HYPERPROLACTINAEMIA AND IMPOTENCE

Clinical, laboratory and radiological findings were evaluated in twenty-nine men who had raised serum prolactin concentrations and pituitary tumours. Twenty-one had functionless pituitary tumours ('prolactinomas') and eight had acromegaly. Suprasellar extension was detected in twenty of the twenty-six men who had lumbar airencephalography. Three patients were studied before, sixteen before and after and ten only after pituitary ablative therapy.
Seventeen of these men complained of complete lack of libido and impotence and six had impaired libido and sexual potency; only six patients in this series denied reproductive symptoms. Thirteen of the impotent subjects had small soft testes, ten reduced facial and body hair and three had marked gynaecomastia. No features of hypogonadism were noted in the six patients without reproductive symptoms and none of the patients had galactorrhoea.
Serum prolactin concentrations were higher and serum testosterone concentrations lower in the impotent men compared with those with normal sexual potency. Serum LH and FSH (both basal and in response to LHRH), oestradiol and oestrone concentrations were not different between the two groups and, except in those with post-operative hypopituitarism, were within the normal range. Following successful lowering of prolactin concentrations by surgery or bromocriptine or both, serum testosterone rose and potency returned; by contrast failure to lower prolactin concentrations was associated with persistent impotence and hypogonadism.
The endocrine profile of low serum testosterone concentrations with gonado- trophins which had not risen into the range usually seen in primary hypogonadism (together with the parallel increase of LH and testosterone in one patient studied sequentially during treatment which suppressed prolactin levels to normal), suggested that the impaired gonadal function was caused by a prolactin-mediated disturbance of hypothalamic-pituitary function.     

MENSTRUAL FUNCTION AND SERUM PROLACTIN LEVELS AFTER LONG-TERM BROMOCRIPTINE TREATMENT OF HYPERPROLACTINAEMIC AMENORRHOEA

Long-term bromocriptine treatment was discontinued in thirty-seven women with hyperprolactinaemic amenorrhoea. After cessation of therapy thirty of the thirty-seven women became hyperprolactinaemic again with amenorrhoea or anovulatory bleeding. Seven of the women continued to have regular ovulatory menstruation but only three were normoprolactinaemic 3 months after stopping treatment. Two of the seven women had evidence of pituitary tumour regression. After the discontinuation they had nearly normal prolactin levels but during 2 years of follow up the serum prolactin levels slowly increased. In the twenty-seven women with pre treatment prolactin levels below 100 μg/l there was no difference between the prolactin levels before starting and 1 month after stopping treatment, while the women with pretreatment prolactin levels above 100 μ/l had lower levels after therapy. Bromocriptine treatment seldom results in permanent cure of hyperprolactinaemic amenorrhoea.     

The effects of dopaminergic blockade on serum TSH and prolactin levels in thyrotoxicosis

In the first part of this study, we have demonstrated that, in 7 patients with untreated thyrotoxicosis, a 7 day regime of the long acting dopamine antagonist metoclopramide (10 mg orally 8 hourly) produces more adequate dopaminergic blockade at pituitary level than a single oral 10 mg dose of the compound as assessed by serum prolactin responses. Subsequently, we have employed this protracted oral metoclopramide regime to evaluate the contribution of dopaminergic tone to the abnormal TSH and prolactin responsiveness of thyrotoxicosis. Serum TSH and prolactin responses to iv TRH (200 micrograms) were measured in 10 untreated thyrotoxic patients before and after a 7 day period of metoclopramide 10 mg orally 8 hourly. Ten euthyroid individuals were studied in similar fashion, their serum samples being analysed for prolactin levels alone, thus providing a control group for prolactin responsiveness to TRH, before and after metoclopramide. In the thyrotoxic patients basal TSH levels did not change as a consequence of metoclopramide therapy and the TSH response to TRH remained flat. Basal prolactin levels were similar in thyrotoxic and euthyroid individuals and the increase in prolactin, seen in both groups after metoclopramide, was smaller in the thyrotoxic group than in the euthyroid group. Prolactin responsiveness to TRH was significantly impaired in the thyrotoxic subjects as compared to euthyroid subjects. After metoclopramide there was a significant decline in prolactin responsiveness in the euthyroid group, and a similar, though insignificant, trend in the thyrotoxic patients. We conclude that in thyrotoxicosis dopaminergic tone plays no major part in the suppression of TSH levels, nor in the impaired prolactin responsiveness to TRH.     

