There can be several reasons for a large ovary in a mare. The three most important are:

(1) A normal ovary during the transition or breeding season with large follicles as frequently detected during early spring, persistent luteal phase and early pregnancy;
(2) A solid neoplastic lesion, such as a granulosa theca cell tumor, teratoma, dysgerminoma, cystadenoma and carcinoma;
(3) Hemorrhagic and luteinised follicles.

Transitional "spring" estrus

Pressure to breed mares early in the year before the onset of their natural breeding season can cause problems for the veterinarian. Because of the considerable variation in the duration of oestrus during the transitional period, efficient breeding of the mare can be difficult. During the transitional period the behaviour is variable, ranging from total rejection of the stallion, to interest but resistance to him mounting, to normal acceptance. These behavioural signs can be consistent or inconsistent. It is recommended that the interval between matings should not exceed 2 or 3 days, although there have been no critical studies on the survival time of sperm in the mares' genital tract. It is important not to begin breeding too early or this will result in the mare being mated many times.

The appearance of uterine edema is an indication that the follicle should ovulate within a few days.

A key factor in the emergence out of vernal transition is the development of steroidogenic competence by the follicle leading to an increase in circulating estrogen concentrations which cause the release of Luteinising hormone (LH) from the pituitary due to a positive feedback mechanism. Estrogen is responsible for the appearance of uterine edema (in the absence of progesterone) and so this may be why the detection of uterine oedema is important in signalling the emergence of the mare from the transitional period.

The diagnosis is by thorough ultrasonic examination and rectal palpation which reveals transitional follicles reaching a preovulatory size of > 30 mm. Visual identification of a corpus luteum or progesterone levels above 4 ng/ml confirms that the first ovulation has occurred and hence the onset of normal ovarian cyclical activity.

The treatment of mares in transitional stage is based on progesterone or progestogens, with or without the addition of estradiol esters, involving several parenteral routes of administration. Progesterone can be administered as an oil based intramuscular injection, orally as the synthetic progestogen altrenogest (Equine Regumate) or by using a silastic progesterone releasing intravaginal device (PRID or CIDR-B).

Progesterone exerts a negative feedback on gonadotrophin secretion which is followed by an increased release of Follicle Stimulating Hormone (FSH) and LH. When the source of progesterone is withdrawn or its effect wanes there is follicular growth, maturation and ovulation. Progesterone treatment is more effective in mares that are in late transitional stage and is ineffective in mares with minimal follicular activity, particularly during deep anestrus.

Currently, the most effective treatment is the use of in-feed medication with the potent progestogen altrenogest (Equine Regumate). This liquid, which contains 2.2 mg/ml of the active substance, should be added to the food once per day at a dose rate of 0.044 mg/kg body weight for 10 consecutive days; oestrus should occur within 6 days and ovulation between 7 and 13 days after the last treatment. Because of the possibility of ovulation occurring during treatment, an injection of Prostaglandin F-2 alpha (PGF2α) on the last day of in-feed medication may be necessary to cause luteolysis of any corpus luteum that may be present. However, if ovulation is thought likely within the next seven days, it would be better to monitor the mare rather than use Regumate. The use of intramuscular injections of progesterone and estradiol-17β in oil for 10 days produces a similar response to altrenogest, but the interval to oestrus is longer due to the suppression of follicular development by the estradiol. PRIDs and CIDRs are used by the author in young mares which are not susceptible to endometritis. A vaginal discharge always results following use of these inserts, but this is not a cause for concern. A penicillin infusion should given on removal of the device. Mares are examined after seven days and depending on the follicular status, the insert can either be removed or left in place for up to seven more days.

There has been much interest recently in using GnRH or its analogues, administered by injection, infusion or subcutaneous implant, to hasten ovulation in transitional or even anoestrus mares.

Irrespective of the hormones used, mares that are being treated early in the season need 16 hours of adequate light and good housing and nutrition to ensure success.

During the transitional period before the first ovulation of the year mares demonstrate erratic oestrous behaviour of varying intensity. The presence of multiple large follicles, possibly as large as 30 mm, makes detection of ovulation difficult by palpation alone. Even outside this transitional period, misinterpretation of ovulation, even by experienced palpators has been shown to be as high as 50% in some studies. It is much easier to visualise the corpus hemorrhagicum/early corpus luteum with ultrasound when the anechoic follicle is replaced by an intensely echoic area representing the early corpus luteum.

