INTRODUCTION

“If I did not know for what purpose I was put here on earth -to become better myself as far as possible and to make better everything around me, that is within my power to improve- I should have to consider myself as lacking very much in worldly prudence to make known for the common good, even before my death, an art which I alone possess, and which it is within my power to make as profitable as possible by simply keeping it secret.” Dr. Samuel Hahnemann

The Organon and The theory of Chronic Diseases are two books by Hahnemann which reveal new thoughts and inspiration everytime one gives a reading to them.

The theory of “The Chronic Diseases” – throws a light on the burning zeal in the heart of Dr Samuel Hahnemann for the alleviation of Human suffering. Hahnemann was a great servant, inquirer and discoverer; he was as true a man, without falsity, candid and open as a child, and inspired with pure benevolence and with a holy zeal for science.

Hahnemann himself observed that homoeopathic medicines were successfully curing his patients' ailments, but that after a period of time some patients returned with similar but stronger symptoms, and he realized that the disease was actually progressing. This led him to think that the Homoeopathic physician with such a chronic (non-venereal) case has not only to  combat the disease presented before his eyes, but that he has always to encounter only some separate fragment of a more deep-seated original disease. This lead to the discovery of Chronic Miasms as the cause of chronic diseases.

            The  true natural chronic diseases are those  that arise  from  a chronic  miasm, which when left to themselves, and  unchecked  by the  employment  of those remedies that are  specific  for  them, always  go on increasing and growing worse,  notwithstanding  the best mental and corporeal regimen, and torment the patient to the end  of  his  life  with  ever  aggravated  sufferings. The most robust constitution, the best regulated mode of living and the most vigorous energy of the vital force are insufficient for their eradication. 

Hahnemann says “In Europe and also on the other continents so far as it is known, according to all investigations, only three chronic miasms are found, the diseases caused by which manifest themselves through local symptoms, and from which most, if not all, the chronic diseases originate; namely, first, syphilis, which I have also called the venereal chancre disease; then sycosis, or the fig-wart disease, and finally the chronic disease which lies at the foundation of the eruption of itch; i. e., the psora.”

This triune of the subversive forces  (chronic miasmata), are the vicarious embodiment of  the internal disease, each having its own peculiar type or  character by  which its sole purpose and effort is to conform the  organism to its nature. Each of these forces becomes a creative force, and at no time is the life force able to free itself the bond of  any of them (either alone or in combination with the others), without some assistance.

The introduction of these subversive forces into the organism (which has undergone a process of adaptation capable of receiving them) is followed by an endless history of subversive changes and diseased phenomena peculiar to each type. They have its primary, secondary and tertiary stages, and world of phenomena peculiar to itself accompanying each stage or setting of the disease.

We can summarize the different stigmata, remembering that  we may  get all shadings of all the stigmata in their  groupings  in our  patient,  but  one stigma will  predominate  above  all  the others.  They all have their  characteristic  differences.  The accentuation of  psora is functional; the  accentuation  of  the syphilitic  taint is ulcerative; the accentuation of  sycosis  is infiltration and deposits.   When  suppressed,  the syphilitic stigma spends  itself  on  the meninges  of  the  brain, and affects the larynx  and  throat  in general, the eyes, the bones and the periosteum.   Psora spends its action very largely upon the nervous system and the  nerve centres, producing functional disturbances, which  are better by surface manifestations.   Sycosis  attacks the internal organs, especially the pelvic  and sexual  organs.  In  this  stigma we  find  the  worst  forms  of inflammation,  infiltration  of the  tissues  causing  abscesses, hypertrophies,  cystic  degeneration; when thrown back  into  the system  by  suppression  this  stigma  causes  dishonesty,  moral degeneracy and mania.

