quinagolide and Hyperprolactinemia

Three dopamine agonists [bromocriptine, cabergoline, and quinagolide (CV)] have been used for hyperprolactinemia treatment for decades. Several studies have reviewed the efficacy and safety of bromocriptine and cabergoline. However, no systematic review or meta-analysis has discussed the efficacy and safety of CV in hyperprolactinemia and prolactinoma treatment.. Five medical databases (PubMed, Web of Science, Embase, Scopus, and Cochrane Library) were searched up to 9 May 2022 to identify studies related to CV and hyperprolactinemia. A meta-analysis was implemented by using a forest plot, funnel plot, sensitivity analysis, meta-regression, and Egger's test. A total of 1,211 studies were retrieved from the five medical databases, and 33 studies consisting of 827 patients were finally included in the analysis. The pooled proportions of patients with prolactin concentration normalization and tumor reduction (>50%) under CV treatment were 69% and 20%, respectively, with 95% confidence intervals of 61%-76% and 15%-28%, respectively. The pooled proportion of adverse effects was 13%, with a 95% confidence interval of 11%-16%.. Our study showed that CV is not less effective than cabergoline and bromocriptine in treating hyperprolactinemia, and the side effects were not significant. Hence, this drug could be considered an alternative first-line or rescue treatment in treating hyperprolactinemia in the future.. https://www.crd.york.ac.uk/PROSPERO, identifier CRD42022347750.

Topics: Aminoquinolines; Bromocriptine; Cabergoline; Drug-Related Side Effects and Adverse Reactions; Humans; Hyperprolactinemia; Pituitary Neoplasms

High prolactin levels can occur as a physiological condition in females who are pregnant or lactating. As a pathological condition, hyperprolactinaemia is associated with gonadal dysfunction, infertility and an increased risk of long-term complications including osteoporosis. The most frequent cause of persistent hyperprolactinaemia is the presence of a micro- (<10mm diameter) or macroprolactinoma (>/=10mm). These pituitary tumours may produce an excessive amount of prolactin or disrupt the normal delivery of dopamine from the hypothalamus to the pituitary; prolactin secretion from the pituitary is inhibited by dopamine released from neurones in the hypothalamus. Medications including anti-psychotics can induce hyperprolactinaemia, while idiopathic hyperprolactinaemia accounts for 30-40% of cases. The prevalence of hyperprolactinaemia is difficult to establish as not all sufferers are symptomatic or concerned by their symptoms and may remain undiagnosed. Symptoms of hyperprolactinaemia include signs of hypogonadism, with oligomenorrhoea, amenorrhoea and galactorrhoea frequently observed. Pharmacological intervention should be considered the first line therapy and involves the use of dopamine agonists to reduce tumour size and prolactin levels. Bromocriptine has the longest history of use and is a well-established, inexpensive, safe and effective therapy option. However, bromocriptine requires multiple daily dosing and some patients are resistant or intolerant to this therapy. The two newer dopamine agonists, quinagolide and cabergoline, provide more effective and better tolerated treatments compared with bromocriptine and may offer effective therapies for bromocriptine-resistant or intolerant patients. Quinagolide can be used until pregnancy is confirmed and may result in improved compliance in females wishing to become pregnant. For patients with hyperprolactinaemia, pregnancy is safe and can frequently be beneficial, inducing a decrease in prolactin levels. There does not appear to be any increased risk of abortion, malformations or multiple births in pregnancies achieved with bromocriptine and this dopamine agonist can be used safely during pregnancy. Surgery should be considered only in certain circumstances, and for the majority of patients, dopamine agonists will be sufficient to alleviate symptoms and restore normal prolactin levels.

Topics: Aminoquinolines; Bromocriptine; Cabergoline; Dopamine Agonists; Ergolines; Female; Humans; Hyperprolactinemia; Male; Pituitary Neoplasms; Pregnancy; Prolactinoma

Hyperprolactinaemia is characterised by gonadal dysfunction, including infertility and reduced libido and, if left untreated, is associated with an increased risk of long-term complications, such as osteoporosis. The first-line therapy for patients with hyperprolactinaemia is pharmacological intervention with a dopamine agonist. Currently, there are three dopamine agonists available for hyperprolactinaemia therapy: bromocriptine, quinagolide and cabergoline. Bromocriptine has a long history of use; however, a range of 5-18% of patients are reported to show bromocriptine resistance, with only partial lowering of plasma prolactin levels and an absence of tumour shrinkage. The newer dopamine agonists, quinagolide and cabergoline, offer improved efficacy over bromocriptine, with a lower incidence of adverse events. Quinagolide and cabergoline have also demonstrated efficacy in many patients intolerant or resistant to bromocriptine. Thus, the selection of dopamine agonists available provides more than one option for pharmacological intervention of hyperprolactinaemia. This review discusses the clinical use of quinagolide in comparison to other dopamine agonists for hyperprolactinaemia therapy. Quinagolide may improve patient compliance to treatment owing to its reduced side effect profile, simple and rapid titration over just 7 days, once-daily dosing regimen and easy to use starter pack (available in some countries). Quinagolide offers an additional benefit for patients wishing to become pregnant, as it can be used until the point of confirmation of pregnancy. Therefore, as a well tolerated and effective therapy, with a simple dosing regimen, quinagolide should be considered as a first-line therapy in the treatment of hyperprolactinaemia.

Topics: Administration, Oral; Aminoquinolines; Bromocriptine; Cabergoline; Dopamine Agonists; Ergolines; Female; Humans; Hyperprolactinemia; Male; Patient Compliance

Topics: Aminoquinolines; Benzothiazoles; Bromocriptine; Cabergoline; Clinical Trials as Topic; Dopamine Agonists; Ergolines; Ergoloid Mesylates; Female; Humans; Hyperprolactinemia; Indoles; Pergolide; Pramipexole; Thiazoles

Topics: Aminoquinolines; Bromocriptine; Cabergoline; Dopamine Agonists; Ergolines; Female; Humans; Hyperprolactinemia; Pergolide; Prolactin; Receptors, Prolactin

Dopamine agonists are the treatment of choice for the majority of patients with hyperprolactinaemic disorders. Although characterised by a relatively high incidence of adverse effects, most commonly gastrointestinal, cardiovascular and neurological, these are usually mild and transient, and can be minimised by starting with a low dose and gradually increasing it, or taking the drug with food or while recumbent. Bromocriptine, introduced in 1971, is the reference preparation against which newer dopamine agonists are compared. It is effective in suppressing prolactin secretion, reducing prolactinoma size and restoring gonadal function. However, up to 12% of patients cannot tolerate the drug at therapeutic dosages. Cabergoline, a long-acting dopamine agonist administered once or twice weekly, has been shown to be significantly more effective than bromocriptine in suppressing prolactin secretion in hyperprolactinaemic patients, and is better tolerated, particularly in terms of nausea and vomiting. In suppressing physiological lactation, cabergoline is at least as effective as bromocriptine, and is associated with significantly fewer rebound symptoms and adverse effects. Quinagolide is a non-ergot dopamine agonist that is administered once daily. It has similar efficacy to bromocriptine, but is probably less effective than cabergoline in hyperprolactinaemic patients; it is not licensed for suppression of lactation. It is better tolerated than twice-daily bromocriptine, but is probably inferior to cabergoline in this regard. Neither bromocriptine, cabergoline nor quinagolide has been associated with any detrimental effect on pregnancy or fetal development. However, experience with bromocriptine is far more extensive; thus, for women requiring treatment for subfertility, this drug remains the treatment of choice in most centres, with cabergoline and quinagolide as acceptable second-line drugs in bromocriptine-intolerant patients. In hyperprolactinaemic men, hyperprolactinaemic women not wishing to become pregnant, and for suppression of physiological lactation, cabergoline is recommended as first-line treatment.

