Abstract Introduction

An Asian elephant (Elephas maximus) at Busch Gardens Tampa Bay (BGT) was diagnosed with hyperprolactinemia with a persistently elevated serum prolactin concentration greater than 15 ng/ml, by the Conservation and Research Center (CRC) laboratory in January 1996. She also had a number of other problems including uterine disorders, that resulted in consistently elevated progesterone. In March 2002 she was given cabergoline orally at a dose of 1 mg twice weekly PO for six months. Cabergoline is a long-acting dopamine receptor agonist with a high affinity for D2 receptors. It exerts a direct inhibitory effect on the secretion of prolactin. Cabergoline (Dostinex®, Pfizer Inc. Kalamazoo, MI) was purchased from a local pharmacy. Serum prolactin concentrations declined almost immediately after treatment initiation, followed about one month later by a drop in progesterone to baseline. Progesterone secretion remained low until November 2002 when she resumed cycling based on the observation of a normal luteal phase based on serum progesterone profile. From November 2002 through January 2004, she exhibited four normal estrous cycles. Prolactin secretion also remained within the normal range for elephants¹ over one year after treatment withdrawal. This female suffered no adverse effects due to the cabergoline treatment. There were no behavioral changes noted or changes in appetite. Given the need to increase reproductive rates of African elephants (Loxodonta africana) to prevent captive extinction, it might be efficacious to treat genetically valuable females with cabergoline in the hope it will reinitiate reproductive cyclicity. Nearly 1/3 of African elephants with hormone data are not cycling normally, and in an earlier study 1/3 of these (11 of 30) were found to have increased serum prolactin levels.¹

Methods and Materials

A clinical trial was undertaken with six captive African elephant females that were identified as good candidates for a cabergoline treatment study (i.e., they are acyclic and had mean prolactin concentrations of >15 ng/ml). The treatment consisted of 1 mg cabergoline given twice weekly PO for six months. Serum was banked and then analyzed at the CRC for progesterone and prolactin.¹ All elephants were thought to be otherwise healthy. Because prolactin is known to be an inflammatory marker,⁴ all candidates were required to have a negative lateral flow immunochromatography (rapid test) and multiple antigen immunoassay (MAPIA) for Mycobacteria tuberculosis.⁵

Results

A summary of the results is given in Table 1. The treatment period is complete for three elephants, all of which showed a decrease in prolactin levels. Elephant 1 showed a good response while on treatment but did not cycle and serum prolactin has subsequently risen to pretreatment levels. Increasing the dose in elephant 2 and 3 reduced prolactin to baseline levels but again, did not result in a return to ovarian cyclicity. Elephant 4 was taken off the study after only a few doses due to increased aggressive behaviors. This is believed to be due to changes in the group social dynamics and not related to the cabergoline, as this behavior has continued after withdrawal of the drug. Based on these findings, the two newest candidates (elephant 5 and 6) with very high prolactin concentrations, have been placed on 2 mg/twice weekly for one year pending continuation of this project.

Table 1. Treatment dates, doses, and responses to cabergoline treatment in captive elephants

^aSerum prolactin.

Discussion

Normalization of prolactin levels facilitated the return of normal cycles in an Asian elephant, but none of the African elephants have resumed cycling so far. Thus, while the use of cabergoline shows promise in reducing elevated prolactin levels in both Asian and African elephants, other factors may need to be considered or a longer course at higher doses may be required, for treatment to be successful in reinitiating ovarian activity. The latter suggestion is supported by two of the animals (elephants 2 and 3) in this limited trial, in which a decline in prolactin occurred after the dose was increased. Understanding the etiology of hyperprolactinemia in elephants may also help in returning females to normal cycling. Relapse of hyperprolactinemia is more common in humans with micro- or macroprolactinomas.² Chronic estrogen stimulation is also known to increase prolactin levels.³ A proposed pathophysiology is that elevated estrogen levels from persistent cycling will lead to elevated prolactin levels and acyclicity. A difference between the two species in the causes of and potential treatment options for hyperprolactinemia should also be evaluated more closely.

Acknowledgments

We would like to thank the participating zoos for their cooperation and patience during this trial.

Literature Cited

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