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The amino acid tyrosine serves as substrate for the catecholamines epinephrine, norepinephrine and dopamine. As neurotransmitters catecholamines control the pulsatile GnRH release and therefore have an influence on the hypothalamic-pituitary-gonadal axis.
This correlation led to a number of studies on the effect of tyrosine on fertility parameters in female domestic animals. As one result, the administration of 100 mg/kg/day tyrosine is recommended in technical literature in order to improve reproductive behavior and fertility during oestrus. However, the evidence of these studies is poor.
Hence, the first aim of this present study was to provide a systematic and statistical analysis of current literature in terms of evidence-based veterinary medicine (article 1).
Subsequent to the first analysis an own study was performed (article 2). The study was designed asacontrolled randomized clinical trial meeting current scientific standards.
The literature research comprised of 17 studies in German and English, which were evaluated and compared on the basis of evidence criteria. The effect of tyrosine on different fertility parameters had been investigated in female cattle, pigs, rats and dogs. The majority of these studies originate from the 1980ies. Repeatedly, methodical deficits such as lack of control groups, randomization, blinding or the analysis of statistical significance were apparent. The two existing investigations on dogs featured all these deficits. To some extent results from different surveys were inconsistent with one another. Therefore we concluded, that consolidated, there are few scientifically proven sources and heterogeneous results indicate a considerable need for further research on the effectiveness and dose of tyrosine to legitimate its appliance in practice.
The objective of our own study was to determine whether oral administration of tyrosine has an effect on oestradiol-17β concentrations and the oestrus behaviour in the bitch. The required number of animals was calculated based on the following hypothesis using Sample Size/Power Calculations: reference value for mean concentration of estradiol-17β on the day of ovulation is 164.4±54.3 pmol/l. An increase by >40 pmol/l (to 204.4 pmol/l) in the verum group at ovulation compared to the control group was hypothesized.
Fifty bitches were randomly allocated to one of two treatment groups in which each dog received 100 mg/kg/day of either tyrosine or milk sugar orally between Day 3 and Day 9 of heat. Every two to three days a gynaecological examination was performed and blood samples were taken to determine estradiol-17β and progesterone concentrations.
Routine gynaecological examination consisted of adspection vaginoscopy and cytological evaluation of a stained vaginal smear. The day of ovulation was estimated by clinical findings and according to the specifications of the laboratory once progesterone values exceeded 12.7 nmol/l.
In addition to clinical examinations owners were asked to observe copulation behaviour and vaginal discharge compared to previous heats. Standardized case report forms were handed out to document these findings. Pregnancy examination was performed 24 to 28 days after first mating using ultrasound. After all data was collected, the study was unblinded and clinical findings and concentrations of progesterone and estradiol-17β were allocated into four distinct, time-related intervals: day of ovulation ±1 day, 2-4 days before ovulation, 5-7 days before ovulation and 8+ days before ovulation.
Mean day of ovulation was 11.4±1.94 days after onset of pro-oestrus (11.4±1.96 days in the verum group and 11.5±1.96 days in the placebo group).In the verum group (n=25), two bitches did not accept the male and in one case the male did not show any interest. 17 bitches (68 per cent) whelped. In the placebo group (n=25), four bitches showed poor copulation behaviour, but all were mated. 20 bitches (80 per cent) whelped. No differences in volume and visual nature of vaginal discharge were observed.
At the day of ovulation mean estradiol-17β concentration in the treated group was 163.4 pmol/l and 162.2 pmol/l in the placebo group, respectively. No significantly different levels in estradiol-17β were found prior to ovulation.
The results of our study indicate that oral administration between Day 3 and Day 9 of heat does not elevate estradiol-17β levels. In contrast to recommendations in technical literature, tyrosine did not improve signs of heat or copulation behaviour. Further researchon the effectiveness and dose of tyrosine is desirable to evaluate if its appliance in practice is sustainable.