The study assessing efficacy and safety of the bi-hormonal contraceptive drug during the long-term experiment
O.A. Zeynalov1, PhD in Biology Science, chief science specialist,
E.E. Belova2, Grand Ph. D in Veterinary Science, Head of the laboratory diagnostics department,
S.V. Mukaseev1, Ph. D in Veterinary Science, the veterinarian (mukaseev@skiff-pharm.ru),
D.V. Beloglazov1, PhD in Biology Science, the veterinarian (beloglazovdv@mail.ru).
1 LLC «RPC «SKiFF» (ap. 204, fl. 2, build. 3, h. 20, Nauchny pr., Moscow, RF, 117246).
2 Veterinary Clinic «BIO-VET» (build. 1, h. 21, Bolotnikovskaya str., Moscow, RF, 117303).
The efficacy and safety of the bi-hormonal contraceptive drug SEX BARRIER for female cats used for over two years (from June 2016 till November 2018) has been studied.
Materials and methods
The drug dosage and its application regimens (for interrupting estrus and for preventing estrus), recommended by the instruction, have been used. During the entire study the cats were constantly monitored for the signs of estrus. From time to time (once every two months) a full clinical check-up of the animals was conducted, ultrasound investigation of the reproductive organs was performed together with cytological examination of the vaginal smear, clinical and biochemical blood tests, and also the level of sex hormones was determined.
Results
A steady suppression of all signs of estrous behavior was observed in female cats receiving the drug, which correlated with the absence of estrus cell markers in vaginal smears, as well as basal levels of estradiol and progesterone in animals throughout the entire study period, which clearly confirms the high efficacy of the drug. The absence of pathological changes in the structure of the ovaries and uterus according to the results of clinical examinations and ultrasonography of the pelvic organs, the stability of the main blood parameters while maintaining their compliance with the physiological norm throughout the entire study, as well as rapid (within 3...4 weeks after discontinuation of months long use of the drug) restoration of the sexual cycle serve as a convincing proof of the safety of a long-term use of the bi-hormonal oral drug for correction of sexual function in female cats.
Key words: efficacy, safety, SEX BARRIER, female cats, bi-hormonal contraceptive drug, long-term use.
Abbreviations: ACM – acetomepregenol, BB –blood biochemistry, HCD – hormonal contraceptive drugs, AS – active substance, ELISA – enzyme-linked immunosorbent assay, LH – luteinizing hormone, SDA – small domestic animals; CBC – complete blood count, US – ultrasound investigation.
Introduction
Correction of sexual function in domestic animals, in particular, in female cats and dogs, remains an important veterinary problem as of today. One of the main practical tasks during the studies on regulation of sexual function in animals kept at home is to suppress the manifestations of estrus, which cause a lot of trouble to the cats’ owners. There are two alternative approaches to solving this problem: surgical (spaying) and conservative method, involving the use of HCD. Each of these methods of SDA contraception has both supporters and opponents in the veterinary community. At the same time, the main disadvantages of the surgical contraception method are the irreversible result of the surgery, its invasive nature, a certain risk of death and complications during the postoperative period, including the development of the ovarian remnant syndrome [1, 2]. The main claims of the opponents of the conservative contraception with HCD, represented mainly by gestagen-containing drugs, relate to the possible consequences of a shift in the hormonal status, manifesting in the occurrence of side effects typical for some gestagens [3].
In this regard, it should be noted that the arguments of modern opponents against the use of HCD for the correction of sexual function in SDA are based mainly on outdated information related to the practice of using mono-hormonal drugs of this type in veterinary medicine. Mono-hormonal contraceptives have been used in the world veterinary practice for over 50 years. For a long time, mainly synthetic modifications of the natural hormone progesterone (megestrol acetate and medroxyprogesterone acetate) were used as AS [4]. At the same time, the common disadvantage of the above-specified compounds, which have been repeatedly criticized by experts, is the need to use high doses of gestagen, which are unsafe for the animal's body due to the possibility of side effects, including a complex of cystic endometrial hyperplasia and pyometra [5], and breast tumors [6, 7].
In this regard, it should be noted that the arguments of modern opponents against the use of HCD for the correction of sexual function in SDA are based mainly on outdated information related to the practice of using mono-hormonal drugs of this type in veterinary medicine. Mono-hormonal contraceptives have been used in the world veterinary practice for over 50 years.
