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Theriogenology2016; 86(7); 1749-1756; doi: 10.1016/j.theriogenology.2016.05.041

Comparison of different regimens of estradiol benzoate treatments followed by long-acting progesterone to prepare noncycling mares as embryo recipients.

Abstract: The present study evaluated the influence of different regimens of estradiol benzoate (EB) treatments followed by a single dose of long-acting progesterone (LA P4) on plasma estrogen and P4 concentrations in noncyclic mares prepared as embryo recipients. Twenty-one anestrous mares were distributed into three groups (n = 7 mares per group), according to the EB dose received (single dose of 2.5 mg, total of 5 mg in decreasing doses, and total of 10 mg in decreasing doses), which was followed by a single administration of 1500 mg of LA P4 in all groups. Mares were reevaluated during the ovulatory phase and seven of them became part of the cyclic nontreated control group. Ultrasonography was performed to monitor endometrial edema, and blood samples were collected to measure estradiol (E2), estrogen conjugate (EC), and P4 by RIA. Maximum uterine edema was achieved 24 hours after administration of EB in all treated groups. Maximum E2 concentrations were observed 24 hours after the first EB injection in treated groups and there were no differences (P > 0.05) among treatments. Maximum EC concentration was observed 24 hours after the single EB injection in the 2.5-mg group, whereas in the 5- and 10-mg groups EC peaks were observed 48 hours after the first EB administration. Maximum P4 concentrations were detected 24 hours after LA P4 injection, although higher P4 concentrations were observed in the group treated with 2.5 mg of EB than in that treated with 10 mg of EB (P < 0.05). Because P4 concentrations were reduced after administration of high doses of EB, we also measured 17α-hydroxyprogesterone (17-OH-P) to test the hypothesis that high concentrations of EB would accelerate the conversion of P4 to 17-OH-P. However, 17-OH-P concentrations paralleled P4 profile in all groups, irrespective of EB doses. In summary, the three EB treatment regimens induced similar E2 peaks, although the observation of EC peaks 24 hours after E2 peaks in the 5- and 10-mg groups indicate that an excess of E2 was given, which was converted into EC to be inactivated. Administration of 10 mg of EB reduced P4 concentrations 24 hours after LA P4 was given. We demonstrated that the mechanism by which this reduction occurred was not by an increase in P4 metabolism to 17α-OH-P. In conclusion, the use of 2.5 mg of EB followed by 1500 mg of LA P4 appears to be a more appropriate regimen to treat noncyclic mares, although additional studies are needed to verify embryo survival with this treatment dose.
Publication Date: 2016-07-05 PubMed ID: 27494983DOI: 10.1016/j.theriogenology.2016.05.041Google Scholar: Lookup
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  • Journal Article

Summary

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This research investigates how varying doses of estradiol benzoate, followed by a long-acting progesterone, affect estrogen and progesterone levels in noncycling mares prepared to receive embryos. The study found similar estrogen peaks across all treatment regimens, but discovered that progesterone reductions when a high dose of estradiol benzoate is administered are not due to an increase in progesterone metabolism. The researchers conclude that the regimen of 2.5 mg of estradiol benzoate followed by 1500 mg of long-acting progesterone might be a suitable regimen to manage noncycling mares, although more studies are needed to ensure embryo survival.

Study Design and Participants

  • The study involved 21 mares in anestrus, or noncycling. They were divided into three groups of 7 each, based on the dose of estradiol benzoate administered. Each group subsequently received 1500 mg of long-acting progesterone.

Procedure and Measures

  • A single dose of 2.5 mg, decreasing doses amounting to 5 mg total, or decreasing doses amounting to 10 mg total of estradiol benzoate were administered. These doses were followed by a single application of 1500 mg of long-acting progesterone.
  • Mares were studied during the ovulatory period, with ultrasonography used to inspect endometrial edema. Blood tests were conducted to measure estradiol, estrogen conjugate, and progesterone levels.

Outcomes and Interpretation

  • Maximum uterine edema was observed 24 hours post-estradiol benzoate administration across all groups. Estrogen peaks were also found 24 hours after the first estradiol benzoate injection.
  • Maximum estrogen conjugate concentrations suggested that excess estradiol was converted to estrogen conjugate for deactivation. These peaks were observed 24 hours after estrogen peaks in the 5 mg and 10 mg groups.
  • The progesterone levels were highest 24 hours post-long-acting progesterone injection, with higher levels observed in the group treated with 2.5 mg of estradiol benzoate compared to the 10 mg group.
  • The study also disproved their hypothesis that higher estradiol benzoate concentrations might hasten conversion of progesterone to an inert form, 17α-hydroxyprogesterone.

