Men Pathological Climacteric

Many doctors still deny an existence of men climacteric. Clinical displays of men climax are not compulsory phenomena in the process of involutio. The main part of middle-aged men have no physiological symptoms of insuffitientio testicularis: secondary sexual symptoms are not subdued to visible regressive changes, a form of body does not change.

On the other hand the main part of women during the climacteric period has an atrophy of a womb, ovaries, extern genitals and breast glands, a voice and outlines of body change, osteoporosis skin turgors decreases and other symptoms of involutio appear.

So if women climacteric is a physiological component of processes old, then men climacteric syndrome does not always follow with involutio processes ( processes of becoming old). A generative function also differs very much. A spermatogenesis of healthy men remains until venerable age - 70-80 years. We need not understand the man climax as we understand women climax. Clinical symptoms of the men climacteric syndromes are visible only for 10-20% men.

Ordinary the men climacteric starts at the age of 45-60, but some pathological climacteric cases occurs at the age of 35-45. For younger men ( 26-34 years old ), the climacteric is characteristic with particularly hard clinical course (course of the disease ) and it is hard to treat the disease. The younger is man, the harder is to treat the climacteric. But for older men with pathological climacteric recovery reactions are started better.

As a base of the etiopathogenetic of the pathological climacteric is inflammative diseases of the genitals connected with degeneratively-distrophycal changes in the prostrate and with degradation of fibrinogens molecule. The degeneratively - distrophycal changes in the genitals cause a fast and premature process of involutio, an impotence in such way negatively influencing men's qualitative as well as quantitative indices. The symptoms of the disease for each patient during different periods depends on a stadium of the inflammation of the prostate, a duration and activity of remission phase, translocation of the STS infection and a degree of defects of next organs.

Pathogenic mechanism features of the men climacteric is prescribed by one's activity's depression enzymatic defect of the proteolytic and fibrinolytic ferment system at the level of tissues. Practically the men climacteric syndrome is an independent of physical - chemical properties of fibrinogen molecule not only regarding circulation of the blood but also in tissues - from tissue plasminogen activator ( T-PA ).

A sight of the men pathological climacteric seldom and shortly is monosymptomatic, mainly varied symptoms which can be local as well as general are characteristic.

•  A syndrome of general disorders - a tiredness, a loss of strength, muscular pains, a decreased capacity for intellectual work which are characteristic in cases of different immune pathologies.

•  A syndrome of psychoneurotical disorders - a uneasiness, a nervousness, a depression, an sleeplessness, disorders of concentration, a weakening of memory, apparently hypochondriac complaints, asthenia and asthenodepressive syndrome caused by unhydrolyzed psychoactive peptides because of discoagulemition.

•  A syndrome of neurological disorders - a headache, pains in nape & sacrum which simulates radikulitis, etc.

•  A syndrome of disorders of the heart & blood -vessels with pains in cardiac region, heart sounds, increased arterial blood -pressure due to hypercoagulemic, discoagulemic and micro circulation.

•  A syndrome of urogenital disorders which has four types: pathology of genitals; exstragenital pathology of genitals; mixed pathology and sympathology of pelvis. Not all persons but only 10-15% of andrologic patients ask for help urologist and sexopathologist.

•  Disorders of reproducing function. It is observed that patients with chronic prostatitis, vezikulitis, koliculitis has a checking of spermatogenezis a change for the worse of functional condition of spermia, oligozoospermia, akinospermia, nekrospermia and impotentia generandi.

•  Impotentia coeundi and sexual non force.

•  A neglected chronic prostatitis is diagnosed almost for the all pathological climacteric patients. In the case of latently passing prostatitis and in the case of a syndrome of other functional disorders the disease mostly is not diagnosed or is diagnosed at the third stage of inflammation when local proliferatical changes are prevailing such as scarred deformation, calcinat, paraprocess, atrophy of prostate , sclerosis, inflammation of urogenital veins plexus with subsequent disorders of erection.

Depending on a prevailing syndrome of subjective feeling disturbances patients undergo treatment at different specialists receiving a symptomatic but not a etipathogenetical therapeutics. Men do not die in the result of inflamed genital diseases and impotence but from the complications caused by the premature involutio. Degeneratively dystrophycal, chronic chlamidic prostatitis, paraprostatitis, inflammation of plexus of urogenital veins with flebotrombozis of little pelvis and secondary hypercoagulemio can make an etipathogenetic mechanism for infarcts myokardi, insultare and other trombembolic complications.