For a long time, mainly synthetic modifications of the natural hormone progesterone (megestrol acetate and medroxyprogesterone acetate) were used as AS [4]. At the same time, the common disadvantage of the above-specified compounds, which have been repeatedly criticized by experts, is the need to use high doses of gestagen, which are unsafe for the animal's body due to the possibility of side effects, including a complex of cystic endometrial hyperplasia and pyometra [5], and breast tumors [6, 7]. In this regard, one of the main tasks of specialists working in the field of contraception during the recent years has been finding a way to reduce the doses of gestagen in HCD. This problem was successfully solved by domestic researchers. Thus, as a result of the search for new AS for gestagen-containing HCD, attributable to the effort of domestic specialists, such synthetic analogues of progesterone as ACM and its complex esters have been synthesized and implemented in the veterinary practice [8... 10]. By showing a high activity, they could be used in a significantly lower dose than their predecessors. However, the most significant step forward in addressing the issues related to improving the efficacy and safety of HCD for regulating estrus in SDA was the proposal to use bi-hormonal compositions for this purpose, where gestagen is presented in combination with estrogen. The prototypes for the creation of veterinary drugs of this type were some medical analogues prescribed for hormonal contraception in women [11... 12], in which the combination of gestagen and estrogen allowed to reduce the therapeutic dosage of gestagen tenfold without the loss of efficacy.
Over the past 20 years, domestic experts have proposed a variety of gestagen-estrogen compositions for regulating estrus in SDA [13... 18], etc., which are based on the idea of bringing the component composition of the two most important sex hormones closer to the natural one, thereby providing a milder effect with a minimal risk of adverse reactions. The practical result of these studies was the development of a number of veterinary drugs that have no analogues in the world. Currently, at the territory of Russia, oral bi-hormonal products for female cats and dogs based on a combination of ACM complex ether and ethinyl estradiol are registered and allowed for use in the veterinary practice: SEX BARRIER in tablets and drops (LLC Research and Production Company SKiFF) containing mepregenol acetate, water-soluble; Gestrenol in drops and tablets containing mepregenol propionate, KontrSex Neo in tablets and drops containing acetobumedon (LLC Research and Innovation Company Astrapharm) as a gestagenic component [19].
Objective of the study
Taking into account the ambiguous attitude of the veterinary community to the use of HCD on the one hand, and the possibility to apply new knowledge and modern approaches in solving this issue on the other hand, it seemed appropriate to conduct a comprehensive experimental study of the effect of a bi-hormonal contraceptive drug on the animal's body under different schemes of the longterm use, which was the objective of this work.
Materials and methods
The drug. The drug SEX BARRIER (drops for female cats) was used as a test drug, which was constantly applied to animals for 2 years in accordance with the Instruction on use [20].
The active pharmacological ingredients of the drug SEX BARRIER are mepregenol acetate watersoluble and ethinyl estradiol (in the ratio of 100:1); 1 ml of the drug contains 1 mg of water-soluble mepregenol acetate and 0.01 mg of ethinyl estradiol. According to the degree of impact on the body, the drug belongs to low-hazard substances (hazard class IV according to GOST 12.1.007-76) [20].
Criteria of animal enrollment and their housing conditions. The effect on the body of female cats of the bi-hormonal contraceptive drug SEX BARRIER was studied during the period from May 2016 till November 2018 in the in-hospital settings of the veterinary clinic BIO-VET (Moscow) under the guidance of Doctor of Veterinary Sciences E. E. Belova.
Ten clinically healthy, vaccinated mongrel cats aged 1 to 2 years old, weighing 2.8...3.2 kg, with the signs of sexual cyclicity were enrolled in the experiment. The animals were taken from a shelter for homeless animals in the Moscow region.
All female cats were subjected to a clinical investigation prior to the experiment start, which included physical examination, determination of the frequency of respiratory movements, heart rate, and thermometry. The doctor registered the body weight, fatness of the animal, condition of its skin and fur, ear shells, teeth and oral mucosa; the doctor conducted an examination of the external genitals, performed palpation of the liver and mammary glands. Received data were entered in the individual registration cards. Before the experiment, all animals received treatment against ectoparasites and helminths, after which they were quarantined for 1...3 months (depending on when they were included in the study).
