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PubMed2001

Basal, pulsatile, entropic, and 24-hour rhythmic features of secondary hyperprolactinemia due to functional pituitary stalk disconnection mimic tumoral (primary) hyperprolactinemia.

Under physiological conditions, PRL secretion is regulated precisely by various stimulating and inhibiting factors. Hyperprolactinemia may arise as a primary consequence of a PRL-secreting pituitary adenoma. Secondary hyperprolactinemia (SH) may emerge in patients with hypothalamic disease, hypophyseal stalk compression, or suprasellar extension of a (nonlactotrope) pituitary adenoma. The latter may reflect diminished delivery of dopamine or other inhibitory factors to normal lactotropes. We hypothesized that diurnal and ultradian rhythms of PRL secretion would differ in secondary (e.g. hypothalamic) and primary (e.g. tumoral states) hyperprolactinemia (PH), assuming that the underlying pathophysiologies differ. To test this clinical postulate, we investigated the patterns of 24-h PRL release in eight patients with SH associated with functional hypothalamo-pituitary disconnection and in eight patients with PH attributable to microprolactinoma. Data in each group were compared with values in healthy gender-matched controls. PRL time series were obtained by repetitive 10-min blood sampling, followed by high- precision immunofluorometric assay. PRL concentration profiles were analyzed by the complementary tools of model-free discrete peak detection, waveform-independent deconvolution analysis, cosinor regression, and the approximate entropy metric to quantitate pulsatile, basal, 24-h rhythmic, and pattern-dependent (entropic) PRL secretion. Patients with tumoral hyperprolactinemia (PH) showed a 2-fold higher 24-h mean serum PRL concentration than patients with SH (62 +/- 13 microg /L vs. 30 +/- 6.9 microg/L, respectively, P = 0.029). Estimated PRL pulse frequency (events/24 h) was similar in the two patient groups (18.5 +/- 0.7 vs. 17.6 +/- 0.8; P = 0.395) but elevated over that in euprolactinemic controls (P < 0.0001 for both). Deconvolution analysis disclosed a mean daily PRL secretion rate of 790 +/- 170 microg in PH patients vs. 380 +/- 85 microg in SH patients (P = 0.030). Nonpulsatile PRL secretion comprised nearly 70% of total secretion in both patient groups and 50% in controls (P < 0.0001). Cosinor analysis revealed similar acrophases in all three study cohorts. The mean skewness of the statistical distribution of the individual PRL sample secretory rates was reduced, compared with controls (P < 10 (-5) for each), but equivalent in SH and PH patients (0.83 +/- 0.12 vs. 0.78 +/- 0.08, respectively), denoting a loss of the normal spectrum of low- and higher-amplitude secretion rates. Approximate entropy, a regularity statistic, was markedly elevated in both patient groups over controls (P < 10 (-6) for each) and was slightly higher in PH patients than in SH patients (1.639 +/- 0.029 vs. 1.482 +/- 0.067, P = 0.048). In summary, patterns of PRL secretion in PH and SH states exhibit an equivalently increased frequency of PRL pulses, a comparably marked rise in nonpulsatile (basal) PRL secretion. Despite overlap, the regularity of PRL release patterns is disrupted even more profoundly in PH (tumoral), compared with SH. Assuming that the orderliness of serial PRL output monitors normal integration within a feedback-controlled neurohormone axis, then the more disorderly patterns of tumoral PRL secretion point to greater regulatory disruption in PH. The latter may reflect abnormal secretory behavior associated with lactotrope neoplastic transformation and/or isolation of the tumor cell mass from normal hypothalamic controls.

Adult↗
PubMed1989

Diagnosis of stress-related hyperprolactinemia. Evaluation of the hyperprolactinemia rest test.

