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Patients were randomly divided into two groups. Group A comprised 21 patients who used unidirectional buccoadhesive bromocriptine methylate discs once daily for 1 month. Group B included 21 patients who used vaginoadhesive bromocriptine methylate discs once daily for 1 month. Serum prolactin (PRL) was measured before and after therapy in all cases.
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To study the prevalence of osteoporosis and hyperandrogenism in neuroleptic-induced hyperprolactinemia, the authors evaluated 10 patients. Three were amenorrheic, while seven had oligomenorrhea. Nine patients had galactorrhea. The Ferriman-Gallway hirsutism score was 12 +/- 2. Vaginal smear maturation value was 53 +/- 8. Bone density, measured by dual photon absorptionometry in the spine, femoral neck, Ward's triangle, and trochanteric region, was 98 +/- 1.5, 92.7 +/- 3, 88.5 +/- 4.2, and 92.6 +/- 3.3 percentile of controls matched for age, sex, weight, and ethnicity, respectively. Serum prolactin, follicle-stimulating hormone (FSH), luteinizing hormone (LH), dehydroepiandrosterone sulfate (DHEAS), total testosterone, and free testosterone were 82 +/- 10 ng/ml, 8.5 +/- 1.1 mIU/ml, 11.1 +/- 2.6 mIU/ml, 4695 +/- 594 ng/ml, 90 +/- 17 ng%, and 2.36% +/- 0.3%, respectively. Serum thyroid-stimulating hormone (TSH) and free thyroxine index were normal. Bone density strongly correlated with vaginal maturation value (r = 0.904, P less than 0.01). It is concluded that (1) neuroleptic-induced hyperprolactinemia is associated with hirsutism and androgen excess primarily of adrenal origin and (2) a subset of these patients is at an increased risk of developing osteoporosis. It may be possible to identify patients at risk of osteoporosis by examining vaginal smears for maturation value. Early detection and management are imperative in this group of patients.
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Twenty-five patients with acromegaly were treated by transsphenoidal microsurgery. Fourteen patients (56%) were considered cured according to the following criteria: a. basal plasma GH less than 10 mU/l; b. glucose suppressed plasma GH less than or equal to 4 mU/l, and c. disappearance of TRH responsiveness if present preoperatively. Thirteen of the cured patients were re-evaluated after a mean follow-up period of 3.5 years (range 1.5 to 5.5 years). At that time, basal plasma GH was still less than 10 mU/l and glucose suppressed plasma GH was still less than or equal to 4 mU/l in all patients, indicating the practical value of our criteria. The remaining 11 patients (44%) received additional treatment by external pituitary irradiation and bromocriptine. Owing to surgery, 5 patients (20%) developed partial or panhypopituitarism.
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PRL responses to 200 microgram of iv TRH were measured in 16 healthy women with normal early pregnancy before and at the endo of bromocriptine treatment of 5.0--7.5 mg daily for 1--2 weeks. Before the start of bromocriptine, TRH caused a PRL elevation from 19.1 +/- 2.2 to 95.2 +/- 12.6 ng/ml (mean +/- SE) after 20 min, with a mean maximal PRL increment of 71.7 +/- 11.6 ng/ml. Bromocriptine suppressed basal plasma PRL level to 3.6 +/- 0.8 ng/ml (P less than 0.001). TRH then caused a PRL rise to 18.8 +/- 1.8 ng/ml at 20 min, with a mean maximal PRL increment of 15.7 +/- 1.8 ng/ml. The absolute PRL response was significantly smaller (P less than 0.001) during bromocriptine intake than before, whereas the mean percent increments in PRL levels after TRH administration were similar in the presence and absence of bromocriptine. Fifteen of these women were restudied with TRH stimulation 4--6 weeks after legal abortion, and the PRL responses to TRH were normal. When 7 of these women were once again treated with bromocriptine and retested with TRH, no absolute or relative PRL response to TRH emerged. These results release differs between the pregnant and nonpregnant states.
