Treatment of hyperprolactinemic amenorrhea with Metergoline

The ergoline derivative, Metergoline, in a dosage of 4 to 24 mg/day, was administered for one to eight months to 42 patients with hyperprolactinemic amenorrhea. Mean serum prolactin (PRL) concentrations before treatment were 91.2 ng/mL in the patients with functional hyperprolactinemia (N = 29) and 256.9 ng/mL in the patients with pituitary tumor (N = 13). Within four weeks, Metergoline treatment reduced these PRL concentrations to 39.5 ng/mL and 82.9 ng/mL, respectively. In this study Metergoline treatment resulted in restoration of menstruation in a total of 37 patients; 28 patients ovulated, and eight became pregnant. It is considerably more effective in functional hyperprolactinemia than in hyperprolactinemia caused by adenoma.     

Hyperprolactinemia: comparison of thyrotropic-releasing hormone and tomography

A group of 95 women with unexplained hyperprolactinemia (over 20 ng/mL) underwent radiologic examination of the sella turcica with hypocycloidal polytomography (N = 58), computed axial tomography (N = 8), or both (N = 29). All patients also underwent a thyrotropin-releasing hormone (TRH) stimulation test, with serum prolactin (PRL) measurement before and 20 and 30 minutes after a 500-micrograms intravenous bolus of TRH. Their PRL responses were compared with those of two control groups, nine normal women in the follicular phase of the menstrual cycle, and 13 women in the first five months of gestation with pregnancy-related hyperprolactinemia. Both control groups exhibited PRL increases with 95% confidence limits at least 200% above baseline levels. In all, 12 patients from the study group also had a normal PRL response (more than a 200% increase) to TRH, and none of these women had tomographic findings consistent with a pituitary tumor. The remaining 83 women all had diminished or absent PRL increases after TRH administration; 46 (55%) of these patients had radiographic evidence of an adenoma, whereas 37 (45%) had no clear signs of a tumor on either polytomography or computed axial tomography. No patient with a baseline PRL level in excess of 60 ng/mL had a normal PRL response to TRH. The results of the study indicate that 1) in patients with PRL between 20 and 60 ng/mL, a normal TRH test can be relied upon to avoid the expense and radiation of tomography (computed axial tomography or polytomography), 2) there is no benefit to be obtained in performing a TRH test in patients with a baseline PRL level over 60 ng/mL, and 3) about 45% of patients with hyperprolactinemia and an abnormal TRH test have a normal computed tomography or polytomography. These patients may have a small adenoma, and thus warrant closer follow-up than patients with a normal TRH test.     

Long-term follow-up of 246 hyperprolactinemic patients

BACKGROUND: We wanted to evaluate the very long-term effects of bromocriptine on prolactin (PRL) levels and pituitary tumor size in a large cohort of hyperprolactinemic patients. METHODS: We conducted a retrospective cohort study in the Department of Endocrinology from Necker Hospital in Paris, France. Two hundred and forty-six patients consulted primarily for menstrual disorders, with diagnosis of hyperprolactinemia. Patients were followed-up for 99.9+/-3.6 months. One hundred and ninety-one were treated with bromocriptine, 32 underwent surgery, and 23 received no treatment. RESULTS: The mean initial plasma PRL level was 135.0+/-20.2 ng/ml. Presence of an adenoma was detected in 60% of our patients and comprised a microadenoma in 64% of cases. Compared to oligomenorrheic women, amenorrheic patients had significantly higher levels of PRL and larger pituitary tumor size. In the bromocriptine group, PRL levels decreased from 99.6+/-7.9 to 20.0+/-1.5 ng/ml (p=0.00001). The medical treatment was associated with disappearance of the adenoma in 45% of the women and with stabilization of pituitary tumor size in 40% of patients. Surgery led to disappearance of the adenoma in almost all cases, but failed to definitively cure hyperprolactinemia. CONCLUSION: In this large-scale retrospective study, the medical treatment of mild hyperprolactinemia was shown to be effective and sufficient after 9 years of follow-up.     