Cystic ovarian disease
The condition as comparable to that described in cattle does not occur in the mare. The persistent follicles which occur during the transitional and other periods are structurally normal; however, their presence may explain why the diagnosis of this condition has been made in the past.

Ovarian neoplasia

Ovarian neoplasia is uncommon in the mare although many types of tumor have been described, with the granulosa theca cell tumors (GTCTs) being by far the commonest (Meagher et al., 1977). GTCTs arise from the sex cord stromal tissue within the ovary and may be hormonally active, producing variable amounts of steroids which cause behavioral changes and alteration to normal cyclical activity. Mares can exhibit nymphomania, anestrus or aggressiveness with signs of virilism (clitoral enlargement, stallion-like conformation). There appears to be no breed predisposition for GTCTs, and there is a wide range of age distribution.

The tumors are often large before they are diagnosed and one grossly enlarged ovary (> 10 cm diameter) with the opposite ovary small and firm on palpation with no visible follicles above 1 cm (resembling an ovary of a mare in deep anestrus) is indicative, but not diagnostic of a GTCT.

In mares with GTCTs, behavioural changes alone can be misleading since many affected mares do not show virilism or any other behavioural changes, and tumours other than GTCTs can also result in elevated plasma testosterone values. Most GTCT are found unexpectedly during routine examination of the mare on arrival at the stud farm.

It has been the author's experience that occasionally owners express the opinion that their mare is "awkward" when in estrus, and request veterinary treatment. Frequently such mares are required to perform to a high level, e.g. advanced dressage. If examination during a reported period of abnormal behaviour reveals marked follicular development it is tempting to diagnose 'cystic ovaries' as the cause of the behavioral changes. On other occasions, the mare may even be in dioestrus when examined. In any case, owner pressure to perform an ovariectomy on suspicion of a GTCT should be resisted, at least until the mare has been monitored throughout several cycles to determine if her behavioral problems are related to oestrus. Where it is felt that the behavioral problems are truly linked to estrus, daily supplementation with progesterone or a synthetic progestagen should prevent the mare showing estrous behaviour. Although rare in an unbred mare, there is a possibility of an increased risk for endometritis in a mare on long-term progesterone supplementation and she should be monitored for this. In addition, the problems may well recur following cessation of treatment. Another possibility would be to get her pregnant. A potential disadvantage of getting the mare pregnant is she will not be able to be shown or compete in the later stages of pregnancy and after giving birth the problems may re-appear. There may be some permanent shape changes due to the pregnancy which could detract from the mare's showing potential. Removal of the ovaries is not successful in many cases and eliminates the mare for breeding and should therefore be considered only after thorough client education. It is very important to not presume a large ovary in a mare with behavioural problems is due to a GTCT. A peripheral blood sample for endocrinological analysis (testosterone, oestrogen and progesterone concentrations) is useful. Increased concentrations of testosterone supports the clinical diagnosis; estradiol concentrations may be raised and progesterone concentrations are usually low. Identification of elevated concentrations of the hormone inhibin may be more reliable than testosterone in confirming the presence of a GTCT. The secretion of high amounts of inhibin by the neoplastic granulosa cells inhibits follicle stimulating hormone (FSH) secretion, and is thought to be the reason for atrophy of the contralateral ovary (Piquette et al 1990).

Ultrasonographic appearance: A GTCT often appears as a large (7-40 cm) mass, spherical and with a multicystic or "honeycomb" appearance.

There is no typical appearance of a GTCT on ultrasound: some are uniformly dense and others have a single, large, fluid-filled cysts or even several large cysts.

The echogenicity of the cyst wall differentiates it from persistent, large anovulatory follicles. Teratomata, depending on their composition, have marked echoic areas in their stroma related to calcified deposits of bone, teeth and hair. However, the ultrasonic appearance of some GTCTs seen by the author can be similar to that of luteinized, unruptured ("hemorrhagic") follicles. Histopathological examination is the only method of obtaining a definitive diagnosis.

