary gland under the brain (head office of testosterone production). This triggers the release of luteinising hormone (LH) into the blood stream, which goes to the testes (the factory of testosterone production) and signals the testes to produce testosterone.  Follicle stimulating hormone (FSH) is also released from the pituitary, and with testosterone, stimulates sperm production in the testes.

         After testosterone has been produced, some of it is naturally converted to estrogen by an enzyme called aromatase (found in fat, brain, gonads, blood vessels, skin and bone). Men have and need low levels of estrogen, as women have and need low levels of testosterone. This estrogen and the testosterone act as a signal to the pituitary to stop making LH / FSH and therefore decrease testosterone production / release from testes. When blood testosterone / estrogen levels decrease, this negative feedback is removed, and the hypothalamus and pituitary begin producing / releasing LH / FSH again. So it’s a dynamic process, much like the temperature-sensitive thermostat that controls your air conditioner in your home.

         Some of the testosterone is converted to dihydrotestosterone by the enzyme 5 alpha reductase. This enzyme is particularly concentrated in the reproductive tract and the skin.    

         Whether you are a 30, 50, 80 or even 110 year old man, having low testosterone levels (hypogonadism) is neither fun nor healthy.

The symptoms of low testosterone in men range from :

General Symptoms

Physical

decreased lean (non-fat) tissue

decreased muscle size

increased body fat

gynaecomastia (breast development)

joint & back pain

decreased skin firmness / fullness

headaches

anemia (low red blood cells)

Energy & Strength

tired & fatigue

feel weaker

decreased endurance

Sleep

insomnia

difficulty falling asleep

difficulty staying asleep

night sweats

Neuro-cognitive Symptoms

Cognitive

decreased mental skills

decreased memory

can’t solve problems

can’t focus attention

can’t remember events

easily confused

decreased memory

Mood & Behavioural

depression

social isolation

less motivated

irritability

mood changes

Sexual Symptoms

erectile dysfunction (fewer and weaker erections)

decreased libido

decreased genital sensation

decreased orgasm experience

decreased ejaculate volume

testicular atrophy

anorgasmia (no orgasm)

pubic hair thinning

Additional Risks

insulin resistance

heart disease

sleep apnea

osteopenia / osteoporosis

Alzheimer’s Disease

high grade prostate cancer

         Low testosterone in men may be caused by problems in the testes (gonads) ability to manufacture testosterone – the factory is broken. This is called primary hypogonadism and can be caused by mumps infection, testicular trauma, testicular cancer, etc, and can only be treated with testosterone replacement therapy i.e. you can’t make testosterone anymore, so you need to replace it with bio-identical (exactly the same molecule as the body makes) testosterone.

         However, the more common causes of low testosterone / hypogonadism result from problems in the pituitary gland and / or hypothalamus in a man’s brain – the head office (headquarters). Low testosterone levels caused by such “brain problems” are collectively described as secondary hypogonadism or hypo-gonadotropic hypo-gonadism and may result from depression / anxiety, head trauma, head radiation (dental X-rays, head CT), iron overload, anabolic steroid overdosing, diabetes, sleep deprivation, some medications, and general cellular degeneration from lifestyle factors – poor diet, physical inactivity, prolonged stress, inadequate sleep, smoking, alcohol, drugs, toxins, allergens etc.

         Male testosterone production decreases by around 1% per year. This process is called ‘andropause’.

         PROSTATE CANCER

         Testosterone is required to maintain a healthy prostate. In terms of testosterone’s effects on prostate cancer:

– prostate cancer risk is unrelated to serum testosterone levels (Roddam et al 2008)

– high testosterone is not associated with worse prostate cancer (Morgentaler 2006)

– low testosterone does not protect against prostate cancer (Morgentaler et al 1996), and is associated with more aggressive, invasive forms (Morgentaler 2007, Isom-batz et al 2005, Massengill et al 2003, Teloken et al 2005)

– testosterone replacement is not associated with higher cancer rates (Rhoden et al 2004)

– testosterone replacement protects against more aggressive forms of prostate cancer, if cancer is present (Berger et al 2004, Bonaccorsi 2006)

Prostate cancer is common in men, but most men who have prostate cancer, die of something else. That is, it is a slowly progressive disease that doesn’t do any damage. Most prostate cancer suffers die with it, but not from it.

