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Serum concentrations of trenbolone-17 beta and estradiol-17 beta and performance of heifers treated with trenbolone acetate, melengestrol acetate, or estradiol-17 beta.

The effects of the growth-promoting steroids estradiol-17 beta (E2), trenbolone acetate (TBA), and melengestrol acetate (MGA) in heifers on serum concentrations of E2 and trenbolone-17 beta (TBOH) were examined. Feed intake and growth performance were also measured. Serum concentrations of E2 and TBOH were measured on d 0, 1, 3, 5, 7, 13, 21, 28, 42, 56, 84, 112, and 140 in finishing heifers administered the following treatments: 1) control; 2) MGA, .5 mg per heifer daily; 3) Revalor-H (140 mg TBA + 14 mg E2); 4) Revalor-H + MGA; 5) Finaplix-H (200 mg TBA); and 6) Finaplix-H + MGA. Revalor-H implantation (Treatments 3 and 4) increased (P < .05) serum E2 concentrations; peak concentrations (67.5 pg/mL) occurred between d 21 and 56. Feeding MGA (Treatment 4) had no effect (P > .05) on this increase in serum E2 concentrations (63.3 pg/mL). From d 84 until d 140, serum E2 was greater (P < .05) for the Revalor-H treatment (average of 19 pg/mL) than for the control (7 pg/mL) or Finaplix-H treatments (6.5 pg/mL). Serum E2 concentrations increased numerically two- to threefold from d 56 to 140 in controls fed MGA, compared with controls not fed MGA. There was the expected increase in serum TBOH concentrations after TBA implantation in the Revalor-H and Finaplix-H treatments; concentrations were similar (P > .05) for Revalor-H (221 pg/mL) and Finaplix-H (280 pg/mL). After d 56, serum TBOH concentrations decreased in both treatments to 10 and 20% of these concentrations, respectively. Feeding MGA increased serum TBOH (P < .05). Dry matter intake by heifers did not differ among treatments. Feeding of MGA improved gains (P = .12) and efficiencies (P < .01) in nonimplanted heifers and had no effect (P > .4) on gains or efficiencies in Finaplix-implanted heifers.

Anabolic Agents↗

Effect of megestrol acetate or melengestrol acetate on preneoplastic and neoplastic mammary growth in mice.

Pellets of megestrol acetate and melengestrol acetate were implanted subcutaneously every one and two months, respectively, into 3-5 month old SHN virgin mice. Spontaneous mammary tumourigenesis was significantly enhanced by both steroids. The formation of preneoplastic mammary hyperplastic alveolar nodules (HAN) was, in contrast, inhibited by both progestins. As these results closely resemble the effects of progesterone and of medroxyprogesterone acetate on the development of mammary tumours both in the SHN mouse and in the woman, it seems likely that this animal model may prove valuable for the study of human breast cancer that is no longer responsive to progestins.

Animals↗

Clinical, morphologic, and clinicopathologic findings in Beagles treated for two years with melengestrol acetate.

Melengestrol acetate (MGA) was administered orally to groups of 10 female and 3 male Beagles at doses of 0, 1, 2, or 8 microgram/kg of body weight/day for 2 years. Treatment was continuous at the same dose rate in the first 3 groups, but in the 4th group, the dose for bitches was reduced to 4 microgram of MGA/kg/day during the 2nd year. Matings were made within MGA-dosage groups and among 10 additional bitches treated at 1 microgram of MGA/kg/day and the dogs treated at 8 microgram/kg/day. Doses of 8 and 4 microgram of MGS/kg caused progestational effects on the uterus resulting in expected histopathologic changes, dystocia, and pyometritis. Leukocytosis, normocytic, hypochromic anemia, and increased alkaline phosphatase values were the results of systemic and uterine effects consistent with the indirect and expected pharmacologic action of progestational agents in the bitch. Doses of 1 and 2 microgram of MGA/kg in dogs and bitches and 8 microgram/kg in dogs produced no significant differences in clinical observations, hematologic findings, blood chemical analysis, urinalysis, organ weights, or gross and microscopic observations at necropsy.