It remains controversial whether two or three random estimations of prolactin (PRL) concentration obviate the need for special testing to rule out stress-related hyperprolactinemia. In order to clarify this issue, we measured PRL, cortisol, and growth hormone (GH) in serial blood samples obtained under resting conditions (HPR test) in 70 women who had had high PRL levels in two or more random blood samples. Twenty out of 70 women were found to have stress-related hyperprolactinemia, and 11 of the 20 would have been misdiagnosed by using only three random samples. Cortisol levels from the HPR test indicated stress-related pituitary adrenal reactivity in all groups, including the idiopathic (N = 30) and prolactinoma (N = 20) groups. However, PRL secretion in response to stress--a downward trend as a function of time--was evident only in the stress-related hyperprolactinemia group. These results suggest that a limited HPR test (ie, serial PRL determinations at 0, 30, and 60 min) is a valuable and simple measure to identify stress-related hyperprolactinemia in order to avoid diagnostic pitfalls and unnecessary treatment.

Adolescent↗
PubMed1979

[Adrenocortical function in hyperprolactinemia. The study of glucocorticoids, mineralocorticoids and androgens in chronic and acute hyperprolactinemias (author's transl)].

Glucocorticoids, mineralocorticoids, and adrenal androgens were studied in 3 groups of patients: control subjects (group I), hyperprolactinemic subjects (group II) and miscellaneous patients including chromophobe adenomas and normalized hyperprolactinemic subjects treated with Bromocriptine (group III). All the patients were studied in the basal state and under various conditions: Metyrapone, ACTH, TRH for glucocorticoids, ACTH, TRH, saline perfusion for mineralocorticoids, ACTH and TRH for androgens. It is concluded that: the adrenal secretion of glucocorticoids, mineralocorticoids and androgens is not altered under basal conditions in chronic hyperprolactinemia nor during dynamic tests in chronic hyperprolactinemia (prolactin adenoma) nor in acute hyperprolactinemia (induced by TRH).

Acute Disease↗
PubMed1989

Hachimijiogan treatment is effective in the management of infertile women with hyperprolactinemia or bromocriptine-resistant hyperprolactinemia.

Twenty-seven infertile women with hyperprolactinemia were treated with Hachimijiogan (5.0 to 10.0 g/day), Chinese herbal medicine. In 15 out of 18 patients, who were treated with Hachimijiogan, the serum prolactin levels dropped to 19.4 +/- 10.5 ng/ml during Hachimijiogan treatment, and the levels in 8 patients remained essentially unchanged during 6 months after the cessation of Hachimijiogan treatment. Three patients with 100 to 300 ng/ml did not drop to the level below 30 ng/ml. Four of 6 patients with amenorrhea ovulated. Eleven patients conceived and delivered normally. The hormonal profiles during or after pregnancy were normal. These results indicate that Hachimijiogan is a new safe treatment for hyperprolactinemic women.

Adult↗
PubMed2003

[Macroprolactinemia in the differential diagnosis of hyperprolactinemia].

INTRODUCTION: Biologically active prolactin and the inactive fraction of macroprolactin can be present in hyperprolactinaemic sera. The reaction of routinely used prolactin assays with macroprolactin is variable. AIMS: The present study was undertaken to analyse the leading clinical signs of hyperprolactinemia in macroprolactinemia and true hyperprolactinemia and to assess the prevalence of macroprolactinemia in hyperprolactinemic females. METHODS: 1571 consecutive female patients were investigated for hyperprolactinemia. Prolactin was measured before and after precipitation of macroprolactin by polyethylene glycol in 285 hyperprolactinemic (> 520 mlU/l) patients. Since not a single case of macroprolactinemia (recovery < 40%) was found in the range of 520-700 mlU/l, only in women with prolactin > 700 mlU/l (N = 254) entered the study. RESULTS: In 59 patients (23%) macroprolactinemia was found. In women, the occurrence of macroprolactinemia increased with advancing age (p < 0.05). "A priori" clinical signs indicating hyperprolactinemia occurred less frequently in patients with macroprolactinemia than in those with true hyperprolactinemia. Pituitary microadenoma was found in 9.8% of macroprolactinemia vs. 31.6% in true hyperprolactinemia (p < 0.01); galactorrhea: 4% in macroprolactinemia vs. 19% in true hyperprolactinemia, (p < 0.05); infertility: 17% in macroprolactinemia vs. 44% in true hyperprolactinemia (p < 0.05). In 8 out of 59 women with macroprolactinemia, true hyperprolactinemia appeared simultaneously (15.3%). Occurrence of polycystic ovaries syndrome was more frequent in the true hyperprolactinemia (12%) that in macroprolactinemia (4.5%). CONCLUSIONS: It has been shown that macroprolactin does not occur in mild hyperprolactinemia. In women, the occurrence of macroprolactinemia increases with age. "A priori" clinical signs indicating hyperprolactinemia and pituitary abnormality are less frequent in macroprolactinemia than in true hyperprolactinemia. The diagnosis of macroprolactinemia should be used only, when the PRL levels fall to the normal range after precipitation. To avoid diagnostic and therapeutic pitfalls the screening for macroprolactin of all patients with prolactin > 700 mlU/L is recommended.