Polycystic ovary syndrome and hyperprolactinemia are distinct entities.

The aims of the present study were to identify the cause of hyperprolactinemia in polycystic ovary syndrome (PCOS) and to compare prolactin (PRL) levels between PCOS women without hyperprolactinemia and women with insulin resistance and without PCOS. A group of 82 women (age: 27.1 +/- 7.6 years) with PCOS was included in the study. Their PRL levels were measured and compared with those of women with insulin resistance without PCOS (controls; n = 42; age: 29.2 +/- 8.2 years). Among the 82 PCOS women, 13 (16%) presented high PRL levels (103.9 +/- 136.0 microg/l). The causes of hyperprolactinemia were: pituitary tumor (responding to cabergoline) in nine cases (69%; PRL range: 28.6 - 538 microg/l); oral hormonal contraceptive treatment in two cases (15%; PRL: 46 and 55 microg/l, respectively); and use of buspirone and tianeptine in one case (8%; PRL: 37.1 microg/l); one case (8%; PRL: 34.4 microg/l) had macroprolactinemia. In drug-induced hyperprolactinemic patients PRL levels normalized after treatment interruption. The average PRL level in the 69 remaining patients was 12.1 +/- 5.5 microg/l, a value not statistically different from that of the control group (11.8 +/- 4.9 microg/l). This result leads us to conclude that PCOS patients with increased PRL levels must be investigated for other causes of hyperprolactinemia, because hyperprolactinemia is not a clinical manifestation of PCOS.     

Effects of pregnancy, delivery and lactation in hyperprolactinemia with prolactin producing pituitary adenoma

The effects of pregnancy, delivery and lactation on changes in serum prolactin (PRL) values were investigated in patients with hyperprolactinemia. Thirty-seven patients with hyperprolactinemia who wished to become pregnant were treated by transsphenoidal surgery, bromocriptine therapy, or a combination of the two. In 33 patients whose pre-pregnancy serum PRL concentration exceeded 30ng/ml, only in two did serum PRL return to the normal range below 30ng/ml after pregnancy, delivery and lactation. However, the serum PRL concentration was decreased in 28 patients. When classified according to the pre-pregnancy serum PRL concentrations, PRL less than or equal to 100 (Group A), 100 less than PRL less than or equal to 200 (Group B) and 200 less than PRL (Group C), patients with the greatest pre-pregnancy serum PRL concentration showed the greatest reduction. The ratios of post-pregnancy serum PRL to pre-pregnancy PRL in group A, B and C were 91.4 +/- 22.1%, 81.5 +/- 7.0% and 65.0 +/- 6.5% (Mean +/- SE), respectively. Group C with the highest pre-pregnancy serum PRL concentration consisted almost entirely of patients with macroadenoma. Thus, the reduction in serum PRL after pregnancy, delivery and lactation was considered to be the result of a decrease in the size of the adenoma due to adenoma enlargement over the sella turcica through the estrogen effects during pregnancy, and from impairment of pituitary circulation.     

The effect of serum prolactin levels on ovarian steroidogenesis

In order to assess the effect of hyperprolactinemia on ovarian steroidogenetic potential, a group of anovulatory hyperprolactinemic patients and a control group of anovulatory normoprolactinemic women were submitted to exogenous gonadotropin (hMG) stimulation under identical experimental conditions. Serum 17 beta-estradiol (E2) concentrations were determined before and after hMG stimulation. The mean basal serum E2 levels in the hyperprolactinemic group (22.7 +/- 3.3 pg/mL, mean +/- 1 SE) were significantly lower than in the normoprolactinemic control group (48.7 +/- 8.4 pg/mL, P less than .01). A significant negative correlation (r = -.6157, P less than .01) between basal serum E2 levels and basal serum prolactin (hPRL) concentrations was found. Following hMG stimulation, the serum E2 increment (delta E2) from basal E2 levels in the control group (491 +/- 91 pg/mL) was significantly higher than the increment in the hyperprolactinemic group (182 +/- 48 pg/mL, P less than .01), and a significant negative correlation was observed between basal serum hPRL levels and the logarithm of delta E2 (r = -.4744, P less than .05). Our results suggest that chronic hyperprolactinemia induces ovarian refractoriness to exogenous gonadotropin stimulation and substantially reduces its steroidogenetic potential.     

