Prolactin, cortisol, and antidepressant treatment.

In four depressed patients with abnormal dexamethasone suppression test results before treatment, plasma prolactin levels significantly increased after successful amitriptyline therapy. Such an increase did not take place in five depressed patients with normal dexamethasone suppression test findings.

Dopamine agonists for reducing depression associated with hyperprolactinemia.

Nine women with prolactinomas studied over 20 weeks were depressed as determined by three separate self-rating scales. The depression improved with bromocriptine or pergolide. Acute depression recurred and prolactins increased after discontinuation of the medication.

Control of hyperprolactinemia with pergolide.

Ten patients with clinical, laboratory and radiographic evidence compatible with the diagnosis of prolactinoma were treated with two dopamine agonists. One group (N = 6) took bromocriptine and the other group (N = 4) used pergolide, a longer-acting agent. Both medications were found to reduce prolactin levels significantly from baseline, but an oscillatory pattern with significant fluctuation was seen in the mean prolactin levels in the patients taking bromocriptine. Three patients did not achieve euprolactinemia on bromocriptine, 2.5 mg qid, the maximum dose used in this study. All of the study group taking pergolide became euprolactinemic rapidly; no more than a single dose of 100 micrograms/day was required. Tumor reduction was noted in two patients taking bromocriptine and two taking pergolide. The duration of side effects was shorter and compliance was improved on pergolide therapy.

Gastric secretion and hormonal interactions in multiple endocrine neoplasia type I.

Results of preparathyroidectomy and postparathyroidectomy studies in a patient with multiple endocrine neoplasia type I and gastrinoma suggest that hyperparathyroidism unmasks occult gastrinoma and related secretory abnormalities. Three of four diagnostic findings were later obscured by parathyroidectomy and normalization of serum calcium concentration. Basal acid output, basal acid output/maximal acid output ratio, and serum gastrin concentration were decreased from values consistent with gastrinoma to normal. The secretin stimulation test, though still positive, was attenuated. These observations suggest that in multiple endocrine neoplasia type I, normal values for serum gastrin concentration, gastric secretion, and secretin stimulation may not exclude gastrinoma. The investigations clarify the interpretation of a voluminous but confusing literature on the interrelationship between hyperparathyroidism and altered gastric function in the presence or absence of Zollinger-Ellison syndrome.

Reduction of distress in hyperprolactinemia with bromocriptine.

In a double-blind placebo-controlled crossover study of bromocriptine in eight hyperprolactinemic patients, self-rated distress decreased and well-being increased parallel with the fall in prolactin levels; for the majority of measures the differences were significant.

Hyperprolactinemia, distress, and hostility.

The scores of 14 women with hyperprolactinemia on the Symptom Rating Test and the Symptom Questionnaire were compared with those of nonpsychotic women attending a psychiatric clinic, women attending a family practice clinic, and female nonpatient employees. The scores of the hyperprolactinemic women were similar to those of the psychiatric patients. Hyperprolactinemic patients were significantly more hostile, depressed, and anxious and had more feelings of inadequacy than family practice patients and nonpatient employees. The authors recommend measuring the serum prolactin levels of women with depression, hostility, anxiety, and symptoms or signs suggestive of hyperprolactinemia.

The value of prolactin dynamics as a predictor of ovulation with bromocriptine in patients with polycystic ovary syndrome.

Six euprolactinemic polycystic ovary syndrome (PCOS) patients were subjected to a 24-hour study with serum sampling every 30 minutes and a perphenazine stimulation test. The serum prolactin (PRL) levels were compared with those of five healthy normoprolactinemic women whose cases were evaluated in a similar fashion. In addition to evaluating the PRL secretory pattern and lactotroph response, the PCOS individuals were given dopamine agonist therapy in a graduated dosage schedule, increasing each month, over a 3-month interval. The PCOS patients exhibited parallel but lower PRL levels than the control subjects during the late evening and early morning hours (P less than 0.0001) and were less responsive to perphenazine at the 6-hour sampling (P less than 0.05). Only one PCOS individual had suggestive evidence of ovulation over the 15 cycles the group was monitored. Therefore, we conclude that euprolactinemic PCOS patients who are nocturnal hyposecretors of PRL and who hyporespond to a perphenazine stimulation test are not likely to ovulate on bromocriptine in the dosages used in this study.

Prolactin, aggression and hostility: a discussion of recent studies.

