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PubMed1982

[Pathological changes of prolactinomas treated with bromocriptine].

In order to investigate the pathological changes of prolactinomas induced by the treatment with bromocriptine, 12 cases of prolactinoma were studied using immunocytology and electronmicroscopy. Eight cases were treated with bromocriptine, 5 mg/day, for a few days before surgery, while 4 cases were given for several months. 1) Cases of the short-term administration All of the adenomas except one appeared to be eosinophilic by H-E stain. Electronmicroscopically, abundant secretory granules, measuring 100-350 nm, were found throughout the cytoplasm, while exocytosis, frequently seen in the common type of prolactinomas, could not be observed. With immunostains, prolactin was diffusely positive in the cytoplasm of most adenoma cells, though the intensity of immunostaining for prolactin was relatively faint compared with that of normal prolactin cells or usual prolactinomas. Immunoreactive prolactin was demonstrated on accumulated secretory granules, while it was negative in the Golgi apparatus and rough endoplasmic reticulum (ER). 2) Cases of the long-term administration The tumors corresponded to chromophobe adenomas and the immunoperoxidase techniques revealed the absence of prolactin in the cytoplasm. Electronmicroscopically, secretory granules, measuring about 100 nm, were infrequent and lined up along the cell membrane. Marked shrinkage of the Golgi apparatus and ER was noted with various stages of degenerative changes in adenoma cells. In conclusion, bromocriptine not only inhibits the release of prolactin, but also suppresses the synthesis of it at the initial phase. With a long-term administration of bromocriptine, the cell organelles related to the hormone production, such as the Golgi apparatus and ER show gradual shrinkage under the prolonged tonic inhibition for prolactin release and synthesis. This might be the mechanism by which bromocriptine leads prolactinomas to the shrinkage.

Adenoma↗
PubMed1982

[Effect of bromocriptine on the endocrine profile during pregnancy].

In this paper, we revealed the changes in maternal plasma concentration of PRL, HCG, HPL, progesterone (P), estradiol-17 beta (E2), estriol (E3), estetrol (E4) and dehydroepiandrosterone-sulfate (DHEA-S) after the administration of bromocriptine during pregnancy. Blood samples were collected from 23 women with gestation ranging from 7 to 28 weeks. Sixteen patients had therapeutic abortion and other 7 patients had inevitable abortion. PRL, HCG, HPL, P, E2, E3, E4 and DHEA-S were measured by radioimmunoassay. The PRL decreased significantly at 120 and 180 minutes after the administration of bromocriptine in any case. In 4 cases out of 10 cases in early normal pregnancy, plasma E2 level decreased to 50% lower than the basal level, but no significant change of E2 occurred after bromocriptine in early and mid pregnancy. Bromocriptine made no change in HCG, HPL, P, E3, E4 and DHEA-S for any group. Our data suggested that bromocriptine had effect on only plasma PRL level, and this drug or the change of PRL level had no effect on P, estrogen, DHEA-S, HPL and HCG concentration during pregnancy.

Bromocriptine↗
PubMedDate not supplied

Additional antitumoral effects of bromocriptine and radiotherapy in patients with prolactinomas or acromegaly.

Thirteen patients with prolactin-secreting and/or growth hormone secreting pituitary tumours have been treated with bromocriptine in doses of about 10 mg/day for several months. Nine of these patients were previously submitted to external or interstitial radiotherapy and one case to pituitary microsurgery. Serum prolactin concentration in patients with prolactinomas was still very high within one year after pituitary irradiation or operation, i.e. 5,125.6 +/- 974 mU/l (mean +/- SEM). It has been reduced to normal level only during bromocriptine therapy, i.e. to 329.1 +/- 88mU/l (p less than 0.001), and increased thereafter, but remained to a significantly lower concentration than before bromocriptine treatment, i.e. 2,709.0 +/- 553 mU/l (p less than 0.05). Serial pneumonecephalotomography has demonstrated the reduction of tumour size afrer bromcriptine therapy to two prolactinomas with suprasellar extension. In patients with acromegaly the effects of bromocriptine were less evident. The antitumoral effects of bromocriptine on prolactin-secreting adenomas is independent and additional to the effects of pituitary radiotherapy or microsurgery, and has therapeuticical implications.