Integrity of central dopaminergic system in women with postpartum hyperprolactinemia

In order to elucidate the role of elevated prolactin (PRL) on the central dopaminergic systems, the suppressive effects of PRL were studied after the administration of l-dopa and l-dopa plus carbidopa on consecutive days to the following three groups: 10 normoprolactinemic subjects, six nonnursing normal puerperal women, and seven hyperprolactinemic women without any evidence of pituitary tumor. In the normoprolactinemic subjects (basal PRL 13 ± 2 ng/ml mean ± SE), the suppressive effects of l-dopa alone and l-dopa plus carbidopa were similar (48% ± 4% and 58% ± 6%, respectively). In puerperal hyperprolactinemic subjects, the basal PRL (116.8 ± 16.4 ng/ml) was suppressed 77% ± 2% after administration of l-dopa and 51% ± 7% after l-dopa plus carbidopa, significantly different from that of l-dopa alone (p < 0.005), but similar to that observed in normal subjects. In the patients with idiopathic hyperprolactinemia, the baseline PRL (131 ± 38 ng/ml) decreased 56.3% after the administration of l-dopa. In the presence of peripheral dopa decarboxylase inhibition, the administration of l-dopa decreased plasma PRL values 30%, a drop significantly different from that of l-dopa alone (p < 0.02). Women with idiopathic hyperprolactinemia exhibit reduced central dopaminergic inhibition of PRL secretion similar to that in patients with pituitary tumor; whereas the response to central dopaminergic inhibition in postpartum women with comparable baseline PRL levels is similar to that in normoprolactinemic subjects. This indicates that hyperprolactinemia per se is not associated with a state of reduced central dopaminergic inhibition. The increased pituitary sensitivity to l-dopa observed in puerperal women may be due to alterations in PRL receptors or vascularity.     

Transient hyperprolactinemia in infertile women with luteal phase deficiency

This study was conducted to evaluate the prevalence of transient hyperprolactinemia in infertile women with luteal phase deficiency. One hundred fifty-one luteal phase deficiency patients and 11 controls had serum prolactin (PRL) measured daily for 3-4 days near ovulation. Thirty-three subjects (21.9%) had transient hyperprolactinemia, with PRL above 20 ng/mL for 1 or 2 days, and were studied further. The blood samples of these 33 subjects and of the controls were also analyzed for LH and FSH. Plasma progesterone was measured on the fourth, seventh, and tenth days after ovulation in both groups. The mean (+/- SD) of the mid-cycle integrated LH surge (125.0 +/- 23.0 mIU/mL; N = 26) and the sum of three plasma progesterone levels (23.8 +/- 4.5 ng/mL; N = 21) in the luteal phase deficiency women were significantly (P less than .001) lower than those of the controls (LH 158.7 +/- 13.8 mIU/mL; progesterone 33.8 +/- 6.5 ng/mL). All 33 luteal phase deficiency subjects with transient hyperprolactinemia were treated with bromocriptine at a dose ranging from 1.25-5 mg/day to maintain mid-cycle PRL levels between 5-15 ng/mL. Both the integrated LH surge and the sum of three progesterone levels increased significantly (P less than .05) during bromocriptine treatment, to 142.6 +/- 22.4 mIU/mL (N = 20) and 28.2 +/- 6.2 ng/mL (N = 18), respectively. Fourteen of the 33 patients conceived. The cumulative probability of conception was 31% for six cycles and 45% for 12 cycles of treatment.(ABSTRACT TRUNCATED AT 250 WORDS)     

