Ovulation inhibition by estetrol in an in vivo model

H.J.T.C. Bennink; S. Skouby; P. Bouchard; C.F. Holinka

Ovulation inhibition by estetrol in an in vivo model

H.J.T.C. Bennink, S. Skouby, P. Bouchard, C.F. Holinka

40 Citations (Scopus)

Abstract

Background: Currently, the synthetic steroid ethinylestradiol (EE) is the preferred estrogen in combined oral contraceptives. The aim of the present study was to evaluate the effectiveness of the natural steroid estetrol (E-4) as an ovulation inhibitor in rats when compared to EE. Study Design: Regularly cycling female rats were treated orally twice daily for four consecutive days, starting on the day of estrus, with E4 (0.03, 0.1, 0.3, 1.0 or 3.0 mg/kg), EE (0.0003, 0.001, 0.003, 0.01 or 0.03 mg/kg) or vehicle control (eight animals per group). In a second experiment conducted under the same experimental protocol, 2.0 mg/kg of E4 was administered as a single daily dose or as a dose of 1.0 mg/kg twice daily. In both studies, the primary end point was the number of ovulated oocytes in the genital tract. Results: Estetrol at the twice daily dose of 0.3 mg/kg and above inhibited ovulation. This effect was statistically significant (P<.05). The comparator, EE, significantly inhibited ovulation (p<.05) at the highest dose (0.03 mg/kg) administered twice daily. An E-4 dose of 2.0 mg/kg administered once daily for four consecutive days inhibited ovulation in four of eight rats. In contrast, when the same dose was administered in two separate doses, that is, 1.0 mg/kg twice daily, ovulation was inhibited in eight of eight rats. The ED50 for the EE and the E-4 dose response curves shows that EE is 18 times more potent than E-4. Conclusion: Twice daily administration of E-4 effectively inhibits ovulation in cycling rats. The effect is dose-dependent. The relative potency of E-4 is about 18 times less compared to that of EE. We conclude that based on these data, combined with available pharmacological and clinical data on the safety and efficacy of E-4, the human fetal estrogenic steroid estetrol is a potential candidate to replace EE in combined oral contraceptives. (c) 2008 Elsevier Inc. All rights reserved
Udgivelsesdato: 2008/3

Original language	English
Journal	Contraception
Volume	77
Issue number	3
Pages (from-to)	186-190
Number of pages	4
ISSN	0010-7824
Publication status	Published - 2008

Cite this

@article{faf4da8004c611deb05e000ea68e967b,

title = "Ovulation inhibition by estetrol in an in vivo model",

abstract = "Background: Currently, the synthetic steroid ethinylestradiol (EE) is the preferred estrogen in combined oral contraceptives. The aim of the present study was to evaluate the effectiveness of the natural steroid estetrol (E-4) as an ovulation inhibitor in rats when compared to EE. Study Design: Regularly cycling female rats were treated orally twice daily for four consecutive days, starting on the day of estrus, with E4 (0.03, 0.1, 0.3, 1.0 or 3.0 mg/kg), EE (0.0003, 0.001, 0.003, 0.01 or 0.03 mg/kg) or vehicle control (eight animals per group). In a second experiment conducted under the same experimental protocol, 2.0 mg/kg of E4 was administered as a single daily dose or as a dose of 1.0 mg/kg twice daily. In both studies, the primary end point was the number of ovulated oocytes in the genital tract. Results: Estetrol at the twice daily dose of 0.3 mg/kg and above inhibited ovulation. This effect was statistically significant (P<.05). The comparator, EE, significantly inhibited ovulation (p<.05) at the highest dose (0.03 mg/kg) administered twice daily. An E-4 dose of 2.0 mg/kg administered once daily for four consecutive days inhibited ovulation in four of eight rats. In contrast, when the same dose was administered in two separate doses, that is, 1.0 mg/kg twice daily, ovulation was inhibited in eight of eight rats. The ED50 for the EE and the E-4 dose response curves shows that EE is 18 times more potent than E-4. Conclusion: Twice daily administration of E-4 effectively inhibits ovulation in cycling rats. The effect is dose-dependent. The relative potency of E-4 is about 18 times less compared to that of EE. We conclude that based on these data, combined with available pharmacological and clinical data on the safety and efficacy of E-4, the human fetal estrogenic steroid estetrol is a potential candidate to replace EE in combined oral contraceptives. (c) 2008 Elsevier Inc. All rights reserved Udgivelsesdato: 2008/3",

author = "H.J.T.C. Bennink and S. Skouby and P. Bouchard and C.F. Holinka",

note = "Times Cited: 2ArticleEnglishBennink, H. J. T. CPantarhei Biosci, POB 464, NL-3700 AL Zeist, NetherlandsCited References Count: 30268EXELSEVIER SCIENCE INC360 PARK AVE SOUTH, NEW YORK, NY 10010-1710 USANEW YORK",

year = "2008",

language = "English",

volume = "77",

pages = "186--190",

journal = "Contraception",

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TY - JOUR

T1 - Ovulation inhibition by estetrol in an in vivo model

AU - Bennink, H.J.T.C.