Alkaline Phosphatase↗

The fate of trenbolone acetate and melengestrol acetate after application as growth promoters in cattle: environmental studies.

The steroids trenbolone acetate (TbA) and melengestrol acetate (MGA) are licensed as growth promoters for farm animals in several meat-exporting countries. Although many studies have explored their safety for both animals and consumers, little is known about their fate after excretion by the animal. Our study aimed to determine the residues and degradation of trenbolone and MGA in solid dung, liquid manure, and soil. In animal experiments lasting 8 weeks, cattle were treated with TbA and MGA. Solid dung and, in case of trenbolone, liquid manure were collected and spread on maize fields after 4.5 and 5.5 months of storage, respectively. Determination of the hormone residues in all samples included extraction, clean-up (solid-phase extraction), separation of metabolites and interfering substances by HPLC (RP-18), and quantification by sensitive enzyme immunoassay. Procedures were validated by mass spectrometry (MS) methods. During storage of liquid manure the level of trenbolone decreased from 1,700 to 1,100 pg/g (17alpha-isomer), corresponding to a half-life of 267 days. Before storage, the concentrations in the dung hill ranged from 5 to 75 ng/g TbOH and from 0.3 to 8 ng/g MGA. After storage, levels up to 10 ng/g trenbolone, and 6 ng/g MGA were detected. In the soil samples trenbolone was traceable up to 8 weeks after fertilization, and MGA was detected even until the end of the cultivation period. The results show that these substances should be investigated further concerning their potential endocrine-disrupting activity in agricultural ecosystems.

Agriculture↗

Quantitative assessment of foetal exposure to trenbolone acetate, zeranol and melengestrol acetate, following maternal dosing in rabbits.

1. Residues of commonly used growth-promoting agents found in animal meat can be hormonally active and they have been implicated as possible endocrine disruptors in man. Although these compounds could be potentially detrimental to the developing foetus, it is not clear whether and to what extent they pass through placental barrier. 2. This issue was addressed using the rabbit as an animal model. Pregnant rabbits were treated with trenbolone acetate, zeranol or melengestrol acetate beginning at gestation day 14. Levels of active substances in plasma were screened by means of specific ELISA systems. The residues of parent compounds and their metabolites were quantified in maternal and foetal tissues on gestation day 27 using validated, sensitive HPLC/ELISA methods. 3. All three compounds crossed the placental barrier and were detectable in foetal tissues. The extent of tissue concentration varied depending on the compound and tissue analysed. Gender differences were observed in some instances.

Abnormalities, Drug-Induced↗

Endometrial hyperplasia and mineralization in zoo felids treated with melengestrol acetate contraceptives.

Melengestrol acetate (MGA) contraceptives are widely used in zoo felids to regulate fertility and may have deleterious effects on endometrial health. To determine whether MGA exposure was associated with endometrial disease, the genital tracts of 212 zoo felids (99 MGA treated and 113 control) representing 23 species were evaluated. Adenomatous and cystic hyperplasia were prevalent in both MGA-treated (85%) and control (61%) groups, and the risk of developing these lesions increased with age. Treatment with MGA further increased the risk of developing advanced hyperplasia regardless of dose, and treatment for >72 months significantly elevated that risk, whereas parous animals had a lower risk. Endometrial polyps, fibrosis, adenomyosis, and hydrometra occurred in both MGA-treated and control animals. MGA treatment was associated with an increased risk of hydrometra and mineralization but not of adenomyosis, polyps, or fibrosis after adjusting for advanced hyperplasia. Acute or chronic endometritis were associated with advanced hyperplasia but not with MGA treatment. These results indicate that proliferative and inflammatory endometrial lesions are common spontaneous diseases in zoo cats, and MGA contraceptives increase the risk of some diseases. The association of MGA with endometrial lesions that could impair fertility should be considered when using this contraceptive in genetically valuable felids.

