LLC «RDE «Astrapharm» (Chief science specialist)
Russian Federation
LLC «AG «Aspect» (Veterinarian)
LLC «RDE «Astrapharm» (Leading veterinarian)
Russian Federation
LLC AG Aspect (Scientific consultant)
LLC «RDE «Astrapharm» (Scientific consultant)
Russian Federation
GRNTI 68.41 Ветеринария
This study was devoted to an urgent problem in the field of veterinary medicine, namely, the safety of long-term use of a monohormonal drug based on megestrol acetate for cats on the example of Sexcontrol (drops). It was found that as a result of the use of Sex Control (drops) in cats, according to the instructions in doses of 2.5 mg per cat per week for 18 months, there is a steady blockage of reproductive function. After discontinuation of the drug for 24 months, there were no signs of resumption of sexual cyclicity. It is likely that Sexcontrol causes profound disturbances in the centers of regulation of sexual function of cats (in the neuroendocrine axis of the hypothalamus-pituitary-gonads), which can be interpreted as severe ovarian dysfunction. It is possible that other centers of neuroendocrine regulation of the body are also affected, which is confirmed by the phenomena observed in experimental animals such as apathy (decreased motor activity, refusal to play, refusal to interact with other cats), prolonged molting, symmetrical hormone-associated alopecia. The data obtained in this work, together with the information provided from numerous other scientific sources, indicate the need for additional studies to clarify the instructions of the group of monohormonal drugs based on MA in terms of clarifying the maximum possible duration of their use without prejudice to the reproductive health of animals (18 months), as well as with respect to the definition of opportunities and deadlines for conducting a repeat course.
cats, estrus, megestrol acetate, glucocorticoid, progesterone, corticosteroid, hypothalamus, cortisol, adrenal glands, pituitary gland, estrus, instructions, safety, infertility, hypothalamus, pituitary gland, ovaries
1. Avdanina, D.A. Gormonal'naya kontracepciya dlya domashnih zhivotnyh / D.A. Avdanina, S.V. Lihotina, V.A. Andryushina // Veterinar. - 2006. - № 1. - S. 18-19.
2. Grinenko, G.S. Izuchenie novyh progestagennyh preparatov dlya regulyacii polovoy funkcii sel'skohozyaystvennyh zhivotnyh / Grinenko G.S., Klinskiy Yu.D., Kadatskiy G.M., Zhirkov G.F., Panfilova L.F. // Gormonal'noe zhivotnovodstvo. - 1977. - № 3. - S. 146-161.
3. Zeynalov, O.A. Bezopasnoe i effektivnoe primenenie oral'nogo bigormonal'nogo preparata dlya dlitel'noy regulyacii reproduktivnoy funkcii u koshek v usloviyah domashnego soderzhaniya / O.A. Zeynalov, E.E. Belova, S.V. Mukaseev, D.V. Beloglazov // Rossiyskiy veterinarnyy zhurnal. - 2020. - № 1. - S. 14-20.
4. Zeynalov, O.A. Vosstanovlenie reproduktivnoy funkcii koshek posle dlitel'nogo primeneniya oral'nogo bigormonal'nogo preparata SEKS BAR'ER®/ O.A. Zeynalov, E.E. Belova, S.V. Mukaseev, D.V. Beloglazov // Veterinariya. - 2021. - №3. - S. 43-49.
5. Zeynalov, O.A. Issledovanie effektivnosti i bezopasnosti bigormonal'nogo kontraceptivnogo preparata v dolgosrochnom eksperimente / O.A. Zeynalov, E.E. Belova, S.V. Mukaseev, D.V. Beloglazov // Rossiyskiy veterinarnyy zhurnal. - 2019. - №3. - S. 12-20.
6. Zeynalov, O.A. Novye gestagennye preparaty dlya veterinarii / O.A. Zeynalov, V.A. Andryushina, D.A. Avdanina // Rossiyskiy veterinarnyy zhurnal. MDZh. - 2005. - № 1. - S. 16-19.
7. Zeynalov, O.A. Sravnitel'naya harakteristika monogormonal'nyh i bigormonal'nyh gestagen-soderzhaschih preparatov dlya podavleniya povedencheskih proyavleniy polovoy ohoty u koshek / O.A. Zeynalov, T.S. Savinova, V.A. Andryushina // Rossiyskiy veterinarnyy zhurnal. - 2017. - № 2. - S. 33-35.