Topics: Aminoquinolines; Animals; Bromocriptine; Cabergoline; Dopamine Agonists; Ergolines; Female; Humans; Hyperprolactinemia; Lactation; Male; Pregnancy

In 1976 we heralded the introduction of bromocriptine (Parlodel-Sandoz) as "an important advance" for the treatment of patients with hyperprolactinaemia. Now two new drugs are available for treating hyperprolactinaemia; cabergoline (Dostinex-Pharmacia) which the manufacturer claims offers "a significant advance in prolactin control" and quinagolide (Norprolac-Sandoz) for which the claim is of a "significant advance in the therapy of hyperprolactinaemia". Do these newer products hold real advantages?

Topics: Aminoquinolines; Bromocriptine; Cabergoline; Clinical Trials as Topic; Ergolines; Hormone Antagonists; Humans; Hyperprolactinemia

Hyperprolactinemic syndromes are a diverse group of disorders that present in widely different age groups. They are common disorders in both men and women and require management over a lifetime. The past 20 years have greatly increased our knowledge about these disorders and simplified their management. Yet, we have made little progress in understanding the origin and dynamics of pituitary tumors and their natural histories, and as yet we have been unable to develop effective tumoricidal therapy or medication that corrects, at the central axis level, neurotransmitter disorders that may produce hyperprolactinemia. Perhaps these issues will be the subject of such reviews in the future.

Topics: Aminoquinolines; Animals; Bromocriptine; Dopamine Agents; Female; Humans; Hyperprolactinemia; Infertility; Ovary; Pituitary Gland; Pituitary Neoplasms; Prolactin; Prolactinoma

With improved radiologic detection and monitoring of prolactinomas, the management has shifted away from surgery toward a more conservative approach and medical management. The natural course of a microadenoma appears to be that of a non-progression, and for asymptomatic patients serial radiologic monitoring for growth may be a safe form of management. For symptomatic women, medical management remains the primary mode of therapy. Although bromocriptine remains the most widely used dopamine agonist, its side effects and short half-life have led to the development of newer agonists with better tolerance and similar or superior efficacy. Patients who tolerate oral bromocriptine poorly may find the medication more acceptable when administered either parenterally as with Parlodel LA (Sandoz, Basel, Switzerland), or vaginally. Different medications that have similar efficacy and tolerance to bromocriptine such as pergolide or cabergoline [corrected] may also represent alternatives, as intolerance to one ergot agonist does not necessarily imply intolerance to another. CV-205-502 (Sandoz), a promising and new long-acting nonergot derivative, appears to be safe, effective, and very well tolerated.

Topics: Aminoquinolines; Bromocriptine; Dopamine Agents; Female; Humans; Hyperprolactinemia; Pergolide

To assess whether dopamine receptor 2 agonists reduced the size of peritoneal lesions in women with endometriosis and elucidate whether affectation of vascular endothelial growth factor (VEGF)/VEGF receptor 2 (VEGFR2)-dependent angiogenesis was mediating the observed effects.. Proof-of-concept study.. University hospital and a university-affiliated private IVF research center.. Hyperprolactinemic patients (n = 9) with endometriosis requiring a first surgical intervention (L1) and benefiting from a second-look laparoscopy (L2) were evaluated.. During L1, four to six peritoneal red lesions were identified. One-half of the lesions were removed and the remaining one-half were labeled with silk knot sutures. After L1, quinagolide was administered in a titrated manner (25-75 μg/d) for 18-20 weeks. During L2, the remaining lesions were surgically excised.. Both L1 and L2 were video recorded to compare the effects of quinagolide treatment on lesion size. Lesions removed at L1 and L2 were compared by means of: 1) histologic analysis; 2) immunohistochemical quantitative analysis of angiogenesis; and 3) quantitative fluorescence polymerase chain reaction array analysis of 84 chemokines and pro-/antiangiogenic molecules.. Quinagolide induced a 69.5% reduction in the size of the lesions, with 35% vanishing completely. Histologic analysis showed tissue degeneration, which was supported by down-regulation of VEGF/VEGFR2, three proangiogenic cytokines (CCL2, RUNX1, and AGGF1) and plasminogen activator inhibitor (PAI) 1, a potent inhibitor of fibrinolysis in the L2 lesions.. By interfering with angiogenesis, enhancing fibrinolysis, and reducing inflammation, quinagolide reduces or eliminates peritoneal endometriotic lesions in women with endometriosis.

Topics: Aminoquinolines; Dopamine Agonists; Endometriosis; Endometrium; Female; Gene Expression Profiling; Humans; Hyperprolactinemia; Laparoscopy; Patient Compliance; Pilot Projects; Polymerase Chain Reaction; Prospective Studies; Severity of Illness Index