Several studies are summarized in which the relationship of high prolactin levels and self-rated anger-hostility was examined. The Symptom Questionnaire, a state measure which contains an anger-hostility scale, was included in all studies. Women with hyperprolactinemic amenorrhea were found to have higher hostility scores than amenorrheic women with normal prolactin levels. In another study, hyperprolactinemic women were found to have higher hostility scores than female family practice patients, random employees and there was a nonsignificant trend for higher hostility scores than in female nonpsychotic psychiatric outpatients. In both studies, depression and anxiety were also significantly higher. When bromocriptine, a prolactin lowering drug, was administered to hyperprolactinemic women in a double blind crossover study, there was a significant and progressive decrease of hostility, depression and anxiety while on bromocriptine, parallel with the decrease in prolactin and no change on placebo. Post-partum women who had high prolactin levels were significantly more hostile than a control group of employees and as hostile as hyperprolactinemic women. Hyperprolactinemic males were no more hostile than controls. The relationship of prolactin to post-partum aggression in mammals is briefly reviewed. The findings are inconclusive; in the three species studied, postpartum aggression is perhaps enhanced, but does not depend on high prolactin levels. There are no studies on the relationship of prolactin levels and violence in women. Hostility associated with high prolactin levels in postpartum women is perhaps a phylogenetic remnant which may have had the evolutionary advantage of protecting the young.

Prolactin, amitriptyline, and recovery from depression.

Spontaneous prolactin patterns were determined at 15-min intervals over 5 h in 13 patients, who were suffering from melancholia, during illness and after treatment with amitriptyline. Plasma prolactin levels were significantly greater at most sampling points after patients had recovered than during their illnesses. One patient, who did not recover, showed the opposite trend.

Mineralocorticoid modulation of prolactin effect on renal solute excretion in the rat.

The effects of ovine PRL (oPRL) on renal solute and water handling were examined in 1) intact, 2) salt-loaded (6 meq NaCl ip X 8 days), 3) adrenalectomized (adx), 4) adx plus corticosterone-treated (133 micrograms/100 g BW im), and 5) adx plus dexamethasone-treated (10 micrograms/100 g BW im) male rats. After 7 days treatment rats received a water load (3% BW ip) before a 4-h urine collection. Rats also received 0.9% NaCl im (controls) or 1.0 mg oPRL on days 4-7. Treatments were continued to day 8 for inulin clearance determination. The effects of arginine vasopressin (AVP) (173 microU im, days 4-7) on renal solute and water excretion were also examined in salt-loaded rats to see if renal effects of oPRL treatment were due to AVP contamination of the oPRL preparation. In intact rats drinking tap water, oPRL decreased sodium clearance (CNa) and potassium clearance (CK) (P less than 0.05) vs. controls, with no change in free water clearance (CH2O). In intact rats receiving 1.0% NaCl and 1.0% glucose as a replacement for drinking water, oPRL decreased CNa (P less than 0.05) and increased CK (P less than 0.05) vs. controls, with no change in osmolar clearance or CH2O. In salt-loaded rats oPRL increased CNa and CK (P less than 0.05) vs. controls, with no change in CH2O. AVP administration to salt-loaded rats, however, had no effect on CNa and decreased CK vs. controls. oPRL increased CK (P less than 0.05) in adx rats, with no effect on CNa. In adx plus corticosterone-treated rats oPRL decreased CNa and CK (P less than 0.005), similar to its effect in intact animals. oPRL had no effect on renal solute or water excretion as compared to control animals in dexamethasone-treated adx rats. oPRL did not alter glomerular filtration rate at any time. These data suggest that 1) oPRL requires the presence of mineralocorticoids for an effect on sodium, but not potassium, excretion, 2) elevated sodium intake reverses the effect of oPRL on potassium excretion, 3) oPRL potentiates the effects of corticosterone on sodium reabsorption, and 4) glucocorticoids may block the effects of oPRL on the kidney.

The 'Alice in Wonderland' experience. Ergot alkaloid therapy for prolactin-secreting pituitary tumors.

This discussion was selected from the weekly Grand Rounds in the Department of Medicine, University of New Mexico School of Medicine and Veterans Administration Medical Center, Albuquerque. Taken from a transcription, it has been edited by Drs Charles Sherman, Resident in Medicine, and Maire T. Buckman, Associate Professor of Medicine and Chief, Endocrinology Section, Veterans Administration Medical Center, Alburquerque.

Body composition of oligo/amenorrheic athletes.

Menstrual dysfunction in athletes may be related to low body weight or low body fat content. To investigate the relationship between body composition and menstrual function, body composition was evaluated by hydrostatic weighing in two groups of women: 14 athletes with oligo/amenorrhea and 28 athletes with regular menstruation. Age and height were similar in the two groups. In all of the weight parameters, including total body weight, percent ideal body weight, Livi Index, percent body fat, fat weight, and lean body weight, athletes with oligo/amenorrhea were significantly lighter than athletes with regular menstruation. We concluded that menstrual dysfunction in athletes is associated with low body weight, which is comprised of smaller amounts of both fat and lean body mass.

Psychosomatic aspects of hyperprolactinemia.