CLINICAL AND ENDOCRINE FEATURES OF HYPERPROLACTINAEMIC AMENORRHOEA

The clinical, radiological and endocrine findings in thirty-five women with hyperprolactinaemia and amenorrhoea are described. Twelve patients had radiological evidence of a pituitary tumour and six were tested after pituitary ablation. Seventeen patients with hyperprolactinaemia and normal pituitary X-rays were also studied. None was on any drug known to increase prolactin secretion and all patients were euthyroid when tested. Basal serum prolactin concentrations were high in the group with untreated pituitary tumours and in those with normal X-rays. The levels were variable in the post-ablation cases. The increase of prolactin after TRH was subnormal in all of the groups. Serum oestradiol concentrations were low in most patients and nineteen of twenty-one patients tested had no withdrawal bleeding after treatment with a progestogen. Mean serum gonadotrophin concentrations (basal and after LHRH) were normal in twenty-nine patients but subnormal in four post-ablative cases. Anovulatory responses to clomiphene were obtained in nineteen of twenty patients tested. Fifteen patients were treated with bromocriptine; twelve ovulated and eight became pregnant; two not responding had impaired LH and FSH production. Hyperprolactinaemic amenorrhoea is a common disorder with characteristic endocrine features. Galactorrhoea is unusual (30%). Treatment with bromocriptine lowers prolactin concentrations and rapidly repairs the reproductive defect.     

Danazol and prolactin status in patients with endometriosis

A group of 55 women with endometriosis was studied before and during danazol therapy. An unexpectedly high proportion (36%) had a raised serum prolactin level before treatment which was reduced after 50 days of danazol (before treatment 783 +/- 333 mU/l; on danazol 243 +/- 113 mU/l, P less than 0.001). In contrast patients with normal serum prolactin levels showed no significant drop on danazol therapy. In all patients serum oestradiol was significantly reduced during treatment (before treatment 449 +/- 188 pmol/l; on danazol 207 +/- 117 pmol/l, P less than 0.001). In one patient with hyperprolactinaemia danazol reduced both basal and stimulated prolactin levels, whereas in 5 women with normal prolactin levels we could detect no gross alteration in metoclopramide or TRH stimulated prolactin levels associated with danazol therapy. The possibility that normalisation of raised prolactin levels may be secondary to reduced oestrogens and that patients with endometriosis have an increased sensitivity to oestrogen-induced prolactin secretion is discussed.     

Persisting suppression of prolactin secretion after long-term treatment with bromocriptine in patients with prolactinomas

The effect of bromocriptine withdrawal after long-term treatment on prolactin levels has been investigated in thirty-seven patients with prolactinomas. In ten patients with macroprolactinomas and post-operatively excessively high prolactin levels persisting suppression of prolactin secretion after bromocriptine withdrawal has been observed. This effect was not observed in patients with microprolactinomas or macroprolactinomas with only moderately elevated prolactin levels. The degree of persisting suppression correlated to the height of prolactin levels before treatment and to the duration of bromocriptine therapy. No correlation was found between the rise of prolactin levels after bromocriptine withdrawal and withdrawal time. It is suggested that the persisting suppression of prolactin levels is a sequence of reduction in tumour size. This anti-proliferative action of bromocriptine seems to be specific for the prolactin secreting cells in macroprolactinomas with high proliferation rate and high prolactin turn-over. These findings offer new possibilities in the management of patients with macroprolactinomas.     

Pituitary tumors and hyperprolactinemia.