The effect of the ergoline derivative, CU 32-085, on prolactin secretion in hyperprolactinemic women

Twelve hyperprolactinemic women were administered the alpha aminoergoline derivative, CU 32-085 (Sandoz, Inc., East Hanover, NJ), in order to determine its effect on prolactin (PRL) secretion. The mean pretreatment serum PRL level was 145.0 +/- 11.5 ng/ml. Significant declines of serum PRL occurred with total daily doses of CU 32-085 of 0.1 to 0.5 mg (P less than 0.001). The magnitude of response to therapy was dose-related. In six patients, PRL levels were reduced to less than 25 ng/ml; this effect lasted at least 24 hours after intake of a single dose. In the other six patients, the response was less dramatic. No subjects developed adverse cardiovascular side effects. The results of this study demonstrate that CU 32-085 exhibits a clinically significant dopaminomimetic action on PRL secretion in hyperprolactinemic women.     

Prolactin responsiveness to TRH in amenorrheic women with and without galactorrhea.

Sixty women were given intravenous injection of 200 microgram TRH to assess its diagnostic potential as a stimulus to PRL release. Following the administration of TRH, there was a prompt increase in serum PRL to 614.6%, to 296%, to 282.1%, and 34% in normal women, amenorrheic patients, non tumoral galactorrheic cases, and patients with pituitary tumors respectively. The TRH response above baseline of PRL levels was statistically significant in all groups, but the women with pituitary tumors which showed a blunted response. The per cent of increment of PRL levels after TRH was similar in amenorrheic women regardless the presence or not of galactorrhea; this increase was significantly greater than in patients with pituitary tumors (p less than 0.01). The per cent of increment above baseline of PRL was significantly greater in menstruating women than in amenorrheic patients (p less than 0.001). In basis of present data: 1) there is a diminished PRL secretion after TRH in amenorrheic women regardless the presence of galactorrhea or hyperprolactinemia; 2) a blunted response to TRH in hyperprolactinemic women may be indicative of a pituitary tumor.     

Prolactin response to perphenazine. A sensitive and specific test for pituitary tumor in hyperprolactinemic women

A simple biochemical screening test for prolactin-secreting pituitary tumors is needed because computed tomography is expensive and may be insensitive in the detection of microadenomas. We compared serial prolactin levels following perphenazine stimulation in 20 women with histologically documented tumors to those in 22 normal controls. In addition, seven women who were diagnosed as having functional (nontumor) hyperprolactinemia were tested. All subjects were given perphenazine, 8 mg orally. Baseline and hourly serum prolactins for six hours were compared. A 200% or greater response occurred in all control patients and functional hyperprolactinemic subjects within six hours following medication. Without exception, tumor patients exhibited a markedly blunted or absent response. This markedly diminished response pattern was compatible with the presence of a pituitary adenoma and suggests that the presence of a tumor interferes with normal pituitary secretory responsiveness.     

Hyperprolactinaemic Amenorrhoea in Hong Kong

In a retrospective study of 595 patients attending the Menstrual Disorder Clinic from January, 1978 to December, 1981, 92 patients (15.5%) had raised serum prolactin (PRL) levels (greater than 25 ng/ml) on 2 or more separate occasions with a mean (+/- S.E.M.) value of 67.1 +/- 2.5 ng/ml. Galactorrhoea was found in 27.2% of the hyperprolactinaemic patients. Primary amenorrhoea was observed in 1 patient (1.1%) with serum PRL level of 68 ng/ml. Secondary amenorrhoea of longer than 6 months' duration occurred in 61 patients (66.3%) with mean PRL level 84.2 +/- 3.3 ng/ml. The 30 patients (32.6%) with irregular menstruation had a mean PRL level of 47.2 +/- 3.3 ng/ml. Investigations revealed that 43 patients (46.7%) had idiopathic hyperprolactinaemia, 14 patients (15.4%) had drug induced hyperprolactinaemia and 1 patient (1.1%) had hypothyroidism; 18 patients (19.5%) had suspected pituitary microadenoma and 16 patients (17.2%) had abnormal radiographic findings. Bromocriptine treatment was given to 38 patients, 13 with abnormal tomographic findings (mean serum PRL greater than 100ng/ml); 18 with suspected pituitary microadenoma (mean serum PRL 94 +/- 2.7 ng/ml) and 7 with idiopathic hyperprolactinaemia (mean serum PRL 65 +/- 4.7 ng/ml). All patients (38/38) responded to treatment with restoration of menstruation and cessation of galactorrhoea within 1 to 3 months. Mean PRL level was 21.6 +/- 5.2 ng/ml at the time of response. Thirteen patients subsequently became pregnant and all delivered healthy babies.     

