Mares are long-day seasonal breeders with suppressed reproductive activity during winter anestrus. Advancing the first seasonal ovulation is a key goal in equine breeding. While artificial photoperiod is most effective, dopamine antagonists, such as sulpiride, combined with estrogens, have shown variable efficacy (Panzani et al., Theriogenology, 2011; Oberhaus et al., J Equine Vet Sci, 2017), but estrogen administration is banned in Europe. Clomiphene citrate, a selective estrogen receptor modulator with mixed estrogenic and antiestrogenic activity, has been proposed as an alternative to estradiol to prepare acyclic recipient mares (Derbala et al., J Equine Vet Sci, 2024). Thirty winter anestrous Standardbred mares, maintained under natural photoperiod, were randomly assigned to two groups (n = 15 each). Treated mares (Group T) received clomiphene citrate (1 mg/kg/day, PO) and sulpiride (0.5 mg/kg/day, IM) for up to 14 days or until ovulation; control mares (Group C) remained untreated. Uterine edema and ovarian activity were monitored via transrectal ultrasound; behavioral estrus was assessed daily using a teaser stallion. Primary outcomes were the proportion of mares developing follicles ≥30 mm and ≥35 mm, and the occurrence of ovulation within 30 days. Statistical analysis used the chi-square test (Jamovi 2.3.28). All treated mares exhibited uterine edema and estrous behavior within 24–48 h. Within 30 days, 11/15 (73.3%) treated mares developed follicles ≥30 mm vs 1/15 (6.7%) controls (P < 0.001), 8/15 (53.3%) developed follicles ≥35 mm vs 1/15 (6.7%) controls (P = 0.017), and ovulation occurred in 7/15 (46.7%) treated mares vs 1/15 (6.7%) controls (P = 0.039). These results demonstrate that combined sulpiride and clomiphene citrate effectively advance ovarian cyclicity and first ovulation in winter anestrous mares, likely via sulpiride-mediated prolactin release and clomiphene’s modulation of hypothalamic–pituitary feedback, providing an estrogen-free pharmacological strategy for early breeding management.

Combined clomiphene citrate and sulpiride treatment advances first ovulation in anestrus mares

Saverio Maltinti
Primo
;
Rebecca Moroni
Secondo
;
Diana Fanelli;Alessandra Rota
Penultimo
;
D Panzani
Ultimo
2026-01-01

Abstract

Mares are long-day seasonal breeders with suppressed reproductive activity during winter anestrus. Advancing the first seasonal ovulation is a key goal in equine breeding. While artificial photoperiod is most effective, dopamine antagonists, such as sulpiride, combined with estrogens, have shown variable efficacy (Panzani et al., Theriogenology, 2011; Oberhaus et al., J Equine Vet Sci, 2017), but estrogen administration is banned in Europe. Clomiphene citrate, a selective estrogen receptor modulator with mixed estrogenic and antiestrogenic activity, has been proposed as an alternative to estradiol to prepare acyclic recipient mares (Derbala et al., J Equine Vet Sci, 2024). Thirty winter anestrous Standardbred mares, maintained under natural photoperiod, were randomly assigned to two groups (n = 15 each). Treated mares (Group T) received clomiphene citrate (1 mg/kg/day, PO) and sulpiride (0.5 mg/kg/day, IM) for up to 14 days or until ovulation; control mares (Group C) remained untreated. Uterine edema and ovarian activity were monitored via transrectal ultrasound; behavioral estrus was assessed daily using a teaser stallion. Primary outcomes were the proportion of mares developing follicles ≥30 mm and ≥35 mm, and the occurrence of ovulation within 30 days. Statistical analysis used the chi-square test (Jamovi 2.3.28). All treated mares exhibited uterine edema and estrous behavior within 24–48 h. Within 30 days, 11/15 (73.3%) treated mares developed follicles ≥30 mm vs 1/15 (6.7%) controls (P < 0.001), 8/15 (53.3%) developed follicles ≥35 mm vs 1/15 (6.7%) controls (P = 0.017), and ovulation occurred in 7/15 (46.7%) treated mares vs 1/15 (6.7%) controls (P = 0.039). These results demonstrate that combined sulpiride and clomiphene citrate effectively advance ovarian cyclicity and first ovulation in winter anestrous mares, likely via sulpiride-mediated prolactin release and clomiphene’s modulation of hypothalamic–pituitary feedback, providing an estrogen-free pharmacological strategy for early breeding management.
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Utilizza questo identificativo per citare o creare un link a questo documento: https://hdl.handle.net/11568/1369474
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