Acromegaly↗
PubMed1981

Antihypertensive action of bromocriptine in neurogenic hypertensive dogs.

The effects of bromocriptine, a dopamine agonist, were studied on blood pressure and heart rate in neurogenic hypertensive (sino-aortic denervated) anaesthetized dogs. Bromocriptine induced a very marked decrease in blood pressure but failed to modify the values of heart rate under our experimental conditions. This anti-hypertensive action of bromocriptine was abolished by pretreatment with dopamine antagonists: haloperidol, sulpiride or metoclopramide. Bilateral nephrectomy or ligature of both renal and mesenteric arteries (i.e. exclusion of the two major beds with postsynaptic dopaminergic receptors) failed to suppress the decrease in blood pressure elicited by bromocriptine in neurogenic hypertensive dogs. These results suggest that the antihypertensive action of bromocriptine in neurogenic hypertensive dogs was mainly due to an action on presynaptic and/or ganglionic peripheral dopaminergic receptors located on sympathetic nerve endings. The potential future importance of dopaminergic agonists as antihypertensive drugs is discussed.

Animals↗
PubMed1994

Prolactin levels in infertility and bromocriptine therapy in hyperprolactinaemia.

Serum prolactin levels were estimated in 100 infertile patients along with the other investigations for infertility. Hyperprolactinaemia was noted in 41% of the infertile patients. Prevalence of hyperprolactinaemia was greater in patients with ovulatory cycles ie, 55% compared to 31.66% in patients with anovulatory and oligo-ovulatory cycles. Fifty per cent of the patients with regular menses had hyperprolactinaemia. Conception occurred in 9 out of 18 hyperprolactinaemic infertile patients (a pregnancy rate of 50%) treated with bromocriptine. Eleven patients (group 1) were treated with bromocriptine from day 5 to day 30 throughout the menstrual cycle and 5 conceptions occurred. Six patients (group 2) with ovulatory cycles were treated with bromocriptine during the luteal phase, from the day of ovulation till next menses and 4 conceived. One patient of prolactinoma treated with bromocriptine failed to conceive. Bromocriptine therapy restricted to the luteal phase in ovulatory patients has yielded successful results. Based on these observations it is suggested that all patients of infertility need serum prolactin estimation.

Adult↗
PubMed1994

Inhibition of growth of human small cell lung cancer by bromocriptine.

Bromocriptine, a dopaminergic agonist, inhibited the growth of human small cell lung cancer (SCLC) implanted as tumor xenografts in athymic nude mice; the effect was dose dependent. In mice bearing a SCLC with ectopic vasopressin production, plasma levels of human vasopressin-associated neurophysin decreased concomitantly. Electron microscopy of tumor tissues revealed marked degenerative changes, including pyknosis, densely aggregated chromatin masses, and vacuolization of cytoplasm after bromocriptine treatment. When a SCLC cell line, NCI-H69, was grown in semisolid medium, bromocriptine inhibited its clonal growth in a dose-related manner. Coincubation with dopamine D2 receptor antagonist, metoclopramide, or domperidone, completely blocked the inhibitory effect of bromocriptine. Receptor studies with a dopamine D2 receptor ligand, [125I]iodosulpride, showed high affinity binding sites on the membranes of SCLC cells. These results indicate that SCLC cells are enriched with dopamine D2 receptors, which may mediate the growth-inhibitory effect of bromocriptine on SCLC. Dopaminergic agonists may be useful in the medical treatment of SCLC.

Animals↗
PubMed1994

Relationship between pituitary reserve and efficacy of bromocriptine in women with euprolactinemic ovulatory dysfunction.

To evaluate the relationship between pituitary reserve and efficacy of bromocriptine therapy in patients with euprolactinemic ovulatory dysfunction, the responses of prolactin (PRL) to thyrotropin-releasing hormone (TRH) and luteinizing hormone (LH), follicle-stimulating hormone (FSH) to gonadotropin-releasing hormone (GnRH) provocation in 46 anovulatory patients were compared with 15 normally cycling ovulatory women. After provocation, the patients were treated with bromocriptine 2.5 mg twice a day for two weeks from the day of menstruation or withdrawal bleeding. Within 12 weeks, 29 of 46 (63.0%) patients had resumption of ovulatory menstruation, and 11 of them became pregnant. There were a significantly (P < 0.001) exaggerated responses of PRL to TRH in bromocriptine responders compared to controls and nonresponders. Also, LH responses to GnRH were higher in responders than in controls and nonresponders, although there was no significant differences. However, FSH responses to GnRH were significantly (P < 0.005) lower in bromocriptine nonresponders, as compared with the controls and responders. These results demonstrate that pituitary reserve of PRL and gonadotropin may correlate with the efficacy of bromocriptine and aid to predict the outcome of therapy in patients with euprolactinemic ovulatory dysfunction.