Clinical, endocrine, roentgenographic, and immune characterization of hyperprolactinemic women

Seventy-one hyperprolactinemic women were analyzed for medical history, gonadotropin and ovarian hormonal levels, and prolactin (PRL) responsiveness to benserazide. Sellar tomography was then performed on a yearly basis for 3 years in all women, computerized coronal and sagittal tomography in 54 of them. Under basal conditions, 30 women had roentgenographic evidence of pituitary adenoma; at the end of the follow-up period, such evidence was seen in 44. Amenorrhea, steady PRL levels, a low LH/FSH ratio, a longer duration of the disease, and low serum progesterone levels were more common in women with a final diagnosis of pituitary adenoma than in those with a persistently normal sella. The benserazide test for PRL release had yielded abnormal results since the beginning in all the 44 women with final roentgenographic evidence of pituitary adenoma, and in about half of the patients with persistently normal aspect of the sella; autoantibodies towards the pituitary gland, the thyroid gland, and gastric parietal cells were found in 3, 2, and 3 patients, respectively. No autoantibodies towards the adrenal gland or the islets of Langerhans were ever found in any cases. These data show that a fair proportion of hyperprolactinemic women have a (micro)adenoma, which becomes apparent over a relatively short period of time. Amenorrhea and steadily raised PRL levels are more common in these women. The benserazide test seems to be adequate for predicting which women will eventually develop a roentgenographically detectable adenoma. Autoimmunity does not seem to be involved in the pathogenesis of hyperprolactinemia and/or pituitary adenoma.     

Spontaneous pregnancy after a pregnancy induced by treatment in hyperprolactinemic women

The relationship between spontaneous pregnancy of hyperprolactinemic patients after a first pregnancy induced by treatment and their serum prolactin levels was examined. Of the 100 patients with hyperprolactinemia studied, 74 became pregnant after treatment; namely, 20 transsphenoidal adenomoidectomy for pituitary prolactinoma (group 1), 26 on treatment with bromocriptine for pituitary prolactinoma (group 2), and 28 on treatment with bromocriptine for hyperprolactinemia without prolactinoma (group 3). After delivery in the first pregnancy, the rates of menstrual restoration and subsequent spontaneous pregnancy in group 1 (72.2% and 75.0%) were significantly (p less than 0.05) higher than those in group 2 (32.0% and 25%) and group 3 (13.6% and 18.2%). The serum levels of prolactin after the first pregnancy and weaning were significantly (p less than 0.05) lower in patients with subsequent spontaneous pregnancy than in patients without spontaneous pregnancy in each group, and the levels in patients with spontaneous pregnancy were significantly (p less than 0.05) lower in group 1 (15.2 +/- 8.8 ng/ml) than in group 2 (46.6 +/- 2.9 ng/ml). These data suggest that the transsphenoidal adenomoidectomy for pituitary prolactinoma may be better than bromocriptine treatment for recovery of reproductive function.     