Hyperprolactinemia was demonstrated in eight of nine patients with clinical evidence of pituitary tumors without acromegaly or Cushing syndrome. Hourly sampling for 24 hours disclosed elevation of serum prolactin concentrations, whereas, measurable serum growth hormone levels were found rarely. Although eight of these patients were hypersecreting prolactin, only four of them were lactating. Prolactin secretion was characterized by moderate hourly fluctuations of serum levels and absence or blunting of the normal sleep-related augmentation of secretion. Patients with the highest serum prolactin concentrations tended to have the largest pituitary tumors, as indicated by pneumoencephalography. In two patients followed-up with serum prolactin determinations after treatment, a fall in serum prolactin concentrations correlated with clinical improvement. Future study will hopefully establish the value of serum prolactin determinations in following tumor growth before and after pituitary ablative therapy.     

The effect of weight gain on gonadotrophins and prolactin in anorexia nervosa

Serum levels of gonadotrophins and prolactin and their response to luteinizing hormone/follicle stimulating hormone--releasing hormone (LRH) and thyrotrophin releasing hormone (TRH) were measured in 14 females with anorexia nervosa when at low body weight and again in 6 cases during, and 12 cases after weight gain. Mean serum luteinizing hormone (LH) and follicle-stimulating hormone (FSH) levels were low initially and whereas FSH increased significantly with weight gain, LH levels remained subnormal in most patients. LH responses to LRH were grossly impaired or absent in patients whose weight was below 75% of the ideal, but increased dramatically above this weight over-shadowing the more modest increase in FSH response. In three patients, however, impaired LH responses persisted as ideal weight was approached. Basal prolactin levels were well within the normal range in all patients. During weight gain there was no change in basal levels but the prolactin level 20 min after TRH was significantly increased.     

Pituitary reactivity, androgens and catecholamines in obstructive sleep apnoea. Effects of continuous positive airway pressure treatment (CPAP).

We studied the effects of chronic nocturnal hypoxaemia due to obstructive sleep apnoea syndrome (OSAS) on the hypothalamic-pituitary-thyroid and hypothalamic-pituitary-testicular axes and on catecholamine and cortisol secretion. We investigated whether hormones other than catecholamines may serve as markers for chronic hypoxic stress and the possible effects of nasal continuous positive airway pressure (nCPAP) treatment on endocrine status. Nocturnal oximetry was performed in 16 male patients with OSAS diagnosed by polysomnography, immediately before nCPAP treatment and in 11 of the patients the oximetry was repeated after 7 months of nCPAP therapy. Plasma and urinary catecholamines, luteinizing hormone (LH) testosterone, cortisol, thyroid stimulating hormone (TSH), prolactin (PRL), and the response of TSH and PRL to a thyroid releasing hormone (TRH) challenge test were measured immediately before and after 7 months of nCPAP treatment. Subnormal LH and TSH and elevated serum cortisol as well as increased nocturnal urinary norepinephrine levels were found in patients prior to treatment; otherwise endocrine values were normal. There was a significant correlation between low pretreatment nocturnal arterial oxygen saturation and high plasma and urinary norepinephrine levels. The nCPAP treatment caused significant reduction in serum prolactin and TSH, and significant reduction in plasma epinephrine and urinary norepinephrine. The reduction in serum TSH and urinary norepinephrine was most pronounced in the subjects with the worst pretreatment nocturnal hypoxaemia. No other significant changes were found in basal hormone levels. The response to TRH challenge was normal before and after treatment and was not influenced by CPAP therapy. OSAS is associated with elevated catecholamine and cortisol and decreased TSH and LH levels but a normal response to TRH challenge and a normal androgen status. Apart from catecholamines, none of the hormones studied is likely to serve as a specific marker for chronic hypoxic stress.     