Animals↗

Melengestrol acetate in experimental diets as an effective alternative to induce a decline in egg production and reversible regression of the reproductive tract in laying hens. I. Determining an effective concentration of melengestrol acetate.

Induced molting increases egg quality and egg production and extends the productive life of hens. Molting is accomplished by feed withdrawal, which has been criticized for not addressing hen well-being, and current alternatives have resulted in poor postmolt performance and inadequate well-being. Molting leads to regression of follicles on the ovary and causes loss of steroidogenic support for the oviduct, leading to cessation of lay. Melengestrol acetate (MGA), an orally active progestin, may decrease support for the ovary, resulting in loss of support for the oviduct, while hens are fed a balanced diet. In this experiment, a dose response study, Hy-Line W-36 hens were fed 0, 0.1, 1, 4, or 8 mg of MGA per hen/d in a balanced diet for 28 d and then returned to a normal diet. Four birds on d 0 and 4 birds per treatment on d 1, 2, 4, 8, 12, 16, 20, 24, 28, 32, 36, 40, and 44 were euthanized. The weight of the ovary with follicles, magnum, shell gland, and oviduct were determined. A decrease in egg production was observed in those groups receiving 4 and 8 mg of MGA, until removal of MGA from the diet. After d 28, egg production increased to the production level of hens fed 0, 0.1, or 1 mg of MGA. The weight of the ovary with follicles, oviduct, magnum, and shell gland were unchanged throughout in groups fed 0, 0.1, or 1 mg of MGA. However, groups fed 4 or 8 mg of MGA exhibited a decrease (P < 0.05) in the weight of the ovary with follicles, oviduct, magnum, and shell gland until d 28. Recrudescence of the large yellow follicles as well as rejuvenation of the oviduct and its components, the magnum and shell gland, in the 4 and 8 mg MGA groups occurred by d 44. Melengestrol acetate, fed to hens on a balanced layer diet, caused reversible regression of follicles and, therefore, removal and return of support for the oviduct.

Aging↗

Effects of melengestrol acetate on reproduction in the Beagle bitch.

Melengestrol acetate orally given to bitches at dose levels of 200 mug or more each day effectively inhibited estrous activity for a treatment period of 243 days and a lapsed period of more than 400 days from the preceding estrous period. The 100-mug dose of the drug, given orally once a day, starting immediately after the bitches were bred or late in gestation, had no effect on conception, pregnancy, or parturition. Gestation was prolonged in bitches given melengestrol acetate starting 1 day after breeding. Drug-polymeric implants blocked reproductive activity, and the progestogen induced cystic endometrial hyperplasia.

Animals↗

A dose-response study of melengestrol acetate on feedlot performance and carcass characteristics of beef steers.

The dose response of melengestrol acetate (MGA) on ADG (kg/d) and gain efficiency (gain/DMI, g/kg) was estimated in beef steers fed a finishing diet under commercial feedlot conditions. Melengestrol acetate is not approved for use in steers as a feed additive. The study design was five blocks of four pens (each pen was assigned a dose of MGA) with 166 to 200 steers per pen. Melengestrol acetate was fed to steers at 0 (n = 899, five pens), 0.1 (n = 900, five pens), 0.2 (n = 899, five pens), and 0.4 (n = 900, five pens) mg of MGA/steer daily. Pens within a block were slaughtered on the same day. Blocks 1 through 5 were fed MGA for 123, 122, 116, 124, and 138 d, respectively. The experimental unit was a pen of steers, and blocking was based on source of steers. The ADG was 1.81, 1.85, 1.80, and 1.83 kg/d for steers fed 0, 0.1, 0.2, and 0.4 mg MGA per day, respectively. For ADG, the dose was significant, but neither linear nor quadratic effects were significant. Compared with steers of the control group, ADG was greater for steers fed 0.1 mg MGA (P < 0.01). Feed efficiencies were 170, 173, 171, and 172 g/kg for steers fed 0, 0.1, 0.2, and 0.4 mg MGA/d, respectively; however, no effects of dose (P = 0.19) or linear (P = 0.21) or quadratic (P > 0.60) effects were observed. There was no evidence for either positive or negative effects of MGA on DMI, hot carcass weight, dressing percent, quality grade, yield grade, back fat thickness, marbling score, longissimus muscle area, and incidence of dark cutter carcasses in response to feeding MGA to steers at doses of 0.1, 0.2, and 0.4 mg daily. The incidence of buller behavior (0.43 to 1.11%) was low and did not permit an accurate test of the clinical observations that feeding MGA to steers decreases the occurrence of buller steers. Melengestrol acetate fed to finishing beef steers produced small improvements in growth performance (ADG, 2.2%) at the 0.1 mg MGA dose, but none of the doses examined produced improvement in carcass quality or yield grade measurements.

