Inhibition of lactation by cyclofenil and bromocriptine

In a double blind controlled study of the inhibition of lactation 13 women received 300 mg of cyclofenil and 11 women 2.5 mg of bromocriptine twice daily for 14 days. Lactation was effectively inhibited by both drugs, but with bromocriptine there was a significantly higher frequency of relapse. The plasma concentration of prolactin, which decreased rapidly with bromocriptine, returned to the pretreatment level the day after drug treatment stopped, but with cyclofenil it remained low. Plasma oestradiol followed a similar pattern. Plasma FSH increased more rapidly with bromocriptine than with cyclofenil. There was no significant difference between the treatment groups at any stage for haematology, coagulation or liver function tests. The more sustained effect of cyclofenil on prolactin secretion with a reduced frequency of relapse, and the lower oestradiol level, which might indicate a reduced risk of thromboembolism, suggest that this drug has some advantage over bromocriptine in the inhibition of postpartum lactation.     

Value of cyclofenil in the inhibition of lactation. Efficacy compared to bromocriptine

The inhibitory effects of cyclofenil and bromocriptine on lactation as well as FSH, prolactin and estradiol levels have been compared in control and treated females. The clinical activity of cyclofenil was lower than that of bromocriptine but was virtually free of side-effects. Cyclofenil and bromocriptine only presented similar hormonal effects at the 20th day ; this suggests that the mechanism of action of cyclofenil is more linked to secondary increases in estrogen levels than to a primary effect. Cyclofenil is of particular value in cases of vascular hypersensitivity yo ergot derivatives and for toxemic patients treated with beta-blockers.     

Lactation-inhibiting and prolactin-lowering effect of lisuride and bromocriptine: A comparative study

The prolactin-lowering and lactation-inhibiting effects of lisuride and bromocriptine, two dopaminergic drugs, were compared in a double-blind study. Twenty-six women took lisuride, 0.2 mg b.i.d., and 24 women took bromocriptine, 2.5 mg b.i.d., during 14 days postpartum. Though both drugs gave satisfactory inhibition of puerperal milk production, in these dosages bromocriptine was a more effective lactation inhibitor and prolactin suppressor. After discontinuation of treatment rebound symptoms were more pronounced in the bromocriptine group than in the lisuride group.     

Lactation inhibition by a single injection of a new depot-bromocriptine

Recently, long-acting injectable forms of bromocriptine have become available for the prevention of lactation. The first developed depot-form was very effective, but had the disadvantage of a slowly metabolized carrier. we investigated the pharmacokinetics, efficacy, tolerance and safety of 40 and 50 mg of a new rapidly eliminated depot-form in 61 postpartum women. Bromocriptine rapidly increased after injection and prolactin was effectively suppressed during the study-period of 60 days. Overall efficacy was very good or good in 98% and no rebound lactation occurred. Sixteen women experienced side effects. Tolerance at the injection site was good and safety tests did not show abnormalities. There were no differences between the two dosages. We conclude that this new depot-bromocriptine is a safe, well tolerated and effective drug in the suppression of prolactin and the prevention of post-partum lactation.     

Puerperal lactation suppression and prolactin.

Five methods for puerperal lactation inhibition were assessed in a randomized fashion. The 90 women were divided into five groups. Four of these received a pharmacologic treatment: oral stilbestrol (15 mg dd for 5 days), a diuretic compound (bendroflumethazide 15 mg dd for 5 days) by mouth, oral bromocriptine (5 mg dd for 14 days), or an intramuscular injection containing estradiol (10 mg and testosterone (200 mg) esters administered immediately after delivery. To the women in the remaining group only physical methods were applied (breast support and local infra-red waves) and they served as controls. Prolactin plasma concentrations were determined daily for five consecutive days and showed a correlation with the clinical effectiveness of the various treatment schedules. While bromocriptine reduced and stilbestrol augmented prolactin levels, both types of treatment were equally effective in preventing lactation during the observation period. Treatment with a diuretic compound or with an injection of steroids, though less effective than the first two regimens, was nevertheless significantly more efficacious than physical treatment.     