Hyperprolactinemia. Long-term effects of bromocriptine

Patients with hyperprolactinemia may be managed by pituitary surgery or irradiation, bromocriptine treatment, or a combination of these methods, and some patients remain untreated. Little is known of the long-term consequences of some of these therapeutic regimens. Forty-six hyperprolactinemic patients (40 female and six male) managed solely with bromocriptine or no treatment over a period of 12 months to six years were therefore evaluated in this study. Nine patients with radiologically normal pituitary fossae were untreated and 10 received bromocriptine, 7.5 to 10 mg daily, while 20 patients with radiologic evidence of a pituitary tumor were treated with bromocriptine, generally 10 to 20 mg daily. Patients were assessed clinically, biochemically, and radiologically before treatment and at least six weeks after discontinuation of therapy. A further seven patients were similarly assessed before and after eight bromocriptine-induced pregnancies. Symptoms persisted in the untreated group of nine patients, although menstruation returned in four of the females with previous amenorrhea; serum prolactin levels remained elevated, other pituitary function did not change, and pituitary fossae remained normal radiologically. In all patients treated with bromocriptine, symptoms improved irrespective of radiologic findings on the pituitary, and were abolished in 67 percent during treatment associated with a decrease in serum prolactin levels in all, and a return of levels to within normal limits in 80 percent of patients. Persistent side effects were usually dose-related, but remained troublesome in 13 percent. Bromocriptine-induced tumor regression was evident radiologically in all patients with suprasellar tumor tissue and in some with purely intrasellar adenomas. This effect occurred rapidly and persisted or increased throughout follow-up. On discontinuation of treatment, prolactin levels remained significantly lower than before therapy (mean 2,934 versus 5,052 mU/liter, p less than 0.05) but were within the normal range in only two patients. Other pituitary function was unaltered, or improved in some patients with definite tumors. Bromocriptine-induced pregnancy produced no permanent change in clinical, biochemical, or radiologic status. Long-term bromocriptine treatment for hyperprolactinemia is thus highly effective in alleviating symptoms and suppressing prolactin secretion, and induces persistent tumor regression on treatment without deterioration of other pituitary function in patients with macroadenomas. On discontinuation of therapy, however, hyperprolactinemia usually recurs, and treatment may therefore need to be continued for years.     

Immobilization stress and prolactin secretion in male rats. Possible roles of dopamine and TRH.

Immoblization stress had a biphasic effect on serum prolactin levels: the early short stimulatory phase followed by a long inhibitory phase in male rats. Stress induced the rise in serum prolactin without concomitant increase in serum TSH levels which declined during the immoblization for 300 min. Other stressors, ether inhalation or formalin s.c. injection, or TSH i.v. injection, which were effective in controls failed to elevate serum prolactin after the 300-min immobilization. Serum TSH responded to TRH after the stress as well. Pimozide, dopamine receptor blocker, was effective in increase of serum prolactin in the stressed rats as well as in controls. In pimozide pretreated rats, elevated serum prolactin levels decrease in 10 min by the immobilization and returned to the preimmobilization levels thereafter which were higher than those in stressed animals without pimozide treatment. It is suggested that TRH is not a physiological PRF in the stress-induced prolactin release and that the dopaminergic system may be activated by the immunoblization stress, resulting in decrease of the prolactin-releasing activity of the pituitary.     

Misinterpretation of prolactin levels leading to management errors in patients with sellar enlargement

Serum prolactin concentrations and clinical features were correlated with the histopathologic diagnosis in 128 patients, without acromegaly or Cushing's syndrome, referred for surgical treatment of a presumed pituitary adenoma. A serum prolactin concentration of more than 8,000 mU/liter was always due to a prolactin-secreting adenoma. Prolactin levels of less than 8,000 mU/liter occurred with a variety of pathologic diagnoses. Fifteen patients had lesions other than pituitary adenomas, most commonly intrasellar craniopharyngioma; 10 of these had modest hyperprolactinaemia (maximum, 5,260 mU/liter) and four had received inappropriate bromocriptine therapy. Adenomas that were not prolactinomas frequently caused mild hyperprolactinaemia, although this was usually less than 3,000 mU/liter; three of these patients, however, had serum prolactin concentrations greater than this (maximum, 8,000 mU/liter). If the serum prolactin concentration is less than 3,000 mU/liter in the presence of significant pituitary enlargement, surgical removal is essential for both diagnosis and treatment since only prolactin-secreting adenomas are likely to shrink with dopamine agonist therapy. A serum prolactin concentration between 3,000 and 8,000 mU/liter is consistent with any diagnosis, whether the fossa is greatly enlarged or not, and great care must be taken with dopamine agonist therapy in such patients.     