There are essential differences in the treatment of the climacteric for men and for women. Metabolytical effect is also different. It is absolutely proved that usage of oestrogen in postmenopausis for women decreases a total level of cholesterol in blood based on fraction of low density aterogenic lipoproteins (1).

In the medical treatment of men pathological climacteric a monotherapy of androgen hormones ( metiltestosteron, proviron ) is ineffective without lipolytical effect and it does not influence a cholesterol level in the blood. It is absolutely proved that hormonal substitution therapy ( HST ) decreases sick - rate with heart diseases for women in post menopause up to 50% and it is more effective than any other preventive treatment (2). On other hand for men with pathological climacteric a regression of syndrome of disorders of the heart & blood - vessels due to androgen hormones therapy is not observed and is ineffective (3).

For women in HST post menopause, metabolytical diseases of bones osteoporosis are decreased, a quality of life is improved and it is also prolonged. A discrepancy of the biological age with the statistical age in a favour of the first one testifies about it because these women look younger at least for 10 years ( than they really are.) On the contrary for men with pathological climacteric hormonal monotherapy does not cause a positive recovery reaction, does not improve the quality and quantity of life. The biological age of these patients does not correspond to the statistical one because due to too intensified involution men look much older than really are.

For women the influence of HST to coagulation and fibrinolysis is not sufficiently studied, there are no also epidemiological believable data which could prove that usage of natural oestrogen in post menopause increases a number of trombembolytical complication. For men with pathological climacteric the monotherapy of androgen hormones promotes induction of discoagulemio and hyperagulemio and complications connected with them. The ethiopathogenetical mechanism of the men pathological climacteric is absolutely different that for women. The treatment of men pathological climacteric must be started with differential diagnostics of the inflamed diseases of urogenital system of organs of little pelvis and etipathogenetical recovery.

Only after full regression of the inflammation it is advisable ordinate androgenetic hormones. For the patients of the pathological climacteric with chronic antibiotic resistant prostatitis, immune deficit of cells and humoral is indicated enzymotherapy using proteolytical ferments of animal, plants, micro-organisms and human and their activators. Before enzymotherapy or also ex juvantibus starting the treatment the level of proteolytic and fibrionalytic enzymatic defect must be fixed. In the practice we come into contact with three levels of this defect. The first level is determined by discoagulemio when making a coagulogramma simultaneously registrate hyper- and hypoagulemio dissociation which are characteristic to inflamed diseases of urogenital organs. Hyperagulemio corresponds to the second level of the enzymatic defect when a translocation of the inflammation, paraprostatitis, inflammation of plexus of urogenital veins, flebotrombosis of little pelvis, etc. are clinically observed. The third level of the enzymatic defect is a depression of the proteolytic and fibrinolytic activity at the cells level with more or less expressed deficit of tissue plasminogen activator in tissues.

The climacteric patients have a deficit of tissue plasminogen activator ( T-PA ) or depression features of the ferment activator what clinically manifestates with increasing of proteolytic resistance. For the climacteric patients with increased proteolytical resistance it is necessary to add (in the constant interval) increased amount of proteolytic ferment (terilytin, papain) to plasma fibrini clot lizis in vitro. It describes the increasing of proteolytic and fibrinolytic resistance not only for blood but also for cells fibrinogen molecule which is connected with the deficit of T-PA in tissues.

The scientists from South Africa have investigated that T-PA content in normal urine is possible to determine only in small amount, but in case of the inflammation of the urogenital organs, "breaking"the anatomical and physiological barriers, the anomalously increased T-PA in the form of urokinase appears in the urine. The cells of inflamed organs loose T-PA. If the positive T-PA test appears in the human urine, it is an obvious evidence of the disease of urogenital system which can't be otherwise clinically proved. As a result of the chronic inflammation the T- PA deficit forms. (3).

The deficit of tissue plasminogen activator causes a decreasing of proteolytic activity of dipeptidasis in such way promoting an accumulation of vasoactive and psychoactive peptide kinin in blood and cells due to the insufficient hydrolysis. The therapy of the men climacteric must be mainly oriented to the activation of plasminogen in blood circulation and cells using proteolytic and fibrionalytic ferments of plants, animals, micro-organism, human blood and their activators depending on the level of enzymatic defect. The most characteristic feature of enzymatic defect for the climacteric patients is a depression of proteolytic and fibrinolytic activity or proteolytic and fibrinolytic resistance. The test of proteolytic resistance shows to changes of physical - chemical properties of patient's fibrinogen molecule to a direction of degradation.

