ANDROPAUSE, TESTOSTERONE AND THE PROSTATE GLAND

ANDROPAUSE, TESTOSTERONE
AND THE PROSTATE GLAND


Introduction

The prostate gland is a walnut sized gland in the male reproductive system just below the bladder that supplies fluid for the sperm during ejaculation.

As men age the prostate gland tends to enlarge, producing a condition called benign prostatic hypertrophy (BPH). Also, the incidence of prostate cancer increases. These two events happen at a time in a man’s life when his testosterone levels are falling. This seems a little puzzling, since it is well known that testosterone stimulates prostate growth and the growth of an existent cancer of the prostate. Obviously there are factors other than testosterone at work to cause the prostate to enlarge and in the initiation of prostate cancer. Because of testosterone’s stimulatory effect on prostate tissue, the physician and the patient must be vigilant monitoring possible changes within the prostate gland in a man being treated with testosterone.

Prostate Anatomy, Growth and Function

The prostate gland is a vital part of the male reproductive system. It’s amazing that today most men know precious little about this gland that does so much for them.

A newborn male’s prostate is very small about the size of a grain of wheat. The prostate remains very small until puberty. At the onset of puberty it begins to grow dramatically until around the age of twenty.

A healthy adult prostate weighs about 20 – 25 grams (2/3 to 3/4 of an ounce). It is walnut shaped and it measures 4 x 2 x 3 centimeters (1.6 x 1 x 1.2 inches). It is divided into 2 lobes. It contains smooth muscle cells capable of contracting to expel the prostatic fluid.





As you can see from the illustration below, the prostate surrounds the urethra, which carries urine from the bladder to the penis.

The seminal vesicles attach to the prostate and produce secretions that mix with prostatic fluid to form semen.

Graphics courtesy of

www.med-ars.it

The tubes (Vas Deferens) from the testicles carry sperm to the prostate where the sperm are mixed with the prostate and seminal vesicle fluid. The fluid (semen) is ejaculated during orgasm by a connection to the urethra called the ejaculatory ducts. Normal ejaculation produces about 3 – 5 cc (teaspoon) of semen.. The sperm makes up less than 1% of this volume with the seminal vesicles and the prostate producing the remainder of the volume. The prostate, which is made up of thousands of fluid-producing glands, itself secretes 25 – 35% of the total fluid volume. It is during high arousal in particular, that the prostate secretes this fluid. If extended arousal is not followed by ejaculation, the prostate can become tender and somewhat sore. This condition seems to account for what some call “blue balls”. The ejaculate is slightly acidic (pH 6.5) and contains proteins, hormones, growth factors, lipids, zinc, potassium, citric acid, fructose, prostaglandins etc.

The prostate is divided into three zones: a central zone, a peripheral zone, which occupies some 70% of the prostate’s volume, and the transitional zone between the peripheral zone and the central zone. The peripheral zone is the most common site of prostate cancer and the transitional zone is the exclusive site of benign prostatic hyperplasia (BPH). It is the peripheral zone that a doctor can feel by a finger in the rectum. The central zone is involved with the connection of seminal vesicles to the prostate and is rarely associated with any disease process.

The size of the prostate is normally fairly constant until the forties. Then, due to hormone changes, the prostate begins to bulk up. This later development and function of the gland are primarily dependent on hormone derivatives of testosterone called DHT (dihydrotestosterone) and estrogens.

Prostate-Specific Antigen

There are many prostatic secretory proteins. In particular we are interested in prostate-specific antigen (PSA). PSA helps to liquefying the ejaculate. Without it, men would ejaculate jellybean-sized globs. Clinically, it is a valuable marker for the detection of prostate cancer and for following response to treatment. PSA density (total PSA/volume of the prostate gland) and velocity (changes in PSA over time) are useful in differentiating benign prostate hyperplasia (BPH) from prostate cancer.

Andropause, Prostate Disease and Testosterone Supplementation in Men

Andropause is a situation associated with low levels of testosterone. Symptoms of Andropause are any combination of the following: fatigue, poor sleep, general aches and pains, forgetfulness, reduced interest in sex, poor ejaculation and poor mood. Andropause can be improved with testosterone replacement therapy (TRT).

A concern of testosterone supplementation is that it will lead to the development or progression of prostate diseases such as BPH and prostate cancer. Both conditions do not develop without exposure to testosterone. Testosterone itself does not cause BPH or prostate cancer, but rather testosterone together with several other factors can combine to cause these problems.