The quarantine and subsequent experiment were conducted in the in-hospital settings with artificial lighting for at least 10 hours a day and controlled microclimate. The animals were kept in individual cages 91 x 57 x 78 cm in size. They were fed twice a day with a complete industrial ration Hill's Science Plan™ Feline Adult Indoor Cat Chicken in accordance with the manufacturer's recommendations. Drinking was ad libitum with tap water.
All animals were divided into two groups: experimental and control, with 5 animals in each group. In order to form the most homogeneous groups, the animals were distributed into the groups according to the body weight, age and type of the body composition.
Design of the experiment, complex of the studied parameters and periodicity of their assessment. The study included 2 stages.
Stage 1 of the study. During the quarantine period, both groups of female cats showed the signs of estrus. In accordance with the plan of the experiment, the animals from the experimental group on Day 1 of the estrus were given the drug SEX BARRIER according to the regimen for interrupting estrus in compliance with the Instruction on use (4 drops once a day, for 3...5 days). Female cats from the control group received the solvent for SEX BARRIER (olive oil) in the same doses as experimental animals within 5 days from the start of estrus. In 10 days after the disappearance of the estrus signs, female cats from the experimental group were switched to the regimen delaying estrus (4 drops once every 14 days) for the next 12 months. Female cats from the control group were given olive oil via the same regimen.
In order to assess the timing of recovery of sexual cyclicity, the drug was canceled after 12 months of continuous intake of SEX BARRIER drops used to delay estrus in female cats from the experimental group. At the same time, female cats from the control group stopped receiving the solvent for the drug SEX BARRIER.
Against the background of drug withdrawal the sexual cycle was restored fairly synchronously in animals from the experimental group, approximately in 4 weeks (with a slight individual difference in time), which manifested as appearance of the signs of estrous behavior.
After restoration of the sexual cycle, administration of SEX BARRIER was resumed in female cats from the experimental group according to the regimen used in the first part of the experiment: at first once to interrupt estrus, and in 10 days after the disappearance of the estrous signs – according to the regimen for estrus prevention for 12 months. Female cats from the control group, as before, received olive oil in accordance with the above described regimens when their estrus began.
In order to assess the effect of a long-term use of the bi-hormonal contraceptive drug SEX BARRIER on the physiological systems of the body, the following examinations were performed every two months during the experiment: assessment of the condition of the skin and fur of the animal, ear shells, teeth and oral mucosa; examination of external genitals; liver and breast palpation; thermometry; determination of the frequency of respiratory movements and heart contractions. In addition, blood was taken for CBC and BB, as well as for determining the content of estradiol and progesterone in the serum; cytological examination of vaginal smears was performed as well as ultrasound of the uterus and ovaries. The general study scheme is demonstrated in tables 1 and 2.
| 1.Design of an experiment to study effect of the bi-hormonal contraceptive drug SEX BARRIER on the cats, stage 1 | ||||||||||||||
|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|
| Month from the experiment start | ||||||||||||||
| 2016 | 2017 | |||||||||||||
| 1th (June) |
2th (July) |
3th (August) |
4th (Sept) |
5th (Oct) |
6th (Nov) |
7th (Dec) |
8th (Jan) |
9th (Feb) |
10th (March) |
11th (Apr) |
12th (May) |
13th (June) |
14th (July) |
15th (Aug) |
| Interrupting estrus | Delaying estrus | |||||||||||||
| Quarantine | ||||||||||||||
Note.* – There were the monitoring of the condition of cats in these months of experiment , it includes the determination of content of estradiol and progesterone in the blood; cytological examination and ultrasound study.
| 2.Design of an experiment to study effect of the bi-hormonal contraceptive drug SEX BARRIER on the cats, stage 2 | ||||||||||||||
|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|
| Month from the experiment start | ||||||||||||||
| 2017 | 2018 | |||||||||||||
| 16th (Sept) |
17th (Oct) |
18th (Nov) |
19th (Dec) |
20th (Jan) |
21th (Feb) |
22th (March) |
23th (Aug) |
24th (May) |
25th (June) |
26th (July) |
27th Aug) |
28th (Sept) |
29th (Oct) |
30th (Dec) |
| Interrupting estrus | Delaying estrus | |||||||||||||
Note.* – There were the monitoring of the condition of cats in these months of experiment , it includes
cat’s examination, the determination of content of estradiol and progesterone in the blood; vaginal
cytology
** – CBC, BB
Blood tests. CBC and of female cats from the experimental and control groups were analyzed in the laboratory of the veterinary clinic BIO-VET. For CBC, blood was drawn from the vein in the morning, before feeding, in a vacuum tube with K3-EDTA in the amount of 1.0 ... 1.5 ml and examined on an automatic hematological analyzer HESKA Element HT5 (USA) using HESKA reagents (USA). The following parameters were determined: hematocrit, hemoglobin, red blood cells, white blood cells, platelets.