PITUITARY FUNCTION IN PROLACTINOMA. EFFECT OF SURGERY AND POSTOPERATIVE BROMOCRIPTINE THERAPY

Forty-five women and fifteen men with prolactinomas have been treated surgically. Patients with large tumours received pituitary irraditation and postoperative hyperprolactinaemia was treated with bromocriptine. The patients have been followed-up for 6–36 months following the operation. The tumours were larger and the levels of production higher in men as compared with women. All women had amenorrhoea. Galactorrhoea was present in forty-three women but not in the men. After surgery serum prolactin levels fell significantly in all women but remained above normal in thirty-six; prolactin remained high in twelve men. Bromocriptine effectively decreased the postoperative hyperprolactinaemia. The surgical complications were oculomotor nerve paresis in one woman and one man. After surgery six (23%) women developed impaired GH secretion, six (15%) impaired thyroid function, eight (18%) impaired cortisol secretion and five (17%) impaired LH secretion in isolation or combination which had not been present preoperatively. Three patients relapsed. Fifteen women menstruated after surgery and ten began to do so during the subsequent bromocriptine treatment. Thus, menstruation was restored in all six women with microadenomas, in sixteen of twenty patients with intrasellar macroadenomas and three of nineteen patients with suprasellar adenomas. The preoperative LH-reserve proved to be an important prognostic indicator. Nine patients, i.e. 50% of patients desiring fertility became pregnant. In the men gonadal function deteriorated in four patients and did not improve in any without testosterone treatment.     

The effect of the menopause on prolactin levels in patients with hyperprolactinaemia

OBJECTIVE: Microprolactinomas have been reported to resolve spontaneously after pregnancy and there have been suggestions that oestrogen therapy increases the size of microprolactinomas. Little is known, however, about the effect of the menopause in patients previously known to be hyperprolactinaemic. The aim of this study was to find out if pregnancy or the menopause leads to an alteration in prolactin levels. DESIGN: We conducted a retrospective study of 148 case notes of patients with hyperprolactinaemia and microprolactinomas treated at the Radcliffe Infirmary during the period 1976-96. Sixty-nine female patients who had not had pituitary surgery as treatment for microprolactinoma were used as a control group. None of this group became pregnant or reached the menopause. They were compared with 25 female patients who became pregnant, 11 who became menopausal and 11 who were male. Subjects were excluded from the analysis if there were no follow-up data off dopamine agonist treatment or if they were surgically cured. Data were gathered on demographic parameters, treatment given, scan abnormalities, prolactin levels at diagnosis and last follow up, prolactin levels pre- and postpregnancy as well as pre- and postmenopause. The pregnancy, postmenopausal and male patient groups were compared with the control group and each other to see if they had a higher frequency of normalization of their prolactin levels during follow up. Various factors were examined as possible variables for the normalization of prolactin, including the detection of scan abnormalities at diagnosis, prolactin levels at diagnosis as well as treatment with dopamine agonists and duration of follow up. RESULTS: Forty-five percent of the menopausal group, 24% of the pregnancy group and 18% of the male group subsequently normalized their prolactin levels during the period of the study in comparison with 7% of the control group. The menopausal groups had a significantly higher chance of normalizing their prolactin compared to the control group (P < 0.005), whilst the pregnancy group showed a non-significant trend towards normalizing their prolactin (P = 0.06). The detection of scan abnormalities, treatment with dopamine agonist therapy and duration of follow up were not associated with normalization of prolactin levels. CONCLUSION: Female patients with hyperprolactinaemia who pass through the menopause have a significant chance of normalizing their prolactin levels. Females who pass through pregnancy may have a higher chance of normalizing their prolactin levels. The menopause is an indication for reassessment of the need to continue to treat hyperprolactinaemia and microprolactinoma.     

Efficacy and tolerability of a long-acting intramuscularly injectable depot preparation of bromocriptine: the results of a double blind study.