Adult↗
PubMed1994

Bromocriptine reverses the inhibitory effect of macrophages on human sperm motility.

OBJECTIVE: To determine the effects of PRL suppression on the activation of murine peritoneal macrophages and their subsequent effects on human sperm motility. DESIGN: Laboratory study. INTERVENTIONS: Mice were treated with subcutaneous implants of 2.5 mg bromocriptine pellets 7 days before bacillus of calmette and guerin (BCG), a strain of Mycobacterium bovis, injection for activation of macrophages. Bromocriptine treatment, which significantly suppressed circulating PRL levels, continued through the day of peritoneal macrophage collection. Macrophages were subsequently cultured for 4 days and culture supernatant was collected. MAIN OUTCOME MEASURES: Human sperm were incubated for 4 hours in the presence of culture medium or culture supernatant from control and treated mice. Motion analysis was performed at 0, 2, and 4 hours. RESULTS: A significant decrease in human sperm motility was observed in the presence of culture supernatant from activated murine peritoneal macrophages. After 4 hours of incubation, sperm motility decreased from 69% +/- 3% in the nonactivated macrophage control group to 37% +/- 6% in the BCG- activated macrophage group. The suppressive effect of soluble products of activated macrophages on human sperm motility was reversed when mice were rendered hypoprolactinemic with bromocriptine. Motility after 4 hours was 56% +/- 3% in the BCG-bromocriptine group. Simultaneous administration of bromocriptine and PRL (100 ng per mouse daily) restored the inhibitory effect of soluble products of activated macrophages on sperm motility (36% +/- 5% motile). CONCLUSIONS: PRL may modulate the deleterious effects of activated macrophages on human sperm motility, thereby suggesting novel and useful methods for the modification of the immune response in early reproduction.

Animals↗
PubMed1996

Effect of bromocriptine on the sensitivity of pituitary tumor cells to radiation.

GH3 cells, a PRL-secreting rat pituitary tumor cell line, are sensitive to bromocriptine, and provide a useful model for the present studies. GH3 cells, in the presence or absence of 2.5 x 10(-5) M bromocriptine, were irradiated at doses ranging from 0 to 10 Gy. After irradiation the bromocriptine was washed out, cells were seeded at a density of 10,000 cells/ml, and growth curves were obtained by counting the cell number at weekly intervals for 1 month. Cell growth was inhibited by the radiation in a dose-dependent fashion, with complete inhibition of cell growth by 9 Gy. However, no protection against radiation damage was afforded by bromocriptine. These results might suggest that the combined therapies of tumor shrinkage by bromocriptine and stereotactic irradiation of the sella might be a useful clinical therapeutic strategy, particularly in patients with large tumors, severe hyperprolactinemia, and pre-existing hypopituitarism.

Animals↗
PubMed1996

Chiasmal herniation as a complication of bromocriptine therapy.

INTRODUCTION: Medical treatment of macroprolactinomas with dopamine agonists decreases tumor mass and improves visual defects. We report an unusual complication of a macroprolactinoma responding to bromocriptine: a visual field defect caused by downward herniation of the optic chiasm. MATERIALS AND METHODS: A 64-year-old woman was found to have a 4.5 cm macroprolactinoma with superior displacement of the optic chiasm, bitemporal hemianopia, and serum prolactin concentration (P) of 17,060 micrograms/L. Bromocriptine was initiated at 2.5 mg/day and increased to 7.5 mg/day over 2 months. RESULTS: After 2 months, visual fields improved significantly and tumor height decreased to 3 cm with resolution of the optic chiasm displacement. P decreased to 1,180 micrograms/L. After 5 months of therapy, visual fields were normal, and P was 8 micrograms/L. After 8 months of therapy, new bilateral visual defects were observed. Magnetic resonance imaging (MRI) revealed further decrease of the tumor height to 1.5 cm, and inferior and leftward traction of the optic chiasm as the probable mechanism for the new visual field deficit. P was < 1 microgram/L. Bromocriptine was decreased to 5 mg/day to allow reduced traction on the optic chiasm and its blood supply. Over the next 4 months, visual field abnormalities resolved. CONCLUSIONS: We report the development of a visual field abnormally that is explained by chiasmal herniation caused by a shrinking macroprolactinoma. This complication resolved with a decrease in the bromocriptine dose. We suggest that patients undergoing bromocriptine therapy for macroprolactinomas be followed for this potential complication.