Blood for CBC was drawn from the vein in the morning, before feeding, in a vacuum tube with a coagulation activator in the amount of 1.5 ... 2 ml. The serum was separated on a laboratory centrifuge CLMN-R10-01-Elecon-M (Russia) at 2700 min for 3...5 minutes and then examined on the automatic biochemical analyzer Super Z (China) using Randox Laboratories reagents (Great Britain). The following analytes were determined: total protein, urea, creatinine, cholesterol, triglycerides, glucose.
The content of estradiol and progesterone in the blood serum was determined in the veterinary laboratory and diagnostic center Neovet (Moscow) via ELISA in semi-automatic mode using kits for ELISA (Hema Medica Ltd., Russia).
Cytological analysis and ultrasound. Vaginal smears were taken using a urogenital probe moistened with saline. Smears were subjected to cytological analysis after their staining using a kit Leucodif 200 (LDF 200), (Erba Lachema, Czech Republic).
A veterinary ultrasound scanner Cysca CD II (China) with a 5 MHz linear sensor was used for the ultrasound of the uterus and ovaries. The study evaluated the size of the ovaries and the body of the uterus, as well as their structure. The obtained data were statistically processed via BioStat 3.03 software.
Results and discussion
Clinical examination. During the entire experiment, no deviations from the physiological norm were registered in the experimental and control groups of animals during physical and instrumental examinations.
The body weight during enrollment in the experiment (June 2016) was within the range of 2.8...3.2 kg. According to the results of the second clinical study (August 2016), the body weight of animals in both groups increased slightly compared to the baseline and constituted on average 2.9...3.8 kg, which is highly likely due to forced hypodynamia.
Monitoring the behavioral signs of estrus. Female cats from the control group during the entire study periodically spontaneously became in heat, which manifested as characteristic clinical signs such as vocalization, anxiety, body friction against the cell walls, decreased appetite, adoption of a characteristic pose for mating, etc. Similar signs were observed in cats of the experimental group before the start of the drug intake, as well as after the restoration of their sexual cycle between stages 1 and 2 of the experiment. Based on these signs, each animal from the experimental group was orally administered a bi-hormonal drug SEX BARRIER according to the regimen for interrupting estrus on the same or the next day after the beginning of estrus. Within 3...5 days of the drug administration, the sexual activity of female cats significantly decreased; by the end of the course, the listed behavioral signs completely disappeared, whereas in control animals, the period of estrus on average lasted 7 ... 15 days. During the use of the drug according to the regimen for delaying estrus (from September 2016 till August 2017 and from September 2017 till November 2018), none of the female cats from the experimental group demonstrated estrous behavior. Female cats from the control group throughout the entire study period became in heat with an average frequency of once every three months.
Ultrasound of the uterus and the ovaries. Baseline ultrasound of the uterus and ovaries in June 2016 revealed the normal size and structure of these organs in all female cats included in the study, which indicated that they had no reproductive organs pathology before the experiment.
During ultrasonography of the pelvic organs at Month 3 of the experiment (August 2016), during the use of SEX BARRIER according to the regimen for interrupting estrus, a slight increase in the uterus body diameter was detected in all female cats from the experimental group without changes in the structure of the organ. However, according to the ultrasound of the uterus, conducted at Month 7 of the experiment (December 2016), all female cats in the experimental group had normal size of the organ, which did not change until the end of the study, although the experimental animals after detected deviation in the size of the uterus at Month 3 continued to constantly receive the drug according to the regimen for delaying estrus. On this basis, detected increase in the diameter of the uterus was interpreted as a short-term reaction of the endometrium to the first administration of a bihormonal contraceptive drug according to the regimen for interrupting estrus.
Ultrasound of the ovaries, also conducted throughout the entire experiment, did not reveal any pathological changes in the structure of these organs in any female cat. This made it possible to rule out polycystosis and ovarian tumor processes.