Adenoma↗
PubMed1998

Anti-prolactin autoantibodies in systemic lupus erythematosus patients with associated hyperprolactinemia.

Hyperprolactinemia has been found in a subset of systemic lupus erythematosus (SLE) patients. In order to explore whether antibodies to prolactin (PRL) play a role in SLE patients with associated hyperprolactinemia, we performed a cross-sectional study in which 259 consecutive SLE patients were tested for hyperprolactinemia and anti-prolactin autoantibodies. Forty-one (15.8%) had prolactin levels above the norm. The frequency of anti-PRL autoantibodies in hyperprolactinemia was 2/14 (14.3%). In the SLE patients with 'idiopathic hyperprolactinemia', 11/27 (40.7 %) had anti-PRL antibodies. The levels of serum PRL were significantly higher in patients with idiopathic hyperprolactinemia and anti-PRL autoantibody compared to the patients with idiopathic hyperprolactinemia who were anti-PRL autoantibody-negative. Patients with idiopathic hyperprolactinemia and anti-PRL autoantibody had relatively low SLE disease activity index (SLEDAI) scores and significantly different laboratory parameters compared to those with idiopathic hyperprolactinemia and no anti-PRL antibody. There was a significant correlation between titers of the anti-PRL autoantibody and serum PRL levels (rs = 0.98, P = 0.0001). These data suggest that anti-PRL antibodies could be the cause of hyperprolactinemia in a subset of SLE patients, especially those with particularly high serum prolactin levels with a diagnosis of 'idiopathic hyperprolactinemia'. The patients with anti-PRL antibody had fewer clinical manifestations and less serological activity, indicating that biological activity of PRL was attenuated by the autoantibody.

Adolescent↗
PubMed2004

Life events in the pathogenesis of hyperprolactinemia.

OBJECTIVE: Little is known about the relationship between recent life events and onset of hyperprolactinemia, despite the well-known effect of acute psychological stress on prolactin levels in healthy subjects. Recent life events in patients with hyperprolactinemia compared with healthy controls were investigated. DESIGN: Case-control study. METHODS: Fifty-two consecutive patients with hyperprolactinemia (45 females/7 males; mean age 34.9+/-10.1 years, range 18-60 years) and 52 healthy subjects matched for socio-demographic variables were studied. Nineteen patients (18 females/1 male) had no pituitary tumor and were diagnosed as suffering from idiopathic hyperprolactinemia. Patients with additional pathology or with high prolactin due to medications were excluded. All patients were interviewed by Paykel Interview for Recent Life Events while on remission after surgery or pharmacological treatment. The time period considered was the year preceding the first signs of hyperprolactinemia, and the year before interview for controls. RESULTS: Patients with hyperprolactinemia reported significantly more life events than control subjects (P<0.001). The same significant difference compared with controls applied to patients with (n=16) and without (n=36) depression. All categories of events (except events that were likely to be under the subject's control) were significantly more frequent. There were no significant differences between patients with prolactinoma (n=33) and those with idiopathic hyperprolactinemia (n=19). CONCLUSIONS: Within the complexity of phenomena implicated in the pathogenesis of hyperprolactinemia, our findings emphasize a potential role of emotional stress in either prolactin-secreting pituitary tumors or idiopathic hyperprolactinemia. Appraisal of life stress may have implications in clinical assessment (e.g. functional hyperprolactinemia) and decisions (e.g. termination of long-term pharmacological treatment).

Adolescent↗
PubMed1997

Chronic hyperprolactinemia and changes in dopamine neurons.

