Thank you to Dr. Pat McCue from the Equine Reproduction Laboratory for last month’s article, Progesterone Therapy for Pregnant Mares – Part 1, in which he reviewed the formulations and use of progesterone therapy in mares. Dr. McCue did a yeoman’s task in outlining the formulations and principles of therapy available to veterinarians for the suppression of estrus, pregnancy support, and treating cases of suspected or diagnosed placentitis. However, the maintenance of pregnancy is by far the most common area in which we receive questions about supplementing mares with exogenous (therapeutic) forms of progesterone.
Starting at the day of breeding, there are five (5) time points that I find critical to ask questions regarding possible progesterone supplementation. In the course of this discussion, I will use the term progesterone or P4 to refer to the compound made by the mare (from her corpus lutea, aka CLs and later placenta), and the term altrenogest/progesterone as the forms we commonly supplement to the mare. Most mare owners ask questions regarding supplementing mares following the 14-day pregnancy evaluation, and only if the mare is pregnant. As Dr. McCue mentioned, there is great debate about the idea of “luteal insufficiency” and the potential for a mare’s CL to make less than the required amount of progesterone for the maintenance of the pregnancy. So, with that in mind, the points to consider supplementing a mare are the following:
1. If her peak P4 level is low following ovulation at 5-6 days post ovulation
2. At the initial pregnancy evaluation
3. At 60-70 days following ovulation
4. At 120 days following ovulation
5. Illness, sickness, or premature udder development
Time Point #1: If her peak P4 level is low following ovulation at 5-6 days post ovulation
In the first case, if a mare has been given Prostaglandin F2 alpha at the time of or following ovulation this may hamper or decrease the rate and peak production of progesterone from the corpus luteum. Therefore, supplemental altenogest/progesterone therapy should begin starting at 3-4 days following ovulation. As such, there has been a push in the last few years, especially for valuable mares carrying their own pregnancy to pull a progesterone assay to determine the level of progesterone production early following ovulation. Arguments exist for and against this practice, but the premise is that by knowing the peak P4 production of a mare at 5-6 days post ovulation, we have time to supplement and hopefully salvage the pregnancy, if the value is low. Some veterinarians report, that an ultra-sonographic exam at days 12-14 is early enough to determine if a mare is pregnant and has signs of low progesterone that should be addressed by supplementation without measuring plasma P4 levels. The jury remains mixed on this practice, but I’m sure more information will come to light in the coming years regarding the practice of early testing and supplementation.
Time Point #2: At the initial pregnancy evaluation
At the initial pregnancy exam, if the mare is pregnant and has a) poor uterine or cervical tone, b) poor appearance of the corpus luteum, c) presence of mild uterine edema, or d) history of pregnancy loss I will begin a treatment protocol of supplemental progesterone/progestogen. Typically, with a standard 0.044mg/kg altrenogest by mouth once a day until a heartbeat check around day 35 of pregnancy. I am a big proponent of assaying endogenous progesterone levels in mares prior to stopping therapy.
It is of note that we can assay for progesterone produced by the mare’s corpus luteum while she is receiving altrenogest. We cannot assay the mare’s production of her own progesterone if we supplement her with either short-acting or long-acting progesterone. Therefore, in our clinical program, if we plan on testing the mare prior to cessation of therapy (either at 35 days or 60 days) we elect to supplement with altrenogest.
Time Point #3: At 60 – 70 days after ovulation
Alternatively, some clients elect to supplement with altrenogest until after the formation of accessory or secondary CL’s between days 50-60 following ovulation. At this pregnancy exam, we often check for fetal viability as well as the presence of multiple CL’s. Most mares, 65-75%, make accessory CL’s and if so, the need for supplemental altrenogest/progesterone is negligible. Your veterinarian can screen the mare’s ovaries for these structures and help make a clinical decision to stop supplementing.
Time Point #4: At 120 days following ovulation
The last time point where we recommend most clients stop supplementation is at day 120 of pregnancy. From day 70 of pregnancy, there are increasing amounts of steroid hormones produced by the equine placenta that begin to take over the maintenance of pregnancy and progesterone/progestogen production. The ovaries do not contribute progesterone after day 120 of gestation. Clinically speaking, when I pull mares off of altrenogest/progesterone support at 120 days, I am doing so not based upon a laboratory test, but solely on the knowledge that a healthy equine placenta will be making enough steroids, termed 5-alpha-pregnanes, progestogens, and small amounts of actual progesterone, to support the pregnancy. If I was inclined to pull a progesterone assay after day 90-120, the actual level of measured progesterone will be variable and is often times, quite low. This is concerning for owners who, seeing a low level of progesterone, will continue to supplement the mare with altrenogest. In fact, many laboratory tests cannot actually measure the 5-alpha-pregnane component of this hormone milieu, therefore, even though the placenta is making more than enough steroid compounds to maintain pregnancy, the progesterone we measure is low.
Time Point #5: Illness, sickness or premature udder development
There are reasons to maintain mares on supplemental altrenogest/progesterone support for longer than 120 days. In my hands, it is a mare with a history of placentitis, cervical dysfunction (tears) or late term pregnancy loss of unknown origin. It is recommended to monitor some progesterone and estradiol levels in late term mares, or mares with suspected placentitis, but that is a whole other topic all-together. In cases of mares that have a period of fever, illness, colic, surgery, premature udder development, or severe lameness in late gestation, I will often recommend a period of double dose altrenogest at 0.088mg/kg once a day, followed by a longer duration of normal 0.044mg/kg per day administration.
I hope these clinical descriptions and common practices help clear up some confusion regarding the types and use of supplemental progesterone and expand on the previous month’s discussion regarding the types of supplemental progesterone/altrenogest available to owners.