Testosterone Replacement Therapy (TRT) and Prostate Safety

Testosterone replacement therapy (TRT) in a man with low testosterone may result in a slight and usually insignificant increase in the volume of the prostate gland. This means that there will be little effect on the PSA levels and the ability to urinate. When it comes to prostate cancer, there is no evidence that testosterone replacement promotes development of prostate cancer; however, an existing cancer may grow from testosterone therapy.1

Benign Prostatic Hypertrophy (BPH)

The development of BPH is caused by DHT (dihydrotestosterone)2 along with the actions of estrogens.3 After 40 the growth of the prostate is uneven. It is concentrated in the transition zone next to the urethra. This can, for some men, squeeze the urethra enough to cause problems with urinating (hesitancy).

Prostate size increases with age in normal men but not in men with low levels of testosterone. When testosterone deficient men are treated, the prostate volume increases but only to the size expected for men with normal levels of testosterone of the same age.4 Many studies have shown no effect of testosterone replacement on PSA or prostate volume.5 We would not give testosterone to a man with severe bladder obstruction due to an enlarged prostate but we have given testosterone therapy to some men with moderate symptoms of a poor urine stream. The physician must use good clinical judgment and monitor closely for any possible detrimental effects; however, the benefits of TRT should not be denied outright because of the presence of mild, stable symptoms of reduced urine flow (obstruction).6




Prostate Cancer

Prostate Cancer

Testosterone therapy should not be given to men suspected of having prostate cancer. This includes men with an abnormal digital rectal exam (DRE) or PSA for whom the diagnosis of cancer has not been ruled out, and those recently treated for prostate cancer in which both the DRE and PSA are normal. After a prudent period (perhaps 2 or 3 years) without evidence of a recurrence of their cancer, the pros and cons of testosterone therapy should be carefully considered and the restriction could be lifted. It is necessary to stress that these men must be monitored closely within the first 2 years of the onset of testosterone therapy, when regrowth of the cancer is most likely to occur.7

Role of Other Factors in the Development of Prostate Cancer

Currently, the evidence does not support the notion that normal levels of testosterone are associated with increased risk of prostate cancer. Other factors (environmental, genetic) are likely to be very significant.

Studies suggest that obesity can be a risk for prostate cancer8 and that dietary factors either directly or through the action of sex hormones may have an important bearing on the development of prostate cancer.9 Saturated fat (found in red meat, etc) consumption is associated with increased risk of prostate cancer: the greater the consumption the higher the risk.

Practical Suggestions for Prostate Safety - Before and During Treatment with Testosterone

Before each man is started on testosterone replacement therapy (TRT) he must have a normal digital rectal examination (DRE) and a PSA below 4.0

If the PSA has increased more than 0.75 units in the last 6 months this should be investigated before treatment starts.

In our clinic we test the following before treatment: testosterone, haematocrit, cholesterol, thyroid, liver enzymes, LH, estradiol, prolactin, DHEA, fasting glucose and insulin.

After testosterone replacement therapy (TRT) has started we recheck these tests at intervals of 4 months, 6 months and 12 months and then twice a year thereafter.

Conclusion

The main concern regarding testosterone administration to an aging man relates to prostate safety. The careful clinician using good judgment and having sufficient knowledge should feel confident in using testosterone therapy in well-screened symptomatic men. Careful follow-up and adherence to available recommendations10 are essential.

Bacopa Monniera

NEER BRAHMI

Bacopa Monniera






Names
Indian Name :Neer Brahmi
Botanical Name :Bacopa monniera
(syn. Herpestis monniera)
Other Names :Bacopa, Bacopa
monniera, Brahmi


Introduction
Bacopa monnieri is a very popular herb in India for longevity and mental function. It is used to decrease fatigue and depression, and to stimulate the sex drive. It energizes the central nervous system, and aids the circulatory system, soothes and minimizes varicose veins and helps to minimize scarring. It is also useful in repairing skin and connective tissues and smoothing out cellulite. It is generally considered an Ayurvedic "age tonic" restoring youth and vitality.
Brahmi has been used by Ayurveda in India for almost 3000 years. The Ayurvedic treatise, the Charaka Samhita (100 A.D.), recommends Brahmi in formulations for a range of mental conditions including anxiety, poor cognition and lack of concentration. In India, Brahmi is currently recognized as being effective in the treatment of mental illness and epilepsy.