8. Zeynalov, O.A. Ekspress-ocenka klinicheskogo statusa i metabolicheskogo profilya koshek pri raznyh metodah regulyacii polovoy funkcii / O.A. Zeynalov, E.E. Belova, S.V. Mukaseev, D.V. Beloglazov // Sovremennaya veterinarnaya medicina. - 2019. -№5. - S. 20-23.
9. Zeynalov, O.A. Sintez i biologicheskaya aktivnost' sinteticheskih proizvodnyh 17α-gidroksiprogesterona / O.A. Zeynalov, V.V. Yaderec, T.S. Stycenko, M.A. Petrosyan, V.A. Andryushina // Himiko-farmacevticheskiy zhurnal. - 2012. - №4. - S.7-10.
10. Instrukciya po veterinarnomu primeneniyu lekarstvennogo preparata SEKS BAR'ER® kapli dlya koshek [Elektronnyy resurshttps://galen.vetrf.ru/files/40f7841e-cdca-417d-a482-1fafad23acea (data obrascheniya: 28.03.2023).
11. Instrukciya po veterinarnomu primeneniyu lekarstvennogo preparata SEKS BAR'ER® kapli dlya koshek [Elektronnyy resurs - https:// galen.vetrf.ru/files/40f7841e-cdca - 417d-a482 -1fafad23acea (data obrascheniya: 28.03.2023).
12. Instrukciya po veterinarnomu primeneniyu lekarstvennogo preparata MÉGÉPIL® Chat [Elektronnyy resurs]. - URL: https://www.med-vet.fr/medicament-megepil-chat-p1083 (data obrascheniya: 09.08.2023).
13. Instrukciya po veterinarnomu primeneniyu lekarstvennogo preparata Pillkan 5 [Elektronnyy resurs]. - URL: https://galen.vetrf.ru/#/registry/pharm/registry?page=1&f_name=Pillkan%205,%2020 (data obrascheniya: 28.03.2023).
14. Instrukciya po veterinarnomu primeneniyu lekarstvennogo preparata SeksKontrol' kapli [Elektronnyy resurs]. - URL: https://galen.vetrf.ru/files/instruction/1c46943c-6267-4785-bc0b-0307be92b9f4 (data obrascheniya: 28.03.2023).
15. Instrukciya po veterinarnomu primeneniyu lekarstvennogo preparata Stop-intim® kapli [Elektronnyy resurs]. - URL: https://galen.vetrf.ru/#/registry/pharm/registry?page=1&f_name=Stop-intim®%20kapli.
16. Instrukciya po veterinarnomu primeneniyu lekarstvennogo preparata EKS-5 [Elektronnyy resurs]. - URL: https://galen.vetrf.ru/#/registry/pharm/registry?page=1&f_name=EKS®-5%20EKS®-7,5 (data obrascheniya: 28.03.2023).
17. Kareva, E.N. Vliyanie struktury sinteticheskih gestagenov na ih svyazyvayuschie svoystva s receptorami progesterona endometriya / E.N. Kareva, G.S. Grinenko, N.D. Gasparyan, E.V. Ovchinnikova, O.S. Gorenkova // Eksperimental'naya i klinicheskaya farmakologiya. - 2006. - №4. - S. 36-38.
18. Lancova, V.B. Sindrom reminantnogo yaichnika u koshek - otdalennoe neblagopriyatnoe posledstvie hirurgicheskoy kastracii / V.B. Lancova // Rossiyskiy veterinarnyy zhurnal. - 2018. - №4. - S. 6-8.
19. Lorikyan A.G. Biohimicheskie osobennosti sekrecii kortizola i degidroepiandrosteron-sul'fata u bol'nyh shizofreniey: diss. kand.med.nauk 03.01.04: zaschischena 12.10.15: utv. 12.10.15 / Lorikyan Ani Gagikovna. M., 2015. - 124 s.
20. Novye sinteticheskie analogi progesterona: ot poiska deystvuyuschego nachala (molekuly) do klinicheskogo primeneniya (obzor sobstvennyh issledovaniy) /O.A. Zeynalov, V.A. Andryushina, V.V. Yaderec // Himiko-farmacevticheskiy zhurnal. - 2022. - T. 56. - № 2. - S. 3-12.