It is important to diagnose accurately the reason for the enlarged ovary. For example, in one report, 39% (11 out of 28) of surgically excised enlarged ovaries did not warrant removal (Bosu et al., 1982). Cases of GTCT may be found at routine examination of mares, maybe even after foaling and rarely have these mares shown any behavioural changes. Larger tumors which have been present for some time are more likely to cause erratic behaviour and colic signs.

Unilateral ovariectomy is the only satisfactory treatment for GTCTs, since the prospect of breeding from the mare is extremely poor unless the neoplastic ovary is removed. It is important not to be too hasty in removing the ovary and a mare should always be scheduled for a second examination some weeks later. In the case of a tumor, the ultrasonic appearance would change little in the short term and would certainly appear similar if re-examined several weeks later. The reproductive prognosis of the mare is generally good, depending on the state of inhibition of the other ovary and provided no uterine tissue had to be removed. Most mares return to normal cyclical ovarian activity although this often takes as long as one breeding season especially in cases of severe suppression of the remaining ovary.
Most GTCTs are benign and unilateral although a bilateral case has been reported. Metastasis of the tumour is rare, but does occur (Meagher et al., 1977).

Ovulatory dysfunction

Anovulatory haemorrhagic follicles
A form of apparent ovulatory failure has been described in the mare in which the preovulatory follicle grows to an unusually large size (7-10 cm), apparently fails to rupture and ovulate, but fills with blood and then gradually regresses. These hematomata persist for a variable period of time, often beyond the next ovulation and corpus luteum formation, and normal cyclic ovarian activity continues. They normally resolve spontaneously and no treatment is required.

The condition is known as "hemorrhagic anovulatory follicle syndrome".

In one study, 12 cases occurred in eight mares during 213 ovulatory intervals monitored by ultrasound (Ginther and Pierson, 1989). Where this occurs, the preovulatory follicle fills with blood and is initially recognized, using transrectal ultrasound, by the presence of scattered free-floating echogenic spots within the follicular antrum. As the blood coagulates, the ultrasonic appearance varies from honeycomb or "net-like" to a uniformly echogenic mass.

These structures can be as large as 8-10 cm, occasionally much larger, and develop an outer wall of luteal tissue. Functionally, they gradually regress in the same way as a normal corpus luteum, but they remain visible ultrasonically over subsequent oestrous cycles. No treatment is usually necessary. Sometimes they may also fail to regress around day 14 to 15 of the cycle and persist.

Hemorrhagic follicles may be difficult to diagnose. The rise in plasma progesterone is not useful for detecting ovulation since most hemorrhagic follicles tend to luteinise, thus producing progesterone and hence their alternative name "luteinised unruptured follicle". These structures cannot be detected by the behavioural responses of the mare since oestrogen concentrations are initially elevated and subsequently progesterone concentrations may increase and terminate oestrous behaviour similar to that following ovulation. The palpation features of these structures are smooth with varying degrees of firmness. This can be confusing, since they may feel like preovulatory follicles, corpora hemorrhagica, or they may increase in size and become very large. The most obvious difference in their appearance is when they are examined ultrasonographically. Commonly, there are multiple echoes from within the follicular cavity giving a net-like appearance within the follicular fluid. The structures may have a similar appearance to that of a granulosa-theca-cell tumour (GTCT): the anechoic areas are separated by trabeculae and are similar to those of a multicystic GTCT.

The diagnosis of a hemorrhagic follicle may be made on the basis of clinical signs, namely maintenance of cyclicity, a normal contralateral ovary, the presence of an ovulation fossa and speed of enlargement and regression of the ovary with time.

Their significance is that the oocyte is not released but remains within the large unruptured hemorrhagic follicle. The abrupt decrease in follicle diameter normally associated with ovulation is not noted, rather a steady increase and the shape change and stigma formation due to follicle softening is not seen. However one cannot unequivocally state that they did not form by rapid filling between examinations.

The cause of these hemorrhagic follicles is not known. Similar structures are seen under continued equine chorionic gonadotrophin (eCG) stimulation during days 40-150 of pregnancy.