Benign prostatic hypertrophy (BPH) is a benign tumor that originates from periurethral prostatic tissue. So, it should be due to underlying sycotic miasm. In BPH, the normal elements of the prostate gland grow in size and number. The important symptoms of benign prostatic hypertrophy (BPH) - progressive urinary frequency, urgency, and nocturia are due to incomplete emptying and rapid refilling of the bladder.

Benign prostatic hypertrophy (BPH) is rare before the age of forty. After the age of fifty, approximately 50 percent of males manifest typical symptoms and lesions histologically, and after the age of eighty, 75 percent of males are so affected. Based on autopsy studies, the prevalence of histologically diagnosed BPH increases from 8% in men aged 31 to 40 year to 40 to 50% in men aged 51 to 60 year and > 80% in men older than 80 year. Based on clinical criteria in men aged 55 to 74 year without prostate cancer, the prevalence of  BPH is 19% using the criteria of a prostate volume > 30 mL and a high International Prostate Symptom score.

Modern Medicine, through Medical textbooks, has taken pains to name various clinical conditions (syndromes) and infections in an attempt to create some order in the chaotic world of disease expression. In spite of this detailing of symptom presentation for a diagnosis of disease, these authors (all well-read and experienced MD's) would be the first to admit it is often difficult to get a grasp of a clear diagnosis when a patient presents clinically. When diagnosis becomes the only basis for treatment (as in Modern Medicine), one is lulled into a false sense of complacency that after making a diagnosis, one has the answer to treating disease! A truly sincere MD will confess that more often than not in the clinical situation, they have NO IDEA what (disease) they are dealing with, much less being able to cure it!

The scope of Homeopathy primarily relates to the dynamic pathology of diseases and not the organic pathology.  Primarily Homeopathy has nothing to do with any product of disease, although secondarily it is related to all of them. The morbid processes from which the gross pathological tissue changes or organic lesions arise or to which they lead are amenable to Homeopathic medication. Homoeopathy is the best therapeutic method which can avoid many dangerous surgeries, injections and hormone therapies.

As is obvious, any patient must be treated on its individuality and not on the disease symptoms. BPH is a condition, which may mislead any physician due to dominance of disease symptoms taking priority in the hands of patient. He is so disturbed, so embarrassed that he will sometimes not give importance to his particular, uncommon peculiar and constitutional symptoms. It is prudent for a physician to take some symptoms for relief of the patient as palliative measure but if he wants to give him permanent or long lasting relief, a proper prescription on the basis of miasm, constitution, individuality, general and particular symptoms is important.

My topic of study is ”Clinical study on the predominance of sycotic background in benign prostatic hypertrophy and the efficacy of homoeopathic constitutional medicine in the management of benign prostatic hypertrophy.” In my observation I found that as a student of Homoeopathic system of medicine, Homoeopathic Medicines especially anti sycotic medicine shows a considerable control upon the growths, and therefore I presume that it can play a vital role in the successful treatment of benign prostatic hypertrophy.  Hence further investigations and studies will be useful in this regard. 

AIMS AND OBJECTIVES: -

1)      To study the predominance of sycotic miasm in benign prostatic hypertrophy. 

2)      To study the efficacy of homoeopathic constitutional medicine in the management of benign prostatic hypertrophy.  

REVIEW OF LITERATURE

              Prostate

? Embryology

? Anatomy

? Histology

? Physiology

? Benign Prostatic Hypertrophy

           Disease Classification

           Chronic Diseases

           Chronic miasm-Sycosis

           Constitutional Medicine

           Homoeopathic Concept of Disease

           Repertorial representation of Benign Prostatic Hypertrophy

Therapeutics of 3 mark remedies from major repertories

PROSTATE - INTRODUCTION

The Prostate (Prostata; Prostate Gland) is an organ linked inextricably with the endocrine system. During the development of the prostate, epithelium and mesenchyme are under the control of testicular androgens, and interact to form an organised secretory organ. Furthermore, many of the disease processes are attributed to, and therapies aimed at the manipulation of, the endocrine system. The gland resides in the true anatomical pelvis and forms the most proximal aspect of the urethra. It has been stated that the prostate gland is the male organ most commonly afflicted with either benign or malignant neoplasms.