The aim of this prospective study was to evaluate the bone mineral density (BMD) at lumbar spine and femoral neck levels and biochemical parameters of bone turnover in 20 consecutive hyperprolactinemic males before and after an 18-month treatment with different dopamine agonists. Six patients received bromocriptine at a dose of 2.5-10 mg/day; 7 patients received quinagolide at a dose of 0.075-0.3 mg/day; 7 patients received cabergoline at a dose of 0.5-1.5 mg/week. BMD, serum PRL, testosterone, dihydrotestosterone, and osteocalcin (OC), and urinary cross-linked N-telopeptides of type I collagen (Ntx) levels were measured before and every 6 months during treatment. At study entry, BMD values were lower in patients than controls at both lumbar spine (0.82 +/- 0.03 vs. 1.18 +/- 0.01 g/cm2; P < 0.001) and femoral neck (0.85 +/- 0.02 vs. 0.92 +/- 0.02 g/cm2; P < 0.05) levels. Osteopenia or osteoporosis was diagnosed in 16 patients at the lumbar spine and in 6 of them at the femoral neck level. A significant inverse correlation was found between lumbar spine and femoral neck BMD values and both PRL levels and disease duration (P < 0.01). In the 20 patients, serum OC levels were significantly lower (2.1 +/- 0.1 vs. 9.3 +/- 2.4 microg/L; P < 0.01), whereas Ntx levels were significantly higher (157.8 +/- 1.1 vs. 96.4 +/- 7.4 nmol bone collagen equivalent/mmol creatinine; P < 0.001) than control values. A significant inverse correlation was found between serum PRL and OC (P < 0.01), but not Ntx, levels. After 18 months of treatment, serum PRL levels were suppressed, and gonadal function was restored in all 20 patients, as shown by the normalization of serum T (from 2.2 +/- 0.2 to 5.0 +/- 0.2 microg/L) and dihydrotestosterone (0.3 +/- 0.02 vs. 0.5 +/- 0.01 nmol/L) levels, without any significant difference among groups. A progressive significant increase in serum OC levels together with a significant decrease in Ntx levels were observed after 6, 12, and 18 months of treatment in the 3 groups of patients. A slight, although significant, increase in BMD values was recorded in all patients after 18 months of bromocriptine, quinagolide, and cabergoline treatment, serum OC levels were normalized after treatment, whereas neither urinary Ntx levels nor BMD values were normalized by 18 months of treatment with dopaminergic agents. In conclusion, treatment with bromocriptine, quinagolide, and cabergoline for 18 months, although successfull in suppressing serum PRL levels and

Topics: Adult; Aminoquinolines; Biomarkers; Bone and Bones; Bone Density; Bone Diseases, Metabolic; Bone Remodeling; Bromocriptine; Cabergoline; Dopamine Agonists; Ergolines; Humans; Hyperprolactinemia; Male; Middle Aged; Prospective Studies

The clinical effects of CV 205-502, a potent and non-ergot-derived dopamine agonist, were investigated in 24 selected patients with hyperprolactinemia previously treated with standard oral bromocriptine, the slow-release oral form of bromocriptine (BRC-SRO) and/or the long-acting injectable form of bromocriptine (BRC-LAR); 14 were chosen because of their resistance to treatment and ten because they were intolerant of the different forms of bromocriptine. A macroprolactinoma was present in seven patients and a microprolactinoma in ten, whereas seven had no radiological images of a pituitary tumor and were classified as having non-tumoral hyperprolactinemia. All the 24 patients were treated with CV 205-502 at a daily dose of 0.075-0.6 mg for 3-12 months. All the patients had gonadal dysfunction and galactorrhea. Basal serum prolactin values ranged from 70 to 1677 ng/ml. CV 205-502 was effective in 11 of the 14 patients resistant bromocriptine, BRC-SRO and BRC-LAR; serum prolactin levels became normal within 6 months and a tumor shrinkage was obtained in five of the seven macroprolactinomas. In general, the drug was effective and well tolerated. Only three patients (two resistant and one intolerant) manifested nausea, vomiting and postural hypotension. In conclusion, this study shows that CV 205-502 is effective in bromocriptine-resistant hyperprolactinemic patients. Furthermore, CV 205-502 has insignificant and tolerable side-effects in patients intolerant of bromocriptine. CV 205-502 can, therefore, be considered a useful and effective drug, and an interesting therapeutic alternative to the ergot-derived dopamine-agonist drugs in use today.

Topics: Administration, Oral; Adult; Aminoquinolines; Bromocriptine; Delayed-Action Preparations; Dopamine Agonists; Drug Resistance; Female; Humans; Hyperprolactinemia; Magnetic Resonance Imaging; Male; Pituitary Neoplasms; Prolactin; Prolactinoma; Time Factors; Tomography, X-Ray Computed

To audit the efficacy of quinagolide (CV205-502, Norprolac, Sandoz) in lowering prolactin, and its tolerability, in patients with bromocriptine resistance (BCR) or bromocriptine intolerance (BCI), in view of the paucity of results published in patients specifically with BCR or BCI, by collating results in our own patients with the reports in the literature.. Open prospective, uncontrolled administration of quinagolide in patients with BCR (defined for this report as failure to attain normal prolactin levels after 4 months of bromocriptine at maximum tolerated doses), or BCI (defined as a patient request to cease bromocriptine treatment because of side-effects at doses that were required, or failed, to normalize PRL levels).. Prolactin levels, menses or pregnancy, and side-effects.. Six with BCR, and six with BCI (microprolactinoma in 7, macroprolactinoma in 5), treated with quinagolide 75 micrograms nightly increasing incrementally to a maximum of 450 micrograms. One patient who had taken part in a multicentre study of quinagolide in macroprolactinomas had BCI, and 11 further patients in the endocrine clinic who had BCR or BCI were offered quinagolide therapy under named-patient compassionate arrangements.. Normal prolactin in 4/5 with BCR (3/6 with side-effects, none of them quinagolide intolerant), and normal prolactin in 2/6 with BCI (4/6 with side-effects, two of them quinagolide intolerant).. Results in our 12 patients are broadly in line with those in 51 patients with bromocriptine resistance and 39 with bromocriptine intolerance extracted from various published reports, which together suggest that prolactin can be normalized in 16% of patients with bromocriptine resistance by quinagolide in doses of 225 micrograms or less, and in a further 20% by higher doses up to 600 micrograms. In bromocriptine intolerance, prolactin was normalized by quinagolide in doses of 225 micrograms or less in 58% of published cases and in 3 more patients by higher doses up to 1050 micrograms. About half the patients with bromocriptine resistance or bromocriptine intolerance who are treated with quinagolide experience side-effects, and around 7% are quinagolide intolerant. Doses need not exceed 225 micrograms, until failure to respond at this dose level is demonstrated.

Topics: Adult; Aminoquinolines; Bromocriptine; Dopamine Agents; Drug Tolerance; Female; Humans; Hyperprolactinemia; Male; Middle Aged; Prospective Studies

Cabergoline and quinagolide, two new dopamine agonist drugs with long-lasting activity, are currently under investigation for the treatment of hyperprolactinemia. At present, studies comparing these drugs for tolerability and efficacy in the same patients are lacking. It was our aim to make such a comparison in an open randomized cross-over trial. Cabergoline (0.5 mg twice weekly) and quinagolide (75 micrograms once daily) were given orally. Each drug was administered for 12 weeks. Treatment with the second drug was started after the recurrence of hyperprolactinemia. Twelve women with hyperprolactinemia due to idiopathic disease (n = 6), microprolactinoma (n = 5) or postsurgical empty sella (n = 1) were evaluated. Six women were amenorrheic and 6 were oligomenorrheic. Ten had spontaneous or provoked galactorrhea. Baseline characteristics (age, clinical signs and PRL levels) of patients initially allocated to the two treatment groups were similar. Nine patients completed both treatment cycles and PRL levels were lower under cabergoline (10.7 +/- 3.7 micrograms/L) than under quinagolide (25.0 +/- 7.7 micrograms/L; p < 0.05). One patient discontinued cabergoline because of dryness of the eyes after having completed the quinagolide cycle and 2 patients initially treated with cabergoline discontinued quinagolide because of gastrointestinal symptoms. After completion of the first treatment cycle, the time of recurrence of hyperprolactinemia was significantly longer after cabergoline (14 +/- 7 weeks) than after quinagolide (5 +/- 1 weeks; p < 0.05). At week 12, normal PRL levels (< 20 micrograms/L) were observed in 10 and 6 women during cabergoline and quinagolide, respectively. Only one case was resistant to both drugs. The clinical effects of the two treatments were similar.(ABSTRACT TRUNCATED AT 250 WORDS)

