|
CLINICAL TREATMENT WITH TRIBESTAN (PHARMACHIM)
IN WOMEN WITH CLIMACTERIC SYNDROME
DR. PAVLETA TABAKOVA
DR. MITKO DIMITROV
DR. BOZIHDAR TASHKOV (HEAD PHYSICIAN)
DIRECTOR OF STUDIES:
(PROF. DR. S. DOKUMOV)
Climacterium is a complicated biological process
with versatile symptoms associated with the gradual
dying out of the hormonal activity of ovaries on
the background of a general aging of the female
organism.
Climacterium is a psychological process with
duration from two to more years, most often at the
age of 40-55. The visible manifestation is the cessation
of menstruation - advancing of menopause. The initial
period of gradual dying out of ovarian function,
known as premenopause is with various duration in
individual women.
A disorder of the cyclic activity of hypothalamic-hypophyseal
axis with predomination of parasympathicus occurs
on the background of age readjustment of the central
nervous system. Various neuro-vegetative symptoms,
neuro-psychic disorders, metabolic changes etc.
are observed during climacterium. Hypothalamic reactivity
is intensified leading to the increase of the production
of hypophysiotropic hormones.
The ovulatory activity of ovaries declines and
the receptive function versus hormones partially
fades. The reduced production of ovarian hormones
leads to a compensatory effect (growth) of gonadotrophic
hormones. On its part, that however is the cause
of hyperthyroidism, virilization, acromegalic manifestations
etc.
Climacterium advances with several phases:
1. Hypoluteinic
2. Hyperesterogenic preclimacterium
3. Hypoesterogenic-hypergonadotropic
4. Afollicular - with light reduction of gonadotrophic
hormones but still higher than the normal values.
The clinical symptoms of that age of the woman
are neuro-vegetative, neuro-physical, cardiovascular,
endocrine, metabolic changes in hepatic function,
disturbances in locomotor apparatus, miction disturbances,
weight gain, etc. In some of the women, the above
mentioned phenomena proceed particularly aggravated
and in fact they are the object of the present study.
Among them, the group of the so-called postcastration
climacterium is rather special - abatement phenomena,
occurring after surgical removal of ovaries due
to various reasons.
In 1984, during the studies of Tribestan effect
on females with anovulatory disturbances, we came
across a favorable effect of the product on trial
both on females in postcastration and on females
in natural climacterium. That was a reasonable ground
to propose the testing the effect of Tribestan (Pharmachim)
on a greater number of females with climacteric
syndrome.
MATERIALS AND METHODS
The product on trial, TRIBESTAN (Pharmachim)
was provided by NIHFI as filmtablets of 250 mg.
It contains a natural product obtained from the
above-the-ground part of the plant Tribulus terrestris,
with the predominating content of steroid saponins
of furostanol type, with prevailing quantity of
protodioscine. Additionally, sufficient quantities
of placebo tablets were also provided.
Administration Schedule
Variety 1 - 3 x 2 tablets, 20
days and reduction of the dose with one tablet every
4-5 days up to 2 x 2 tablets, 3 x 1 tablet and 2
x 1 tablet - always strictly individual.
Variety 2 - 2 x 2 tablets - 30 days with reduction
every 4-5 days up to 2 x 1 tablet.
Variety 3 - 3 x 1 tablet, uninterruptedly and for
a long time.
Clinical Groups. The object of the present study
were 50 females with data about natural and postcastration
climacteric syndrome. A pilot study on another 12
females was carried out in 1984. In 46 of 50 females
(92%), treatment with placebo, 2 tablets three times
daily for 15-20-30 days, was initiated immediately
after making the diagnosis and the manifestation
degree of the clinical symptoms.
After recording the status at the end of placebo
period, Tribestan treatment was initiated according
to the above schedules.
Parameters for observation and evaluation. The
final result from the treatment was classified according
to the clinical picture: complete elimination of
the climacteric complaints; abrupt reduction of
the complaints and no effect on the complaints.
That classification was possible on the base of
periodical follow up of a series of subjective,
objective clinical and paraclinical parameters:
- changes in neurovegetative and
neuropsychic complaints - intensity and frequency
of hot flashes, sweat, depression, overexcitation,
easy fatigability, apathy, etc.
- changes in cardiovascular system - changes in
pulse, blood pressure, oppression in heart region,
palpitation, tachycardia and/or extrasystoles, etc.
- changes as pruritus, miction disturbances.
- characteristics of the stage of climacterium according
to estrogen-progesterone level, evaluated by vaginal
hormonal cystosmears.
- blood count
- blood sugar profile
- ultrasound diagnosis
- radioimmunological control of the level of gonadotrophic
and steroid hormones - FSH, LH, prolactine, progesterone,
testosterone, E 2.
- changes in libido sexualis.
Conclusion.
The option of the research, based on the experience
from the treatment of 50 patients with natural and
postoperative climacterium during that experiment,
as well as on the data from the previous pilot study
on another 12 women with the same clinical picture
is that Tribestan (Pharmachim) can successfully
be used in the treatment of climacteric syndrome
in females, both natural or postcastration. The
absence of any adverse effects, the ready tolerance
and its excellent effect makes it a desired agent
for the treatment of all patients with similar complaints.
It should be stressed here that the effect is
gradually attained within a rather long period of
time by a rather great number of tablets. Furthermore,
a maintenance therapy for about 2 - 2.5 years is
necessary.
That means that each woman should pay 600 levs
for the provision of the necessary number of Tribestan
tablets. With consideration given to the fact that
a great part of the women will prefer the considerably
cheaper hormonal depot-agents, the attention of
the manufacturer should be drawn either on the price
of the product or on the dose of the active principle
in one tablet.