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To study the prolactin secretion and its dependence on the sex steroid concentrations during pregnancy, we measured the circulating prolactin, oestradiol-17 beta, progesterone and testosterone levels following vacuum curettage for termination of early pregnancy in 10 normal women and in 10 other women whose prolactin levels had been lowered with bromocriptine treatment. In normal women, anaesthesia and vacuum curettage led to consistent and significant (p < 0.01) rises in prolactin levels between 0.5 to 5 hours after abortion. This increase was not seen in women treated with bromocriptine whose prolactin level of 8.6 +/- 1.4 ng/ml (mean +/- SE) before abortion was lower than that of 29.6 +/- 6.4 ng/ml found in normal women. The oestradiol and progesterone concentrations decreased rapidly but similarly in both groups of patients following the evacuation of the uterus, whereas the testosterone level did not change significantly. These results indicate: (i) vacuum curettage stimulates prolactin secretion, (ii) the prolactin-stimulating effect of stress appears to be stronger than the prolactin-suppressing effect of postabortal oestradiol and/or progesterone declines, and (iii) bromocriptine blocks the stress-induced prolactin rise.
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1) In selected cases the conservative treatment of young women diagnosed with type I endometrial carcinoma Stage I A/G1 could be indicated. 2) Conservative pharmacological treatment of young women with well-defined endometrial carcinoma Stage I A/G1 type I should be monitored with followup histopathological examinations of material obtained from D&C of the endometrium and assessment of concentrations of sex hormones in the serum. 3) This kind of therapy requires frequent and thorough gynecological and clinical follow-up.
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To assess the effectiveness of dopamine agonist bromocriptine in reducing the incidence and severity of OHSS in patients undergoing assisted reproduction and its effect on pregnancy rates.
Young female mice were grouped on Day 21 after birth and subjected to removal of the vomeronasal organ. Soiled bedding from intact adult males failed to advance the onset of first oestrus in these lesioned mice compared to the various control groups. Vomeronasal organ lesions of prepubertal females also prevented increases in uterine weight following exposure to soiled bedding for 48 h on Day 23 when compared to controls. Lowering prolactin by injections of bromocriptine for 48 h on Day 26, but not Day 23, advanced the onset of puberty in intact and vomeronasal organ-lesioned females. Elevating prolactin by injections of domperidone were without effect on the early onset of oestrus when compared to sham-injected controls. It is concluded that marked similarities exist in both the receptor system and neuroendocrine mechanism of male pheromone action observed in prepubertal females and that seen in the adult.
1. The effects of treatment with the dopaminergic agonist bromocriptine were studied in nine patients with essential hypertension receiving methyldopa as sole therapy. 2. In Phase 1 of the study, the addition of bromocriptine on a single-blind basis caused a significant fall in lying and standing blood pressures. Plasma prolactin fell significantly but there was no significant change in the other biochemical parameters measured. All patients volunteered that they felt a sense of well-being after starting bromocriptine treatment. 3. In Phase 2 of the study the substitution of placebo for bromocriptine in a randomized double-blind trial significantly increased lying and standing blood pressures and plasma prolactin. No consistent or significant changes were observed in methyldopa-induced side-effects following the substitution of placebo for bromocriptine. 4. In Phase 3 of the study, a gradual increase in blood pressure was observed in all patients over a few months after stopping bromocriptine therapy. 5. The significance of these findings in relation to the role played by plasma prolactin and central dopaminergic activity in blood pressure regulation is discussed.
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This report describes 200 women in the childbearing age group with prolactin-secreting pituitary adenomas treated by transsphenoidal microsurgery. There were 136 patients with microadenomas (10 mm or less in diameter), 30 with macroadenomas, 11 with invasive adenomas, and one with hyperplasia. The overall rate for postoperative normalization of serum prolactin was 57%, and it was 72% for those patients with microadenomas. Pregnancy was desired by 90 women, and 78 (84%) became pregnant, although 10 required postoperative bromocriptine to do so. Serious postoperative complications were rare, and produced no major morbidity. The results of surgery were most favorable in women with microadenomas and preoperative serum prolactin levels of 100 ng/ml or less.