AU - Skouby, S.

AU - Bouchard, P.

AU - Holinka, C.F.

N1 - Times Cited: 2ArticleEnglishBennink, H. J. T. CPantarhei Biosci, POB 464, NL-3700 AL Zeist, NetherlandsCited References Count: 30268EXELSEVIER SCIENCE INC360 PARK AVE SOUTH, NEW YORK, NY 10010-1710 USANEW YORK

PY - 2008

Y1 - 2008

N2 - Background: Currently, the synthetic steroid ethinylestradiol (EE) is the preferred estrogen in combined oral contraceptives. The aim of the present study was to evaluate the effectiveness of the natural steroid estetrol (E-4) as an ovulation inhibitor in rats when compared to EE. Study Design: Regularly cycling female rats were treated orally twice daily for four consecutive days, starting on the day of estrus, with E4 (0.03, 0.1, 0.3, 1.0 or 3.0 mg/kg), EE (0.0003, 0.001, 0.003, 0.01 or 0.03 mg/kg) or vehicle control (eight animals per group). In a second experiment conducted under the same experimental protocol, 2.0 mg/kg of E4 was administered as a single daily dose or as a dose of 1.0 mg/kg twice daily. In both studies, the primary end point was the number of ovulated oocytes in the genital tract. Results: Estetrol at the twice daily dose of 0.3 mg/kg and above inhibited ovulation. This effect was statistically significant (P<.05). The comparator, EE, significantly inhibited ovulation (p<.05) at the highest dose (0.03 mg/kg) administered twice daily. An E-4 dose of 2.0 mg/kg administered once daily for four consecutive days inhibited ovulation in four of eight rats. In contrast, when the same dose was administered in two separate doses, that is, 1.0 mg/kg twice daily, ovulation was inhibited in eight of eight rats. The ED50 for the EE and the E-4 dose response curves shows that EE is 18 times more potent than E-4. Conclusion: Twice daily administration of E-4 effectively inhibits ovulation in cycling rats. The effect is dose-dependent. The relative potency of E-4 is about 18 times less compared to that of EE. We conclude that based on these data, combined with available pharmacological and clinical data on the safety and efficacy of E-4, the human fetal estrogenic steroid estetrol is a potential candidate to replace EE in combined oral contraceptives. (c) 2008 Elsevier Inc. All rights reserved Udgivelsesdato: 2008/3

AB - Background: Currently, the synthetic steroid ethinylestradiol (EE) is the preferred estrogen in combined oral contraceptives. The aim of the present study was to evaluate the effectiveness of the natural steroid estetrol (E-4) as an ovulation inhibitor in rats when compared to EE. Study Design: Regularly cycling female rats were treated orally twice daily for four consecutive days, starting on the day of estrus, with E4 (0.03, 0.1, 0.3, 1.0 or 3.0 mg/kg), EE (0.0003, 0.001, 0.003, 0.01 or 0.03 mg/kg) or vehicle control (eight animals per group). In a second experiment conducted under the same experimental protocol, 2.0 mg/kg of E4 was administered as a single daily dose or as a dose of 1.0 mg/kg twice daily. In both studies, the primary end point was the number of ovulated oocytes in the genital tract. Results: Estetrol at the twice daily dose of 0.3 mg/kg and above inhibited ovulation. This effect was statistically significant (P<.05). The comparator, EE, significantly inhibited ovulation (p<.05) at the highest dose (0.03 mg/kg) administered twice daily. An E-4 dose of 2.0 mg/kg administered once daily for four consecutive days inhibited ovulation in four of eight rats. In contrast, when the same dose was administered in two separate doses, that is, 1.0 mg/kg twice daily, ovulation was inhibited in eight of eight rats. The ED50 for the EE and the E-4 dose response curves shows that EE is 18 times more potent than E-4. Conclusion: Twice daily administration of E-4 effectively inhibits ovulation in cycling rats. The effect is dose-dependent. The relative potency of E-4 is about 18 times less compared to that of EE. We conclude that based on these data, combined with available pharmacological and clinical data on the safety and efficacy of E-4, the human fetal estrogenic steroid estetrol is a potential candidate to replace EE in combined oral contraceptives. (c) 2008 Elsevier Inc. All rights reserved Udgivelsesdato: 2008/3

M3 - Journal article

SN - 0010-7824

VL - 77

SP - 186

EP - 190

JO - Contraception

JF - Contraception

IS - 3

ER -