Animals↗

Inhibition of pregnancy in heifers, using a repositol formulation of melengestrol acetate.

Efficacy of a repositol formulation of melengestrol acetate (MGA) for inhibition of pregnancy was determined in one hundred 14- to 16-month-old beef heifers. Nonpregnant heifers were allocated on the basis of weight into 5 groups of 20 heifers each and were given 0, 30, 60, 90, or 120 mg of repositol MGA, SC, on day 0. Four bulls, determined to be satisfactory potential breeders, were pastured with the heifers from postinjection days (PID) 7 to 177. The day of gestation was estimated for each heifer by rectal palpation at PID 59, 91, 134, 177, and 225. Heifers not pregnant by PID 177 were assigned a day of conception of greater than 177. For heifers given 0, 30, 60, 90, and 120 mg of MGA, respectively, the percentage pregnant at PID 177 was 95, 95, 50, 15, and 15%, and the median day of estimated conception was PID 21, 87, 175, greater than 177, and greater than 177. Repositol MGA significantly (P less than 0.001) affected the distribution of conception times over all doses. Average daily gain (+/- SEM) for 178 days was 0.28 +/- 0.04 kg, 0.24 +/- 0.03 kg, 0.33 +/- 0.04 kg, 0.40 +/- 0.03 kg, and 0.35 +/- 0.03 kg for heifers given 0, 30, 60, 90, and 120 mg of MGA, respectively. Increased dose of repositol MGA was associated with increased average daily gain, but this effect was not apparent when days pregnant were taken into account. Repositol MGA was an effective contraceptive for pastured heifers and the duration of its effect was dose-dependent.

Animals↗

Determination of melengestrol acetate in bovine tissue: collaborative study.

Seven laboratories collaboratively studied a method for the assay of melengestrol acetate at the 0, 10, and 20 ppb levels in bovine fat, liver, muscle, and kidney. The study included fortification of tissue by each laboratory and analysis of fat samples taken from treated heifers which had endogenous levels of 0, 10, and 20 ppb melengestrol acetate. The multistep cleanup procedure used included extraction, solvent partition, column chromatography, and electron capture gas-liquid chromatographic, determination. Results of the study for muscle, liver, kidney, and fat showed that the method gave satisfactory recoveries and accuracy. In fat, the most critical tissue, recovery was greater than 93%. A statistical comparison of the results reported for fat tissue from treated heifers demonstrated that 5 of the 7 laboratories obtained similar results. The results produced by the method can be expected to be repeatable within and among laboratories. On the basis of the collaborative results the method has been adopted as official first action.

Adipose Tissue↗

Efficacy and effects of short- and medium-term contraception in the common marmoset (Callithrix jacchus) using melengestrol acetate implants.