Conclusion

  • The treatment regimen consisting of 2.5 mg of estradiol benzoate followed by 1500 mg of long-acting progesterone has been recommended as more suitable for noncycling mares. However, the potential impact on embryo survival requires further investigation.

Cite This Article

APA
Silva ES, Roser JF, Gomes AR, Fritsch SC, Pantoja JC, Oliveira-Filho JP, Meira C. (2016). Comparison of different regimens of estradiol benzoate treatments followed by long-acting progesterone to prepare noncycling mares as embryo recipients. Theriogenology, 86(7), 1749-1756. https://doi.org/10.1016/j.theriogenology.2016.05.041

Publication

ISSN: 1879-3231
NlmUniqueID: 0421510
Country: United States
Language: English
Volume: 86
Issue: 7
Pages: 1749-1756
PII: S0093-691X(16)30242-4

Researcher Affiliations

Silva, E S M
  • Department of Animal Reproduction and Veterinary Radiology, School of Veterinary Medicine and Animal Science, Universidade Estadual Paulista, Botucatu, São Paulo, Brazil. Electronic address: elisa_santanna@yahoo.com.br.
Roser, J F
  • Department of Animal Science, University of California, Davis, California, USA.
Gomes, A R C
  • Department of Animal Reproduction and Veterinary Radiology, School of Veterinary Medicine and Animal Science, Universidade Estadual Paulista, Botucatu, São Paulo, Brazil.
Fritsch, S C
  • Department of Animal Reproduction and Veterinary Radiology, School of Veterinary Medicine and Animal Science, Universidade Estadual Paulista, Botucatu, São Paulo, Brazil.
Pantoja, J C F
  • Department of Veterinary Hygiene and Public Health, School of Veterinary Medicine and Animal Science, Universidade Estadual Paulista, Botucatu, São Paulo, Brazil.
Oliveira-Filho, J P
  • Department of Veterinary Clinical Science, School of Veterinary Medicine and Animal Science, Universidade Estadual Paulista, Botucatu, São Paulo, Brazil.
Meira, C
  • Department of Animal Reproduction and Veterinary Radiology, School of Veterinary Medicine and Animal Science, Universidade Estadual Paulista, Botucatu, São Paulo, Brazil. Electronic address: meira@fmvz.unesp.br.

MeSH Terms

  • Animals
  • Delayed-Action Preparations
  • Drug Administration Schedule
  • Embryo Transfer / veterinary
  • Estradiol / administration & dosage
  • Estradiol / analogs & derivatives
  • Estradiol / pharmacology
  • Female
  • Horses / physiology
  • Pregnancy
  • Pregnancy, Animal / drug effects
  • Progesterone / administration & dosage
  • Progesterone / pharmacology

Citations

This article has been cited 3 times.
  1. Silva ESM, Newcombe JR, Cuervo-Arango J. The Effect of Treatment with Oestradiol Benzoate on Oestrus Expression and Endometrial Oedema in Anovulatory and Cyclic Mares. Animals (Basel) 2023 Mar 5;13(5).
    doi: 10.3390/ani13050938pubmed: 36899795google scholar: lookup
  2. Segabinazzi LGTM, Andrade LRP Jr, Alvarenga MA, Dell'Aqua JA Jr, Canisso IF. Use of Intravaginal Progesterone-Releasing Device Results in Similar Pregnancy Rates and Losses to Long-Acting Progesterone to Synchronize Acyclic Embryo Recipient Mares. Vet Sci 2021 Sep 10;8(9).
    doi: 10.3390/vetsci8090190pubmed: 34564584google scholar: lookup
  3. Barbosa LA, Maran AP, de Almeida MER, Guimarães EC, Bringel B, Douglas RH, Lima TFG, da Silva ESM. Plasma Estradiol and Endometrial Edema Profile in Acyclic Mares After Single Administration of 17-β Estradiol, Estradiol Benzoate and Estradiol Cypionate. Reprod Domest Anim 2025 Aug;60(8):e70108.
    doi: 10.1111/rda.70108pubmed: 40760876google scholar: lookup