Thus, ultrasound of the reproductive sphere did not reveal any negative effect of the drug on the uterus and ovaries of female cats in during its constant use for 2 years
Vaginal cytology. During the study, vaginal cytology was evaluated during the drug use. Microscopy results of vaginal smears in the experimental animals indicated that they had no cytological signs of estrus during the entire experiment and these data were fully consistent with the data collected when monitoring their behavior during the use of bi-hormonal drug SEX BARRIER according to the regimen for interrupting and delaying estrus.
Cytological pattern of vaginal smears in the control group was represented by a different ratio of non-nuclear and nuclear cells of the surface epithelial layer. This indicated that the cats were in different stages of the estrous cycle. The onset of estrus and pronounced manifestations of estrus in animals of the control group were registered once in every three months.
Thus, the results of a cytological investigation of vaginal smears obtained from cats of the experimental group during the use of bi-hormonal contraceptive drug SEX BARRIER for interrupting and delaying estrus (characterized by the absence of cellular signs of the estrous phase of the sexual cycle) correlated with the absence of behavioral signs of the estrus. In the control group, vaginal cytology indicated that the animals were at different stages of the sexual cycle.
Monitoring of the behavior of female cats from the experimental group which did not show the signs of estrus, and correlating results of vaginal сytology indicated with sufficient certainty that the cats who constantly received SEX BARRIER did not have the estrus stage.
In female cats from the experimental and control groups, the cytological pattern of vaginal smears during the entire observation period did not contain red blood cells, bacteria and fungi, which indicates the absence of an inflammatory process in the genital tract [19].
Determination of sexual hormones. The concentration of estradiol and progesterone was determined.
Estradiol. The results of studying changes in estradiol levels in female cats from the experimental and control groups over time are shown in figure 1.
Concentration of estradiol in female cats from the experimental group during the entire period of the drug use according to the regimen for delaying estrus corresponded to the level characteristic of anestrus (less than 20 pg/ml). This result is completely consistent with the absence of estrous behavior and the results of vaginal cytology.
The data of monitoring the level of estradiol in female cats from the control group during the study fully correspond with the idea of natural fluctuations in concentration of this sex steroid. Thus, several spikes of estradiol levels were recorded in the range of values characteristic of estrus (20 ... 60 pg/ml), consistent with the periodic heat of control animals and the presence of estrus signs in vaginal smears
Figure 1
- Control
- Experiment
Progesterone. In the sexual cycle of female cats in anestrus, proestrus and estrus phases before ovulation, the level of progesterone remains at the basal level (less than 2 ng/ml) [21]. During ovulation, the concentration of progesterone increases and usually is within the range of 2 ... 10 ng/ml. In case of fertilization of the egg and pregnancy, the level of progesterone continues to increase and remains high throughout the gestation period [21, 23]. It is known that ovulation following the release of LH in female cats is mainly inducible [21, 22], where the stimulating factor is contact with the male. Taking into account the fact that all female cats in the study were in the inhospital premises where there were no cats, and the process of spontaneous ovulation is a rare phenomenon, it should be expected that in the control animals progesterone during the entire experiment will be at a level close to basal.
As for the experimental animals that were in the same conditions as the control ones, if a long-term administration of a gestagen-containing contraceptive does not lead to any unexpected changes in the hormonal status of the animal, monitoring of their progesterone should have provided approximately the same results as in control female cats. The results of monitoring progesterone levels in two groups of female cats which confirm this conclusion are shown in figure 2.
Complete blood count and blood biochemistry. Along with a detailed study of the function of the reproductive organs, the morphological and biochemical parameters of the cats’ blood were evaluated during the entire period of the experiment
Taking into account that monitored morphological and biochemical blood parameters in female cats from the experimental and control groups were within the normal physiological limits, the frequency of their monitoring starting from the second half of 2017 was adjusted to once in 3...5 months.
Figure 2
- Control
- Experiment
Morphological blood parameters. CBC results of female cats from experimental and control groups during the use of the drug SEX BARRIER for delaying estrus demonstrated that the concentration of hemoglobin, the number of red blood cells, white blood cells and platelets did not significantly change and maintained within the control values (table 3). This indicates the safety of a long-term use of the drug in relation to possible adverse effects on blood morphology.