This study examines the effect of melengestrol acetate (MGA) implants on reproductive function and various biochemical parameters, ovarian activity, and uterine morphology in ten female common marmosets implanted for either 6-8 or 19-21 months. Measures of body weight, concentrations of urinary glucose and blood liver enzymes were taken. Ovarian activity was assessed by analysis of urinary progestin levels and ultrasound examinations of the ovaries. Ultrasonography was also used to evaluate uterine morphology. MGA was highly effective in preventing pregnancies in the study animals. No changes in biochemical parameters were found; however, seven females developed a substantial weight gain during the study. Follicular development was not suppressed, as indicated by the presence of antral follicles, luteinized structures, and elevated urinary progestin levels. The uteri of the MGA-treated subjects were moderately enlarged with a thickened endometrium that showed a marked change in structural appearance indicative of hypertrophy and decidualization. After implant removal these changes quickly disappeared and all females ovulated within 3 weeks and conceived within 4 months post-treatment. MGA appears to be an acceptable contraceptive in the marmoset, although non-steroidal methods should be evaluated as possible potential alternatives.

Animals↗

The effects of melengestrol acetate on the ovaries of captive wild felids.

Melengestrol acetate (MGA) is the most widely used contraceptive in zoo felids, but the mechanism of contraception and the pathologic effects have not been investigated. For this study, the effects of MGA on folliculogenesis were assessed, and the association of MGA with ovarian lesions was evaluated. Comparisons were made among the histopathologic findings in the ovaries from 88 captive wild felids (representing 15 species) divided into three groups: 37 currently contracepted with MGA, eight previously exposed to MGA, and 43 never contracepted. Ninety-one percent of the felids evaluated had tertiary follicles, and no differences were noted between contracepted and uncontracepted cats. Some MGA-contracepted cats also had corpora lutea indicating recent ovulation. These results indicate that folliculogenesis not suppressed by current doses of MGA and ovulation occurred in some cats. Therefore, the contraceptive actions of MGA do not occur by suppressing folliculogenesis, and MGA-contracepted felids likely have endogenous estrogens that may confound progestin effects on the uterus. Cystic rete ovarii was the most common pathologic finding, but they were not more prevalent in MGA-contracepted cats. These findings indicate that MGA is not associated with ovarian disease, including ovarian cancer, in contrast to the uterine lesions noted in MGA-treated cats.

Animals↗

Successful contraception in a herd of Chinese goral (Nemorhaedus goral arnouxianus) with melengestrol acetate.

Thirteen Chinese goral (Nemorhaedus goral arnouxianus) (five males and eight females) were each given 0.8 mg of melengestrol acetate orally in pelleted food for 224 days. The previous breeding season, six of the eight females calved (two were immature). No calf was born during the treatment season. The season after treatment, six females calved (one was immature prior to treatment). Two females were moved to other institutions, and the status of these is unknown. On the basis of this information, melengestrol acetate in feed was successful in preventing conception and was reversible. This treatment did not prevent the siring of offspring the following year and did not prevent a female that was subadult prior to the treatment from calving.

Administration, Oral↗

Evaluation of melengestrol acetate and equine chorionic gonadotropin for out-of-season breeding in sheep on Prince Edward Island.

The purpose of this study was to compare the efficacy of a recommended protocol of oral melengestrol acetate (MGA) to intravaginal medroxyprogesterone acetate (MPA), with or without equine chorionic gonadotropin (eCG), for out-of-season breeding of sheep on Prince Edward Island. One hundred and twenty ewes were assigned to 1 of 4 groups in a factorial design and were treated with either an intravaginal MPA sponge or oral MGA. Ewes received either an intramuscular injection of eCG or a saline placebo at cessation of progestogen treatment. The reproductive performance was best for the MPA-eCG group, followed by the MGA-eCG, MGA-saline, and MPA-saline. Pregnancy rates of 66.7%, 43.3%, 31.0%, and 16.7%, respectively, and ratios of lambs born to ewes exposed to the ram of 1.17, 0.63, 0.52, and 0.23, respectively, were recorded for these groups. We concluded that, under the conditions of this study, the use of oral MGA resulted in fewer lambs than did the use of MPA sponges with eCG. Nonetheless, the use of MGA may be attractive to producers because it is less expensive and more convenient than the use of sponges.