A review of some recent studies on the psychosomatic aspects of hyperprolactinemia is presented. Women seem to be more prone to suffer from the behavioral effects of prolactin than males. Women with hyperprolactinemic amenorrhea rated themselves significantly more hostile, more depressed and more anxious than women with amenorrhea only and other control groups. Hyperprolactinemic males did not rate themselves more hostile and depressed than matched controls. Psychological distress and hostility appear to remit upon treatment with bromocriptine. Postpartum patients matched for prolactin levels with hyperprolactinemic women showed significantly less depression and anxiety but about the same levels of hostility. Hostility, depression and loss of libido may coexist in the same hyperprolactinemic patient but they may be also present independently.

Neonatal treatment with antiserum to prolactin lowers blood pressure in rats.

Prolactin administration reportedly increases blood pressure in rats and rabbits. To study the effects of prolactin deficiency on blood pressure, rats were given saline, normal rabbit serum, or rabbit antiserum to rat prolactin on postnatal days 2 to 5. Both males and females given antiserum had significantly lower blood pressure at 14 weeks than rats given saline or normal rabbit serum. Blood pressure differences between females given antiserum and females given saline disappeared during and following pregnancy. The antiserum also lowered the concentration of prolactin in plasma 49 percent in males and decreased the prolactin response to ether stress in both sexes. These results suggest that endogenous prolactin is involved in blood pressure regulation.

Patterns of spontaneous LH release in normo- and hyperprolactinaemic women.

Hyperprolactinaemia may be associated with functional amenorrhoea. In order to evaluate the possible role of abnormal spontaneous LH secretion in hyperprolactinaemic amenorrhoeic women, plasma LH was measured at 15 min intervals for 300 min in 12 normal women during the early follicular phase of the menstrual cycle and compared to that observed in 11 hyperprolactinaemic amenorrhoeic subjects. Mean plasma prolactin was 9.1 +/- 3.6 ng/ml (X +/- SEM) in the euprolactinaemic and 168 +/- 32 ng/ml in the hyperprolactinaemic group. Sex steroids including oestrone, oestradiol, progesterone and 17-hydroxyprogesterone were similar in the 2 groups. Mean plasma LH levels over the 300 min sampling period were 9.4 +/- 1.6 mIU/ml in the normal subjects and 7.5 +/- 1.0 mIU/ml in the hyperprolactinaemic patients (P greater than 0.10). Every normal woman exhibited at least one LH spike in excess of 10 mIU/ml. Five hyperprolactinaemic patients failed to exhibit any LH spikes above 10 mIU/ml (P less than 0.02 compared to controls). Thus, hyperprolactinaemia was associated with an absence of LH spike activity in 45% of patients studied and this abnormality may play an aetiologic role in the hypogonadism observed in these subjects; in those hyperprolactinaemic subjects with pulsatile LH secretion, however, other explanations for their amenorrhoea should be considered.

Differential lipemic and proteinemic response to oral ethinyl estradiol and parenteral estradiol cypionate.

Oral synthetic estrogen administration to normal women has been shown to result in both a lipemic and a proteinemic response. To determine whether parenteral estrogen administration would have similar results, the effects of intramuscular depo-estradiol cypionate on serum lipids and ceruloplasmin were examined. The oral and parenteral estrogens chosen for this study are frequently used therapeutically and varying doses in the range of those commonly employed clinically were given to the experimental subjects. Following oral ethinyl estradiol (20, 50, and 100 micrograms every 12 hr) comparable and significant increases in triglyceride (73 +/- 6 to 128 +/- 10 mg/dl, p < .001), ceruloplasmin (87 +/- 4 to 188 +/- 11 mg/dl, p < .001), and HDL-cholesterol (60 +/- 2 to 74 +/- 3 mg/dl, p < .001) were observed. In contrast, despite substantial increases in serum estrogens, parenteral estrogen administration (depo-estradiol cypionate, 5 and 10 mg) failed to result in alterations in any of the measured parameters. Thus, the route and/or type of estrogen administered may determine the proteinemic and lipemic effects of estrogen in man.

PIP: This study looked at the effect of a commonly used estrogen preparation, parenteral depo-estradiol cypionate, on several metabolic parameters and compared the results of known alterations which follow oral ethinyl estradiol. The metabolic parameters studied were serum cholesterol, triglyceride (TG), ceruloplasmin, and high-density lipoprotein (HDL) cholesterol. Doses of agents used are common therapeutic ones. After oral ethinyl estradiol (20, 50, and 100 mcg every 12 hours) significant increases in TG (73+ or -6 to 128+ or -10 mg/dl, P .001), ceruloplasmin (87+ or -4 to 188+ or -11 mg/dl, P .001), and HDL-cholesterol (60+ or -2 to 74+ or -3 mg/dl, P .001) were observed. In contrast, despite substantial increases in serum estrogens, parenteral estrogen administration (depo-estradiol cypionate, 5 and 10 mg) failed to result in alterations in any of the measured parameters. Thus, the route of contraceptive agent administration may affect the proteinemic and lipemic responses in humans.