Biochemistry parameters. Parameters determined by CBC included total protein, creatinine and urea indicating the status of protein metabolism; cholesterol and triglycerides reflecting the state of the fat metabolism; glucose as an indicator of the state of carbohydrate metabolism. As follows from the data shown in table 4, all biochemical parameters of protein, lipid and carbohydrate metabolism determined during the experiment in female cats from both groups maintained within the normal physiological limits. However, no significant differences between experimental and control animals were detected. Based on the obtained results, it can be concluded that the long-term use of a bihormonal contraceptive drug according to the regimens proposed in the instructions for terminating and delaying estrus does not lead to significant changes in the main links of metabolism in the female cat bodies. This indicates that the long-term use of the drug does not negatively affect the metabolism of macronutrients.
| The results of the complete blood count test of the cats during experiment | ||||||||
|---|---|---|---|---|---|---|---|---|
| Date of experiment | Hemoglobin, g/l | Erythrocytes, 1012/l | Leukocytes, 109/l | Platelets, 109/ | ||||
| Exp | Control | Exp | Control | Exp | Control | Exp | Control | |
| Reference interval of the veterinary laboratory AssistantVet” | ||||||||
| The results of the biosheical blood test of the cats during experiment | ||||||||||||
|---|---|---|---|---|---|---|---|---|---|---|---|---|
| Date of experiment | Total protein, g/l | Urea, mmol/l | Creatinine, μmol/L | Cholesterol, mmol/l | Triglycerides, mmol/l | Glucose, mmol/l | ||||||
| Exp | Control | Exp | Control | Exp | Control | Exp | Control | Exp | Control | Exp | Control | |
| Reference interval of the veterinary laboratory AssistantVet” | ||||||||||||
Conclusion
Efficacy and safety of the bi-hormonal contraceptive SEX BARRIER for female cats, which was used for over two years (from June 2016 till November 2018), according to the Instructions developed by the manufacturer, has been investigated.
The efficacy of the drug is convincingly confirmed by a set of the following experimental data obtained during this study:
- the use of the drug according to the regimen for interrupting estrus for 3 days...5 days completely eliminated behavioral manifestations of estrus in clinically healthy female cats;
- during 24 months of the drug use according to the regimen for delaying estrus (from September 2016 till August 2017 and from November 2017 till October 2018), no case of estrous behavior (heat) was registered in animals receiving the drug;
- concentration of estradiol in the plasma of cats receiving SEX BARRIER did not change throughout the entire study period and was constantly at the basal level typical for anestral phase of the sexual cycle;
- the cytological picture of vaginal smears obtained from the experimental animals throughout the entire experiment did not contain estrus cell markers.
The safety of a long-term use of the bi-hormonal contraceptive drug for the body of cats can be clearly concluded from the following results of our experiment:
- during the entire study period, no deviations from the physiological norm were registered in female cats receiving SEX BARRIER during physical examination and instrumental tests;
- during the entire period of monitoring, no pathological changes in the structure of the ovaries and uterus were detected in animals receiving the drug during ultrasonography of the pelvic organs;
- according to the CBC of female cats from the experimental group, the concentration of hemoglobin, red blood cell count, white blood cell count and platelet count have not changed during the drug use; the values of all examined parameters were consistent with physiological norm and did not show reliable differences from the similar parameters in the control animals;
- according to the CBC data, markers of protein, lipid and carbohydrate metabolism did not change for 2 years of the study and were within the normal physiological limits;
- at Week 4 after discontinuation of the drug in all experimental female cats (with a slight individual time difference), the sexual cycle was restored and behavioral manifestations of estrus were registered, which fully confirms the terms specified in the Instructions on the drug use.
Thus, our study confirmed high efficacy of the bi-hormonal contraceptive in various regimens of its administration and did not reveal any early (occurring prior to Month 6), or late (appearing after 6 months of the drug use) complications of the drug use from the genital area of the animal body, as well as metabolic disorders.
In November 2018, the part of the planned experiment described in this article was completed. Considering the fact that already in 3 weeks after the drug discontinuation female cats from the experimental group started to show signs of estrous behavior, indicating the resumed functioning of the hypothalamus-pituitary-ovary axis and the restart of sexual cyclicity, the next stage of the experiment has been started. Its objective is to comprehensively assess the degree of restoration of the reproductive function in female cats in 2...3 months after SEX BARRIER discontinuation. In this regard, further it is planned to breed animals, monitor the progress of pregnancy and monitor the physiological status of female cats and their offspring.
Conflict of interests
The manufacturer of the drug Sex Barrier® for veterinary use and the sponsor of this study is LLC Research and Production Company SKiFF. The decision to publish the results of scientific work belongs to the developer LLC Research and Production Company SKiFF.
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