21. Nuralieva N.F., Yukina M.Yu., Troshina E.A. Vtorichnaya nadpochechnikovaya nedostatochnost' - novye aspekty diagnostiki i lecheniya. - Doktor.Ru. - 2021. - № 20(2). - S. 51-59. DOI:https://doi.org/10.31550/1727-2378-2021-20-2-51-59.
22. Osobennosti sekrecii kortizola i degidroepiandrosteron - sul'fata u bol'nyh s pervym psihoticheskim epizodom / L.N. Gorobec, A.G. Lorikyan, N.M. Kutuzova // Social'naya i klinicheskaya psihiatriya. - 2014. - T. 24. - № 2. - S. 5-10.
23. Agudelo, C.F. Cystic endometrial hyperplasia-pyometra complex in cats. A review. / C.F. Agudelo // Vet Q. - 2005. - No. 27. - pp. 173-182.
24. Barakat, R.R. Principles and Practice of Gynecologic Oncology / R.R. Barakat, M. Markman, M. Randall. - Lippincott Williams & Wilkins, 2009. - pp. 447-449.
25. Canetta, R. Megestrol acetate / R. Canetta, S. Florentine, H. Hunter, Lenaz L. // Cancer Treatment Reviews. - September 1983. No. 10 (3). - pp. 141-157.
26. Chastain, C.B. Adrenocortical suppression in cats given megestrol acetate / Chastain C.B., Graham C.L., Nichols C.E. // Am J Vet Res. - 1981 Dec. - No. 42(12). - pp. 2029-2035.
27. Concannon. P.W. Current and proposed methods for contraception and termination of pregnancy in dogs and cats / P.W. Concannon, V.N. Meyers-Wallen // J Am Vet Med Assoc. -1991 Apr. - Vol. 1. - No. 198(7). - pp. 1214-1225.
28. Cuerda, C. Treatment with nandrolone decanoate and megestrol acetate in HIV-infected men / C. Cuerda, A. Zugasti, I. Bretón, M. Camblor, P. Miralles, P. García // Nutrition in Clinical Practice. - February 2005. - No. 20 (1). - pp. 93-97.
29. Delitala, A.P., Primary symptomatic adrenal insufficiency induced by megestrol acetate / A.P. Delitala, G. Fanciulli, M. Maioli, G. Piga, G. Delitala // Neth J Med. - 2013 Jan. - No. 71(1). - pp. 17-21. PMID: 23412818.
30. Demirel, M.A. Ovarian remnant syndrome and uterine stump pyometra in three queens / M.A. Demirel, D.B. Acar // J Feline Med Surg. - 2012. - No. 14(12). - pp. 913-918.
31. Enginler, S.O. The effects of progesterone hormone applications used for suppression of estrus on mammary glands in queens / S.O. Enginler, A. Senunver // Kafkas Universitesi Veteriner Fakultesi Dergisi. - 2011. - No. 17. - pp. 277-284.
32. Farrar, D.J. Megestrol acetate: promises and pitfalls / D.J. Farrar // AIDS Patient Care and STDs. - March 1999. - No. 13 (3). - pp. 149-152.
33. Fettman, M.J. Effects of neutering on bodyweight, metabolic rate and glucose tolerance of domestic cats / M.J. Fettman, C.A. Stanton, L.L. Banks, Hamar D.W., D.E. Johnson, R.L. Hegstad, S. Johnston // Res. Vet. Sci. - 1997. - No. 62. - pp. 131-136.
34. Geller, J. Megestrol acetate plus low-dose estrogen in the management of advanced prostatic carcinoma // The Urologic Clinics of North America. - February 1991. - No. 18 (1). - pp. 83-91.
35. Geller, J. Acute therapy with megestrol acetate decreases nuclear and cytosol androgen receptors in human BPH tissue. - Geller J., Albert J., Geller S. - The Prostate. - 1982. - No. 3 (1). - pp. 11-15.
36. Gosselin, Y. The use of megestrol acetate in some feline dermatological problems / Y. Gosselin, A. Chalifoux, M. Papageorges // Can Vet J. - 1981 Dec. - No. 22(12). - pp. 382-384. PMID: 7337916; PMCID: PMC1790016.
