Drug-induced Hyperprolactinemia Research Articles

Hysterical neurosis of the conversion type: therapeutic activity of neuroleptics with different hyperprolactinemic potency.

To show a possible correlation between drug-induced hyperprolactinemia and improvement of hysterical neurosis of the conversion type, we followed 18 patients monitoring clinical somatic and psychic symptoms as well as serum prolactin levels. Six patients were treated with haloperidol and 12 with sulpiride; after 2 months sulpiride was administered at half the daily dose to 6 patients previously treated with the same drug. Clinical evaluation showed that sulpiride treatment led to a greater improvement compared to the haloperidol group. The different effectiveness of treatment could be explained by the different hyperprolactinemic potency. The therapeutic efficacy of neuroleptics suggests also that hyperactivity of dopaminergic transmission is involved in the pathophysiology of hysterical neurotic symptoms.

Calcium and Prolactin Secretion in Humans: Effects of the Channel Blocker, Verapamil, in the Spontaneous and Drug-Induced Hyperprolactinemia

The effects of the intravenous administration of a calcium channel blocker, verapamil (0.0833 mg/min for 2-3 h after a 5 mg bolus) on prolactin (PRL) and thyrotropin (TSH) circulating levels were assessed in 7 normal subjects and in 17 patients with hyperprolactinemia (11 with prolactinoma and 6 sulpriride-induced). In the normal group a non-significant increase in PRL levels occurred (mean +/- SEM = 11.7 +/- 2.9 micrograms/l verapamil vs. 8.5 +/- 1.4 micrograms/l saline). In this control group the peak response of PRL and TSH to TRH (thyrotrophin releasing hormone) during verapamil or saline was also determined: PRL = 112.0 +/- 27.0 micrograms/l on verapamil vs. 53.6 micrograms/l on saline, p = 0.02; TSH 7.1 +/- 0.7 microU/l on verapamil vs. 9.0 +/- 0.6 mU/l on saline, p = 0.01. In the hyperprolactinemic subjects verapamil induced opposite effects on PRL levels, the prolactinoma group exhibiting an increase in the mean values (168.5 +/- 22.3 micrograms/l vs. 150.8 +/- 23.6 micrograms/l on saline, p = 0.04) whereas in the sulpiride-induced there was a reduction in the mean PRL levels (61.1 +/- 13.8 micrograms/l vs. 78.5 +/- 19.3 micrograms/l on saline, p = 0.002). In both groups of hyperprolactinemic patients no effects on TSH levels were observed. The authors discuss the possibility that the divergent effects of verapamil in hyperprolactinemia of different etiologies could be related to the balance between dopamine and calcium channel effects on hypothalamus and/or pituitary.

Effects of long-term administration of clozapine on body weight and food intake in rats

Previous reports have shown that long-term administration of typical and atypical neuroleptics induced obesity in female but not in male rats. It has been suggested that impaired ovarian steroidogenesis related to neuroleptic-induced hyperprolactinemia is necessary to observe the body weight changes. This hypothesis was tested with clozapine, an atypical neuroleptic that produces in rats a shorter increase in serum prolactin levels than do other neuroleptics. The effects of clozapine on body weight and food intake were assessed in female and male rats under treatment with any of the following doses: 0.5, 1, 2.5, 5, 10, and 20 mg/kg IP for 21 days. Vaginal cycle under clozapine treatment, as an indirect indicator of ovarian steroidogenesis, was also assessed. Obesity was not observed in any group. By contrast, clozapine at the doses of 10 and 20 mg/kg significantly decreased body weight and feeding in male rats. Clozapine at the doses of 5 and 10 mg/kg IP induced permanent diestrus. The failure of clozapine to induce obesity in female rats, despite impaired vaginal cycle, can be considered indirect evidence that drug-induced hyperprolactinemia is not sufficient to observe neuroleptic-induced obesity in rats.

Psychotic exacerbation attributed to low‐dose bromocriptine treatment of galactorrhea and hyperprolactinemia

Low-dose bromocriptine administered for antipsychotic drug-induced hyperprolactinemia and galactorrhea precipitated an acute psychotic state in a female patient. Discontinuation of the bromocriptine and increase in antipsychotic dosage resulted in complete remission. We advise caution in the use of bromocriptine especially in patients with a pre-existing psychiatric history and recommend monitoring for changes in mental status when bromocriptine is prescribed.

Effects of the benzazepine SCH 23390 on prolactin release from isolated pituitary.

The benzazepine, SCH 23390 (10(-5) M), is able to block D2 anterior pituitary receptors and their interaction with a maximal concentration of dopamine (10(-7) M) in an experimental setting involving superfused pituitary slices and prolactin release by lactotrophs as a functional model of such receptors; this finding which correlates nicely with binding studies and drug-induced hyperprolactinaemia supports a SCH 23390 D1 dose-related selectivity; given at doses higher than those inducing behavioural changes, the compound may affect D2 receptor-driven functions, e.g. prolactin secretion.

Asymptomatic hyperprolactinaemia and prolactinoma in the general population--mass screening by paired assays of serum prolactin.

A total of 10,550 'normal' adults (8450 men and 2100 women) in the general population were screened by a paired assay method for serum PRL and 40 subjects with hyperprolactinaemia (greater than 75 micrograms/l) were detected. Of these, five patients (three men and two women) with pituitary prolactinoma, one man with empty sella syndrome, 10 cases of 'big' prolactinaemia, seven pregnant women and 13 subjects with drug-induced hyperprolactinaemia were found. The patients with prolactinoma had few if any complaints (asymptomatic prolactinoma).