An endocrinological study of hyperprolactinemia and its treatment (author's transl)

Twenty-six cases of women with pituitary adenoma and seven cases of women with functional hyperprolactinemia were studied to evaluate the effects of neurosurgery and Bromocriptine treatment. In the patients with pituitary adenoma, the mean serum PRL level was significantly higher than that in the functional cases. Among the patients with pituitary adenoma, the serum PRL levels were roughly correlated to the size of the tumors. Basal serum LH, FSH and 17 beta-estradiol levels were lower in the patients with pituitary macroadenoma than in those with microadenoma. Neurosurgery was performed on fourteen patients of pituitary adenoma. Of ten cases with visual disturbance, it was necessary to use Bromocriptine to reduce the serum PRL to the normal level after operation. In the treatment of sixteen patients with microadenoma, Bromocriptine alone was used for eight of them and surgery was performed on four. As a result, there was a significant lowering of the serum PRL level and induction of regular menses in ten patients. Regular menses were induced by means of Bromocriptine treatment in all of the patients with functional hyperprolactinemia. Our data indicate that neurosurgery, either selective or combined with Bromocriptine, can normalize PRL levels and induce regular menses in patients with hyperprolactinemia.     

Laboratory and clinical significance of macroprolactinemia in women with hyperprolactinemia

The role of macroprolactinemia in women with hyperprolactinemia is currently controversial and can lead to clinical dilemmas, depending upon the origin of macroprolactin, the presence of hyperprolactinemic symptoms and monomeric prolactin (PRL) levels. Macroprolactinemia is mostly considered an extrapituitary phenomenon of mild and asymptomatic hyperprolactinemia associated with normal concentrations of monomeric PRL and a predominance of macroprolactin confined to the vascular system, which is biologically inactive. Patients can therefore be reassured that macroprolactinemia should be considered a benign clinical condition, resistant to antiprolactinemic drugs, and that no diagnostic investigations or prolonged follow-up should be necessary. However, a significant proportion of macroprolactinemic patients appears to suffer from hyperprolactinemia-related symptoms and radiological pituitary findings commonly associated with true hyperprolactinemia. The symptoms of hyperprolactinemia are correlated to the levels of monomeric PRL excess, which may be explained as coincidental, by dissociation of macroprolactin, or by physiological, pharmacological and pathological causes. The excess of monomeric PRL levels in such cases is of primarily importance and the diagnosis of macroprolactinemia is misleading or inadequate. However, macroprolactinemia of pituitary origin associated with radiological findings of pituitary adenomas may rarely occur with similar hyperprolactinemic manifestations, exclusively due to bioactivity of macroprolactin. Therefore, in such cases with hyperprolactinemic signs and pituitary findings, macroprolactinemia should be considered a pathological biochemical condition of hyperprolactinemia. Accordingly, individualized diagnostic investigations with the introduction of dopamine agonists, or other treatment with prolonged follow-up, should be mandatory. The review analyses the laboratory and clinical significance of macroprolactinemia in hyperprolactinemic women suggesting clinically useful diagnostic and treatment strategies.     

Prolactin and thyroid-stimulating hormone responses to thyrotropin-releasing hormone in cases of hyperprolactinemia with normal and abnormal sella tomograms

An intravenous bolus of 500 micrograms of thyrotropin-releasing hormone (TRH) was used to test prolactin and thyroid-stimulating hormone (TSH) responses in normoprolactinemic patients and in hyperprolactinemic patients with normal and abnormal sella turcica. The prolactin response showed a mean increment of 64.1 +/- 46.3 ng/ml in normoprolactinemic women. In patients with hyperprolactinemia, the mean increment was 14.1 +/- 22.4 ng/ml and 13.8 +/- 33.1 ng/ml for patients with normal and abnormal sella, respectively. The difference in the prolactin response between the normoprolactinemic patients and either group of hyperprolactinemic patients is significant (P less than 0.005). The mean baseline TSH in normoprolactinemic patients is significantly higher than in patients with hyperprolactinemia with normal and abnormal sella. The mean increment of TSH after TRH stimulation is significantly higher in normoprolactinemic patients than in either group of patients with hyperprolactinemia (P less than 0.005). These results suggest an inhibitory action of hypothalamic dopamine on the response of both prolactin and TSH to TRH in patients with hyperprolactinemia. The hypothalamic dopamine mechanism might also be the factor leading to suppression of baseline TSH levels in hyperprolactinemic patients. In addition, these results suggest that patients with hyperprolactinemia, with or without changes in the sella turcica, might have various degrees of the same pathology affecting the lactotropes.     