Topics: Administration, Oral; Adult; Aminoquinolines; Cabergoline; Dopamine Agents; Dose-Response Relationship, Drug; Ergolines; Female; Humans; Hyperprolactinemia; Middle Aged; Prolactin

To investigate the effect of dopaminergic drugs on the well being in hyperprolactinemic patients.. A psychometric test for well being, the SCL-90, was applied at baseline and in the 24th week of a double-blind randomized prospective study comparing the effectiveness and safety of the new dopamine d2 agonist CV 205-502 with bromocriptine.. Outpatient department of a university clinic for obstetrics and gynecology.. Twenty-four women with hyperprolactinemia, 9 of whom had a prolactinoma. Twenty had been treated before, and 11 were known to react unfavorably to bromocriptine.. The effectiveness of CV 205-502 was identical to bromocriptine: its tolerability appeared to be better, especially in the initial phase of treatment. At baseline, the mean scores of the SCL-90 were significantly elevated over the reference values. Sixteen patients had normal scores. The elevations were caused by 8 patients with scores in the range found in psychiatric disease (211 +/- 30 [SD] [CV 205-502] and 182 +/- 32 [bromocriptine]). They were depressed, anxious, and hostile. At 24 weeks, the patients treated with CV 205-502 scored better (130 +/- 23.5) in the SCL-90 than the patients treated with bromocriptine (149.5 +/- 20).. The markedly increased well being in patients treated with CV 205-502 cannot be explained by its better tolerability and is probably caused by a specific central activity of CV 205-502. Further research into the antidepressive properties of this compound is warranted.

Topics: Adult; Amenorrhea; Aminoquinolines; Bromocriptine; Depression; Dopamine Agents; Female; Humans; Hyperprolactinemia; Menstruation; Oligomenorrhea; Prolactin; Prospective Studies; Psychological Tests

Forty-seven hyperprolactinaemic patients with serum prolactin (PRL) concentrations persistently above 1500 mU/l were treated with the new dopamine agonist CV 205-502 or bromocriptine in a prospective, randomized and double-blind fashion during a 24-week period. Two women had to be excluded because of poor compliance in the first month. Therefore 45 patients remained for evaluation. 81% of the patients in the CV 205-502 group and 70% of the patients in the bromocriptine group normalized their prolactin levels within the study period with a treatment dose as permitted in this protocol. In general serum prolactin normalized within 8 to 12 weeks of treatment. There were no differences between the two tested drugs regarding restoration of the menstrual cycle or disappearance of galactorrhoea. Both drugs gave rise to adverse reactions, especially during the initiation of therapy. However, the adverse reactions reported during CV 205-502 treatment were less severe and persistent than those attributed to bromocriptine. Patient acceptance of the new drug with regard to tolerability was judged by 90% of the women in that treatment group as very good or good, while 75% of those treated with bromocriptine evaluated its tolerability as very good or good. We conclude that CV 205-502 is highly effective in the treatment of hyperprolactinaemia with concomitant restoration of gonadal function and prevention of galactorrhoea. The tolerability of the drug seems better than of bromocriptine and therefore this drug is of value in the treatment of hyperprolactinaemic patients.

Topics: Adolescent; Adult; Aminoquinolines; Bromocriptine; Dopamine Agents; Double-Blind Method; Drug Evaluation; Drug Tolerance; Female; Galactorrhea; Humans; Hyperprolactinemia; Menstrual Cycle; Middle Aged; Patient Compliance; Prolactin

Quinagolide (CV 205-502, Sandoz), an octahydrobenzo (g) quinoline, is a new non-ergot dopamine agonist which has specific D2 receptor activity and a long half-life, making it suitable for once-daily treatment. Recent uncontrolled reports have suggested that quinagolide may be successfully used for the clinical management of hyperprolactinemia with fewer adverse reactions than bromocriptine. This study is the first to compare quinagolide in a double-blind manner with bromocriptine, given only once-daily instead of the usual multidose regimen. In the first phase we compared, in 7 hyperprolactinemic patients, the effects over 24 h of a single oral dose of 0.05 mg quinagolide with 2.5 mg bromocriptine. Compared with placebo, both bromocriptine and quinagolide showed potent PRL-inhibiting and GH-releasing effects, with comparable effects at 24 h; no significant changes were observed in TSH, LH, FSH or cortisol. Twelve hyperprolactinemic patients were then randomized to receive either once-daily bromocriptine or quinagolide in incremental doses for a period of six months. Both drugs were found to be equally effective, and no differences were seen either in adverse reactions or PRL levels during repeated diurnal sampling. We therefore conclude that quinagolide and bromocriptine are therapeutically equivalent in long-term use, and both are equally effective when given once a day. However, some patients intolerant of bromocriptine may respond better to quinagolide, and vice versa.

Topics: Adult; Aminoquinolines; Blood Pressure; Bromocriptine; Dopamine Agents; Double-Blind Method; Drug Administration Schedule; Female; Hormones; Humans; Hyperprolactinemia; Male; Middle Aged; Prolactin; Time Factors

Twenty-two hyperprolactinaemic women were randomly allocated to two groups and treated with bromocriptine or the new, non-ergot, long-acting dopamine agonist, CV 205-502. The study was double-blind for 6 months. Four patients in the bromocriptine group, but none in the CV 205-502 group, discontinued the study because of adverse reactions. Adverse reactions in those receiving the new drug were milder and more transient than with bromocriptine. With once-daily doses of 0.075 mg CV 205-502, eight of 11 women achieved normal PRL concentrations after 8 weeks treatment (median (95% confidence limits), 352 (70-987) mU/l) compared with two of nine receiving a divided daily dose of 5 mg bromocriptine (1802 (1205-4438) mU/l) (P less than 0.002). With doses of 0.075-0.15 mg of CV 205-502, 10 of 11 women achieved normal PRL concentrations at 24 weeks compared with three of the remaining seven women on doses of 5-10 mg of bromocriptine. Regular menstrual bleeding was restored and galactorrhoea relieved in the majority of patients, with marginally greater efficacy with CV 205-502. CV 205-502 is highly effective for the long-term treatment of hyperprolactinaemia. It is better tolerated than bromocriptine, is effective in a once-daily dose, appears to be safe, and provides a valuable alternative to the dopamine agonist drugs in use today.

