RECURRENCE OF HYPERPROLACTINEMIA AND CONTINUATION OF OVARIAN ACYCLICITY IN CAPTIVE AFRICAN ELEPHANTS (LOXODONTA AFRICANA) TREATED WITH CABERGOLINE

Abstract

Hyperprolactinemia is associated with reproductive acyclicity in zoo African elephants (Loxodonta africana) and may contribute to the non-self-sustainability of the captive population in North America. It is a common cause of infertility in women and other mammals and can be treated with the dopamine agonist cabergoline. The objectives of this study were to assess prolactin responses to cabergoline treatment in hyperprolactinemic, acyclic African elephants and to determine the subsequent impact on ovarian cyclic activity. Five elephants, diagnosed as hyperprolactinemic (>11 ng/ml prolactin) and acyclic (maintenance of baseline progestagens for at least 1 yr), were treated with 1-2 mg cabergoline orally twice weekly for 16-82 wk. Cabergoline reduced (P < 0.05) serum prolactin concentrations during the treatment period compared to pretreatment levels in four of five elephants (11.5 +/- 3.2 vs. 9.1 +/- 3.4 ng/ml; 20.3 +/- 16.7 vs. 7.9 +/- 9.8 ng/ml; 26.4 +/- 15.0 vs. 6.8 +/- 1.5 ng/ml; 42.2 +/- 22.6 vs. 18.6 +/- 8.9 ng/ml). However, none of the females resumed ovarian cyclicity based on serum progestagen analyses up to 1 yr posttreatment. In addition, within 1 to 6 wk after cessation of oral cabergoline, serum prolactin concentrations returned to concentrations that were as high as or higher than before treatment (P < 0.05). One elephant that exhibited the highest pretreatment prolactin concentration (75.2 +/- 10.5 ng/ml) did not respond to cabergoline and maintained elevated levels throughout the study. Thus, oral cabergoline administration reduced prolactin concentrations in elephants with hyperprolactinemia, but there was no resumption of ovarian cyclicity, and a significant prolactin rebound effect was observed. It is possible that higher doses or longer treatment intervals may be required for cabergoline treatment to result in permanent suppression of prolactin secretion and to mitigate associated ovarian cycle problems.

Reproductive Health Assessment of Female Elephants in North American Zoos and Association of Husbandry Practices with Reproductive Dysfunction in African Elephants (Loxodonta africana)

“…However, too much prolactin can have negative consequences for normal ovarian function [ 20 – 22 ]. Prolactin is under inhibitory control from hypothalamic dopamine, and a similar mechanism is suggested for elephants based on observations of expected changes in prolactin secretion after administration of dopamine agonists and antagonists [ 5 , 28 ]. Hyperprolactinemia is often related to the development of prolactinomas, the most common pituitary tumor, as a result of reduced dopamine concentrations or sensitivity, or vasculature isolation that prevents dopamine from reaching the lactotrophs [ 26 , 27 ].…”

“…The negative effects of chronic elevated prolactin secretion on reproductive function generally involve inhibition of hypothalamic GnRH release and subsequent suppression of pituitary LH and FSH secretion, resulting in anovulation [ 25 ]. Pituitary prolactin secretion is under inhibitory control by dopamine [ 25 – 27 ] and there is evidence the same negative feedback mechanism works in elephants, based on findings that a dopamine agonist (cabergoline) decreases and an antagonist (domperidone) increases prolactin secretion [ 5 , 28 ]. In addition to hypothalamic inhibition by dopamine, other factors can stimulate prolactin synthesis or have a suppressive effect on dopaminergic tone: vasoactive intestinal polypeptide, estradiol, serotonin, oxytocin, thyrotropin-releasing hormone (TSH) and vasopressin [ 29 ].…”

Zoo elephant research: contributions to conservation of captive and free‐ranging species

“…For this reason, research goals may at times appear diametrically opposed. For example, studies have focused on ways to improve the reproductive performance of captive elephants (Morfeld, Ball & Brown, ), while immunocontraception is being developed as a management tool for controlling free‐ranging populations in resource‐limited habitats (Bechert & Fraker, ).…”

Prolonged ovarian acyclicity is associated with a higher likelihood of developing hyperprolactinemia in zoo female African elephants

“…In other species, prolactin is controlled primarily through a dopamine negative feedback mechanism, and in women can be treated with drugs that increase dopamine production (Moult, Rees, & Besser, ). A clinical trial with one such agonist, cabergoline, in hyperprolactinemic African elephants (1–2 mg twice weekly for 4–12 months; n = 8) ended with mixed results (Ball & Brown, ; Morfeld et al, ). Prolactin was decreased significantly in all but one of the females, but only during treatment.…”

“…In general, blood samples were collected once or twice a week without anesthesia from either an ear or leg vein, as part of routine hormone monitoring performed at the Smithsonian Conservation Biology Institute (SCBI), and in conjunction with other studies (e.g., Brown & Lehnhardt, ; Brown et al, , 2016; Dow & Brown, ; Morfeld, Ball, & Brown, ; Prado‐Oviedo et al, ), including the Using Science to Understand Zoo Elephant Welfare study (Carlstead, Mench, Meehan, & Brown, ). Serum samples collected for the 2012 elephant welfare study were used to establish current cyclicity and prolactin status for all elephants included in this study ( n = 78 at 37 institutions).…”