The tuberoinfundibular dopaminergic (TIDA) system is known to inhibit prolactin (PRL) secretion. In young animals this system responds to acute elevations in serum PRL by increasing its activity. However, this responsiveness is lost in aging rats with chronically high serum PRL levels. The purpose of this study was to induce hyperprolactinemia in rats for extended periods of time and examine its effects on dopaminergic systems in the brain. Hyperprolactinemia was induced by treatment with haloperidol, a dopamine receptor antagonist, and Palkovits' microdissection technique in combination with high-performance liquid chromatography was used to measure neurotransmitter concentrations in several areas of the brain. After 6 months of hyperprolactinemia, dopamine (DA) concentrations in the median eminence (ME) increased by 84% over the control group. Nine months of hyperprolactinemia produced a 50% increase in DA concentrations in the ME over the control group. However, DA response was lost if a 9-month long haloperidol-induced hyperprolactinemia was followed by a 1 1/2 month-long extremely high increase in serum PRL levels produced by implantation of MMQ cells under the kidney capsule. There was no change in the levels of DA, norepinephrine (NE), serotonin (5-HT), or their metabolites in the arcuate nucleus (AN), medial preoptic area (MPA), caudate putamen (CP), substantia nigra (SN), and zona incerta (ZI), except for a decrease in 5-hydroxyindoleacetic acid (5-HIAA) in the AN after 6-months of hyperprolactinemia and an increase in DA concentrations in the AN after 9-months of hyperprolactinemia. These results demonstrate that hyperprolactinemia specifically affects TIDA neurons and these effects vary, depending on the duration and intensity of hyperprolactinemia. The age-related decrease in hypothalamic dopamine function may be associated with increases in PRL secretion.

Age Factors↗
PubMed1986

[Studies on prolactin secreting capacity in the ovulatory infertile patients with transient hyperprolactinemia].

The changes in serum prolactin levels during the menstrual cycle have not been clarified yet. The present study was conducted to investigate whether the changes in serum prolactin levels during the menstrual cycle exist in ovulatory infertile patients having high prolactin release due to TRH administration described below (transient hyperprolactinemia) and control cases. Serum prolactin levels in both groups were less than 25 ng/ml at daytime. In the patients with transient hyperprolactinemia, serum prolactin levels showed more than 150 ng/ml at 30 min. after the administration of 500 micrograms of TRH, and those were less than 150 ng/ml in the normal control group. The daily changes of serum FSH, LH, prolactin, estradiol and progesterone levels were determined by radioimmunoassay in 6 cases of transient hyperprolactinemia and 5 controls which showed normal ovulatory cycles in the patterns of the BBT charts and other hormones. An estrogen feedback test was also carried out at the mid-luteal phase in 9 cases of transient hyperprolactinemia and the controls to determine serum levels of FSH, LH, prolactin and estradiol. In the patients with transient hyperprolactinemia, 5 mg of bromocriptine was administered every day for more than 30 days, and the effects of bromocriptine on the changes in serum gonadotropin levels by the estrogen feedback test were also analysed. Serum prolactin levels in the follicular, ovulatory and mid-luteal phases increased significantly in the patients with transient hyperprolactinemia, compared to the controls (p less than 0.005). The pattern of serum prolactin levels in the patients with transient hyperprolactinemia was almost synchronized with that of serum estradiol levels. There was also a significant correlation (r = 0.5782, p less than 0.005) between the prolactin and estradiol levels in the serum of the patients. The obvious change was not noted in serum prolactin levels during the menstrual cycle of the controls. No significant change in other hormones was observed during the cycle between these two groups. After the administration of estradiol benzoate (100 micrograms/kg), serum estradiol levels increased markedly, serum prolactin levels increased with the similar change in serum estradiol levels, and serum prolactin levels in the patients with transient hyperprolactinemia were significantly higher compared to those of the controls (p less than 0.01 approximately 0.005). The responses of serum gonadotropin levels by the administration of estradiol benzoate had good positive and negative feedback effects in the patients with transient hyperprolactinemia as well as those of the control group.(ABSTRACT TRUNCATED AT 400 WORDS)

Adult↗
PubMed2005

Medication-induced hyperprolactinemia.

