ergoline and Weight-Gain

Gender differences in tumor size are supposed to exist in hyperprolactinemia since microadenomas are more commonly found in women and macroadenomas in men. Whether this reflects only a delay in diagnosis in men or a true gender difference in tumor pathogenesis is still unclear.. To prospectively analyze gender differences in the presentation and response to cabergoline treatment in 219 consecutive newly diagnosed patients with hyperprolactinemia.. An open prospective design.. Of the 219 patients of which 145 were women; 107 patients had macroprolactinoma, 97 had microprolactinoma, and 15 had non-tumoral hyperprolactinemia.. Presenting clinical symptoms, prolactin levels and tumor size at magnetic resonance imaging were measured before and 3-6 Months after cabergoline therapy.. Prevalence of microprolactinomas (56% vs 22%, P=<0.0001) and non-tumoral hyperprolactinemia (10% vs 0%, P=0.01) was higher in women than in men. Men and women were of similar age (median 32 vs 29 Years; P=0.2) and a similar number had gonadal/sexual dysfunction (85 vs 83%, P=0.6); weight gain (70 vs 46%; P=<0.0001) and galactorrhea (52 vs 19%; P=<0.0001) were more common in women. Prolactin levels were higher in men than in women, whether exhibiting macro- (2848+/-2954 vs 1132+/-2351 microg/l, P=<0.0001) or microadenomas (187.8+/-51.8 vs 135.4+/-60.5 microg/l, P=0.009) and the size of the adenoma was larger in men than in women irrespective of macro- (25.8+/-12.4 vs 17.2+/-7.2 mm, P=<0.0001) or microadenoma diagnosis (8.0+/-1.4 vs 7.1+/-1.6 mm, P=0.04). After treatment, prolactin levels decreased by 89.2-96.4% in all groups, and normalized more frequently in micro- than in macroadenoma patients (86 vs 64%, P<0.0001), regardless of gender (70% vs 69%, P=0.9). Menses resumed in 82% of women, libido disturbances improved in 57% of men. Tumor size was reduced by 45+/-25% and 52+/-24% in macroprolactinoma patients and by 44+/-31 and 38+/-29% in microprolactinoma patients in women and men respectively. Visual field defects disappeared in 61% of women and in 71% of men (P=0.6).. Prevalence of macroprolactinomas was similar in men and women; microprolactinomas and non-tumoral hyperprolactinemia were more frequent in women. Clinical symptoms at presentation differed according to gender, with galactorrhea and weight gain more frequent in women. The successful response to cabergoline treatment for 6 Months was higher in micro- than in macroprolactinoma patients and was similar in women and men.

Topics: Adolescent; Adult; Aged; Antineoplastic Agents; Cabergoline; Ergolines; Female; Follow-Up Studies; Galactose; Humans; Hyperprolactinemia; Magnetic Resonance Imaging; Male; Middle Aged; Pituitary Neoplasms; Prolactin; Prolactinoma; Prospective Studies; Sex Characteristics; Sexual Dysfunction, Physiological; Treatment Outcome; Visual Fields; Weight Gain

Hyperprolactinemia might be related to weight gain, metabolic syndrome (MS), and insulin resistance (IR). Treatment with dopamine agonist (DA) has been shown to reduce body weight and improve metabolic parameters. The objectives of this study were to determine the prevalence of obesity, overweight, MS, and IR in patients with prolactinoma before and after therapy with DA and to evaluate the relation between prolactin (PRL), body weight, fat distribution, leptin levels, IR, and lipid profile before treatment. In addition, we investigated the correlation of the reduction in PRL levels with weight loss and metabolic profile improvement. Twenty-two patients with prolactinoma completed 6 months of treatment with DA. These patients were submitted to clinical (BMI, waist circumference, blood pressure (BP)), laboratory evaluation (leptin, glucose, low-density lipoprotein (LDL)-cholesterol, and triglyceride (TG) levels) and abdominal computed tomography (CT) before and after treatment. The statistical analyses were done by nonparametric tests. At the beginning of the study, the prevalence of obesity, overweight, MS, and IR was 45, 27, 27, and 18%, respectively. After 6 months of treatment with DA, PRL levels normalized, but no significant difference in BMI was observed. However, there was a significant decrease on homeostasis model assessment of insulin resistance (HOMA(IR)) index, glucose, LDL-cholesterol, and TG levels. This study suggests a possible involvement of prolactinoma on the prevalence of obesity. We should consider that DA may be effective on improving metabolic parameters, and we speculate that a period longer than 6 months of treatment is necessary to conclude whether this drug can interfere in the body weight of patients with prolactinoma.