Administration, Intravaginal↗

Effect of melengestrol acetate on growth and reproduction in rats.

Effects of melengestrol acetate on reproductive performance of 48 female rats and 20 of their female progeny were evaluated in two experiments. Treatments of 0, .01, and .1 mg in .1 ml of propylene glycol were given three groups of 16 rats for 7 days. From day 7 following sperm detection (10-day breeding period), half from each group received .1 mg per day for 14 days. Experiment 2 tested performance of 10 progeny exposed or unexposed to in utero treatment. Cyclic changes in Experiment 1 were inhibited only in animals receiving daily initial treatment of .1 mg. Estrus was detected in 61.5% of animals within 48 h of treatment withdrawal. Synchronization caused no significant changes in conception rates or postbreeding results of treatment. Treatment during gestation lowered weight gain for dams, increased gestation length, and decreased number of pups per litter. Treatment lowered mean weight per litter and weight per pup. It also caused high mortality among pups. In Experiment 2, there were no differences between progeny groups in gestation length, litter size, weight per litter, weight per pup, or mortality rate.

Animals↗

Effects of melengestrol acetate on reproductive behavior and concentrations of LH and testosterone in bulls.

We investigated the use of an orally active progestin (melengestrol acetate; MGA) to suppress reproductive activity in yearling beef bulls. Twenty-four crossbred bull calves were given a daily dose of 0, 0.5, 1.0, or 2.0 mg MGA for 99 d. Pulsatile patterns of LH and concentrations of testosterone and MGA were characterized on d 8, 36, 63, and 92 of the experiment. Numbers of aborted mounts, mounts with intromission, total mounts, and flehmen responses were assessed on d 15, 43, 71, and 99. Plasma concentrations of MGA were proportional to dose of MGA. Melengestrol acetate did not consistently affect mounting behavior in a dose-related manner, but, on d 99, number of total mounts for MGA-treated bulls was lower (P = 0.07) than that for control bulls. On d 15, MGA suppressed (P = 0.07) numbers of flehmen responses in a dose-dependent manner, but this effect was not sustained throughout the experiment. On d 8, concentrations of testosterone in control bulls were higher (P = 0.02) than in MGA-treated bulls, but this effect was not observed at other time periods. Overall, MGA caused slight decreases in mean concentrations of LH (P = 0.09) and LH pulse frequency (P = 0.06). Scrotal circumference was not affected by MGA. None of the behavioral traits was correlated with mean concentrations of LH or LH pulse frequency. Mounting activity was not correlated with testosterone concentrations, but number of flehmen responses was positively correlated with testosterone concentrations (P = 0.01). These results fail to support the hypothesis that progestins impair male sexual behavior or fertility in males.

Animals↗

Gas-liquid chromatographic determination of melengestrol acetate in cattle feed supplements: collaborative study.

The assay for melengestrol acetate (MGA) in cattle feed supplements was the subject of a collaborative study using 6 laboratories. Two feed formulations were each fortified with 0, 0.0625, 0.125, 0.500, 1.00, and 1.50 mg MGA/lb of supplement, and each laboratory assayed 4 samples of each level of each formulation by electron capture gas chromatography after liquid-liquid extraction of each sample followed by solvent partition and column chromatography cleanup procedures. Overall recovery was 83.2% with a pooled within-laboratory sample-to-sample standard deviation of 9.5%. This includes the variability due to formulation, batches, days, levels of MGA, samples, and their interactions. Including the collaborators as a source of variance results in an overall standard deviation of 15.0%. The major sources of variability were associated with collaborator, formulation, and level of MGA. Lower than expected recoveries were attributed to difficulty in recovering MGA from samples containing concentrations of MGA below the range of the method and the inadvertent substitution by some laboratories of ethanol-free chloroform for the ethanol-containing reagent grade chloroform specified in the methodology. On the basis of the collaborative results, the method has been adopted as official first action for MGA in cattle feed supplements at concentrations from 0.125 to 1.00 mg MGA/lb.

Acetates↗