Medication use is a common cause of hyperprolactinemia, and it is important to differentiate this cause from pathologic causes, such as prolactinomas. To ascertain the frequency of this clinical problem and to develop treatment guidelines, the medical literature was searched by using PubMed and the reference lists of other articles dealing with hyperprolactinemia due to specific types of medications. The medications that most commonly cause hyperprolactinemia are antipsychotic agents; however, some newer atypical antipsychotics do not cause this condition. Other classes of medications that cause hyperprolactinemia include antidepressants, antihypertensive agents, and drugs that increase bowel motility. Hyperprolactinemia caused by medications is commonly symptomatic, causing galactorrhea, menstrual disturbance, and impotence. It is Important to ensure that hyperprolactinemia in an Individual patient is due to medication and not to a structural lesion in the hypothalamic/pituitary area; this can be accomplished by (1) stopping the medication temporarily to determine whether prolactin levels return to normal, (2) switching to a medication that does not cause hyperprolactinemia (in consultation with the patient's psychiatrist for psychoactive medications), or (3) performing magnetic resonance imaging or computed tomography of the hypothalamic/pituitary area. If the patient's hyperprolactinemia is symptomatic, treatment strategies include switching to an alternative medication that does not cause hyperprolactinemia, using estrogen or testosterone replacement, or, rarely, cautiously adding a dopamine agonist.

Antidepressive Agents↗
PubMed1982

Effects of nomifensine on growth hormone and prolactin secretion in normal subjects and in pathological hyperprolactinemia.

We have studied the effect of the oral administration of 200 mg nomifensine (nom), a drug which activates the dopaminergic system, on GH and PRL secretion in 15 normal subjects, 18 patients with idiopathic hyperprolactinemia, and 17 patients with tumoral hyperprolactinemia. GH levels increased significantly after nom in normal subjects (basal, 0.96 +/- 0.76 ng/ml; peak 4.6 +/- 0.61 ng/ml; P less than 0.01) and patients with hyperprolactinemia, both idiopathic (basal, 1.0 +/- 0.38 ng/ml; peak, 4.2 +/- 1.0 ng/ml; P less than 0.05) and tumoral (basal 0.88 +/- 0.3 ng/ml, peak 6.68 +/- 1.2 ng/ml; P less than 0.01). Peak GH levels higher than 5 ng/ml were observed in 8 of 15 normal subjects, 6 of 18 patients with idiopathic hyperprolactinemia, and 8 of 17 patients with tumoral hyperprolactinemia. PRL levels decreased in response to nom in normal subjects, but not in patients with idiopathic or tumoral hyperprolactinemia. A reduction in plasma PRL levels of at least 30% below the baseline was observed only in two patients with idiopathic hyperprolactinemia and in none of the patients with tumoral hyperprolactinemia. These results demonstrate that nom does not discriminate between idiopathic and tumoral hyperprolactinemia. Since nom probably requires a hypothalamic pool of dopamine to bring about its GH stimulatory effect, the suggestion that the lack of a PRL-lowering effect of the drug is attributable to a dopamine deficiency is not supported by our data.

Adult↗
PubMed2003

Prevalence of hyperprolactinemia in schizophrenic patients treated with conventional antipsychotic medications or risperidone.