Lactation inhibition by a single injection of a new depot-bromocriptine

Summary. Recently, long-acting injectable forms of bromocriptine have become available for the prevention of lactation. The first developed depot-form was very effective, but had the disadvantage of a slowly metabolized carrier. We investigated the pharmacokinetics, efficacy, tolerance and safety of 40 and 50 mg of a new rapidly eliminated depotform in 61 postpartum women. Bromocriptine rapidly increased after injection and prolactin was effectively suppressed during the studyperiod of 60 days. Overall efficacy was very good or good in 98% and no rebound lactation occurred. Sixteen women experienced side effects. Tolerance at the injection site was good and safety tests did not show abnormalities. There were no differences between the two dosages. We conclude that this new depot-bromocriptine is a safe, well tolerated and effective drug in the suppression of prolactin and the prevention of postpartum lactation.     

Inhibition of lactation by a long-acting bromocriptine

A long-acting form of bromocriptine, a prolactin (PRL) secretion inhibitor, was administered to 122 postpartum women in single intramuscular injections of 20 (N = 24), 30 (N = 22), 40 (N = 46), and 50 mg (N = 30). In 91 women the substance was administered immediately after delivery to prevent galactopoiesis and in the remaining 31 women to inhibit established lactation. Effectiveness was estimated by the absence of breast engorgement and of milk secretion. Successful prevention or inhibition of lactation was highest among women receiving 50 mg bromocriptine (97%), and comparison between dosages revealed a close linear dose-response relationship (r = 0.98). Persistent and significant (P less than .001) PRL inhibition could be recorded for up to 22 days in successfully treated puerperas in comparison with 12 normally breast-feeding women who served as control subjects. No significant side effects or local reactions were recorded. Eleven of 46 postpartum women receiving 20 or 30 mg bromocriptine experienced onset of milk secretion or lactation rebound, and responded to oral administration of the drug. The presence of milk was associated with plasma PRL concentrations persistently above 25 ng/mL in all of them, whereas nine women in the same dosage range in whom lactation suppression was effective exhibited values below this limit. Dose-response data allow the establishment of a putative PRL threshold for induction of milk secretion of about 25 ng/mL. Maintenance of plasma PRL values below this limit prevents lactogenesis and inhibits lactopoiesis.     

Cabergoline versus bromocriptine in suppression of lactation after cesarean delivery

We evaluated the efficacy of cabergoline, a new ergoline derivative, in blocking puerperal lactation in a group of women delivered by cesarean section. In a single-blind controlled trial 36 women were randomly allocated to treatment with cabergoline 1 mg in a single dose p.o. (n = 18) or bromocriptine 5 mg/day p.o. for 14 days (n = 18). Treatment was started about 50 h after delivery. Clinical assessment of breast signs and determination of serum prolactin were performed just before treatment and at 3, 5, 7 and 14 days. In the cabergoline-treated group milk secretion was inhibited in 17 women (94.4%). Maximum decrease of serum prolactin was -89.7% at 5 days, and the prolactin-lowering effect of cabergoline was still present at 14 days. In the bromocriptine group milk secretion was inhibited in 16 women (88.9%). Maximum prolactin decrease (-86.9%) was reached at 3 days. Persistent side effects were comparable in the two groups. This study demonstrates that a single oral dose of 1 mg cabergoline is as effective in suppressing puerperal lactation as a full treatment with bromocriptine, even in women delivered by cesarean section.     

Effects of therapy and pregnancy on hyperprolactemia caused by a pituitary adenoma. A clinical case

A woman who presented with amenorrhea and galactorrhea with a large prolactinoma (8.5 mm) which regressed on bromocriptine therapy is described. When treatment with bromocriptine was instituted (10 mg/daily) mean serum prolactin concentration fell from 490 ng/ml to 108 ng/ml. Despite a progressive reduction in size up to disappearance of the adenoma after the first 5 years of therapy, prolactin levels remained high. Bromocriptine treatment was stopped after 6 years, when pregnancy was diagnosed. Pregnancy proceeded without complications and lactation was initiated and maintained. After 8 months of breast-feeding, menstrual function resumed spontaneously and bromocriptine therapy was no longer required. Bromocriptine can cause not only a decrease in serum prolactin levels but also a regression in the size of prolactinomas in hyperprolactinemic women. No problems associated with pregnancy and/or breast-feeding were noted in these patients.     