EMBRYOLOGY

The development, growth and cytodifferentiation of the prostate are androgen dependent and occur via reciprocal mesenchymal-epithelial interactions, the latter referring to a cell-cell interaction initiated during embryonic periods in which mesenchyme (undifferentiated connective tissue) induces epithelial development, while the epithelium reciprocally induces mesenchymal differentiation.

In the developing prostate, urogenital sinus mesenchyme acting under the influence of testicular androgens induces ductal morphogenesis, the expression of epithelial androgen receptors, regulates epithelial proliferation and specifies the expression of prostatic-lobe specific secretory proteins. Reciprocally, the developing prostatic epithelium induces the differentiation and morphological patterning of smooth muscle in the urogenital sinus mesenchyme. In the prostate, it is traditional to consider androgens as promoters of growth, while activin and TGFbeta are regarded as potent growth inhibitors These factors do not act independently, however, and cross-talk occurs between the signalling pathways at a sub-cellular level.

The first step in development of the prostate begins with the urogenital sinus mesenchyme signalling to the epithelium, causing it to form epithelial buds. Androgens then induce bud elongation, branching and epithelial differentiation. Prenatally, the androgen receptor (AR) is expressed only in the mesenchyme, not in the epithelium. Initial epithelial development is thus controlled via paracrine interactions where activation of stromal androgen receptors stimulates growth factors and induces growth in adjacent prostatic epithelial cells.

At the 5th week, the mesonephric (Wolffian) duct opens onto the lateral surface of the urogenital sinus and gives rise to the ureteric bud (Figure 1). By the 7th week, the growth of the urogenital sinus involves the progressive incorporation of the terminal part of the mesonephric duct into the wall of the urogenital sinus. They eventually open into the Mullerian tubercle, which is the future veru montanum of the prostate. At their termination, the paramesonephric (Mullerian) ducts fuse and are surrounded by the mesonephric ducts. At 10 weeks, prostatic epithelial buds begin to arise from the circumference of the urethra, around the orifice of the paramesonephric ducts. They develop predominantly on the posterior surface of the junction of the mesonephric ducts, forming two levels, above and below them.

During the fetal period at about 6 months, multiple outgrowths arise from the prostatic portion of the urethra, particularly the posterior surface of the urethra, and grow into the surrounding mesenchyme. Glandular epithelium of the prostate differentiates from the endodermal cells of the urethra, and the associated mesenchyme into which the outgrowths grow differentiates into the dense stroma and smooth muscle fibres of the prostate. In contrast, the outgrowths situated on the anterior surface regress and are replaced by fibromuscular tissue. This region becomes the future anterior commissure of the prostate.

 ANATOMY

The prostate is a firm, partly glandular and partly muscular body, which is placed immediately below the internal urethral orifice and around the commencement of the urethra. It is situated in the pelvic cavity, below the lower part of the symphysis pubis, above the superior fascia of the urogenital diaphragm, and in front of the rectum, through which it may be distinctly felt, especially when enlarged. It is about the size of a chestnut and somewhat conical in shape, and presents for examination a base, an apex, an anterior, a posterior and two lateral surfaces. The base (basis prostatae) is directed upward, and is applied to the inferior surface of the bladder, The greater part of this surface is directly continuous with the bladder wall; the urethra penetrates it nearer its anterior than its posterior border. The apex (apex prostatae) is directed downward, and is in contact with the superior fascia of the urogenital diaphragm.