Topics: Adult; Aminoquinolines; Bromocriptine; Dopamine Agents; Double-Blind Method; Female; Humans; Hyperprolactinemia; Iodine Radioisotopes; Menstruation; Middle Aged; Prolactin; Radioimmunoassay; Randomized Controlled Trials as Topic

Topics: Adolescent; Adult; Aminoquinolines; Bromocriptine; Dopamine Agents; Female; Follow-Up Studies; Humans; Hyperprolactinemia; Menstruation; Pituitary Neoplasms; Pregnancy; Pregnancy Complications; Prolactin; Radiography; Sella Turcica

CV 205-502 is a nonergot oral dopamine agonist with specific D2 activity, which has a prolonged suppressive effect on serum PRL and may have fewer side-effects than other dopamine agonists. We treated 26 hyperprolactinemic women with this compound given as a single bedtime (hs) dose for up to 12 weeks. All had gonadal dysfunction, either amenorrhea or oligomenorrhea, and 15 had galactorrhea. The initial and subsequent doses were administered in a randomized fashion; the initial dose ranged from 0.01-0.05 mg, and the dose at 12 weeks ranged from 0.03-0.09 mg. The women were evaluated every 2 weeks, and the dose was increased by 0.02 mg every 4 weeks if the serum PRL level was greater than 20 micrograms/L. Of the 26 women initially enrolled, 24 completed 12 weeks of therapy, and 2 discontinued therapy because of side-effects. Thirteen women (54%) had return of menses, and 12 (80%) had either a decrease in or disappearance of galactorrhea. Serum PRL concentrations decreased to a variable degree in all patients; 13 (54%) achieved a normal serum PRL level (less than or equal to 20 micrograms/L). The mean (+/- SE) pretreatment serum PRL concentration was 129 +/- 34, and it was 29.9 +/- 5.9 micrograms/L after 12 weeks of treatment (P = 0.005). The mean (+/- SE) percent reduction in serum PRL was 66.5 +/- 5.0% (median, 78.0%). A dose response was not demonstrated (r = -0.08; P = 0.70) among the 6 dose groups during the last 4 weeks of therapy. In 5 women, serum PRL levels, measured frequently for 24 h after treatment remained low. Side-effects after the initiation of therapy included nausea, headache, and morning fatigue in 10 women. These symptoms caused 2 women to discontinue therapy; they subsided in the other women. An optimal dose was not determined and will probably need to be determined by titration in each patient. CV 205-502, given once daily, appears to be a safe and effective alternative to other dopamine agonists in the treatment of hyperprolactinemia.

Topics: Amenorrhea; Aminoquinolines; Dopamine Antagonists; Dose-Response Relationship, Drug; Female; Humans; Hyperprolactinemia; Oligomenorrhea; Ovary; Prolactin; Receptors, Dopamine D2

CV 205-502 (Sandoz), an octahydrobenzol [g]quinoline, is a long-acting dopamine agonist which inhibits prolactin secretion. We conducted a phase 2 clinical study in 10 hyperprolactinaemic women (nine of whom were previously intolerant of bromocriptine) in order to determine (1) the dose at which CV 205-502 exerted its prolactin-lowering effect; (2) the nature of adverse reactions associated with long-term therapy; and (3) whether patients who were intolerant of bromocriptine could tolerate CV 205-502. At first patients were randomized to take initial doses of either 0.02 or 0.05 mg daily at bedtime. Thereafter these doses of medication were gradually increased either to the point of normalizing serum prolactin (to 0.70 IU/l or 20 ng/ml) or to a maximum dose of 0.14 mg daily. The lower initial dose was ineffective and had to be increased in all patients. The higher initial dose (0.05 mg) normalized prolactin in three of five women within 24 h. During chronic administration of the final dose of CV 205-502 (mean 0.09 mg a day), serum prolactin decreased from a mean level of 9.19 +/- 4.9 (SEM) IU/l to a mean level of 1.55 +/- 0.49 IU/l (n = 10 patients). Prolactin was normalized in five patients. Two patients, one of whom had been previously unresponsive to bromocriptine, and another unresponsive to pergolide with regard to prolactin inhibition, were also unresponsive to CV 205-502. Nausea, the side-effect responsible for these patients' previous intolerance of bromocriptine, occurred in six of 10 patients taking CV 205-502 but was much less disabling and did not cause any of the patients to stop this medication. Only one patient taking CV 205-502 discontinued treatment because of adverse effects (light-headedness).

Topics: Adult; Aminoquinolines; Bromocriptine; Dopamine Agents; Drug Evaluation; Drug Tolerance; Female; Humans; Hyperprolactinemia; Menstruation Disturbances; Middle Aged; Prolactin

Twenty-four hyperprolactinaemic women were treated for 6 months with the new, non-ergot, long-acting dopamine agonist, CV 205-502. The treatment resulted in normalization of PRL secretion in 17 of the 24 women at once-daily doses of 0.05 to 0.15 mg of the drug. Sixteen of these women as well as 4 of those who remained hyperprolactinaemic had regular menstrual bleeding. Five of the patients had previously discontinued bromocriptine therapy because of adverse effects but had no problems tolerating CV 205-502. Of three bromocriptine-resistant women, two responded partially while one also remained unresponsive to CV 205-502 treatment. Mild to moderate galactorrhoea was recorded at baseline in 19 of the 24 women. After 6 months' treatment mild galactorrhoea was still present in six patients, four of whom had attained normal PRL levels. Side-effects were mild and transient. CV 205-502 seems to be a valuable compound in the management of patients with hyperprolactinaemia.

Topics: Adult; Aminoquinolines; Clinical Trials as Topic; Dopamine Agents; Double-Blind Method; Female; Galactorrhea; Humans; Hyperprolactinemia; Middle Aged; Time Factors

CV 205-502 (CV) is a potent dopaminergic compound which exerts a strong and sustained suppression of prolactin secretion in healthy volunteers. In a prospective double-blind, randomized, placebo-controlled trail, 12 hyperprolactinemic women (greater than or equal to 2000 mU/l), divided into 2 groups of 6 women each, were treated for 4 weeks. Combined pituitary challenge tests (GnRH, TRH, CRH and GHRH) were performed before and after treatment. The 6 CV-treated women (0.05 micrograms daily) showed approximately a 64% decrease of their initial prolactin serum concentrations after 4 weeks of capsule intake. Placebo-treated women showed no change in their prolactin serum level. After TRH administration, a blunted prolactin response was present in all women before treatment. After CV treatment a trend towards normalization of the prolactin response to TRH was seen, whereas the response pattern in the placebo group remained unaltered. The responses of GH, TSH, LH and ACTH to their releasing hormones and cortisol showed no significant changes after administration. FSH, however, showed a significant decrease in response to LH-RH, which could be explained by an increase in estradiol (E2) as ovarian function normalized in CV-treated women. In conclusion, CV shows strong dopamine agonistic properties in hyperprolactinemic women treated with 0.05 micrograms daily. The profile of this new quinoline compound, as judged from the pituitary challenge tests, does not differ from that of dopamine agonists of the ergoline type.