37. Hayden, D.W. Morphologic changes in the mammary gland of megestrol acetate treated and untreated cats: a retrospective study / D.W. Hayden, D.M. Barnes, K.H. Johnson // Vet Pathol. - 1989. - No. 26. - pp. 104-113.
38. Hayden D.W., Feline mammary hypertrophy/fibroadenoma complex: clinical and hormonal aspects / D.W. Hayden, S.D. Johnston, D.T. Kiang et al. // Am J Vet Res - 1981. - No. 42. - pp. 1699-1703.
39. Houdeshell, J.W. Megestrol acetate for control of estrus in the cat / J.W. Houdeshell P.W. Hennessey // Vet Med Small Anim Clin. - 1977 Jun. - No. 72(6). - pp. 1013-107. PMID: 586070.
40. Howell, M.P. Effects of genetically altered brain glucocorticoid receptor action on behavior and adrenal axis regulation in mice / M.P. Howell, L.J. Muglia // Front. Neuroendocrinol. - 2006. - Vol. 27. - No. 3. - pp. 275-284.
41. Kamstock, D.A. Cystic endometrial hyperplasia in cats: pathogenesis and implications for feline population control / D.A. Kamstock, T.J. Rosol // J Feline Med Surg. - 2008. - No. 10(5). - pp. 452-462.
42. Kutzler, M. Non-surgical methods of contraception and sterilization / M. Kutzler, A. Wood // Theriogenology. - 2006. - No. 66. - pp. 514-525.
43. Loprinzi, C.L. Phase III evaluation of 4 doses of megestrol acetate as therapy for patients with cancer anorexia and/or cachexia / C.L. Loprinzi, A.M. Bernath, D.J. Schaid, J.A. Malliard, L.M. Athmann, J.C. Michalak, et al. // Oncology. - October 1994. - 51 Suppl 1. - pp. 2-7.
44. Lucas, S.S. Pyometra in Dogs and Cats: Review of 103 cases / S.S. Lucas, A.L. Lima de Oliveira, J.E. Wallau // Revista da Faculdade de Zootecnia, Veterinaria e Agronomia Uruguaiana. - 2000. - No. 7. - pp. 99-103.
45. MacDougall, L.D. Mammary fibroadenomatous hyperplasia in a young cat attributed to treatment with megestrol acetate / L.D. MacDougall // Can Vet J. - 2003. - No. 44. - pp. 227-229.
46. Mansfield, P.D. The effects of megestrol acetate treatment on plasma glucose concentration and insulin response to glucose administration in cats / P.D. Mansfield, R.J. Kemppainen, J.L. Sartin // J Am Anim Hosp Assoc. - 1986. - No. 22. - pp. 515-518.
47. Megestrol acetate: product profile end position paper (Feb.2009) [Elektronnyy resurs]. - URL:http://stray-afp.org/wp-content/uploads/2012/07/Megestrol-Acetate-Product-Profile-and-Position-Paper.pdf (Data obrascheniya 09.08.2023).
48. Mehta, K. Megace Mystery: A Case of Central Adrenal Insufficiency [Elektronnyy resurs]. - URL:https://pubmed.ncbi.nlm.nih.gov/26770843/ (Data obrascheniya 20.08.2023).
49. Middleton, D.J. Suppression of cortisol responses to exogenous adrenocorticotrophic hormone, and the occurrence of side effects attributable to glucocorticoid excess, in cats during therapy with megestrol acetate and prednisolone / D.J. Middleton, A.D. Watson, C.J. Howe, I.D. Caterson // Can J Vet Res. - 1987 Jan. - No. 51(1). - pp. 60-65.
50. Nguyen, P.G. Effects of dietary fat and energy on body weight and composition after gonadectomy in cats / P.G. Nguyen, H.J. Dumon, B.S. Siliart, L.J. Martin, R. Sergheraert, V.C. Biourge // Am. J. Vet. Res. - 2004. - No. 65. - pp. 1708-1713.
51. O'Dair, H.A. Focal and generalized alopecia / O'Dair H.A., Foster A.P. // Vet Clin North Am Small Anim Pract. - 1995 Jul. - No. 25(4). - pp. 851-870.