Surfaces —The posterior surface (facies posterior) is flattened from side to side and slightly convex from above downward; it is separated from the rectum by its sheath and some loose connective tissue, and is  about 4 cm distant from the anus. Near its upper border there is a depression through which the two ejaculatory ducts enter the prostate. This depression serves to divide the posterior surface into a lower larger and an upper smaller part. The upper smaller part constitutes the middle lobe of the prostate and intervenes between the ejaculatory ducts and the urethra; it varies greatly in size, and in some cases is destitute of glandular tissue. The lower larger portion sometimes presents a shallow median furrow, which imperfectly separates it into a right and a left lateral lobe: these form the main mass of the gland and are directly continuous with each other behind the urethra. In front of the urethra they are connected by a band which is named the isthmus: this consists of the same tissues as the capsule and is devoid of glandular substance. The anterior surface (facies anterior) measures about 2.5 cm. from above downward but is narrow and convex from side to side. It is placed about 2 cm. behind the pubic symphysis, from which it is separated by a plexus of veins and a quantity of loose fat. The urethra emerges from this surface a little above and in front of the apex of the gland. The lateral surfaces are prominent, and are covered by the anterior portions of the Levatores ani, which are, however, separated from the gland by a plexus of veins. The prostate measures about 4 cm. transversely at the base, 2 cm. in its antero-posterior diameter, and 3 cm. in its vertical diameter. Its weight is about 8 gm. It is held in its position by the puboprostatic ligaments; by the superior fascia of the urogenital diaphragm, which invests the prostate and the commencement of the membranous portion of the urethra; and by the anterior portions of the Levatores ani, which pass backward from the pubis and embrace the sides of the prostate. These portions of the Levatores ani, from the support they afford to the prostate, are named the Levatores prostatæ. The prostate is perforated by the urethra and the ejaculatory ducts. The urethra usually lies along the junction of its anterior with its middle third. The ejaculatory ducts pass obliquely downward and forward through the posterior part of the prostate, and open into the prostatic portion of the urethra.

Structure —The prostate is immediately enveloped by a thin but firm fibrous capsule, distinct from that derived from the fascia endopelvina, and separated from it by a plexus of veins. This capsule is firmly adherent to the prostate and is structurally continuous with the stroma of the gland, being composed of the same tissues, viz.: non-striped muscle and fibrous tissue. The substance of the prostate is of a pale reddish-gray color, of great density, and not easily torn. It consists of glandular substance and muscular tissue. The muscular tissue according to Kölliker, constitutes the proper stroma of the prostate; the connective tissue being very scanty, and simply forming between the muscular fibers, thin trabeculae, in which the vessels and nerves of the gland ramify. The muscular tissue is arranged as follows: immediately beneath the fibrous capsule is a dense layer, which forms an investing sheath for the gland; secondly, around the urethra, as it lies in the prostate, is another dense layer of circular fibers, continuous above with the internal layer of the muscular coat of the bladder, and blending below with the fibers surrounding the membranous portion of the urethra. Between these two layers strong bands of muscular tissue, which decussate freely, form meshes in which the glandular structure of the organ is imbedded. In that part of the gland which is situated in front of the urethra the muscular tissue is especially dense, and there is here little or no gland tissue; while in that part which is behind the urethra the muscular tissue presents a wide-meshed structure, which is densest at the base of the gland—that is, near the bladder—becoming looser and more sponge-like toward the apex of the organ. The glandular substance is composed of numerous follicular pouches the lining of which frequently shows papillary elevations. The follicles open into elongated canals, which join to form twelve to twenty small excretory ducts. They are connected together by areolar tissue, supported by prolongations from the fibrous capsule and muscular stroma, and enclosed in a delicate capillary plexus. The epithelium which lines the canals and the terminal vesicles is of the columnar variety. The prostatic ducts open into the floor of the prostatic portion of the urethra, and are lined by two layers of epithelium, the inner layer consisting of columnar and the outer of small cubical cells. Small colloid masses, known as amyloid bodies are often found in the gland tubes.

Vessels and Nerves. —The arteries supplying the prostate are derived from the internal pudendal, inferior vesical, and middle haemorrhoidal arteries. Its  veins form a plexus around the sides and base of the gland; they receive in front the dorsal vein of the penis, and end in the hypogastric veins. The nerves are derived from the pelvic plexus.