OBJECTIVE: The prevalence of hyperprolactinemia during treatment with conventional antipsychotic drugs or risperidone is under-recognized and requires further investigation. This open-label study was designed to determine the extent of this potential problem in a routine clinical setting. METHODS: Four hundred and two adult inpatients or outpatients with a diagnosis of schizophrenia, schizophreniform disorder, or schizoaffective disorder were studied in a 1-day, point prevalence trial. Neither clinicians nor patients had any prior knowledge of serum prolactin levels or any potential associated adverse events, and patients were required to have been treated with a conventional antipsychotic drug or risperidone for a minimum of 3 months prior to study entry. Patients taking concomitant medications known to elevate prolactin were excluded. Rigorous assessment of serum prolactin was performed to estimate the prevalence rate of hyperprolactinemia, defined as a level above the upper limit of normal (>18.77 ng/ml for males, and >24.20 ng/ml for females). Patients were stratified within antipsychotic treatment by gender and, for females, by menopausal status. RESULTS: Serum prolactin was obtained from 147 females (age range: 21-69 years; mean age=44.51 years) and 255 males (age range: 18-66 years; mean age=40.76 years). The prevalence of hyperprolactinemia among women of reproductive age (n=90) was 65.6% (mean serum prolactin=69.0 ng/ml), and among postmenopausal women (n=51), it was 45.1% (mean serum PRL=49.0 ng/ml). The prevalence of hyperprolactinemia across all males (n=255) was 42.4% (mean serum PRL= 32.4 ng/ml). The prevalence of hyperprolactinemia among females taking risperidone (N=42) was 88% versus 47.6% of those taking conventional antipsychotic drugs (N=105), with 48% of those females of reproductive age on risperidone experiencing abnormal menstrual cycles (secondary amenorrhea, oligomenorrhea, or polymenorrhea). Of all premenopausal females with hyperprolactinemia, 31.6% had estradiol levels <or=19.8 pg/ml (which is the mean estradiol level in postmenopausal female patients with normal prolactin). Across both genders, there were trends of low key reproductive hormone levels associated with prolactin elevations. Additionally, there was a trend correlation (p=0.064) between prolactin concentration and the risk of menstrual abnormality among females of reproductive age. CONCLUSIONS: Hyperprolactinemia is very prevalent among women and men treated with conventional antipsychotic medications or risperidone. Due to the adverse effects associated with hyperprolactinemia, this likelihood should be seriously considered when choosing an antipsychotic suitable for the patient.

Adolescent↗
PubMed2002

Postoperative hyperprolactinemia could predict longer disease-free and overall survival in node-negative breast cancer patients.

OBJECTIVES: Breast manipulation determines a physiological increase in prolactin (PRL) blood levels, but the clinical and biological impact of surgery-induced changes in PRL secretion still has to be clarified. The postoperative hyperprolactinemia has been related to aggressiveness of the tumor, early disease relapse or metastases, and poor overall survival in node-negative breast cancer patients. Surgery-induced hyperprolactinemia may be associated with a longer disease-free survival in both patients with or without node involvement. METHODS: One hundred twenty-seven consecutive node-negative breast cancer patients, who were hospitalized from June 1985 to September 1990, were included in this study. The median follow-up was 12 years. To evaluate PRL secretion, venous blood samples were obtained at day 7th after surgery. In order to exclude the influence of stress and gonadal status, GH and estradiol serum levels were measured in the same blood samples. All endocrine examination were made during the morning, starting at 8.00 a.m. after overnight fasting. Hormonal serum levels were determined by the double antibody radioimmunoassay method. RESULTS: Hyperprolactinemia was significantly more frequent in women younger than 50 years compared with the older ones, while the premenopausal status and T1 stage showed only a borderline significant association with hyperprolactinemia. Patients with normal postsurgical prolactinemia had 5- and 10-year disease-free survival rates of 64 and 56%, respectively, and 5- and 10-year overall survival rates of 84 and 70%, respectively. Patients with postsurgical hyperprolactinemia had 5- and 10-year disease-free survival rates of 89 and 81%, respectively, and 5- and 10-year overall survival rates of 94 and 81%, respectively. The difference in overall survival between the hyperprolactinemic and the normoprolactinemic groups, assessed by the log-rank test, was statistically significant (p = 0.02), and the difference in disease-free survival was highly significant (p = 0.0008). CONCLUSIONS: Our study shows that postsurgical hyperprolactinemia is associated with a significantly lower recurrence rate and longer disease-free and overall survival in operable node-negative breast cancer patients. Our data suggest that postoperative hyperprolactinemia could be crucial in the development of recurrence in operable breast cancer. Looking at results, the recurrence rate of node-negative patients who did not show postoperative hyperprolactinemia would be, in theory, similar to that of patients with node-positive disease, suggesting that normal postoperative PRL levels could identify a group of node-negative patients at high risk for recurrence.

Adult↗
PubMed1987

Suppression of pulsatile LH secretion, pituitary GnRH receptor content and pituitary responsiveness to GnRH by hyperprolactinemia in the male rat.