Effects of lisuride and bromocriptine on inhibition of lactation and on serum prolactin levels: Comparative double-blind study

The effects of lisuride (Schering) and bromocriptine (Parlodel^®, Sandoz), two dopaminergic drugs, on the inhibition of puerperal lactation were compared in a double-blind study.At the dosages selected, lisuride was as effective as bromocriptine for the inhibition of lactation but bromocriptine was more effective in lowering serum prolactin levels.     

Lactation inhibition by the dopamine agonist CV 205-502.

In an open pilot study with a parallel group design 30 bottle feeding women were randomly assigned in a two to one ratio to receive either the new dopamine agonist CV 205-502 or bromocriptine for lactation inhibition. Ten women who intended to breast feed served as normal controls. All treated women reached prepregnant prolactin levels within 72 h with once-daily 0.075 mg of CV 205-502 or twice-daily 2.5 mg of bromocriptine, at starting doses of 0.05 mg and 2.5 mg respectively. Fifteen of the 20 women treated with CV 205-502 reported breast symptoms, 50% occurring on days 3 and 4 of treatment. Three of the 10 women treated with bromocriptine had breast symptoms between days 2 and 28. Overall efficacy and tolerance in the two groups was very good. Side effects did not differ between the groups, with the exception of pulse rate in the standing position, which was significantly higher in the bromocriptine treated group than in either the CV 205-502 group (P = 0.02) or the breast feeding group (P less than 0.01). The coagulation tests (fibrinogen, AT III, PTT and APTT) showed no significant differences between the three groups.     

Rapid re-enlargement of a macroprolactinoma after initial shrinkage in a young woman treated with bromocriptine

We report the case of a macroprolactinoma in a 32-year-old woman, who presented with secondary amenorrhea, galactorrhea, increased plasma prolactin level (3259?ng/ml), headache and bi-temporal visual field defect. Magnetic resonance imaging showed a large pituitary tumor. The patient responded well to bromocriptine (7.5?mg/day) with improvement of clinical symptoms and normalization of plasma prolactin within a few weeks. After 4 months of treatment, tumor size was also reduced markedly. During continued treatment at the same dose of bromocriptine the plasma prolactin level remained normal, but after 8 months of treatment the patient suddenly complained of worsening of her visual fields, and magnetic resonance imaging indicated re-enlargement of the tumor. Bromocriptine was discontinued and transsphenoidal pituitary surgery was performed. After surgery the visual field defect improved, but postoperative plasma prolactin level (1104?ng/ml) and magnetic resonance imaging indicated a residual tumor. Postoperative treatment with quinagolide (0.15?mg/day) resulted in disappearance of all clinical symptoms, normalization of prolactin level and a reduction in size of the residual tumor. This case demonstrates that a dissociation of the inhibitory effect of bromocriptine on tumor size and prolactin level may rarely develop during the course of drug treatment in a patient with macroprolactinoma.     

Rapid re-enlargement of a macroprolactinoma after initial shrinkage in a young woman treated with bromocriptine.

We report the case of a macroprolactinoma in a 32-year-old woman, who presented with secondary amenorrhea, galactorrhea, increased plasma prolactin level (3259 ng/ml), headache and bi-temporal visual field defect. Magnetic resonance imaging showed a large pituitary tumor. The patient responded well to bromocriptine (7.5 mg/day) with improvement of clinical symptoms and normalization of plasma prolactin within a few weeks. After 4 months of treatment, tumor size was also reduced markedly. During continued treatment at the same dose of bromocriptine the plasma prolactin level remained normal, but after 8 months of treatment the patient suddenly complained of worsening of her visual fields, and magnetic resonance imaging indicated re-enlargement of the tumor. Bromocriptine was discontinued and transsphenoidal pituitary surgery was performed. After surgery the visual field defect improved, but postoperative plasma prolactin level (1104 ng/ml) and magnetic resonance imaging indicated a residual tumor. Postoperative treatment with quinagolide (0.15 mg/day) resulted in disappearance of all clinical symptoms, normalization of prolactin level and a reduction in size of the residual tumor. This case demonstrates that a dissociation of the inhibitory effect of bromocriptine on tumor size and prolactin level may rarely develop during the course of drug treatment in a patient with macroprolactinoma.     