According to McNeal’s model of the prostate, four different anatomical zones may be distinguished that have anatomo-clinical correlation (Figure 3):

1.      The peripheral zone : is the area forming the postero-inferior aspect of the gland and represents 70% of the prostatic volume. It is the zone where the majority (60-70%) of prostate cancers form.

2.      The central zone : represents 25% of the prostate volume and contains the ejaculatory ducts. It is the zone which usually gives rise to inflammatory processes (eg prostatitis).

3.      The transitional zone : this represents only 5% of the total prostatic volume. This is the zone where benign prostatic hypertrophy occurs and consists of two lateral lobes together with periurethral glands. Approximately 25% of prostatic adenocarcinomas also occur it this zone.

4.      The Anterior Zone : Predominantly fibromuscular with no glandular structures.

The prostate weighs approximately 20g by the age of 20 and has the shape of an inverted cone, with the base at the bladder neck and the apex at the urogenital diaphragm.The prostatic urethra does not follow a straight line as it runs through the centre of the prostate gland but it is actually bent anteriorly approximately 35 degrees at the verumontanum (where the ejaculatory ducts joins the prostate).

HISTOLOGY

The prostate consists of stromal and epithelial elements. Smooth muscle cells, fibroblasts and endothelial cells are in the stroma and the epithelial cells are secretory cells, basal cells and neuroendocrine cells (Figure 4).

The columnar secretory cells are tall with pale to clear cytoplasm. These cells stain positively with prostate specific antigen. Basal cells are less differentiated than secretory cells and so are devoid of secretory products such as Prostate Specific Antigen (PSA). Finally, neuroendocrine cells are irregularly distributed throughout ducts and acini; with a greater proportion in the ducts .The prostate has the greatest number of neuroendocrine cells of any of the genitourinary organs. Glands are structured with open and closed cell types with the open type facing the inside of the duct having a monitoring role over its contents. Most cells contain serotonin but other peptides present include somatostatin, calcitonin, gene-related peptides and katacalcin. The cells co-express PSA and prostatic acid phosphatase. Their function is unclear but it is speculated that these cells are involved with local regulation by paracrine release of peptides. Prostatic ducts and acini are distinguished by architectural pattern at low power magnification. The prostate becomes more complex with ducts and branching glands arranged in lobules and surrounded by stroma with advancing age

PHYSIOLOGY

At present, there is only limited knowledge of all of the secretory products of the prostate and how this relates to reproduction and infertility. However, the main role of the prostate as a male reproductive organ is to produce prostatic fluid, which accounts for up to 30 per cent of the semen volume. Sperm motility and nourishment are aided by the prostatic fluid constituents and the environment they create. Prostatic fluid is a thin, milky alkaline fluid containing citric acid, calcium, zinc, acid phosphatase and fibrinolysin among its many constituents (Table 1). Prostate specific antigen (PSA) is also a constituent found in prostatic secretions. During ejaculation, alpha-adrenergic stimulation results in transport of the seminal fluid containing sperm from the ampulla of the vas deferens into the posterior urethra. Interestingly, abnormal growth of the prostate is only experienced by humans and dogs and why other mammals are spared is a mystery.

ENDOCRINE CONTROL OF PROSTATIC GROWTH

It is becoming clear that intraprostatic signalling systems are important for the regulation of cell proliferation and extracellular matrix production in prostatic stroma. Central to this premise is the balance between factors such as tumour growth factor beta 1 (TGFb1), that induces extracellular matrix production, suppresses collagen breakdown and cell proliferation and factors such as fibroblast growth factor 2 and insulin-like growth factors that are mitogenic in the stromal compartment. Other endocrine pathways are being investigated and there is experimental data suggesting an abnormality in the insulin-like growth factor axis playing a role in the pathogenesis of BPH.