Topics: Adult; Aftercare; Aged; Blood Glucose; Body Composition; Body Mass Index; Body Weight; Bromocriptine; Cabergoline; Cholesterol, HDL; Cholesterol, LDL; Dopamine Agonists; Ergolines; Female; Humans; Insulin; Insulin Resistance; Leptin; Male; Metabolic Syndrome; Metabolome; Middle Aged; Obesity; Prevalence; Prolactinoma; Waist Circumference; Weight Gain; Young Adult

The dietary subacute toxicity of the ergot alkaloid alpha-ergocryptine was studied in Sprague-Dawley rats. Rats were fed 0, 4, 20, 100 or 500 mg ergocryptine/kg diet for 28-32 days (equal to 0, 0.36, 1.7, 8.9 and 60 mg ergocryptine/kg body weight/day for females and 0, 0.34, 1.4, 6.6 and 44 mg ergocryptine/kg body weight/day for males). The present study describes the general toxicological effects; the effects on metabolic and hormonal parameters will be reported separately. Body weight, body weight gain, food intake and food efficiency were all decreased with a U-shaped dose-response curve, as in both sexes the ranking severity of effects was in the order 100-20-500 and 4 mg/kg diet. Other changes with a U-shaped dose-response relationship included: hematological parameters (decreased MCV and MCH), serum enzyme activities (slightly increased/decreased ALAT, ASAT, GGT), increased serum urea concentrations, decreased glomular filtration (creatinine and urea clearances), decreased absolute organ weights, increased and decreased relative organ weights, atrophy of thymus and in females atrophy of ovary and uterus with in the mid-dose groups no detectable morphological features of an oestric cycle in the uterus. Other parameters, including increased relative liver, heart and ovarian weights and necrosis of the tail, were influenced in a dose-related manner or only in the high dose group. The U-shaped changes for the parameters mentioned above might be caused by the U-shaped dose-response relationship for food intake, which may be explained by the dopaminergic properties of alpha-ergocryptine. It is concluded that in rats fed ergocryptine for 28 days the dose-effect curve is rather steep and that the NOAEL is 4 mg/kg diet.

Topics: Animals; Body Weight; Clinical Chemistry Tests; Dopamine Agonists; Dose-Response Relationship, Drug; Eating; Energy Metabolism; Ergolines; Estrus; Female; Male; No-Observed-Adverse-Effect Level; Organ Size; Rats; Rats, Sprague-Dawley; Weight Gain

Amesergide is a selective serotonin 5-HTIC/2 receptor antagonist being developed for the treatment of depression. The potential developmental toxicity of amesergide was evaluated in CD rats and New Zealand white rabbits. Pregnant rats and rabbits were dosed once daily by gavage on Gestation Days 6-17 and 6-18, respectively. Doses for rats were 0, 3, 10, and 30 mg/kg; doses for rabbits and 0, 0.2, 2, and 15 mg/kg. Cesarean sections were performed on rats and rabbits on Gestation Days 20 and 28, respectively. In rats, maternal effects expressed as depression of body weight gain and food consumption were observed at the 30 mg/kg dose level. Fetal viability and morphology were not affected at any dose level. Fetal weight was depressed at the 30 mg/kg dose level. The no-observed-effect level (NOEL) in the rat was 10 mg/kg. In rabbits, maternal effects expressed as a decrease in food consumption occurred at the 2 and 15 mg/kg dose levels; weight gain was depressed at 15 mg/kg. Fetal viability, weight, and morphology were not affected at any dose level. The NOELs for maternal and developmental effects in the rabbit were 0.2 and 15 mg/kg, respectively.

Topics: Abnormalities, Drug-Induced; Animals; Eating; Ergolines; Female; Fetal Viability; Fetus; Intubation, Gastrointestinal; Pregnancy; Rabbits; Rats; Rats, Sprague-Dawley; Serotonin Antagonists; Teratogens; Uterus; Weight Gain

To determine the effects of chronic perinatal exposure to a kappa opioid agonist on the neurochemical and motor development of rat offspring, osmotic pumps containing trans-(+-)-3,4-dichloro-N-methyl-N-[2-(1-pyrrolidinyl)-cyclohexyl]- benzeneacetamide methane sulfonate (U-50,488H), 79 mg/ml, or vehicle were implanted into anesthetized pregnant female rats. On postnatal day 10, the nucleus accumbens (NAc) of male offspring were dissected and assayed for dopamine (DA) receptors. Male offspring from other litters were injected subcutaneously with the D2 agonist quinpirole, 0.05 mg/kg, the D1 agonist SKF 38393, 10 mg/kg, or 0.9% saline vehicle. Their locomotor activity was then monitored for 1 h. The binding of DA D1 and D2 receptors was significantly increased by 26% and 90%, respectively, in the NAc of 10-day-old offspring exposed to U-50,488H. There was a significant, 52%, decrease in the locomotor response to quinpirole by 10-day-old offspring exposed to U-50,488H. Exposure to U-50,488H had no significant effect on the locomotor response to SKF 38393 at this age. The results indicate that perinatal exposure to a kappa agonist alters the development of brain DA receptors and DA-mediated motor behavior. The data suggest that motor deficits observed in offspring exposed to opioids in utero may involve brain kappa opioid receptor mechanisms.

Topics: 2,3,4,5-Tetrahydro-7,8-dihydroxy-1-phenyl-1H-3-benzazepine; 3,4-Dichloro-N-methyl-N-(2-(1-pyrrolidinyl)-cyclohexyl)-benzeneacetamide, (trans)-Isomer; Animals; Ergolines; Feeding Behavior; Female; Litter Size; Male; Motor Activity; Nucleus Accumbens; Pregnancy; Prenatal Exposure Delayed Effects; Pyrrolidines; Quinpirole; Rats; Rats, Sprague-Dawley; Receptors, Dopamine; Receptors, Dopamine D1; Receptors, Dopamine D2; Receptors, Opioid, kappa; Weight Gain