The tolerability and efficacy of a long-acting im applicable form of bromocriptine (Parlodel LAR) was tested in a double-blind approach in 20 patients with hyperprolactinemia or prolactinoma, 17 of them complaining of persistent side effects on oral treatment with dopamine agonists. The study-code revealed similar characteristics for age, sex, weight, clinical symptoms and previous therapy in both groups but prolactin serum levels were higher in the verum group even though the difference was not significant. In all 10 patients receiving Parlodel LAR prolactin serum concentrations were significantly suppressed and tumor size was reduced in 5 of the 9 patients with visible tumors when controlled after 28 days. In contrast, no significant change in serum prolactin levels was observed in the placebo group and tumor size of all visible tumors was not altered. Side effects typically reported for dopamine agonists started 3 h after application in the verum group and were significantly different to the unspecific side effects reported in the placebo group during the first 72 h. Thereafter systemic tolerability was indistinguishable between both groups. The local tolerability at the injection site was excellent for both, Parlodel LAR and placebo.     

Pre-operative dopamine agonist therapy improves post-operative tumor control following prolactinoma resection

Objective Normalization of serum prolactin concentrations in patients with prolactinomas is an accepted endpoint of therapy. Clinical signs and symptoms of hyperprolactinemia are usually resolved when prolactin levels are lowered to within the normal range. While most patients are treated with dopamine agonist drugs, some patients require surgical resection of their tumors. We sought to determine whether preoperative treatment with dopamine agonists alters the outcome of surgical intervention. Methods and results We present an analysis of 253 patients with prolactinomas treated surgically during the period of time when dopamine agonist therapy was first introduced and prior to its widespread use as first-line therapy. We compared both short- and long-term outcomes of patients treated with dopamine agonists prior to surgery with those undergoing surgery as their initial treatment modality. Our data showed that that patients treated with dopamine agonists prior to surgery experienced greater reductions in prolactin levels, had lower prolactin levels, were more likely to have normal prolactin levels at long term follow-up, and were less likely to require additional therapy to control their prolactin levels. Conclusion Our study provides strong evidence suggesting that, regardless of initial prolactin level, preoperative dopamine agonist therapy is not detrimental. In fact, pretreatment with dopamine agonist drugs, possibly by inducing tumor regression, seemed to improve the surgeon’s ability to resect a greater percentage of the tumor and led to better control of the prolactin level.     

PROLACTIN CONCENTRATIONS IN PATIENTS WITH ACROMEGALY: CLINICAL SIGNIFICANCE AND RESPONSE TO SURGERY

Basal serum prolactin and growth hormone (GH) concentrations were measured by radioimmunoassay in forty patients with acromegaly. GH concentrations were elevated in all patients studied before treatment and prolactin levels were raised in seven of twenty-six patients. Of the thirty-two patients reviewed after treatment which in most cases was transsphenoidal hypophysectomy) twenty-five had GH concentrations below 5 ng/ml and twenty-nine had normal prolactin levels. In eighteen patients hormone measurements were made both before and after hypophysectomy: though GH levels fell in but one, prolactin fell in only six patients. They were not significantly changed in eleven patients. There was no correlation of GH and prolactin either before or after surgery. Seven patients had greatly elevated prolactin levels and in four of these there was evidence of upward extension of a pituitary tumour on air encephalogram (AEG). Only one patient with a normal prolactin level had an abnormal AEG. Two patients with elevated prolactin concentrations and normal AEGs had a parallel fall of prolactin and GH in response to surgery. Four of the five hyperprolactinaemic men complained of loss of libido: in three gonadotrophin concentrations before and after treatment were normal. We conclude that there is no overall correlation of GH and prolactin levels in patients with acromegaly. Seven of twenty-six untreated patients (27%) had hyperprolactinaemia. We suggest that in these patients a raised prolactin level may be due either to interference with the normal inbhitory control mechanism of prolactin by suprasellar extension or, more rarely, to secretion of both GH and prolactin by the tumour itself. A high prolactin concentration may be the cause of the impotence of which some patients with acromegaly complain.     