Topics: Adult; Aminoquinolines; Clinical Trials as Topic; Dopamine; Double-Blind Method; Estradiol; Female; Humans; Hyperprolactinemia; Pituitary Hormone-Releasing Hormones; Pituitary Hormones, Anterior; Progesterone; Prospective Studies; Random Allocation

CV 205-502, an octahydrobenzo(g)quinoline, is a new non-ergot long-acting prolactin inhibitor. The substance was given to 24 hyperprolactinaemic women for 7 d. The women were randomized to one of three dose regimens, 0.01 mg, 0.03 mg or 0.06 mg daily. Two patients in each group were given placebo. Frequent blood samples were obtained during days 1, 7 and 8. The prolactin levels in serum were depressed dose-dependently in all patients given active substance. In group 1 (0.01 mg) the dose was insufficient to induce normal serum prolactin levels except in one woman, while two women in group 2 (0.03 mg) and four in group 3 (0.06 mg) became normoprolactinaemic. The depressant effect on prolactin secretion lasted for 24 h in group 2 and 3. Side-effects were mild and transient. No change in blood pressure was observed. CV 205-502 was an effective and long-acting drug for treatment of patients with hyperprolactinaemia in this short-term study and this new drug deserves investigation of its usefulness in long-term treatment.

Topics: Adolescent; Adult; Aminoquinolines; Clinical Trials as Topic; Dose-Response Relationship, Drug; Female; Humans; Hyperprolactinemia; Middle Aged; Prolactin; Random Allocation

The aim of this article is to investigate the phenotype and etiology of prolactinoma-associated headache as well as present and discuss the plausible pain-relieving effect of dopamine agonist treatment.. In this case-based audit we included 11 patients with prolactinomas and one patient with idiopathic hyperprolactinemia presenting with headache that subsequently improved or resolved after dopamine agonist treatment.. A significant ipsilateral location of tumor mass and reported headache symptoms was observed (p = 0.018). After dopamine agonist treatment seven out of 12 patients became pain free within 2.5 months; after one year of treatment 11 out of 12 reported headache improvement or resolution. Average tumor volume reduction after treatment was 47 ± 22% during 9.5 ± 8.4 months of follow-up. There was no significant association between headache relief and tumor shrinkage (p = 0.43) or normalization of serum prolactin (p = 1.00), respectively.. 1) The significant association between lateralization of tumor and headache suggests a mechanical origin of the headache, 2) headache responded to dopamine agonist treatment in most patients, and 3) our observations encourage future prospective controlled trials to investigate the role of hyperprolactinemia in the pathogenesis of headache as well as the therapeutic effects of dopamine agonists.

Topics: Adult; Aminoquinolines; Cabergoline; Case-Control Studies; Dopamine Agonists; Ergolines; Female; Headache; Humans; Hyperprolactinemia; Magnetic Resonance Imaging; Male; Middle Aged; Pituitary Neoplasms; Prolactinoma; Recurrence; Substance Withdrawal Syndrome

It is accepted that care must be taken in initiating testosterone replacement in hypogonadal individuals with historically low androgen levels. However less is reported about the influence of restoration of normal endogenous testosterone production on behaviour.Here we report how the adverse sequelae of successful treatment of hypogonadism secondary to hyperprolactinaemia, manifesting as irritability and low threshold to aggression, were managed through a joint approach between psychiatrist and physician.

Topics: Adult; Aminoquinolines; Behavior Therapy; Dopamine Agonists; Humans; Hyperprolactinemia; Hypogonadism; Male; Pituitary Neoplasms

Prolactin is a hormone with a multidirectional proinflammatory action. It has an anti-apoptotic effect, enhances proliferative response to antigens and mitogens, as well as enhances the production of immunoglobulins and autoantibodies. Increased prolactin levels are commonly observed in various organ and multi-organ specific autoimmune diseases. In our article, we report a case of a woman who developed progression of autoimmune thyroid disorder and developed insufficiency of the zona glomerulosa when her prolactin levels were increased. A normalization of plasma prolactin levels by quinagolide and replacement of risperidone with aripiprazole improved her clinical condition. Our study suggests that, in some patients, hyperprolactinemia may predispose to the development and progression of autoimmune disorders of endocrine glands.

Topics: Aminoquinolines; Disease Progression; Dopamine Agonists; Female; Humans; Hyperprolactinemia; Prolactin; Thyroiditis, Autoimmune; Young Adult; Zona Glomerulosa

According to current concept, macroprolactin is biologically inactive and, therefore, its accumulation in serum has little, if any, pathological significance. Authors present the history of a 80-year-old man who proved to have, among other associated disorders, an intra- and parasellar pituitary tumor measuring 21x12x12 mm in size which was revealed by pituitary MRI. His hormonal evaluation indicated a marked hyperprolactinemia mainly due to macroprolactinemia (total prolactin, 514 ng/ml; reference range, 1.6-10.7 ng/ml; macroprolactin 436 ng/ml, monomer prolactin 78.2 ng/ml). Tests for function of the pituitary-thyroid axis showed a mild subclinical primary hypothyroidism. The function of the pituitary-adrenal axis was normal, and other hormonal tests revealed low-normal serum gonadotropins and decreased testosterone level, whereas serum insulin-like growth factor I was normal. Although the majority of current guidelines state that dopamine-agonist treatment which is successfully used in prolactin-producing pituitary tumors and in other hyperprolactinemic disorders is unnecessary in patients with macroprolactinemia, the authors introduced a dopamine-agonist, quinagolide. During prolonged treatment, plasma prolactin returned close to the upper limit of normal (12.3 ng/ml) and 9 months after the beginning of treatment pituitary MRI showed a remarkable shrinkage of the pituitary tumor. Authors propose that in this patient the pituitary tumor secreted macroprolactin, and they recommend a treatment trial with dopamine-agonist in pituitary macroadenomas associated with macroprolactinemia.

Topics: Aged, 80 and over; Aminoquinolines; Dopamine Agonists; Humans; Hyperprolactinemia; Magnetic Resonance Imaging; Male; Pituitary Neoplasms; Prolactin; Time Factors; Treatment Outcome

Topics: Aminoquinolines; Cabergoline; Diagnosis, Differential; Dopamine Agonists; Ergolines; Female; Humans; Hyperprolactinemia; Magnetic Resonance Imaging; Pituitary Gland; Pituitary Neoplasms; Pregnancy; Prolactin; Prolactinoma

Prolactin has been shown to have immunomodulatory as well as lactogenic effects. Generally less well known is that prolactin may also play a role in the activity of autoimmune diseases such as systemic lupus erythematosus and rheumatoid arthritis. Studies have shown decreasing prolactin production to be beneficial in animal models of autoimmune disease. Thus far, double-blinded, placebo-controlled studies of dopamine agonist treatment in humans with autoimmune disease have been done only in lupus patients, and support the potential efficacy of such agents. Small, open-label trials have also suggested potential benefit in patients with rheumatoid arthritis, Reiter's syndrome, and psoriasis. More studies are required to further delineate the mechanisms by which prolactin affects autoimmune disease activity, to determine in which specific diseases prolactin plays a significant role, and to test the efficacy of prolactin-lowering agents as therapy for such diseases.