According to the theory of T.Astrup fibrinogen is a matrix consisting of fibroplast. The productive proliferative form of the inflammation with expressed proliferate of connective tissue, sclerotic changes in organs, a scarred deformation of prostate, sclerosis of prostate, nefrosclerosis is connected with a degradation of fibrinogen molecule. The tissue plasminogen activator eliminates the degradation of the fibrinogen molecule and allows to reach a regression of the productive inflammation. Using an adequate enzymotherapy is possible to achieve a total regression of the scarred deformation of prostate and a regeneration of the smooth musculature.

Tissue Plasminogen Activators( T-PA)

Already in 1947 T.Astrup proved that plasminogen can become an active ferment - plasmin after influence of tissue activators (5). As a matter of fact the all known tissue plasminogen activators are proteolytic ferments which can hydrolyse peptide chords of the main amino acids (6). In 1969 P.Kok and T.Astrup worked out a quite simple method for obtaining of tissue plasminogen activator from ovaries of pigs (7).

Plasmin fibrinolyzini is the main proteolytic ferment of plasma which can hydrolyse different proteins. Plasmin is one of the main components of blood-clotting system. The absolutely biggest mass of the plasmin is located in the blood in the form of inactive plasminogen profibrolizin (8). In the organism plasminogen synthesises mainly in the cells of bone marrow from where it comes to the blood and other tissues. The transformation of the inactive plasminogen to the active ferment - plasmin can take place in three ways: auto catalysis spontaneous fibrinolysis, in the presence of tripsinis or by the effect of urokinase. As urokinase is synthesised by kidneys, urology and nephrological patients have a definite deficit of this ferment and an effective eksogen plasminogen activator - streptokinasis is necessary for the treatment.

In 1933 V. S. Tilett and R. L. Garner from haemolytic streptococcus obtained streptokinase which activate plasminogen into plasmin. ( 9 ). In 1941 H. Millstone proved that streptokinase can't lise a clot of fibrin. The streptokinase is not proteolytic and fibrinolytic ferment. The streptokinase has neither proteolytic nor esterase's activity. ( 10 ). In 1945 L .R. Christensen ascertained that streptokinase acts only as a plasminogen activator. Christensen obtained proplasminogen which later he activated with tripsin or streptokinase and obtained plasmin fibrinolyzin (11).

The preparations of fibrinolyzin which are made from the blood of donors were used in the clinics from 1960 till 1985 when the doctors rejected from using of fibrinolyse due to a risk of getting infected by serum hepatitis and other yatrogenetic infections. The preparation of the bacterial origin - streptokinase provides the effective trombolytic therapy without any infection risk. More than 50 years have passed since sreptokinase was discovered and the usage of it in the trombolytic therapy was proved. At present streptokinase is the most often used preparation in the treatment of coagulopatio although this preparation has some undesirable and even dangerous beside occurrences , for example, allergic and anaphylactic reactions.

Many doctors are afraid from anaphylactic shock therefore streptokinase is limitedly used in the clinics. On a purpose of a prophylactic of the anaphylactic shock first of all an individual desensibilatis course of hyperergical reactions of streptokinase must be done with duration of 15- 30 days and a small dosage of the preparations containing streptokinase (12). Less dangerous and more effective is the trombolytic preparation of the second extent -urokinase. Contrary to streptokinase urokinase almost never causes allergic and anafilactical reactions. Many Western clinics use this ferment as the most effective activator of fibrinolytic ferment system in the treatment of trombolytic complication and myokarda infarcts. Enzymotherapy with urokinase is a selective method in the treatment of antibiotic resistant urogenital.

In the process of finding of less dangerous and more effective means the trombolytic preparations of the third extent were created - tissue T-PA obtained in gene engineering. The main property of T-PA differing from streptokinase is the similarity to the fibrin of the thrombus in the presence of which T-PA has trombolytic effect. The second positive feature is a short half-exit period. The third positive feature is a lock of antigen properties. The Tissue Plasminogen Activator is the protein of human plasma and it has no antigen features therefore it is possible to lead in it intravenous repeatedly. The short half exit period (5-9 min) allows to stop the infusion of the preparation and to stop the influence of T-PA in the case of bleeding (14,15).