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)     

Dopaminergic tone and obesity: an insight from prolactinomas treated with bromocriptine

OBJECTIVE: It has recently been shown that increased body weight is associated with prolactinomas and that weight loss occurs with normalization of prolactin levels. On the other hand, decreased dopaminergic tone in humans is well correlated with obesity. The objective of this study was to correlate changes in prolactin levels with leptin and body mass index (BMI) in patients with prolactinomas treated with the long-acting dopamine agonist bromocriptine (BC). METHODS: Eleven female and twelve male patients, aged 36.7+/-2.6 years with BMI in males of 30.4+/-1.7 kg/m(2) and in females of 24.4+/-1.2 kg/m(2), were evaluated after 1 and 6 months and 11 patients were further evaluated after 2 years of BC therapy. Plasma prolactin is presented as the mean of four samples taken daily. Serum leptin was determined in the pooled serum from three samples taken at 15-min intervals at 0800 h after an overnight fast. Multivariate linear regression and repeated measures analysis of covariance were used. RESULTS: In males, pretreatment prolactin levels were 71 362+/-29 912 mU/l while leptin levels were 14.9+/-1.8 microg/l. In females, pretreatment prolactin levels were 11 395+/-5839 mU/l and leptin levels were 16.7+/-2.5 microg/l. The sexual dimorphism of serum leptin levels at initial presentation was preserved after adjusting for BMI and prolactin-induced hypogonadism. After 1 month of therapy, prolactin levels significantly decreased (males: 17 618+/-8736 mU/l, females: 3686+/-2231; P<0.05), BMI did not change (males: 30.2+/-1.7 kg/m(2), females: 24.1+/-1.2 kg/m(2); P>0.05), while serum leptin levels decreased (males: 12.5+/-1.5 microg/l, females: 13.6+/-2.1 microg/l; P<0.05). After 6 months of treatment, prolactin further decreased (males: 3456+/-2101 mU/l, females: 677+/-360 mU/l; P<0.05) as did BMI (males: 28.6+/-1.6 kg/m(2), females 23.1+/-1.0 kg/m(2); P<0.05). The difference was more pronounced in male patients. Leptin levels were 12.8+/-2.8 microg/l in males and 12.9+/-1.8 microg/l in females (P<0.05). After 2 years of BC treatment, prolactin levels were near normal (males: 665+/-439 mU/l, females 447+/-130 mU/l; P<0.05) and BMI remained 26.5+/-1.9 kg/m(2) for males and 23.6+/-0.8 kg/m(2) for females (P<0.05). Leptin levels were 9.5+/-2.2 microg/l in males and 18.7+/-3.1 microg/l in females (P<0.05). There was a gradual increase in the gender difference in serum leptin levels over time. Changes in serum leptin levels significantly correlated with changes in BMI (r=0.844, P<0.001) but did not correlate with changes in plasma prolactin levels after 1 month (r=0.166), 6 months (r=0.313) and 2 years (r=0.234, P>0.05). CONCLUSION: The long-acting dopamine agonist BC, by increasing dopaminergic tone, may influence body weight and likely body composition by mechanisms in addition to reducing hyperprolactinemia in patients with prolactinomas.     

Failure of melatonin to increase serum prolactin levels in ovariectomized rats subjected to superior cervical ganglionectomy or pinelaectomy.

The effects of melatonin on serum prolactin levels were examined in ovariectomized rats primed with oestradiol and progesterone, and subjected to bilateral superior cervical ganglionectomy or pinealectomy. Ganglionectomy resulted in a significant depression of the serum prolactin concentrations, as well as in impairment of the prolactin release evoked by administration of steroid. Treatment with melatonin increased serum prolactin in control but not in ganglionectomized rats. Injection of melatonin protentiated the steroid-induced release of prolactin in control rats; this effect of melatonin was not detected in ganglionectomized rats. Pinealectomy did not affect basal prolactin levels, nor impair the release of prolactin evoked by steroid treatment; however, it was effective in blocking the melatonin-induced release of prolactin in vehicle-treated rats, as well as the potentiation of steroid-induced prolactin release by melatonin. Intracranial surgery by itself increased prolactin release. These results suggest that systemically administered melatonin needs an intact pineal gland to augment serum prolactin levels.