52. Oen, E.O. The oral administration of megestrol acetate to postpone oestrus in cats / Oen E.O. // Nordisk Veterinaermedicin. - 1977. - No. 29. - pp. 287-291.
53. Peterson, M.E. Effects of megestrol acetate on glucose tolerance and growth hormone secretion in the cat / M.E. Peterson // Res Vet Sci. - 1987. - No. 42(3). - pp. 354-357.
54. Pukay, B.P. A hyperglycemia-glucosuria syndrome in cats following megestrol acetate therapy / B.P. Pukay // Can Vet J. - 1979. - No. 20. - pp. 117.
55. Reine, N.J. Cystic endometrial hyperplasia and pyometra in cats treated with megestrol acetate / N.J. Reine, E.C. Feldman, R.W. Nelson, et al. // J Am Vet Med Assoc. - 1987. - No. 191(3). - pp. 299-304.
56. Resume des caracteristiques du produit Megecat [Elektronnyy resurs]. - URL: https://www.ircp.anmv.anses.fr/rcp.aspx?NomMedicament=MEGECAT (data obrascheniya: 09.08.2023).
57. Romagnoli, S., Concannon, P. W. Clinical Use of Progestine in Bitches and Queens: A review. [Elektronnyy resurs]. - URL: https://www.ivis.org/library/recent-advances-small-animal-reproduction/clinical-use-of-progestins-bitches-and-queens-a (data obrascheniya: 28.03.2023).
58. Romatowski, J. Use of megestrol acetate in cats / J. Romatowski // Journal of the American Veterinary Medical Association. - 1989. - No. 194. - pp. 700-702.
59. Russians are world's biggest cat lovers [Elektronnyy resurs]. - URL: https://www.rbth.com/news/2017/04/11/russians-are-worlds-biggest-cat-lovers_739937 (data obrascheniya: 28.03.2023).
60. Schacter, L.P. Overview of hormonal therapy in advanced breast cancer / L.P. Schacter, M. Rozencweig, R. Canetta, S. Kelley, C. Nicaise, L. Smaldone // Seminars in Oncology. - December 1990. - No. 17 (6 Suppl 9). - pp. 38-46.
61. Schindler, A.E. Pharmacology of Progestogens / A.E. Schindler // Progestogens in Obstetrics and Gynecology. - 2015. - No. 4. - pp. 33-40.
62. Schindler AE, Campagnoli C, Druckmann R, Huber J, Pasqualini JR, Schweppe KW, Thijssen JH. Classification and pharmacology of progestins. Maturitas. 2008 Sep-Oct;61(1-2):171-80. doi:https://doi.org/10.1016/j.maturitas.2008.11.013. PMID: 19434889.
63. Schumacher, M. Rapid membrane effects of steroid hormones: an emerging concept in neuroendocrinology / M. Schumacher // Trends Neurosci. - 1990. - Vol. 13. - pp. 359-362.
64. Stubbs, W.P. Megestrol acetate-induced endometrial hyperplasia in cats / W.P. Stubbs, M.S. Bloomberg, S.L. Scruggs // Vet Pathol. - 1988. - No. 25(1). - pp. 45-51.
65. Tejani, S. Davis's Pocket Clinical Drug Reference / S. Tejani, C Sanoski // F.A. Davis. 16 March 2009. - pp. 167-186.
66. Tisell, L.E. Androgenic properties and adrenal depressant activity of megestrol acetate observed in castrated male rats / L.E. Tisell, H. Salander // Acta Endocrinologica. - February 1975. - 78 (2). - 316-324.
67. Tomlinson, M.J. Feline mammary carcinoma: a retrospective evaluation of 17 cases / M.J. Tomlinson, L. Barteaux, L.E. Ferns et al. // Can Vet J. - 1984. - No. 25. - pp, 435-439.
68. Willemse, P.H. A randomized comparison of megestrol acetate (MA) and medroxyprogesterone acetate (MPA) in patients with advanced breast cancer / P.H. Willemse, E. van der Ploeg, D.T. Sleijfer, T. Tjabbes, H. van Veelen // European Journal of Cancer. - March 1990. - No. 26 (3). - pp. 337-343.
69. Wirfs, M.J. The APRN's Complete Guide to Prescribing Pediatric Drug Therapy 2 / M.J. Wirfs. - Springer Publishing Company, 26 July 2017.