To assess whether gonadotropin-releasing hormone (GnRH) release from the hypothalamus might be altered by hyperprolactinemia in the male rat, we measured in chronically hyperprolactinemic rats the pituitary GnRH receptor content and described the pattern of luteinizing hormone (LH) release during the postcastration rise in gonadotropin secretion 24 and 72 h after gonadectomy. In intact rats, the effect of hyperprolactinemia was determined by describing the pattern of LH secretion, pituitary GnRH receptor content and assessment of pituitary responsiveness to small doses of GnRH (1.0 ng). In addition, to determine the role endogenous opioids might play in inhibiting GnRH release in hyperprolactinemic rats, we examined the effect of both a continuous infusion and a bolus injection of the opioid antagonist naloxone on the pattern of LH release. Chronic hyperprolactinemia was achieved by implanting 4 pituitaries under the kidney capsules 3-4 weeks before study. Acute hyperprolactinemia was achieved by injecting rats with 1 mg ovine prolactin every 12 h for 3 days. Control animals were untreated or were chronically hyperprolactinemic rats in which the hyperprolactinemia was transiently reversed by treatment for 3 days with the dopamine agonist 2-alpha-bromoergocryptine. The mean LH concentration was greatly decreased at 24 postcastration in chronically hyperprolactinemic rats relative to controls. This decrease was associated with a decrease in LH pulse height and pulse amplitude and pituitary GnRH receptor content, but not with an increase in the LH interpulse interval. In contrast, the decrease in mean LH concentrations in hyperprolactinemic animals at 72 h postcastration was primarily associated with a significantly longer LH interpulse interval than that observed in control animals. Chronic hyperprolactinemia in intact rats decreased the pituitary GnRH receptor content, in addition to decreasing the mean LH concentrations during pulsatile GnRH administration. Chronic hyperprolactinemia also inhibited LH release relative to controls during the continuous 4-hour infusion of naloxone and in response to a bolus injection of naloxone. However, in acutely hyperprolactinemic intact male rats a bolus injection of naloxone increase LH secretion 20 min later to levels similar to those obtained in control rats. In summary, these results indicate that chronic hyperprolactinemia decreased LH secretion by primarily decreasing GnRH secretion as suggested by a decrease in pituitary GnRH receptor content and a decrease in LH pulse frequency and pulse amplitude.(ABSTRACT TRUNCATED AT 400 WORDS)

Acute Disease↗
PubMed1988

Clomiphene citrate attenuates hyperprolactinemia associated with ovarian hyperstimulation in the primate menstrual cycle.

Exogenous human menopausal gonadotropin (hMG) therapy produces transient hyperprolactinemia during ovulation induction or ovarian hyperstimulation for in vitro fertilization, and hyperprolactinemia has been linked to decreased fertility. Coadministration of clomiphene citrate (CC) with hMG is often used to decrease the total amount of hMG used in such patients, but whether this results in less hyperprolactinemia is not known. As the hyperprolactinemia in this setting is a threshold phenomenon dependent on the strength and duration of estrogen exposure, we investigated whether CC acted as an estrogen to enhance PRL secretion or as an antiestrogen deterring estradiol (E2)- and progesterone (P4)-induced hyperprolactinemia in nonhuman primates. Normally cycling (control) monkeys (n = 4) received E2 benzoate (12.5 micrograms/kg, im, daily) on menstrual cycle days 6-33 and continuous crystalline P4 via Silastic implants on days 20-33, a regimen known to initiate hyperprolactinemia. Treated monkeys (n = 5) received the same regimen, except that oral CC (15 mg daily) was given on days 6-33. Daily serum samples were assayed for E2, P4, and PRL. Both treatments caused significant (P less than 0.05) increases in serum PRL concentrations during P4 administration. The CC-treated monkeys had significantly smaller increases in mean PRL [21 +/- 1.5 (+/- SEM) vs. 44 +/- 6.3 ng/mL (micrograms/L); P less than 0.05] and smaller mean area under the PRL response curve [288 +/- 35 (+/- SEM) vs. 588 +/- 121 ng/day.mL (micrograms/day.L); P less than 0.05] than the control monkeys. We conclude that CC attenuates the hyperprolactinemia response to E2/P4 synergy in monkeys by acting as an antiestrogen. If coadministered with hMG for ovulation induction or ovarian hyperstimulation for in vitro fertilization, CC should attenuate hMG-induced hyperprolactinemia, thereby reducing its potentially adverse effects on fertility.