Comparing to the streptokinase, it is observed that during the time of the leading in of the tissue plasminogen activator men sicking with climacteric have less expressed decreasing of fibrinogen level in the plasma. Contrary to streptokinase leading in T-PA intravenous the allergic reactions are not observed and a desensibilisation course is not needed. Just after the intravenous leading in a longer time of blood-clotting and kaolin is observed. Almost for he all climacteric patients in the result of the intravenous infusion of T-PA the fibrinolysis time of eiglobulin fraction decreases essentially and even several times. Even one hour after the leading in of T-PA the increased fibrinolysis on the fibrin plates is observed ( corresponding to the Method of T.Astrup). If for the achieving of the regression symptoms of the proteolytic resistance using streptokinase was necessary a repeated enzymotherapy course lasting for weeks or even months then T-PA achieves an immediate decrease of the proteolytic resistance of the fibrin clot ( in vitro). The spontaneous changes of fibrinolysis are insignificant and are not characteric.

Since 1997 in Urology Section of Riga Clinical Hospital No.7 T-PA is used for the treatment of the men pathological climacteric and the urogenital inflammations connected with it. Using the T-PA preparation Actilyse 23 patients (at the age 27-73 years) were treated.

Indications for the therapy using actilyse:

1) A durable, ineffective, repeated enzymotherapy using the streptokinase;
2) Allergic and anaphilactical reactions in the case of using the streptokinase;
3) The decreasing of the treatment duration as a result of desensibilisation course of streptokinase;
4) Hypercoagulemio;
5) The usage of streptokinase in the case of a secondary induced hypercoagulemio;
6) Antibiotic resistance;
7) Proteolytic resistance and dysaminoacidemio;
8) Anti inflammation therapy.

The tissue plasminogen activator monotherapy for the most part of the climacteric patients is not necessary due to financial reasons. It must be used proteolytic and fibrinolytic ferments and their activators in the treatment of the men climacteric in order to have an effect on the all three levels of the enzymatic defect simultaneously or alternately using enzymatic preparations of plants, animals, micro-organisms and human. The effective proteolytic ferments in the enzymotherapy are papain, bromelain, agavin (of the plants' origin); tripsin, chimotripsin - of animal origin; teritilin and streptokinase - micro biologically obtained; urokinase (created from human urine) and the tissue T-PA - obtained in the process of gene engineering.

For example, papain, teritilin or tapers containing tripsin are ordinated rectal, additionally vobenzim tablets can be ordinated peroral, simultaneously streptokinase, urokinase or tissue plasminogen activator are leaded into parenteral or introvenozi. The streptokinase is and will be the part of the enzymotherapy of the men climacteric because the production of this preparation is cheap and resources are unlimited. On the contrary urokinase and T-PA are the ferment preparations of the human origin which are and will be expensive and limited.

Therefore treated using the streptokinase must be additionally introvenozi leaded in a small dosage (5-15 mg) of the tissue plasminogen activator. Potentiating the effect of the ferments the fibrionalytic and the proteolytic activity grows, the allergic and the anaphylactic reactions sharply decreases and disappears. The tissue plasminogen activator need not to be ordinated every day but taking to account the data of the coagulogramma. On the other hand the streptokinase have to be introvenozi leaded in every day. If the interval of infuse of the streptokinase is more then one day then the recovery reaction disappears and the therapy becomes ineffective. An interaction of streptokinase, uronikase and T-PA promotes the clinical effect of the proteolytic and the fibriolytic activity of the enzymotherapy.

Samples of treatment

The patient B.R., 60 years old, underwent the treatment in the Urology Section for 32 days. The diagnosis - climacteric, chronic chlamidius prostatitis, double pneimofybrosis.

Before the treatment the patient complained of burning in the urin -channel, pains in the eggs, stomach - ache around the navel, pains in rectum, in joints of the elbows, a feeling of the pressure in the head, disorders of sexual potency for a several years. The objective finding: prostate edematoza, soft, diffuse painful. In the radiogram of lungs the double pneimofibrosis of the lungs was noticed. The coagulogramma was normal except the increased proteolytic resistance - 160 units. A fibrosis in the lungs testified indirectly about the level of the enzymatic defect of T-PA.