Anovulatory follicles in aged mares
While there is no documented menopause in mares, an age-related ovulation failure has been documented (Vanderwall et al 1993). Some aged mares, particularly over 20 years of age, fail to ovulate despite showing oestrous behaviour, and hence it may not be detected. On ultrasound examination their ovaries resemble those of seasonally anovulatory mares with a few small (< 10 mm) follicles. Endometrial biopsy shows evidence of gland atrophy. Currently there is no treatment, but identification of such mares is important to avoid unnecessary coverings.

References

Bosu WTK Van Camp SC Miller RB et al: Ovarian disorders: clinical and morphological observations in 30 mares. Can vet J 23: 6, 1982
Ginther OJ and Pierson RA: Regular and irregular characteristics of ovulation and the interovulatory interval in mares. J Equine Vet Sci 9: 4, 1989
Meagher DM Wheat JD Hughes, JP et al: Granulosa cell tumours in mares: A review of 78 cases. Proc 23rd Ann Conv Am Ass equine Pract: 133, 1977
Piquette GN Kenney RM Sertich PL et al: Equine granulosa-theca cell tumors express inhibin - and A-subunit messenger ribonucleic acids and proteins. Biol Reprod 43: 1050, 1990
Vanderwall DK Woods GL Freeman DA et al: Ovarian follicles, ovulations and progesterone concentrations in aged versus young mares. Theriogenology 40: 21, 1993

Summary:

The Large Ovary Syndrome
Dr. Jonathan F Pycock, B.Vet.Med., Ph.D., D.E.S.M., M.R.C.V.S.
Equine Reproductive Services, Messenger Farm, Ryton, Yorkshire

There can be several reasons for a large ovary in a mare. The three most important are: A normal ovary during the transition or breeding season with large follicles; A solid neoplastic lesion; Hemorrhagic and luteinised follicles.

Transitional "spring" estrus
Because of the considerable variation in the duration of oestrus during the transitional period, efficient breeding of the mare can be difficult. It is important not to begin breeding too early or this will result in the mare being mated many times.
The appearance of uterine edema is an indication that the follicle should ovulate within a few days.
Diagnosis is by thorough ultrasonic examination and rectal palpation which reveals transitional follicles reaching a preovulatory size of > 30 mm. Visual identification of a corpus luteum or progesterone levels above 4 ng/ml confirms that the first ovulation has occurred. Treatment is based on progesterone or progestogens.

Ovarian neoplasia
Tumors arise from the sex cord stromal tissue within the ovary and may be hormonally active, producing variable amounts of steroids which cause behavioral changes and alteration to normal cyclical activity. There appears to be no breed predisposition for GTCTs, and there is a wide range of age distribution. The tumors are often large before they are diagnosed and one grossly enlarged ovary (> 10 cm diameter) with the opposite ovary small and firm on palpation with no visible follicles above 1 cm (resembling an ovary of a mare in deep anestrus) is indicative, but not diagnostic of a GTCT. Behavioural changes alone can be misleading since many affected mares do not show virilism or any other behavioural changes, and tumours other than GTCTs can also result in elevated plasma testosterone values. Most GTCT are found unexpectedly during routine examination of the mare at the stud farm.
There is no typical appearance of a GTCT on ultrasound: some are uniformly dense and others have a single, large, fluid-filled cyst or several large cysts.

Unilateral ovariectomy is the only satisfactory treatment for GTCTs.

Ovulatory dysfunction
A form of apparent ovulatory failure has been described in which the preovulatory follicle grows to an unusually large size (7-10 cm), apparently fails to rupture and ovulate, but fills with blood and then gradually regresses. These hematomata persist for a variable period of time, often beyond the next ovulation. They normally resolve spontaneously and no treatment is required. The condition is known as "hemorrhagic anovulatory follicle syndrome".
Hemorrhagic follicles may be difficult to diagnose. The rise in plasma progesterone is not useful for detecting ovulation since most hemorrhagic follicles tend to luteinise, thus producing progesterone and hence their alternative name "luteinised unruptured follicle".
Their significance is that the oocyte is not released but remains within the large unruptured hemorrhagic follicle. The abrupt decrease in follicle diameter normally associated with ovulation is not noted, rather a steady increase and the shape change and stigma formation due to follicle softening is not seen. However one cannot unequivocally state that they did not form by rapid filling between examinations.