Vaginal bromocriptine: pharmacology and effect on serum prolactin in normal women

Oral bromocriptine treatment of hyperprolactinemia is frequently associated with gastrointestinal side effects. To assess the efficacy and safety of an alternate route of treatment, we randomly administered 2.5, 5.0, and 7.5 mg of bromocriptine vaginally to five normal women at 1-week intervals. Plasma bromocriptine and prolactin (PRL) levels were measured hourly for 12 hours, then every 2 hours for 12 hours after each dose. At the end of each study, the vagina was flushed with saline for measurement of residual drug. For comparison of serum PRL levels, six additional women were given 2.5 mg bromocriptine orally. After administration of 2.5, 5.0, and 7.5 mg vaginally, plasma bromocriptine was initially detectable at 5.4 +/- 0.4, 4.4 +/- 0.7, and 3.5 +/- 0.6 hours, respectively. For the same vaginal doses, the mean (+/- SEM) peak plasma levels were 555 +/- 164 pg/mL at 12 +/- 0.6 hours, 702 +/- 252 pg/mL at 11.2 +/- 0.9 hours, and 1055 +/- 220 pg/mL at 10.7 +/- 1.7 hours, respectively. After each dose, there was a slow decline in plasma bromocriptine levels, remaining above 50% of peak values at 24 hours. Less than 1% of the administered drug was recovered from the vagina at 24 hours. The pattern of PRL inhibition with all three doses was similar. The mean plasma PRL level decreased by 7 hours, the maximum PRL decrease (64 +/- 3, 75 +/- 1, and 66 +/- 4% after 2.5, 5.0, and 7.5 mg, respectively) occurring at 11 hours, and the plasma PRL levels changed little during the remaining 13 hours.(ABSTRACT TRUNCATED AT 250 WORDS)     

Lactation inhibition by the dopamine agonist CV 205–502

Summary. In an open pilot study with a parallel group design 30 bottle feeding women were randomly assigned in a two to one ratio to receive either the new dopamine agonist CV 205–502 or bromocriptine for lactation inhibition. Ten women who intended to breast feed served as normal controls. All treated women reached prepregnant prolactin levels within 72 h with once-daily 0.075 mg of CV 205–502 or twice-daily 2.5 mg of bromocriptine, at starting doses of 0.05 mg and 2.5 mg respectively. Fifteen of the 20 women treated with CV 205–502 reported breast symptoms, 50% occurring on days 3 and 4 of treatment. Three of the 10 women treated with bromocriptine had breast symptoms between days 2 and 28. Overall efficacy and tolerance in the two groups was very good. Side effects did not differ between the groups, with the exception of pulse rate in the standing position, which was significantly higher in the bromocriptine treated group than in either the CV 205–502 group (  P = 0.02  ) or the breast feeding group (   P < 0.01  ). The coagulation tests (fibrinogen, AT III, PTT and APTT) showed no significant differences between the three groups.     

Bromocriptine therapy in normoprolactinemic women with unexplained infertility and galactorrhea

Forty-three women with unexplained infertility and 16 women who ovulated with clomiphene citrate therapy, yet failed to conceive, were evaluated because of the presence of expressible galactorrhea and normal random prolactin levels. The overall mean duration of infertility for these women was 5.68 +/- 0.33 years (mean +/- standard error) and their mean age was 30.20 +/- 0.46 years. Fifty-two of these women had primary infertility. Three treatment protocols were evaluated. Twenty-five women with unexplained infertility (Group A) received low-dose bromocriptine (1.25 to 2.5 mg) at bedtime for the first 18 days of the cycle; 18 women with unexplained infertility (group B) received 100 mg of pyridoxine continuously; and 16 women receiving clomiphene citrate (group C) also received bromocriptine in a manner similar to that for group A. All subjects were followed for six treatment cycles or until pregnancy occurred. The estimated cumulative pregnancy rate after six treatment cycles was 65% for groups A and C, which is significantly higher than the 22% rate for group B (Lee-Desu statistic = 4.66, P = 0.03). Women treated with bromocriptine were 2.3 times more likely to conceive than women treated with pyridoxine. Furthermore, those infertile galactorrheic women whose random prolactin level was greater than or equal to 15 ng/ml were most likely to conceive. Expressible galactorrhea in women with unexplained infertility and high normal prolactin concentrations may serve as a clinical sign indicating those women who may benefit from low-dose bromocriptine treatment administered at bedtime.     