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The dopamine agonist bromocriptine and L-dopa significantly inhibited whereas dopamine antagonist haloperidol aggravated the gastric lesions induced by pylorus ligation in mice as found earlier for rats. Furthermore, the successful use of a dopamine antagonist alone for the induction of gastric lesions also in mice was demonstrated, since the gastric lesions were induced by a single dose of haloperidol without any additional noxious treatment. Bromocriptine successfully inhibited both the gastric lesion-potentiating as well as the gastric lesion-inducing effect of haloperidol.
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34 crossbred and purebred bitches referred for possible pregnancy termination. Seven additional pregnant bitches were used as controls.
Bromocriptine has been found to be an effective agent in the treatment of advanced cancer of the uterine cervix, and it was thus possible that the tumours were prolactin-dependent. A prolactin receptor assay was established and validated, but no receptors were found in cervical tissue whether normal or with benign or malignant disease. It is unlikely that cervical tumours are prolactin-dependent.
Parkinson's disease is a neurodegenerative disorder characterized mainly by a loss of the dopaminergic neurons of the nigrostriatal pathway. The symptomatic treatment, which consists of the supply of the deficient neurotransmitter dopamine, does not, however, prevent the progression of the disease and is frequently associated with major motor and psychiatric side effects. Recent basic and clinical investigations have led to the development of new therapeutical strategies for Parkinson's disease. The authors review and describe these new approaches which include:  treatments aimed at slowing down the progression of the disease,  treatments aimed at decreasing the motor side effects and  the use of intracerebral transplantations.
Student's t test and proportion test were used.
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There was a history of menorrhagia, swelling of the feet and increasing coarsening of the facial appearance. She had biochemical evidence of acromegaly and subsequently had a transsphenoidal macroadenectomy. There was postoperative clinical and biochemical remission. Magnetic resonance imaging done six months postsurgery showed no evidence of tumour regrowth. Clinical and biochemical evidence of acromegaly recurred after pregnancy. Magnetic resonance imaging confirmed tumour regrowth.
A macroprolactinoma recurred in a 25-year-old lady, who had initially presented with inability to conceive, secondary amenorrhea, galactorrhea and persistent headache. She was diagnosed as a patient of pituitary macroadenoma of 1.7 cm with elevated serum prolactin level. She was given Bromocriptine, which normalized her menstruation as well as the prolactin level followed by conception during treatment. Pregnancy remained uneventful till 27 weeks when she developed severe headache and total loss of vision from left eye and partial from right eye at 27 weeks. MRI showed enlargement of macroadenoma upto 2.5 cm with compression on optic chiasma. Transsphenoidal adenectomy was performed. After surgery visual field defect improved but plasma prolactin level remained elevated. She delivered vaginally at 39 weeks. Later, treatment with Bromocriptine (15 mg/day) failed to keep prolactin level normal and Lisuride hydrogen (0.8 mg/day) reduced the prolactin levels.
Prolactin was isolated and identified as a separate pituitary hormone distinct from human growth hormone. Since that time a rapidly expanding literature has accumulated on the physiology of pituitary prolactin secretion in normal and pathologic conditions. Currently the physiology and pathophysiology of pituitary prolactin secretion are under intensive investigation. Development of sensitive, specific radioimmunoassay for prolactin and improved roentgenographic techniques have increased the diagnostic acumen for incipient pituitary microadenomas. Dynamic function tests of prolactin secretion have not helped to distinguish whether a patient has a microadenoma or not. The basal prolactin level is probably the most useful single investigation for diagnosis a pituitary tumour. If women with pituitary tumours have ovulation induced with bromocriptine therapy, then there is a considerable risk of rapid enlargement of the tumour with the development of serious visual field defects often during the last trimester. The precise level of the risk is not clear, but is probably not great. The introduction of bromocriptine has heralded a major change in the menagement of the hyperprolactinaemia-hypogonadism syndromes and resulted in safer and easier treatment of many cases of infertility, menstrual disorders and, to a lesser extent of impotence. At present, bromocriptine therapy is the treatment of choice for hyperprolactinaemia.