Testosterone

Prostatic epithelial cells express the androgen receptor. From the beginning of embryonic differentiation to pubertal maturation and beyond, androgens are a prerequisite for the normal development and physiological control of the prostate. Androgens also help maintain the normal metabolic and secretory functions of the prostate. They are also implicated in the development of benign prostatic hyperplasia (BPH) and prostate cancer. Androgens do not act in isolation and other hormones and growth factors are being investigated.

Androgens also interact with prostate stromal cells which release soluble paracrine factors that are important in the growth and development of the prostate epithelium. These paracrine pathways may be critical in regulation of the balance between proliferation and apoptosis of prostate epithelial cells in the adult.

The appropriate balance between testosterone and its 5 alpha reduced metabolites are key to normal prostate physiology). The metabolism of testosterone to dihydrotestosterone (DHT) and its aromatisation to estradiol are recognised as the key events in prostatic steroid response.

Testosterone, to be maximally active in the prostate, must be converted to dihydrotestosterone (DHT) by the enzyme 5alpha-reductase (Figure 5).

Figure 5. Conversion of Testosterone to Dihydrotestosterone by 5alpha-Reductase

DHT has a much greater affinity for the androgen receptor than does testosterone which allows it to accumulate in the prostate even when circulating levels of testosterone are low. DHT is about twice as potent as testosterone in studies of rats at equivalent androgen concentrations. Therefore, DHT concentrations may remain similar to those in young men in the prostate of elderly men, despite the fact that serum testosterone levels may decline with age. In the prostate, the total level of testosterone is 0.4 ng/g and the total of DHT is 4.5 ng/g. The total concentration of testosterone in the blood (18.2nnmol/L) is approximately 10 times higher than that of DHT. Circulating DHT, by virtue of its low serum plasma concentration and tight binding to plasma proteins, is of diminished importance as a circulating androgen affecting prostate growth.

Estrogen

A role for estrogens in the prostate pathology of the ageing male appears likely with accumulating evidence that estrogens, alone or in combination with androgens, are involved in inducing aberrant growth and/or malignant change. Animal models have supported this hypothesis in the canine model, where estrogens “sensitize” the ageing dog prostate to the effects of androgen. The evidence is less clear in humans. Estrogens in the male are predominantly the products of peripheral aromatization of testicular and adrenal androgens. While the testicular and adrenal production of androgens declines with ageing, levels of total plasma oestradiol do not decline. This has been ascribed to the increase in fat mass with ageing (the primary site of peripheral aromatization) and to an increased aromatase activity with ageing. However, free or bioavailable estrogens may decline due to an increase in sex hormone binding globulin, which could translate to lower intraprostatic levels of the hormone. The potentially adverse effects of oestrogens on the prostate may be due to a shift in the intra-prostatic estrogen:androgen ratio with ageing.

Estrogen, which acts through estrogen receptors (ER) alpha and beta, has been implicated in the pathogenesis of benign and malignant human prostatic tumors. As stated above benign prostatic hyperplasia is thought to originate in the transitional zone (TZ) and prostate cancer the peripheral zone (PZ) of the prostate. Receptor studies have found ER-alpha and ER-beta types distributed in human normal and hyperplastic prostate tissues, using in situ hybridization and immunohistochemistry. ER-alpha expression was restricted to stromal cells of the PZ. In contrast, ER-beta was expressed in the stromal and epithelial cells of PZ as well as TZ. These findings suggest that estrogen may play a crucial role in the pathogenesis of benign prostatic hyperplasia through ER-beta. Investigations are ongoing and could result in a new range of therapies directed against BPH and prostate cancer. Dietary phytoestrogens (in soy and other vegetables) or selective estrogen receptor modulators are currently being investigated with regard to their role in the development of BPH and prostate cancer. Such ER modifiers may oppose some of the effects of natural oestrogen by modulating ER receptors, thus reducing the local impact of androgens that need active ER receptors, effectively making them anti-androgenic compounds however this requires more investigation.