The enzymotherapy lasted for 32 days. The patient got streptasis 10,000- 125,000 f .v. i/v once a day with the total dosage of the course 2,310,000 f .v. ; urokinase 25,000 - 50,000 SV i/v once a day - 11 days, total 300,000 SV; Actilyse (T-PA) 10-15 mg i/v once a day - 4 days, total 50 mg. At the same time he got anticlamidius antibiotics : doxicylin 0,1 three times a day (tablets); rovomicin 1,5 MUI i/v twice a day - 15 days and rocefin 1,0 i/v once a day - 10 days. At the end of the enzymotherapy course - 1 hour after leading in 15 mg of Actilyse (T-PA) the time of blood - clotting was 15 minutes; protombin index was 69%, a fibrinolysis time of the fraction of plasma eiglobulin was 50 minutes, the fibrinolysis on the fibrin plates - 300mm2 and the proteolytic resistance normalized down to 140 units. The inflammation of the prostate absolutely regressed. The polimorfiscal subjective complaints also disappeared. Remission.

The enzymotherapy of the men climacteric using streptokinase, urokinase and alternately with T- PA is the selective method because it work to all three levels of the enzymatic defect simultaneously. Streptokinase, urokinase and T-PA decrease duration the treatment of the men climacteric for several times. The tissue plasminogen activator decreases antibiotic resistance. It has the anti inflammation properties. The men pathological climacteric is not a local urogenital disease but a general disease. In the case of the men climacteric the activity of peptidases decreases, the vasoactive or psychoactive peptides ( kinins and disaminoacidemio) can form. (16)

The patient V.M., 35 years old. The diagnosis - an early climacteric with a syndrome of psychoneurothic disorders and thoughts about the committing of a suicide. A chronic prostatitis. Disaminocidemio.

During the enzymotherapy course the patient got streptokinase 30,000 - 100,000 f .v. i/v once a day - 22 days with the total dosage of 1,730,000 f .v. Due to a Artralgic and hyperpireksion 6-8 hours after the streptokinase infusion the bigger dosage of the ferment was not possible. On the 12-th day of the enzymotherapy additionally the urokinase was ordinated to the patient - 15,000 - 25,000 SV once a day i/v- 6 days, total 100,000 SV, and after that Actilyse 5 mg i/v once/day - 4 days, total 20 mg and at the same time 8500 v. heparin i/v every day.

During the treatment regularly controlling hemocoagulation, the time of the blood-clotting extended from 13 to 16 minutes and the fibrinolysis time of the fraction of plasma eiglobulin shorted from 160 to 120 minutes. The dates of coagulogram did not testify about the activation of the fibrinolytical ferment system what should be beared in mind. If before the treatment investigating amino acids in the blood we diagnosed disaminoacidemation then after the enzymotherapy using the Actilyse the disaminoacidemation regressed. A spectrum of the amino acids normalised, the enzymatic defect of peptidases disappeared. after the leading in of urokinase and Actilyse also the psycho neurotic disorders absolutely disappeared due to a hydrolization of the psychoactive peptides (kinins).

Conclusions

•  Kinetics of the activation of tissues' plasminogen for patients sicked with men pathological climacteric essentially differs from trombolytical therapy because there are not fibrin clots in blood-vessels and fibrinolysis does not take place.

•  In the result of T-PA decreasing of the level of fibrinogen concentration for patients with pathological climacteric is insignificant.

•  The spontaneous blood fibrolysis for climacteric patients after the T-PA injection does not sharply increase and it is not a typical test.

•  A decreasing for several times of the fibrinolysis time of eiglobulin fraction of plasma testifies the T-PA recovery reaction.

•  After the medical treatment using T-PA the plasma of climacteric patients effected on thermally - coagulated fibrin plate, increases area of lise for several times. It has similarity with trombolysis in blood-vessels.

•  After a enzymotherapy course using T-PA a proteolytic resistance of the plasma decreases.

•  Human tissue plasminogen activator has a typical anti-inflammation effect.

•  Actilyse (T-PA) enables to reduce the treatment time of the pathological climacteric by 30-50% as a result of desensibilization course of streptokinase allergic and anaphylactic reactions.

•  Monotherapy using T-PA is not necessary. The most optimal results are achieved using simultaneously streptokinase, urokinase, actilyse and other proteolytic and fibrinolytic ferments and their activators of flora and animals origin, effecting on whole three levels of enzymatic defect.

•  Usage of human tissue plasminogen activator open new opportunities for the treatment of men climacteric.