Bromocriptine↗
PubMed1997

Long-acting injectable bromocriptine does not reduce relapse in alcoholics.

Dopamine is one of several neurotransmitters that may mediate alcohol intake and dependence. A randomized, double-blind, placebo-controlled international, multicentre study was conducted to assess the effects of a long-acting injectable preparation of bromocriptine, a dopamine agonist, (Parlodel-LAR) in reducing relapse in 366 moderately/severely dependent alcoholics (DSM-III-R), drinking approximately 200 g alcohol (14.5 standard drinks) per day. After detoxification they were randomized to receive six monthly injections of bromocriptine 25 mg (n = 120), bromocriptine 50 mg (n = 124), placebo (n = 122). Brief psychosocial treatment was allowed. At 6 months there were no significant differences between treatment groups in rates of relapse to any drinking or to drinking > or = 5 days per month and > or = 3 drinks per day. Pre-treatment alcohol intake did not determine response. Efficacy ratings by subjects and investigators and adverse events, reported by 51% of subjects, did not differ between treatments. The results of this large study, in which compliance was enhanced by Parlodel-LAR, do not indicate that bromocriptine is efficacious in the maintenance of abstinence or reduced drinking. Possible reasons for the discrepancy between these conclusions and those of some previous clinical trials, in which bromocriptine was reported to reduce symptoms of alcohol withdrawal and dependence, are discussed.

Adolescent↗
PubMed1999

Efficacy and tolerability of tolcapone compared with bromocriptine in levodopa-treated parkinsonian patients. Tolcapone Study Group.

The catechol-O-methyltransferase inhibitor tolcapone was compared with the dopamine agonist bromocriptine in an open-label, randomized trial involving 146 levodopa-treated parkinsonian patients with end-of-dose deterioration of efficacy. Tolcapone was given at a dosage of 200 mg three times daily; bromocriptine was titrated from 1.25 mg once daily at baseline to, at most, 10 mg three times daily by day 24 (mean final dose 22.4 mg/day). After 8 weeks, the tolcapone group had a significant reduction in daily levodopa dose compared with the bromocriptine group (p<0.05). No significant differences in the "on/off" time and motor disability were seen between the tolcapone and bromocriptine treatment groups. Bromocriptine induced more hallucinations, orthostatic hypotension, and nausea, whereas tolcapone therapy was associated with more muscle cramps and dystonia. These results suggest that when added to levodopa therapy, the two drugs have a different side effect profile, with the advantages for tolcapone being absence of titration and quicker efficacy.

Aged↗
PubMed1985

Low-dose bromocriptine therapy in Parkinson's disease.

The efficacy of low-dose bromocriptine mesylate administration (20 mg daily or less) was evaluated in a double-blind study. Nine of 16 individuals receiving bromocriptine completed the 40-week study. Modest, but significant, improvement was derived from bromocriptine therapy. Improvement was most evident in tremor. Maximum improvement was achieved with doses between 7.5 and 15.0 mg daily, with some decline in efficacy as doses approached 20 mg. Adverse effects were common, but were generally mild in severity. Our results suggest that bromocriptine in low doses may be an effective adjunct to carbidopa and levodopa (Sinemet) in the treatment of Parkinson's disease.

Aged↗
PubMed1978

Brain dopamine receptor stimulation and the relief of Parkinsonism: relationship between bromocriptine and levodopa.

