1. Efficacy of medroxyprogesterone in suppression of estrus in mares
Patrick McCue, DVM, PhD Diplomate ACT

2. Estrus Suppression in the Mare
Options:
Hormone administration
Progesterone/progestins
Oxytocin
GnRH vaccine
‘Equity’ vaccine (Australia)
Intrauterine devices
Marbles, etc.
Herbal supplements
Surgery
Ovariectomy

3. Progesterone Compounds
Natural progesterone
Intramuscular injection preparations
Subcutaneous cattle implants (Synovex®)
Synthetic progestins (i.e. Regu-Mate®)
Other synthetic progestins
Hydroxyprogesterone caproate (Hyproval®)
Norgestomet (Synchro-Mate B®)
Megesterol acetate (Ovaban®)
Medroxyprogesterone acetate (Depo-Provera®)

4. Medroxyprogesterone Acetate (Depo-Provera®)
Hormonal birth control agent for women
Complete inhibition of follicular development and ovulation
Compounded medroxyprogesterone acetate is used to suppress estrus in performance mares
Dose regimens utilized by owners, trainers, DVMs
1,600 mg - once per month
800 mg - once every 2 weeks
400 mg - once per week
No controlled studies to determine efficacy for suppression of estrus in mares
Dose rates and frequencies reported

5. Research Goals
Determine the effect(s) of administration of medroxyprogesterone acetate on
Behavioral estrus
Does MPA block or prevent expression of heat?
Follicular activity and ovulation
Does MPA prevent cycling and ovulation?
Endocrine parameters
Does MPA suppress luteinizing hormone (LH) secretion from the pituitary?

6. Materials and Methods 18 normal, healthy light horse mares
Age range: 5 to 13 years
Parameters for inclusion in study:
Expression of normal estrous behavior
Cycling with normal follicular development and ovulation as detected on transrectal ultrasonography

7. Materials and Methods
Mares were randomly assigned to one of 3 treatment groups (n=6 mares per group)
Treatment was initiated 7 days after ovulation; mares were treated for 6 weeks
Group 1. Sterile saline injection once each week for 6 weeks (control)
Group 2. MPA injection once each week for 6 weeks
1,600 mg loading dose (1st treatment)
400 mg once per week (all additional treatments)
Group 3. Altrenogest (Regu-Mate®; 10 ml, orally, once daily for 6 weeks)

8. Materials and Methods
Mares were teased to a stallion once per day, every day, to monitor estrous behavior (direct contact)
Transrectal ultrasound initially performed 3 times per week
Daily exams when a follicle was ≥ 30 mm in diameter

9. Materials and Methods Blood samples collected
Once per week for progesterone analysis
Once daily for 10 days for luteinizing hormone (LH)
Investigators were blinded to treatment
No knowledge of teasing behavior, ultrasound exam results or hormone analyses

10. Results: Behavior
All saline (placebo) treated mares expressed normal estrus
All medroxyprogesterone treated mares expressed normal estrus
None of the altrenogest treated mares showed behavioral estrus
Treatment Group
Duration of Estrus
Saline
8 ± 2 days
MPA
7 ± 1 days
Altrenogest
0 days
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11. Results: Behavior
Yellow = estrus Green = diestrus

12. Results: Ovarian Follicular Development
All saline treated mares developed large follicles, normal uterine edema and ovulated
All MPA treated mares developed large follicles, normal uterine edema and ovulated
None of the altrenogest treated mares developed large follicles, or edema and none ovulated during the treatment period
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13. Results: Progesterone Concentrations
___________________
Blue = Saline Pink = MPA Green = Altrenogest

14. Results: Luteinizing Hormone
All saline treated mares exhibited an increase in luteinizing hormone (LH) associated with estrus
All MPA treated mares exhibited an increase in LH associated with estrus
None of the altrenogest treated mares exhibited an increase in LH; none of the mares were in estrus
___________________

15. Results: Serum LH Concentrations
Blue = Saline Pink = MPA Green = Altrenogest

16. Conclusion
A loading dose of 1,600 mg MPA followed by once per week doses of 400 mg of MPA for 6 weeks:
Did not suppress behavioral estrus
Did not inhibit follicular development
Did not prevent ovulation
Did not block the increase in LH associated with estrus
There was no difference in efficacy between MPA treatment and a saline placebo

17. Conclusion
Altrenogest treatment resulted in suppression of behavioral estrus, prevented formation of large follicles, and suppressed secretion of luteinizing hormone
No mares treated with altrenogest ovulated during the treatment period

18. Hypothesis for lack of efficacy of MPA:
Final Conclusion
Medroxyprogesterone had no apparent biological activity relative to alteration of behavioral estrus or follicular development or modulation of pituitary LH secretion
Hypothesis for lack of efficacy of MPA:
It is theorized that MPA, a synthetic progestin, does not bind to the equine progesterone receptor