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