Hormone Therapy in Mare Reproduction

Introduction

Progesterone insufficiency and progesterone supplementation are recurrent themes in equine gynecology. This is likely a reflection of the frustration we as clinicians endure when facing mares that fail to conceive or to carry a pregnancy to term. It is certainly also a reflection of our lack of understanding of early pregnancy failure. Currently, the use of exogenous progestins in pregnant mares is widespread, and a rational method for selection of mares for progestin therapy is lacking. In many cases, progestin supplementation does not appear warranted and may even be counterproductive. However, there is a growing body of evidence that progestin supplementation may be useful under specific circumstances. Rational application of progestin therapy requires some consideration of mechanisms that might lead to pregnancy failure and the relationship of these mechanisms to progesterone.

When trying to make an informed decision as to whether or not implement progesterone supplementation we need to consider the role of progesterone during pregnancy, the source of progesterone during equine pregnancy, the choice of progestagen, route of administration and the measurement of endogenous progesterone levels. It is only when we fully understand these elements that we can come to an informed decision and make a well-founded recommendation to our clients.

Role of Progesterone

It has been demonstrated that progesterone is the only hormone that needs to be replaced to maintain pregnancy. Pregnant mares that are ovariectomized during the first 3 months of pregnancy or mares that have received a luteolytic dose of prostaglandin F2α remain pregnant if supplemented with progesterone. Similarly, ovariectomized and anoestrous mares remain pregnant after embryo transfer if they are supplemented with progesterone. However, this does not necessarily mean that progesterone is the only hormone that plays a role during early pregnancy. It has been demonstrated that the equine embryo produces measurable amounts of estrogens only days after conception. An interaction between locally secreted estrogens and progesterone (produced by the corpus luteum or administered) is very likely to play a role in the well-being of the early embryo.

During Pregnancy

During the first 120 days of gestation, progesterone is produced by the primary corpus luteum (CL). After 40 days of gestation, progesterone production by the primary CL is supplemented with progesterone produced by secondary CLs. Luteal production of progesterone persists through approximately Day 100 to Day 210 of gestation. Beginning around Day 50 to 70 of gestation, there is a measurable production of progestogen by the placenta, and the placenta is the only source of progestogen during the second half of gestation in the mare. Placental progesterone is rapidly metabolized to 5α- pregnanes in the placenta. These 5α-metabolites cannot be measured by most conventional progesterone assays. Therefore, after mid-gestation [...]