Dr. Palveta Tabakova
Dr. Mitko Dimitrov (Head Physician)
Dr. Bozhidar Tashkov
Director of Studies:
(Prof. Dr. S. Dokumov)
- EFFECT OF TRIBESTAN (PHARMACHIM) DURING
MENOPAUSE
- (Dr. P. P. Tabakova et al.)
-
- RADIOIMMUNOASSAYS
| Hormone |
Tribestan treatment |
No. |
Limit of confidence
(Mean +/- 1.96 SEM) |
|
E2
|
Before
After
|
42
40
|
0.10 ÷ 0.22
0.20 ÷ 0.54
|
|
Prg
|
Before
After
|
32
34
|
5.00 ÷ 10.30
4.14 ÷ 7.44
|
|
Tst
|
Before
After
|
41
45
|
1.15 ÷ 1.74
0.96 ÷ 1.30
|
|
FSN
|
Before
After
|
46
42
|
51.38 ÷ 72.34
42.30 ÷ 59.74
|
|
LH
|
Before
After
|
42
43
|
32.45 ÷ 46.05
29.62 ÷ 38.88
|
|
Prl
|
Before
After
|
42
37
|
265.20 ÷ 378.20
200.60 ÷ 267.60
|
- DISTRIBUTION OF PATIENTS BY LEVEL OF PROGESTERONE/ESTROGEN
ACCORDING TO HORMONAL CYTOLOGICAL EXAMINATIONS
|
LEVEL
|
Number of Patients
|
Percentage
|
| High |
7
|
14
|
| Normal |
1
|
2
|
| Low |
6
|
12
|
| Very low |
16
|
32
|
|
Total
|
30*
|
100
|
* 20 patients without cytological examination
DISTRIBUTION OF PATIENTS BY THE MAINTENANCE
DOSE OF TRIBESTAN
|
Maintenance dose
(tabl/day)
|
Number of patients
|
Percentage
|
|
2 x 1
|
27
|
55.1
|
|
3 x 1
|
14
|
28.6
|
|
2 x 2
|
8
|
16.3
|
|
Total
|
49*
|
100
|
* 1 patient without effect
TOTAL EFFECTIVE DOSE OF TRIBESTAN
|
Dose
(tabl/day)
|
No
|
Total effective dose
|
|
Mean
|
Limit of confidence
Mean +/- 1.96 SEM
|
|
3 x 1
|
7
|
68.6
|
53.0
|
84.2
|
|
2 x 2
|
13
|
115.4
|
93.7
|
137.1
|
|
3 x 2
|
30
|
141.5
|
113.7
|
169.3
|
DISTRIBUTION OF PATIENTS BY THE TOTAL EFFECTIVE
DOSE OF TRIBESTAN
|
Total number of patients
|
Initial dose (tablets/day)
|
|
3 x 1
|
2 x 2
|
3 x 2
|
Total
|
|
No
|
%
|
No
|
%
|
No
|
%
|
No
|
%
|
|
<60
|
2
|
4
|
-
|
-
|
-
|
-
|
2
|
4
|
|
60-100
|
5
|
10
|
5
|
10
|
8
|
16
|
18
|
36
|
|
110-180
|
-
|
-
|
7
|
14
|
18
|
36
|
25
|
50
|
|
190-220
|
-
|
-
|
1
|
2
|
1
|
2
|
2
|
4
|
|
>220
|
-
|
-
|
-
|
-
|
3
|
6
|
3
|
6
|
DISTRIBUTION OF PATIENTS BY DURATION OF PLACEBO
TREATMENT
|
Duration of treatment
(days)
|
Number of patients
|
Percentage
|
|
0
|
4
|
8.0
|
|
14
|
6
|
12.0
|
|
15-20
|
32
|
64.0
|
|
21-30
|
8
|
16.0
|
|
Total
|
50
|
100
|
DISTRIBUTION OF PATIENTS BY TYPE LIBIDO SEXUALIS
|
Type of libido sexualis
|
Number of patients
|
Percentage
|
|
Normal
|
2
|
4.0
|
|
Low
|
20
|
40.0
|
|
Very low
|
28
|
56.0
|
|
Total
|
50
|
100
|
DISTRIBUTION OF PATIENTS BY INCIDENCE OF SOME
SYMPTOMS BEFORE TRIBESTAN TREATMENT
| Symptoms |
Number of patients
|
Percentage
|
| Head waves |
50
|
100
|
| Perspiration |
39
|
78
|
| Depression |
27
|
54
|
| Hyperexcitation |
22
|
44
|
| Tenseness |
18
|
36
|
| Sense of heaviness in the heart region |
30
|
60
|
| RR-changes |
11
|
22
|
| ECG-changes |
8
|
16
|
DISTRIBUTION OF PATIENTS BY DURATION OF MENOPAUSE
|
Duration of menopause
(months)
|
Number of patients
|
Percentage
|
|
<12
|
19
|
38.0
|
|
12-35
|
16
|
32.0
|
|
36-50
|
7
|
14.0
|
|
>60
|
8
|
16.0
|
|
Total
|
50
|
100.0
|
DISTRIBUTION OF PATIENTS BY TYPE OF MENOPAUSE
|
Type of menopause
|
Number of patients
|
Percentage
|
| Natural |
26
|
52.0
|
| Postoperative |
24
|
48.0
|
|
Total
|
50
|
100.0
|
DISTRIBUTION OF PATIENTS BY AGE
|
Age group (years)
|
Number of patients
|
Percentage
|
|
30-34
|
1
|
2.0
|
|
35-39
|
3
|
6.0
|
|
40-44
|
8
|
16.0
|
|
45-49
|
19
|
38.0
|
|
50-54
|
13
|
26.0
|
|
55-59
|
4
|
8.0
|
|
60+
|
2
|
4.0
|
|
Total
|
50
|
100.0
|
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