Endometrial Adenocarcinoma Associated With Drug-Induced Hyperprolactinemia

A 54-year-old woman with hyperprolactinemia and amenorrhea that occurred with phenothiazine and tricyclic antidepressant use developed a stage IBG2 endometrial adenocarcinoma. This is believed to be the first case reported of endometrial carcinoma associated with drug-induced hyperprolactinemia.

Prolactin and sexual behavior: A review

Despite the large body of evidence showing that prolactin (PRL) can suppress sexual behavior in humans and rodents, it is still unclear how this hormone affects sexual capacity of male subjects. Few studies have been performed on the effects of PRL on female sexual behavior. Short-term hyperprolactinaemia seems to facilitate some elements of sexual behavior in male rats. Furthermore, contrasting findings exist on the effects of drug-induced hyperprolactinaemia on sexual capacity of male animals. The possible mechanisms of action (on peripheral organs, endocrine, central) of PRL on male sexual behavior are discussed in details.

Effect of chlorpromazine on hypothalamic-pituitary-gonadal function in 10 adolescent schizophrenic boys.

Low basal plasma testosterone levels with normal response to human chorionic gonadotropin (HCG) stimulation and mild hyperprolactinemia and blunted luteinizing hormone (LH) response to luteinizing-releasing hormone (LRH) stimulation were found in 10 adolescent schizophrenic boys who had been treated with chlorpromazine for more than 6 months. These findings may indicate a disturbance of the hypothalamic-pituitary-gonadal function in these patients, probably due to the prolonged administration of chlorpromazine. It remains to be established whether the decrease in basal testosterone secretion is caused directly by chlorpromazine or secondarily by the drug-induced hyperprolactinemia.

Phospholipid liposomes and prolactin secretion: Effects on spontaneous and drug-induced hyperprolactinaemia

Bovine brain phospholipid liposomes (BC-PL) reduce plasma prolactin (PRL) levels in humans after acute administration and counteract the metoclopramide- and sulpiride-induced hyperprolactinaemia. However, BC-PL, like nomifensine, a dopaminergic compound, does not influence TRH-induced hyperprolactinaemia. Moreover BC-PL and nomifensine reduce plasma PRL levels in hyperprolactinaemic PCO syndromes but not in PRL secreting pituitary adenomas. The results obtained indicate that BC-PL antagonizes the DA blockade-induced hyperprolactinaemia and that the main site of action of BC-PL seems to be at the hypothalamic level; however a concomitant pituitary effect cannot be ruled out.

Semen characteristics and serum and seminal plasma hormones in drug-induced hyperprolactinaemia.

Semen volume, density, motility, viability, and morphology of spermatozoa, and serum and seminal plasma levels of the hormones FSH, LH, prolactin, progesterone, 17-alpha-hydroxyprogesterone, androstenedione, testosterone, dihidrotestosterone, and estradiol 17-beta have been measured in 22 men subjected to experimental hyperprolactinaemia by the simultaneous administration of the antidopaminergic drugs metoclopramide and sulpiride. Hyperprolactinaemia produces a decrease of semen volume and seminal quality. In hyperprolactinaemia, normozoospermic patients had an increase of serum androstenedione. In both normo- and oligozoospermic groups, a decrease of serum testosterone was observed. Hyperprolactinaemia also causes an inhibition of the secretory activity of the accessory sexual glands of the reproductive tract, as well as either a decrease of 17-ketosteroid reductase or an increase of 17-alpha-hydroxysteroid dehydrogenase (enzymes that participate in the androstenedione-testosterone interconversions). This change appears to be more pronounced in individuals with good seminal quality.

A practical approach to the investigation of the hyperprolactinaemic patient.

Pituitary function was assessed in 39 patients with previously untreated hyperprolactinaemia. Primary hypothyroidism, drug-induced hyperprolactinaemia and chronic renal failure were excluded in all patients. All of the 22 patients (group 1), who had either a normal pituitary fossa or a minor radiological change on lateral skull X-ray, had completely normal pituitary function with the exception of 2 who were partially growth hormone-deficient. However, 9 of the 17 patients with macroadenomas (group 2) had a deficit of one or more anterior pituitary hormones. After the lateral skull X-ray 13 patients in group 1 had further neuroradiological investigations. In only one was a minor abnormality noted which had not been observed on the plain film and this was not of practical significance. In centres where hyperprolactinaemic patients with a normal pituitary fossa or a minor radiological change on lateral skull X-ray are treated with bromocriptine, further neuroradiological investigations and dynamic tests of pituitary function are not required.

Hyperprolactinaemia as a cause of gallium-67 uptake in the breast

Mammary tissue uptake of Gallium-67 (67Ga) is well recognized (Larson et al., 1973; Gelrud and Arseneau, 1973). A patient is presented in whom such accumulation led to the discovery of druginduced hyperprolactinaemia. A 19-year-old girl with Hodgkin's “Paragranuloma” involving neck glands was successfully treated with radiotherapy in 1969. Five years later a recurrence in neck and inguinal glands, together with diffuse lung mottling, responded to combination therapy with mustine, vincristine, procarbazine and prednisolone.