BENIGN PROSTATIC HYPERPLASIA (BPH)

Benign Prostatic Hyperplasia (BPH) is an age-related and progressive neoplastic condition of the prostate gland. BPH may only be defined histologically. BPH in the clinical setting is characterised by lower urinary tract symptoms (LUTS, see Table 2). There is no causal relationship between benign and malignant prostatic hypertrophy. Clinically apparent BPH represents a considerable health problem for older men, due to the negative effects it has on quality of life (QOL)

Incidence and Prevalence

            A recent study has demonstrated an overall prevalence of 10.3%, with an overall incidence rate of 15 per 1000 man-years, increasing with age (3 per 1000 at age 45-49 years, to 38 per 1000 at 75-79 years). For a symptom free man at age 46, the risk of clinical BPH over the coming 30 years, if he survives, is 45%. The true prevalence and incidence of clinical BPH will vary according to the criteria used to describe the condition. It is crucial to acknowledge that LUTS can exist without signs of BPH – as the symptoms can be caused by variations in the sympathetic nervous stimulation of prostatic smooth muscle, variability of prostatic anatomy (viz., enlarged median lobe of the prostate), and the variable effects of bladder physiology from the obstruction and aging.

There have been several studies demonstrating the fact that clinical BPH is a progressive disease. The Olmsted county study showed that with each year there were deteriorations in symptom scores, peak flow rates, and increases in prostate volumes based on transrectal ultrasound scanning (TRUS). The risk of acute urinary retention (AUR) increased with flow rates below 12 ml/sec and with glands greater than 30ml. Studies have also demonstrated that those with larger prostates (>40 ml) and with serum PSA greater than 1.4 ng/ml were more likely to develop acute urinary retention. Treatment however has changed with the advent of effective non-surgical therapies. Between 1992-1998 there has been a significant lengthening of the period between first diagnosis of LUTS secondary to clinical BPH and surgery, associated with the earlier and increased use of specific medical treatments. From the patients perspective the goals of therapy are to improve quality of life, reduce symptoms, and avoid surgery while ensuring safety from the complications of BPH.

Risk Factors for BPH

The only clearly defined risk factors for BPH are age and the presence of circulating androgens. BPH does not develop in men castrated before the age of forty. But other factors may influence the prevalence of clinical disease. These include:

1. Genetics

Clinical BPH appears to run in families. If one or more first degree relatives are affected, an individual is at greater risk of being afflicted by the disorder. In a study by Sanda et al the hazard-function ratio for surgically treated BPH amongst first degree relatives of the BPH patients as compared to controls was 4.2 (95% CI, 1.7 to 10.2). The incidence of BPH is highest and starts earliest in blacks than Caucasians and is lowest in Asians. Interestingly, despite having larger prostate glands, the age-adjusted risk of BPH was the same for blacks as for whites (RR = 1.0, 95% Cl 0.8-1.2). Furthermore, in an Asian population, men presenting with BPH are likely to have higher symptom scores than blacks or Caucasians.

2. Diet

Diet has been reported as a risk factor for the development of BPH. Large amounts of vegetables and soy products in the diet may explain the lower rate of BPH in the orient when compared to westernized countries. In particular, certain vegetables and soy are said to be high in phyto-oestrogens, such as genestin, that have ant-androgenic effects by an as yet determined mechanism on the prostate in vitro.

By studying migrant populations with their heterogeneous exposures to the environment, it increases the probabilities of identifying potential risk factors for BPH. Therefore, the association of alcohol, diet, and other lifestyle factors with obstructive uropathy was investigated in a cohort of 6581 Japanese-American men, examined and interviewed from 1971 to 1975 in Hawaii. After 17 years of follow-up, 846 incident cases of surgically treated obstructive uropathy were diagnosed with BPH. Total alcohol intake was inversely associated with obstructive uropathy (P < 0.0001). The relative risk was 0.64 (95% confidence interval: 0.52-0.78) for men drinking at least 25 grams of alcohol per month compared with nondrinkers. Among the 4 sources of alcohol, a significant inverse association was present for beer, wine, and sake, but not for spirits. No association was found with education, number of marriages, or cigarette smoking. Increased beef intake was weakly related to an increased risk (p = 0.047), while no association was found with the consumption of 32 other food items in the study.