Gonadotropic responsiveness to clomiphene, LRH, estradiol, and bromocriptine in galactorrheic women.

Twenty hyperprolactinemic patients with galactorrhea were studied to determine their gonadotropic responses to various stimuli. Five women lacked response to gonadotropin following the administration of clomiphene citrate. Ten patients who had luteinizing hormone releasing hormone (LRH) tests before and during bromocriptine administration exhibited varied FSH and LH responses that apparently were unaffected by bromocriptine therapy. A loss of the normal positive feedback of estrogens at the level of the hypothalamus was demonstrated in most patients before and during bromocriptine therapy. Long-term treatment with bromocriptine in 11 women resulted in a decrease of serum prolactin, cessation of lactation in all, and pregnancy in 8. These results suggest that the failure of normal secretion of gonadotropins in hyperprolactinemic women may result from 1) inadequate release of endogenous LRH, and 2) loss of the positive feedback of estrogens, as a result of the same hypothalamic disturbance that provokes the hyperprolactinemia. In turn, the elevated prolactin levels may exert a short-loop negative feedback at the hypothalamic level, inhibiting cyclic gonadotropin release.     

Plasma FSH, LH and prolactin levels in postmenopausal women undergoing cyclofenil treatment

Ten postmenopausal women were studied in an attempt to identify the mechanism of action of cyclofenil, a non-steroidal anti-estrogen which has proved to be effective in the climacteric syndrome. A double-blind inter-patient clinical investigation was undertaken, with patients assigned randomly to treatment for 10 days with cyclofenil, 400 mg/day, or else conjugated estrogens, 1.25 mg/day, always given orally at 8 a.m. Serum FSH, LH and PRL levels were determined daily 2 days before, during and for 2 days after treatment. On the first and tenth day of treatment, five blood samples were drawn between 8 a.m. and 4 p.m. to ascertain if there was any drug-induced variation in the hormonal secretory patterns. Furthermore, endometrial biopsies of all patients were taken before and immediately after the 10-day treatment. In 5 patients, endometrial biopsies were repeated after 3-6 months of therapy with cyclofenil. The results indicate that cyclofenil has two opposing actions on the hypothalamic-hypophyseal axis, one estrogen-like, in that it depresses serum FSH levels, and the other antiestrogen-like, in that it depresses serum PRL levels. They also show that at both the peripheral and the central level cyclofenil is a drug of first choice for postmenopausal women at risk for endometrial and mammary neoplastic pathology.     

Prolactin stimulation tests: different response patterns after bromocriptine, lisuride, and metergoline treatment of puerperal women

To elucidate different mechanisms by which bromocriptine, lisuride, and metergoline may inhibit prolactin (PRL) secretion and lactation in puerperal women, the PRL secretion patterns were examined by means of a stimulation test using an intravenous bolus of metoclopramide. After seven and 14 days of treatment, no significant difference in basal serum PRL levels was observed. However, women subjected to metergoline treatment had significantly higher responses of PRL to metoclopramide as compared with those treated with either bromocriptine or lisuride. Thus, the PRL-lowering mechanism of metergoline appears to be different from those of bromocriptine and lisuride.     

Bromocriptine for treatment of benign breast disease. A double-blind clinical trial versus placebo

Over the last few years bromocriptine has been used for treatment of mastodynia and benign breast disease, but with contradictory results. This double-blind clinical trial was performed to determine the efficacy of this prolactin inhibitor as compared with placebo. Subjective discomfort, clinical examination of the breast lesions, echomammography and breast thermography were evaluated before, during and after 3 months of treatment and in a further follow-up. Plasma levels of estradiol, progesterone and prolactin were measured over the same time. Significant reduction of mastodynia and significant improvement of the breast lesions were observed in the group given bromocriptine, though echomammography and breast thermography did not reveal any significant differences between the two groups. Plasma prolactin levels were significantly reduced by bromocriptine administration.