Origin
An annual creeping plant found throughout India in wet, damp and marshy areas.

Chemical composition / key active constituents
The herb contains the alkaloids brahmine, herpestine, and a mixture of three bases. It also contains the saponins, monnierin ; hersaponin, bacoside A and bacoside B. Other constituents present in the plant are D-mannitol, betulic acid, ß- sitosterol, stigmasterol and its esters, heptacosane, octacosane, nonacosane, triacontane, hentriacontane, dotriacontane, nicotine, 3-formyl-4-hydroxy-2H-pyran, luteolin and its 7-glucoside. The presence of a-alamine, aspartic acid, glutamic acid and serine is also reported.


Pharmacology
Alcoholic extract increases the learning performance of rats and the activity is attributed to saponin mixture consisting of bacosides A,B & other saponins. Other pharmacological effects of the extracts include sedative, antiepileptic, cardiotonic, vasoconstrictor and anti-inflammatory activities.

Remedies For
It is used in indigenous systems of medicine for the treatment of asthma, hoarseness, insanity, epilepsy and as a potent nerve tonic; cardio tonic and diuretic. The leaves are also useful as a diuretic and aperient.
Brain and Nervous System Conditions
Brain tonic, Epilepsy, Headaches, Insanity, Improves memory, improves mental capacities, such as concentration and learning, Nerve tonic, Nervous breakdown, Nervous deficit due to injury and stroke Nervous exhaustion.

Gymnema sylvestre

Gymnema sylvestre


Names
Indian Name :Gurmar
Botanical Name :Gymnema Sylvestre
Other Names :Meshasringi


Introduction
This plant was called Meshashringi or "ram’s horn" in Sanskrit. Its use in snake bite as a remedy was well known to the natives of the Konkan in India and the natives of Southern India. Gymnema leaves have been used for centuries in the traditional Indian system of Ayurvedic medicine. The term "destroyer of sugar" is traditionally used for Gymnema because chewing the leaves will abolish the taste of sweetness. That is, sweet foods no longer tasted sweet, but rather became almost completely tasteless. The medicinally active parts of the plant are the leaves and the roots. Recent clinical trials conducted in India have shown that an extract of Gymnema sylvestre is useful for controlling Blood Sugar.

Origin
It is found in the Deccan Peninsula, extending to parts of northern and western India. It is occasionally cultivated as a medicinal plant. Today, Gymnema has become increasingly popular in the United States as a supportive treatment for diabetes.

Chemical composition / key active constituents
The presence of Gymnemic acid (GA), (+) quercitol, lupeol, ß-amyrin, stigmasterol etc., have been reported. GA I, II, III and IV are anti sweet substance from the leaves of G. sylvestris. They all contain a glucuronic acid moiety, and the gymnemagenin aglycone esterified at position C-21 and C-28. A second series of Gymnemic acid V-VII has also been reported. GA VII is the 3-O-glucuronide of gymnemagenin and GA V is the O-3-glycuronyl- 22, 21-bis-O-tigloyl substitution pattern. GA VIII-IX are also esters of saponin, have an oxoglycoside moiety attached to the glucuronic acid residue. Gurmarin, another constituent of the leaves, and gymnemic acid have been shown to block sweet taste in humans.Some researchers have suggested gymnemic acid as one possible candidate responsible for antidiabetic activity.

Pharmacology
Leaves are found to be antidiabetic, and insulinotropic. The active principles which have been identified as glycosides (several gymnemic acids) suggest that the topical and selective anaesthetic effect of the plant might result from the reaction of the receptor sites between glycosides and the sweet substances. Gymnemic acids inhibited glucan formation by streptococcus mutans in vivo and also markedly inhibited the activity of glucosyltransferase from bacterial coat.ecreasing capillary fragility.

Remedies For
It is used as an anti-diabetic. It stimulates the heart and circulatory system,activates the uterus and increases urine secretion. Gymnemic acids are useful for prevention of the formation of dental plaque and caries.

Dosage
Recent studies in India have used 400 mg per day of a water-soluble acidic fraction of the gymnema leaves. In adult-for diabetics, ongoing use for periods as long as eighteen to twenty-four months has proven successful. In IDDM (juvenile onset) diabetic patients, a similar amount has been usedsuccess-
fully as an adjunct to ongoing use of insulin. Traditionally, 2-4 grams of the leaf powder per day is used.