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The return of menses in amenorrheic normoprolactinemic women after treatment with bromocriptine is well documented. To determine whether an increased pituitary prolactin-secreting capacity may be the underlying mechanism, 14 women with amenorrhea were studied. None complained of galactorrhea, but in all 14 it was possible to express a few drops of milk from the nipple. All women were normoprolactinemic and had normal sellar tomography. A standard thyrotropin-releasing hormone (TRH) test was performed and bromocriptine (2.5 mg twice daily) was administered. Within 8 weeks, 9 of 14 patients had return of menses. The second group of five patients did not respond to bromocriptine. The mean prolactin response to TRH was significantly greater in those women who experienced return of menses, although there was individual overlap between both groups. This finding suggests that enhanced prolactin secretory capacity may account for amenorrhea is some apparently normoprolactinemic patients. The TRH test may serve to identify those patients who may benefit from bromocriptine.
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Single 1, 2, 5 and 10mg doses of pergolide produced mean peak plasma concentrations (Cmax) of 2.09, 4.57, 20.3 and 26 μg/L, respectively, in rhesus monkeys (administration of therapeutic doses to volunteers was considered unethical). The time to Cmax ranged between 2.4 and 2.7 hours at all dose levels. Mean steady-state pergolide plasma concentrations of 0.0275 to 1.167 μg/L were recorded during treatment with pergolide 2.25 to 9 mg/day in patients with Parkinson's disease; extensive interpatient variability was noted. 55% of a 0.138mg radiolabelled oral dose of pergolide was excreted in the urine of volunteers; a further 40 to 50% of radioactivity appeared in the faeces and approximately 3% appeared in expired air. Analysis of urine and faecal extracts indicated the formation of 10 or more metabolites.
We report four patients with Parkinson's disease who had an unusual pattern of severe chorea and dystonia in the evenings only. The temporal pattern of abnormal movements and simultaneous monitoring of plasma levodopa and clinical state were consistent with dyskinesias associated with subtherapeutic (low dopa dyskinesias) rather than peak concentrations of levodopa (high dopa dyskinesias). In two patients, addition of a direct-acting dopamine receptor agonist was helpful in ameliorating this complication of antiparkinson therapy.
At 24 weeks, pramipexole alleviated LID with more efficiency in the switch group.
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From July 1981 to September 1988, 106 infertile patients with hyperprolactinemia treated with bromocriptine were reviewed retrospectively with special attention to the dosage of bromocriptine and the evaluation of infertility before treatment 84 patients (79.2%) became pregnant. The patients were divided into 3 groups according to the following doses of bromocriptine: 7.5, 5.0, and less than 5.0 mg/day. The pregnancy rate was 90.7%, 84.6%, and 66.7% respectively with the highest at 7.5mg/day, which was significantly higher than that at less than 5.0mg/day (P less than 0.02). The average duration from treatment to pregnancy was 3.6, 3.4, and 7.4 months respectively. The duration in the less than 5mg/day group was twice that in the other two groups. 84.5% of the pregnancies occurred within 6 months of treatment. Pretreatment of organic lesions and additional therapy for induction of ovulation were given to 29.8% of patients who later became pregnant. Systematic evaluation of the causes of infertility other than hyperprolactinemia before the use of bromocriptine and an optimal dose of 5-7.5mg/day will give the best results.
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Glycoprotein-secreting pituitary tumors are uncommon. With increased awareness that pituitary tumors may secrete FSH, LH, TSH, and the alpha-subunit, either as a sole product or in any combination, these tumors are more likely to be recognized. The standard therapy is surgical resection and, possibly, postoperative radiotherapy for residual tumor mass or persistent hormonal secretion. We report a patient with a FSH- and alpha-subunit-secreting tumor who refused surgery and was treated with the dopamine agonist bromocriptine as primary therapy. Bromocriptine treatment resulted in reduction of serum FSH and alpha-subunit levels to normal, improvement of visual field defects, and improvement in hypogonadism despite lack of demonstrable change in tumor size, as assessed by computed tomographic scan. Chromatographic analysis of the serum revealed distinct peaks corresponding to those of labeled FSH and alpha-subunit. The clinical and biochemical responses in this patient suggest that some glycoprotein-secreting tumors may be responsive to dopamine agonist therapy.