Animals↗
PubMed2002

[Hyperprolactinemia: from diagnosis to treatment].

Hyperprolactinemia means the presence of abnormally high values of prolactin. It's the most common clinical hypothalamic-hypophysis disorder. Amenorrhea and anovulation are the most usual clinical findings but we can find milder alterations of gonadal function as oligomenorrhea or luteal phase alterations. Galattorrhea appears in approx 30% of patients, but its presence in women with ovulation disorders is highly suggestive of hyperprolactinemia. Subjects with primary amenorrhea and delayed puberty can present hyperprolactinemia. Male hyperprolactinemia can cause hypogonadism (decreased testosterone levels), libido decrease, infertility due oligospermia and gynecomastia while galactorrhea rarely occurs. Accurate anamnesis is very important for a correct diagnosis. It's necessary to exclude pregnancy and primary hypothyroidism. The use of many drugs can be associated with hyperprolactinemia but the most common causes are idiopathic hyperprolactinemia and hypophysis secreting adenoma. Diagnostic examinations are: PRL, FT3, FT4, TSH in case of hypothyroidism, testosterone in men, eventually sampling GH, IGF, ACTH, cortisol, free urinary cortisol. Dynamic tests are used just for idiopathic hyperprolactinemia, but today their meaning is widely discussed. CAT and MNR are necessary to observe hypotalamus, hypophysis and optic chiasm. Twenty years ago the sole option for prolactinoma patients was adenomectomy, today idiopathic hyperprolactinemia can be treated with drugs, while prolactinoma can be treated with a pharmacological, surgical or radiological therapy.

Adolescent↗
PubMed2002

Modulation of stress-induced and stimulated hyperprolactinemia with the group II metabotropic glutamate receptor selective agonist, LY379268.

It is well recognized that glutamate is an integral excitatory neurotransmitter in the neuroendocrine control of several hormonal factors. While the ability of pharmacological agents acting at ionotropic glutamate receptors to modulate the levels of serum prolactin levels has been investigated, there have been few reports of the effects mediated by the G-protein coupled, metabotropic glutamate (mGlu) receptors. The present work was undertaken to investigate the role of the Group II mGlu receptors, mGlu2 and mGlu3 in the regulation of serum polactin levels. LY379268, a Group II selective agonist, did not alter basal levels of circulating prolactin in young (36-40 day old) male rats. However, when an immobilization stress-induced hyperprolactinemia was examined, 10 mg/kg s.c. of LY379268 significantly lowered serum prolactin levels. Similarly, pretreatment with LY379268 was able to reverse the hyperprolactinemia induced with the catecholamine synthesis inhibitor, alpha-methyl-p-tyrosine (aMPT). This inhibition of hyperprolactinemia could be prevented by pretreatment with LY341495, a Group II mGlu receptor antagonist. The Group II antagonist alone had no effect on either basal nor stimulated prolactin levels. The agonist LY379268 was able to prevent the transient hyperprolactinemia associated with stimulation of serotonin 5-HT2A receptors by 2,5-dimethoxy-4-iodoamphetamine (DOI), but did not alter the high levels of circulating prolactin induced with the D2 antagonist, haloperidol. When treatment with LY379268 was delayed until 1 h after aMPT, a time demonstrated to show a full effect of aMPT on serum prolactin levels, the Group II agonist was similarly able to reverse hyperprolactinemia, suggesting LY379268 did not act by preventing the partial catecholamine depletion by aMPT. Similarly, high doses of amphetamine, a dopamine (DA) releaser, were able to reverse the aMPT-induced hyperprolactinemia, consistent with sufficient levels of dopamine remaining after aMPT treatment to modulate prolactin levels. LY379268 did not alter the hyperprolactinemia seen in estrogen-primed, ovariectomized female rats. Taken together the results indicate that stimulation of mGlu2/3 has an indirect inhibitory action on pituitary prolactin release. It is speculated that disinhibition of tubero-infundibular DA release by presynaptic Group II mGlu receptors located on inhibitory inputs to the arcuate hypothalamic nucleus is a possible explanation for the findings.

Amino Acids↗