Prolactin hyperstimulation in response to thyrotropin-releasing hormone in patients with endometriosis

In order to clarify the role of hyperprolactinemia as a possible cause of infertility in patients with endometriosis, baseline serum prolactin (PRL) concentrations and the PRL response to thyrotropin-releasing hormone (TRH) stimulation were measured in 14 infertile women with endometriosis and in 13 normal, fertile women. Baseline PRL concentrations were 2-fold greater in the endometriosis group than in normal subjects, but the mean values did not differ significantly. Following TRH administration, a significant increase in peak PRL concentrations was observed in patients with endometriosis (211.5 +/- 34.9 ng/ml) when compared with corresponding values in control subjects (117.1 +/- 14.9 ng/ml, P less than 0.05). This hypersecretory state was selective for PRL because no significant differences between the baseline and TRH-stimulated thyroid-stimulating hormone (TSH) concentrations or total serum thyroxine concentrations were observed. In summary, some infertile women with endometriosis exhibit a greater capacity for PRL secretion than normal women. These results suggest that relative hyperprolactinemia may be responsible for the infertility associated with endometriosis, and that PRL suppression may be indicated in these patients.     

A new oral slow release form of bromocriptine, Parlodel SRO, in the chronic treatment of 26 hyperprolactinemic patients.

Parlodel SRO, a new slow release form of bromocriptine, was studied in 26 patients with tumoral and non-tumoral hyperprolactinemia. Prior to the treatment, serum prolactin (PRL) levels ranged from 45 ng/ml to 7000 ng/ml and they decreased to within the normal range in all but one patient after 7 days-1 year of treatment with this new formulation of bromocriptine. The clinical improvement paralleled the normalization of PRL secretion. Tolerability was rated good or very good in 24 patients, even in the three patients who had been intolerant of oral Parlodel. In conclusion, Parlodel SRO administered as a single daily dose resulted in very effective lowering of serum PRL in patients with hyperprolactinemic disorders.     

Effect of a histamine H2-receptor antagonist, cimetidine, on prolactin secretion in women

The effect of acute intravenous injection of 400mg cimetidine, a histamine H2-receptor antagonist, on prolactin (PRL) secretion was investigated in women with normal menstrual cycles (n = 12) and normoprolactinemic secondary amenorrhea (n = 10). In addition, the PRL response to cimetidine was also examined in women with puerperal (n = 10) and idiopathic (n = 10) hyperprolactinemia. The administration of cimetidine provoked a rapid rise in plasma PRL in both normal and amenorrheic women, with peak values occurring at 10-15 minutes, followed by a return toward the baseline by 2 hours. The PRL response was significantly greater (p less than 0.001) in normal women [mean (+/- SE) basal vs. peak values: 15.3 +/- 1.5 vs. 124.6 +/- 10.3 ng/ml (p less than 0.001)] than in amenorrheic women [13.5 +/- 1.3 vs. 71.7 +/- 7.2 ng/ml (p less than 0.001)]. There were no significant changes in plasma LH or FSH levels in any group. The cimetidine injection caused a remarkable increase in plasma PRL in women with puerperal hyperprolactinemia [110.8 +/- 31.1 vs. 288.8 +/- 39.6 ng/ml (p less than 0.001)], while the PRL response was diminished or absent in women with idiopathic hyperprolactinemia [103.3 +/- 19.3 vs. 122.9 +/- 14.6 ng/ml (p greater than 0.1)]. The mean incremental PRL response was 1.6 times greater than that observed in normal women. These results suggest that histamine may exert an inhibitory effect on PRL secretion through H2-receptors and that an altered central histaminergic tone may be involved in amenorrheic or pathological hyperprolactinemic state.