Low testosterone doesn’t protect from prostate cancer. Prostate biopsy of men with low testosterone and normal PSA showed the same cancer rate (14%) as the general male population (normal digital rectal examination and PSA) – 15.2% (Morgentaler et al 1996, Raynaud 2006)). Also, studies of prostate cancer in men undergoing testosterone replacement treatment, showed the same cancer rate as general prostate cancer screening programs – about 1% (Rhoden et al 2004). These confirm the view that prostate cancer is common (1 in 7 men have prostate cancer on biopsy), but prostate cancer is rarely severe enough to be detected by standard screening tests (only 1 in 100 are found on screening tests – DRE and PSA).

The bottom line is that testosterone doesn’t cause prostate cancer, neither does it cause worsening of existing prostate cancer when in the normal reference range (which is very broad). Also, prostate cancer is quite common, but rarely fatal.

Established prostate cancer can be inhibited by lowering serum testosterone levels to those of a castrated male (Androgen Deprivation Therapy), by surgery (testicle removal) or via drugs to inhibit testosterone production (more common nowadays). This slows down prostate cancer growth, but doesn’t destroy the cancer cells. Usually, eventually the testosterone deficiency fails to slow the prostate cancer growth, and the disease progresses to ‘castrate-resistant prostate cancer’ that progresses in severity.

Testosterone levels only slightly higher than this ADT (castration) level will cause maximal growth of most prostate cancers. Additional testosterone, which is needed for optimal function of the rest of the body, makes no additional change to prostate cancer growth (Calouf et al 2005, Roddam et al 2008). However, the androgen deprivation therapy does deprive the rest of the body of testosterone’s positive influence, and is associated with osteoporosis, skeletal fractures, metabolic disruptions, diabetes, cardiovascular disease and mortality, reduced cognitive function and sexual side effects (decreased libido, erectile dysfunction, etc).

This low threshold for testosterone insensitivity is because the testosterone receptor (Androgen Receptor) that testosterone binds to trigger its effect, is saturated (working maximally) at testosterone levels just above those of a castrated male. Normal, and even low testosterone males, have blood testosterone levels much higher than this. Hence their testosterone levels don’t change their prostate cancer growth.

References:

Berger R, Febbo PG, Majumder PK, Zhao JJ, Mukherjee S, Signoretti S, Campbell KT, Sellers WR, Roberts TM, Loda M, Golub TR, Hahn WC. Androgen-induced differentiation and tumorigenicity of human prostate epithelial cells. Cancer Res 2004:64:8867-75.

Bonaccorsi L, Muratori M, Marchiani S, Forti G, Baldi E. The androgen receptor and prostate cancer invasion. Mol Cell Endocrinol 2006:246:157-62.

Calouf OM, Singh AB, Lee ML, Kenny AM, Urban RJ, Tenover JL et al. Adverse events associated with testosterone replacement in middle-aged and older men: a meta-analysis of randomised, placebo-controlled trials. J Gerontol A Biol Sci Med Sci 2005:60:1451.

Isom-batz G, Bianco FJ, Kattan MW, Mulhall JP, Lilja H, Eastham JA. Testosterone as a predictor of pathological stage in clinically localized prostate cancer. J Urol 2005;173:1935-7.

Massengill JC, Sun L, Moul JW, Wu H, MclEod DG, Amling C, Lance R, Foley J, Sextom W, Kusuda L, Chung A, Soderdahl D, Donahue T. Pretreatment total testosterone level predicts pathological stage in patients with localized prostate cancer treated with radical prostatectomy. J Urol 2003;169:1670-5.

Morgentaler A, Brunning CO III, DeWolf WC. Incidence of occult prostate cancer among men with low total or free serum testosterone. JAMA 1996;276:1904-6.

Morgentaler A. Testosterone and prostate cancer: An historical perspective on a modern myth. Eur Urol 2006;50:935-9.

Morgentaler A. Testosterone deficiency and prostate cancer: Emerging recognition of an important and troubling relationship. Eur Urol 2007;52:623-5.

Raynaud JP. Prostate cancer risk in testosterone-treated men. J Steroid Biochem & Mol Biol. 2006;102:261-6.

Rhoden EL, Morgentaler A. Risks of testosterone-replacement therapy and recommendations for monitoring. N Eng J Med 2004;350482-92.

Roddam AW, Allen NE, Appleby P, Key TJ. Endogenous Hormones, Prostate Cancer Collaborative Group. Endogenous sex hormones and prostate cancer: A collaborative analysis of 18 prospective studies. JNCI 2008:100:170-83.

Teloken C, Teodosio Da Ros C, Caraver F, Weber FA, Cavalheiro AP, Meyer Graziottin T. Low serum testosterone levels are associated with positive surgical margins  in radical retropubic prostatectomy: hypogonadism represents bad prognosis in prostate cancer. J Urol 2005;174:2178-80.