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Journal of equine veterinary science2026; 106125; doi: 10.1016/j.jevs.2026.106125

The effects of clomiphene citrate on reproductive parameters in the mare.

Abstract: Clomiphene citrate (CC) is a longstanding human fertility drug that has yet to be investigated in horses. The objective was to evaluate effects of CC on mare reproduction. After follicle ablation on Day 0, treatment mares (n=5) received 2 grams of CC intravenously on Days 1-5 while control mares (n=4) received no treatment. Transrectal ultrasonography was performed on Days 1-5 and 8, and transvaginal oocyte aspiration occurred on Day 8. Hormones were analyzed on Days 0-5, 8, 11, and 15. Mares receiving CC exhibited higher uterine edema grades compared to control mares (P=0.009). Antral follicle count and size of largest follicle did not differ between groups (P>0.05). Treated mares had higher luteinizing hormone (LH, P=0.04) and anti-müllerian hormone (AMH, P=0.05) compared to control mares. While CC treated mares had higher uterine edema and serum LH and AMH, significant changes in follicle stimulating hormone, estradiol, and follicular development were not demonstrated.
Publication Date: 2026-08-11 PubMed ID: 42580606DOI: 10.1016/j.jevs.2026.106125Google Scholar: Lookup
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Summary

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Overview

  • This study investigated the effects of clomiphene citrate (CC), a common human fertility medication, on reproductive parameters in mares (female horses).
  • The goal was to see how CC influences ovarian activity, hormone levels, and uterine changes in mares after follicle ablation.

Background

  • Clomiphene citrate is widely used in human medicine to stimulate ovulation in women facing fertility issues.
  • Despite its extensive use in humans, CC’s effects on horse reproduction had not been studied prior to this research.
  • Mares have distinct reproductive physiology compared to humans, so it’s important to understand CC’s role specifically in equine reproductive cycles.

Study Design and Methodology

  • The experiment involved nine mares divided into two groups: a treatment group (5 mares) and a control group (4 mares).
  • On Day 0, all mares underwent follicle ablation, a procedure to remove or disrupt follicular development, to standardize starting conditions.
  • Treatment mares received 2 grams of CC intravenously daily from Days 1 through 5; control mares did not receive any treatment.
  • Transrectal ultrasonography was performed on Days 1-5 and Day 8 to assess ovarian follicles and uterine condition.
  • On Day 8, transvaginal oocyte aspiration was done to collect oocytes for assessment of follicular development.
  • Blood samples were collected for hormone measurement on Days 0-5, 8, 11, and 15, focusing on key reproductive hormones.

Main Findings

  • Mares treated with CC showed greater uterine edema grades compared to the control group, suggesting uterine tissue responded to CC (statistically significant, P=0.009).
  • No significant differences were observed in the number of antral follicles (follicles with fluid-filled cavities) or size of the largest follicle between treated and control mares.
  • The treatment group had significantly higher levels of luteinizing hormone (LH) and anti-müllerian hormone (AMH) compared to controls, indicating some hormonal stimulation by CC (LH: P=0.04, AMH: P=0.05).
  • Levels of follicle-stimulating hormone (FSH), estradiol (a form of estrogen), and follicular development overall did not show significant changes with CC treatment.

Interpretation and Implications

  • CC administration to mares can influence the uterine environment, as seen by increased uterine edema, which may affect fertility or readiness for conception.
  • The increase in LH and AMH suggests that CC does affect aspects of endocrine regulation related to mare reproduction, potentially enhancing signals involved in ovulation or follicular activity.
  • The absence of significant changes in FSH, estradiol, and follicle growth indicates that CC’s effects might be selective or limited in scope within the mare’s reproductive system.
  • These results imply that while CC has some impact on reproductive hormones and uterine changes, it may not strongly stimulate follicular development or estradiol production in mares as it does in humans.
  • Further research might be needed to explore optimal dosing, timing, and combinations to fully understand CC’s potential for improving equine fertility.

Conclusion

  • This pioneering study demonstrated that clomiphene citrate affects certain reproductive parameters in mares, especially uterine edema and specific hormone levels.
  • Despite these effects, CC did not produce major changes in follicle size or key ovarian hormones like estradiol and FSH.
  • Therefore, CC shows promise but requires additional investigation before being used routinely in equine reproductive management.

Cite This Article

APA
Maxwell HE, Lyman CC, Foradori CD, Moore HL, Chaves-Cordoba B, Armstrong CL, Klabnik JL. (2026). The effects of clomiphene citrate on reproductive parameters in the mare. J Equine Vet Sci, 106125. https://doi.org/10.1016/j.jevs.2026.106125

Publication

ISSN: 0737-0806
NlmUniqueID: 8216840
Country: United States
Language: English
Pages: 106125
PII: S0737-0806(26)00360-6

Researcher Affiliations

Maxwell, H E
  • Department of Clinical Sciences, College of Veterinary Medicine, Auburn University, 1500 Wire Rd., Auburn, AL, 36832, USA.
Lyman, C C
  • Department of Clinical Sciences, College of Veterinary Medicine, Auburn University, 1500 Wire Rd., Auburn, AL, 36832, USA.
Foradori, C D
  • Department of Anatomy, Physiology, and Pharmacology, College of Veterinary Medicine, Auburn University, 1130 Wire Rd., Auburn, AL, 36849, USA.
Moore, H L
  • Department of Clinical Sciences, College of Veterinary Medicine, Auburn University, 1500 Wire Rd., Auburn, AL, 36832, USA.
Chaves-Cordoba, B
  • Department of Agriculture, Auburn University, 107 Comer Hall, Auburn, AL, 36849, USA.
Armstrong, C L
  • Department of Clinical Sciences, College of Veterinary Medicine, Auburn University, 1500 Wire Rd., Auburn, AL, 36832, USA.
Klabnik, J L
  • Department of Clinical Sciences, College of Veterinary Medicine, Auburn University, 1500 Wire Rd., Auburn, AL, 36832, USA. Electronic address: jlk0066@auburn.edu.

Conflict of Interest Statement

Declaration of competing interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper.

Citations

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