Topics: Aminoquinolines; Animals; Arthritis, Rheumatoid; Autoimmune Diseases; Bromocriptine; Cabergoline; Cyclosporine; Dopamine Agonists; Double-Blind Method; Drug Therapy, Combination; Ergolines; Female; Humans; Hyperprolactinemia; Immunosuppressive Agents; Lupus Erythematosus, Systemic; Male; Mice; Mice, Knockout; Penicillamine; Prednisone; Prolactin; Rats; Receptors, Prolactin

Quinagolide has a strong dopaminerg activity, suppresses prolactin secretion and restores gonadal function in women with hyperprolactinemic anovulation. The aim of our study was to investigate the effectiveness of quinagolide in the treatment of 16 hyperprolactinemic patients. The clinical diagnosis was functional hyperprolactinemia in 13 patients, microprolactinoma in 2 and empty sella syndrome in 1. The drug was administered orally and initially daily dose was 0.025 mg for the first three days, 0.050 mg for the next three days and 0.075 mg for the following 6 months. The serum prolactin level was measured monthly before pregnancy, three monthly during the pregnancy and six weeks after delivery. Serum prolactin levels decreased in most of the patients during the first month and only in one case remained in the pathological range after six months quinagolide++ treatment. Prolactin secretion changed (mean and range) from 3120 (780-5790) mU/l to 370 (84-1076) mU/l. Out of 16 hyperprolactinemic patients nine women were infertile. During quinagolide treatment 5 pregnancies occurred. In conclusion, our results show that quinagolide has a good efficacy on regulation of prolactin secretion and it is a well tolerated dopamin-agonist drug.

Topics: Adult; Aminoquinolines; Anovulation; Dopamine Agonists; Empty Sella Syndrome; Female; Humans; Hyperprolactinemia; Pituitary Neoplasms; Postpartum Period; Pregnancy; Prolactin; Prolactinoma; Treatment Outcome

Introduction of the dopamine agonist bromocriptine heralded a major advance in the management of hyperprolactinemic disorders. Although its side effects of nausea, dizziness and headache and its short elimination half-life are limiting factors, its efficacy established it as a reference compound against the activity of which several dopamine agonists, like pergolide, lysuride, metergoline, terguride and dihydroergocristine, fell by the wayside. More recently, two new agents, cabergoline and quinagolide, have been introduced and appear to offer considerable advantages over bromocriptine. Cabergoline, an ergoline D2 agonist, has a long plasma half-life that enables once- or twice-weekly administration. Quinagolide, in contrast, is a nonergot D2 agonist with an elimination half-life intermediate between those of bromocriptine and cabergoline, allowing the drug to be administered once daily. Comparative studies indicate that cabergoline is clearly superior to bromocriptine in efficacy (prolactin suppression, restoration of gonadal function) and in tolerability. In similar studies, quinagolide appeared to have similar efficacy and superior tolerability to that of bromocriptine. Results of a small crossover study indicate that cabergoline is better tolerated, with a trend toward activity superior to that of quinagolide. In hyperprolactinemic men and in women not seeking to become pregnant, cabergoline may be regarded as the treatment of choice.

Topics: Aminoquinolines; Cabergoline; Dopamine Agonists; Drug Administration Schedule; Ergolines; Female; Humans; Hyperprolactinemia; Male; Pregnancy; Pregnancy Complications

The aim of this study was to evaluate the effects of a chronic treatment with the non-ergot-derived dopamine agonist quinagolide (CV 205-502) on sexual and gonadal function in hyperprolactinemic males. Thirteen males with macroprolactinoma and one with microprolactinoma were treated with CV 205-502 at the dose of 0.15-0.6 mg/day for 6-24 months. Baseline prolactin (PRL) was 464 +/- 75.7 microg/l. All the patients suffered from libido impairment, five of reduced sexual potency, six had infertility and in four bilateral induced galactorrhea was shown. The semen analysis revealed a severe oligoasthenospermia with reduced sperm count, motility and forward progression, with an abnormal morphology and decreased viability. A significant reduction of serum PRL levels (nadir PRL = 12.3 +/- 5.4 microg/l) was obtained during the treatment. Normalization of prolactinemia was reached in 13 of the 14 patients after 3 months. After 1 year, a significant improvement of sperm parameters, in terms of increase of number (from 5600 +/- 111 to 20,564 +/- 587 mm3), motility at 1 h (from 24.8 +/- 0.1 to 52.6 +/- 0.5%), forward progression (from 24 +/- 1.4 to 62.3 +/- 2.9%) and normal morphology (from 53.8 +/- 2.5 to 62.2 +/- 2.4%), was recorded. In addition, a significant increase of serum follicle-stimulating hormone (from 5.3 +/- 0.6 to 7.8 +/- 0.4 U/l), luteinizing hormone (from 4.4 +/- 0.5 to 7.7 +/- 0.4 U/l) and testosterone (from 3.4 +/- 0.4 to 4.7 +/- 0.2 microg/l) was recorded. A significant increase of luteinizing hormone (9.4 +/- 0.7 U/l) and testosterone (5.2 +/- 0.4 microg/l), as well as a further improvement of sperm parameters, was found after 2 years of therapy. Sellar computed tomography and/or magnetic resonance showed a considerable shrinkage (> or = 30%) of tumoral mass in 8 out of 13 patients with macroprolacinoma. Side effects were recorded in only one patient. In conclusion, the treatment with CV 205-502 normalizing PRL levels improves gonadal and sexual function and fertility in males with prolactinoma, providing good tolerability and excellent patient compliance to medical treatment. This result demonstrates that the impairment of gonadal function in hyperprolactinemic patients is a functional modification.

Topics: Aminoquinolines; Animals; Dopamine Agonists; Humans; Hyperprolactinemia; Male; Middle Aged; Oligospermia; Pituitary Neoplasms; Prolactin; Prolactinoma; Sperm Count; Spermatozoa; Testis; Time Factors

The cases are reported of two patients who developed benign intracranial hypertension after the withdrawal of the novel non-ergot derived dopamine agonist CV 205 502 (quinagolide).