3. Other Risk Factors

It has not been possible to delineate any other risk factors for BPH such as coronary artery disease, liver cirrhosis or diabetes mellitus. There is also no causal relationship between malignant and benign prostatic hypertrophy.

PATHOPHYSIOLOGY OF BPH

Natural History

BPH is a histological diagnosis but its clinical manifestations occur after growth has occurred to such a degree and in such a strategic location within the gland, namely the transitional zone, that it impairs bladder emptying and results in LUTS. One can therefore consider the natural history of BPH as involving two phases:

1.      The pathological or first phase of BPH is asymptomatic and involves a progression from microscopic to macroscopic BPH. Microscopic BPH will develop in almost all men if they live long enough but in only about half will progress to macroscopic BPH. This would suggest that additional factors are necessary to cause microscopic to progress to macroscopic BPH. The pathological phase involves development of hyperplastic changes in the transitional zone of the prostate. While there is wide variability in prostate growth rates on an individual level, prostate volume appears to increase steadily at about 1.6% per year in randomly selected community men.

2.      The clinical or second phase of BPH involves the progression from pathological to ‘clinical BPH’ which is synonymous with the development of LUTS. Only about one half of patients with macroscopic BPH progress to develop clinical BPH. BPH consists of mechanical and dynamic components and it is these components that are responsible for the progression from pathological to clinical BPH. In clinical BPH, the ratio of stroma to epithelium is 5: 1 whereas in the case of asymptomatic hyperplasia the ratio is 2.7:1. A significant contribution is therefore made by stroma to the infravesical obstruction of BPH.

DISEASE MANIFESTATIONS OF BPH

Lower Urinary Tract Symptoms (LUTS)

Lower urinary tract symptoms (LUTS) suggestive of BPH are highly prevalent and the majority of LUTS in men is produced by BPH, but may be contributed to by a variety of conditions. LUTS are traditionally divided into voiding or obstructive and storage or irritative symptoms (Table 2).

Voiding symptoms are more common, however it is storage symptoms that are most bothersome and have a greater impact on a patient’s life. The prevalence of clinical BPH rises with age and approximately 25% of men age 40 or over will suffer from LUTS.

In the past, LUTS suggestive of bladder outflow obstruction (BOO) secondary to BPH were referred to as ‘prostatism’, once other causes such as a urinary tract infection or prostate cancer were excluded. The pathology behind the symptoms was thought to be obstruction due to prostatic gland enlargement alone. However, today it is recognised that voiding/obstructive symptoms result from direct urinary flow obstruction whilst storage/irritative symptoms appear to be due to secondary bladder dysfunction.

This concept has been further refined in that obstructive symptoms are thought to result not only from mechanical obstruction due to glandular enlargement, but also dynamic obstruction secondary to contraction of the smooth muscle of the prostate, urethra and bladder neck. This dynamic obstruction is a result of sympathetic nervous system mediated stimulation of alpha-1adrenoceptors. Storage symptoms appear to be caused by detrusor instability related to detrusor muscle changes in response to obstruction, such as bladder wall hypertrophy and collagen deposition in the bladder. The role of adrenoceptor subtypes in the bladder in this process is currently being investigated. Adrenoceptors may be further sub-divided into alpha1A and alpha1D subtypes, with alpha1A predominant in the prostate and alpha 1D in the bladder. Thus blockade of alpha1A may be necessary for reduction of obstruction whereas the blockade of alpha1D may be required to relieve storage symptoms.