The relationship between dopamine receptor stimulation by bromocriptine or levodopa and the relief of parkinsonism was studied in 24 patients with Parkinson disease. Bromocriptine, 30 mg daily for 20 weeks, elicited an improvement in the parkinsonian clinical features, but this was less than the subsequent improvement with levodopa and benserazide, 800 mg and 200 mg daily, respectively. There was a negative correlation between the pretreatment severity of the disease or changes in cerebrospinal fluid homovanillic acid (HVA) and improvement in parkinsonian disability during bromocriptine treatment. Futhermore, it was found that clinical improvement and HVA responses in the cerebrospinal fluid after dopamine receptor stimulation by bromocriptine may predict the clinical response to levodopa.

Benserazide↗
PubMed1988

A double-blind randomized crossover trial of bromocriptine and placebo in restless legs syndrome.

A double-blind randomized crossover study of 7.5 mg bromocriptine at bedtime versus placebo was conducted in 30-day phases (with a 2-week washout period between phases) in 6 patients with idiopathic restless legs syndrome. Five patients experienced partial subjective improvement in restlessness and paresthesias on bromocriptine as opposed to placebo and expressed a desire to continue on the medication. On bromocriptine, the patients showed polysomnographically a mean decrease of 43% from control and a mean decrease of 57% from placebo in the number of periodic movements of sleep per hour of sleep (p less than 0.025). Two of 3 patients with abnormally decreased total sleep time and sleep efficiency showed an improvement in these measures on therapy. The dopamine agonist bromocriptine may be a useful therapy in some patients with restless legs syndrome.

Bromocriptine↗
PubMed1978

A double blind trial of the prolactin inhibitor bromocriptine in painful benign breast disease.

A double blind crossover trial of the prolactin inhibitor bromocriptine in painful benign breast disease is reported. Twenty-nine women with cyclical mastalgia and 11 with non-cyclical pain were treated with bromocriptine, 5 mg daily, and placebo over six menstrual cycels. Assessment of response to treatment was made by a linear analogue system and clinical examination together with plasma prolactin estimations. Bromocriptine produced a significant improvement in breast symptoms and a significant fall in prolactin levels in the cyclical pain group, but had no effect in the non-cyclical group. These results suggest that bromocriptine offers a new and effective approach in the management of cyclical breast pain.

Breast Diseases↗
PubMed1982

The lactation-blocking drug bromocriptine and its application to studies of weaning and behavioral development.

An experimental method for blocking maternal lactation is reviewed and the possible application of this technique for experimentally manipulating weaning is considered. Maternal milk production can be inhibited using the prolactin-suppressing drug bromocriptine. The suitability of bromocriptine for use in behavioural experiments is considered. The pharmacology of bromocriptine (CB 154) is briefly outlined and a compilation of the reported lactation-inhibiting doses for various species is presented. The possible endocrine and behavioral side-effects and the toxicity of the drug are discussed. It is concluded that, in most species studied so far, the drug is relatively free from significant side-effects at the low doses needed to suppress lactation. Guidelines for the practical use of bromocriptine are suggested. Finally, some ideas about the possible application of the drug to the study of behavioral development and parent-offspring relationships are discussed.

Animals↗
PubMed1989

Bromocriptine prevents the castration-induced rise in porphyrin concentration in the harderian glands of the male Syrian hamster, Mesocricetus auratus.

The Harderian glands in Syrian hamsters exhibit a striking sexual dimorphism. Male Harderian glands show two cell types and low levels of porphyrins and melatonin. Of the enzymes involved in the synthesis of melatonin, N-acetyltransferase (NAT) and hydroxyindole-O-methyltransferase (HIOMT) show high and low activity levels, respectively. Female Harderian glands show but one cell type and have high porphyrin and melatonin levels, low NAT activity, and high HIOMT activity. In castrated males, the Harderian glands exhibit a female pattern of morphology, porphyrin levels, and indoleamine metabolism. In an attempt to determine whether prolactin in involved in this sexually dimorphic response of the Harderian glands, intact and castrated male and intact female hamsters were injected daily with 500 micrograms of bromocriptine, a dopamine agonist. Bromocriptine led to reduced serum prolactin levels in all groups. It had no apparent effect on the Harderian glands of intact males. In contrast, in castrated males bromocriptine prevented the postcastrational rise in porphyrin levels but had no effect on NAT or HIOMT activities. In females, bromocriptine treatment had no effect on porphyrin concentrations or HIOMT activity; it led to a statistically significant increase in NAT activity. We propose that testosterone inhibits Harderian porphyrin synthesis while dopamine or prolactin stimulates it.

Animals↗