Topics: Adult; Aminoquinolines; Cerebrovascular Circulation; Dopamine Agents; Female; Humans; Hyperprolactinemia; Migraine Disorders; Pseudotumor Cerebri; Substance Withdrawal Syndrome

CV 205-502 (octahydrobenzol[g]quinoline), a non-ergot dopamine agonist drug, was administered to 40 patients with hyperprolactinemic syndrome: 16 patients with macroprolactinoma, 14 with microprolactinoma and 10 with non-tumoral hyperprolactinemia. Twenty-four out of 40 patients had previously been treated by surgery and/or bromocriptine, with variable results. All had gonadal dysfunction and 22 patients had galactorrhea. Eight patients with macroprolactinoma had defects of the visual field. Pre-treatment serum PRL levels ranged from 60 to 2050 micrograms/l. The daily dose of CV 205-502 used in this trial ranged from 0.075 to 0.600 mg. After 6-12 months of treatment, serum PRL level decreased in all the patients reaching normoprolactinemia in 31 of them (77.5%) who demonstrated restoration of menses and disappearance of galactorrhea. The remaining nine patients (22.5%) had only a decrease of PRL levels without reaching normoprolactinemia and without any clinical effect. In 12 out of 16 patients with macroprolactinoma not previously surgically treated, a significant tumor shrinkage was shown by means of Computed Tomography and/or Magnetic Resonance Imaging. The disappearance of visual defects was obtained in four out of eight patients. CV 205-502 was tolerated satisfactorily: mild side-effects occurred in four patients in the first week of treatment and spontaneously disappeared, whereas six patients (15%) needed to withdraw the therapy after 6 months because of side-effects. In conclusion CV 205-502 is a potent and well-tolerated drug in the treatment of tumoral and non-tumoral hyperprolactinemic states and is an effective alternative to other dopamine agonists in use today.

Topics: Adult; Aminoquinolines; Dopamine Agonists; Drug Administration Schedule; Female; Humans; Hyperprolactinemia; Male; Middle Aged; Pituitary Neoplasms; Prolactinoma

CV205-502 is a new non-ergot dopamine agonist currently being studied for the treatment of hyperprolactinaemia. We have assessed the effects of CV205-502 on prolactin secretion and the clinical consequences of hyperprolactinaemia in 16 patients with hyperprolactinaemia who had previously been unsuccessfully treated with bromocriptine. These patients had been either intolerant of and/or resistant to the effects of bromocriptine. Sixteen patients, all women in an age range between 20 and 49 years (mean 31.5 years), were treated for periods of between 8 and 52 weeks with doses of CV205-502 ranging from 0.075 to 0.3 mg taken once daily at night. Seven out of 10 of the patients, who were intolerant of bromocriptine, tolerated CV205-502 better with fewer side effects although the nature of the side effects was similar to that associated with bromocriptine. Only 1 patient from this group stopped taking CV205-502 due to side effects. Six of 11 patients exhibiting bromocriptine resistance showed a significant reduction in the degree of hyperprolactinaemia but normoprolactinaemia was achieved in only 1. Galactorrhoea ceased in 2 of 6 patients, menstruation resumed in 6 of 11 patients presenting with amenorrhoea, and 2 patients conceived. In patients with bromocriptine intolerance and/or resistance, CV205-502 is useful as a second line treatment.

Topics: Adult; Amenorrhea; Aminoquinolines; Bromocriptine; Dopamine Agents; Drug Resistance; Drug Tolerance; Female; Galactorrhea; Humans; Hyperprolactinemia; Middle Aged; Pregnancy; Prolactin

Twenty hyperprolactinemic women (median prolactin [PRL] 2,989 mU/L, range 1,149 to 11,910 mU/L), previously unsuccessfully treated with bromocriptine, were treated in a prospective study, for 3 to 24 months with the new, nonergot, long-acting, dopamine agonist, CV 205-502. Treatment resulted in normalization of PRL in 14 patients, in one daily dose of 0.075 to 0.150 mg of the drug. Three patients were treated in doses above 0.150 mg up to 0.300 mg, but PRL was not normalized during the study. Menstrual function was restored in 15 of 18 amenorrheic patients. Galactorrhea, present in 7 patients, disappeared in 5. Four patients became pregnant and gave birth to healthy children. In conclusion, we found CV 205-502 effective in one daily dose, with good tolerability; it is safe and provides a valuable alternative to the dopamine agonist drugs in use today.

Topics: Adult; Amenorrhea; Aminoquinolines; Dopamine Agents; Female; Humans; Hyperprolactinemia; Menstrual Cycle; Middle Aged; Pituitary Gland; Pregnancy; Prolactin; Prospective Studies

Twenty-four hyperprolactinemic women of whom 23 previously had been given bromocriptine, were treated between 6 and 24 months with a new non-ergot dopamine agonist, CV 205-502 (quinagolide; Norprolac, Sandoz Ltd, Basle Switzerland). Twenty-four weeks of treatment resulted in normalization of prolactin secretion in 16 of the 24 women. All of these women as well as 4 of those who remained hyperprolactinemic had regular menstrual bleedings. Fifteen of the 24 women were treated for 24 months and all had normalized prolactin levels in serum at the end of this period. Regular menstrual bleedings were observed in 13 women. Mild to moderate galactorrhea was recorded at baseline in 14 of the 15 women. After 24 months of treatment, mild galactorrhea was still present in 3 women. All 15 women had been treated with bromocriptine or other dopamine agonists before they entered the study. In 9 of the women the tolerability had been judged to be fair (N = 4) or poor (N = 5). Five of the 15 women had previously discontinued bromocriptine treatment because of adverse effects but had few problems tolerating CV 205-502. Prolactin in serum increased in all the patients after discontinuation of the medication. The results confirm that CV 205-502 seems to be a valuable compound in the management of patients with hyperprolactinemia.

Topics: Adult; Aminoquinolines; Dopamine Agents; Female; Humans; Hyperprolactinemia; Middle Aged; Osmolar Concentration; Prolactin; Time Factors

Forty-one hyperprolactinemic women (prolactin [PRL] greater than 2,000 mU/L) were treated between 12 and 52 weeks with the new nonergot, long-acting dopamine agonist octahydrobenzo [g] quinoline (CV 205-502). The treatment resulted in normalization of PRL secretion in 71% of the women at a once-daily dose of less than or equal to 0.100 mg. All women responded with a significant decrease in serum PRL. Menstrual function normalized in all women except 1, whereas galactorrhea disappeared in all but 2 patients. During the observation period, four pregnancies were recorded with an additional three in the immediate posttreatment period. Until now, four healthy children have been born. Regarding tolerability, women with fair or poor response bromocriptine (Parlodel) in the past tolerated CV 205-502 better. Two women with no PRL decrease while on Parlodel responded with a decrease while on CV 205-502. All safety parameters remained normal while on treatment, and no significant changes were observed in blood pressure (supine and standing), pulse rate, or electrocardiogram (ECG) recordings. CV 205-502 therefore seems to be a valuable new compound in the management of patients with hyperprolactinemia.

Topics: Aminoquinolines; Drug Administration Schedule; Female; Galactorrhea; Humans; Hyperprolactinemia; Menstrual Cycle; Prolactin