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In order to investigate the effect of cyproheptadine, a compound with antiserotoninergic activity, on the secretion of thyrotrophin (TSH) and prolactin (PRL), the nocturnal secretory patterns of these hormones have been studied in 4 normal men in the basal state and after an oral treatment with the drug. In addition, the TSH and PRL responses to TRH of 6 women were compared in the basal conditions and after cyproheptadine treatment. The TSH nocturnal secretion was slightly modified by drug treatment. The response to TRH as well as the basal levels were comparable in the treated and non-treated subjects. In contrast, the PRL secretion measured through the nocturnal investigation was significantly inhibited by cyproheptadine administration as were the PRL basal levels in the TRH test. The PRL response to TRH was comparable in both situations.

Nine patients suffering from hypothyroidism due to thyroid ectopia or hypogenesis, with a large sella turcica, were examined at adolescence or during adult life. TSH, prolactin and growth hormone function were studied. Basal plasma TSH, evaluated in 5 cases, was raised and responded explosively to stimulation with TRH. The administration of L-dopa was not associated with any notable changes in TSH. In one case, the chronic administration of l-T3 resulted in a fall followed by normalisation in plasma TSH levels. Basal plasma prolactin, explored in 6 patients, was high in 4 females and normal in 2 males. TRH stimulation resulted in a marked increased in prolactin in the female cases and a moderate increase in the male cases. L-dopa caused a fall only in high prolactin values. Stimulation of GH by argininehydrochloride, insulin hypoglycaemia and L-dopa gave variable responses. In one case, substitutive thyroid hormone therapy restored the GH response to L-dopa and arginine hydrochloride to normal. Paradoxically, GH increase following stimulation with TRH.

Eighteen hyperprolactinaemic patients were orally treated for up to 16 months with pergolide mesylate, a new potent long-lasting dopaminergic ergot derivative. In all cases, Prl normalization (less than 25 ng/ml) was achieved at a once-a-day dose of 50-300 micrograms. All women recovered and/or exhibited normal menstrual function. Among the 6 women wishing to become pregnant, 4 of them conceived within 4 months; there were other causes for infertility than hyperprolactinaemia in the 2 other couples. A macroprolactinoma man experienced important improvement in well-being as well as objective regression of his visual fields defect. This suggests a shrinkage effect of pergolide on the tumoural process. Another man regained normal potency and normal testosterone within 2 weeks. While 10 patients were completely free of any side effect, 7 experienced transiently mild gastro-intestinal side effects or postural hypotension. Only one patient discontinued her treatment because of dizziness. The present study demonstrates the high potency, the good tolerance and the excellent efficacy of pergolide in the treatment of hyperprolactinaemia.

Twenty-nine anorectic female patients were subdivided in three groups: group I when primary amenorrhoea; group II when secondary amenorrhoea together with a weight (for their height) equal or above the 10th percentile of the ratio of total water over body weight (TW/B Wt); group III when secondary amenorrhoea was associated with a weight below this 10th percentile. Despite very low mean oestradiol levels (respectively 22, 36 and 32 pg/ml), prolactin secretion remained normal both in basal conditions as well as after 200 micrograms TRH iv. For group III patients, a delay in the peak prolactin response to TRH was observed but it was not statistically significant.

Impaired LH response to LH-RH has been found in 2/4 cases of primary amenorrhoea, in 2/8 cases of psychogenic secondary amenorrhoea, in 2/4 cases of secondary amenorrhoea associated to a pituitary tumour and in 1/5 cases of iatrogenic secondary amenorrhoea post hormonal contraception. Therefore, this test appears not to differentiate these pathologic conditions.

After treatment with CB 154 of a prolactin-secreting pituitary adenoma a morphological study reveales that many cells present a positive immunofluorescent reaction with anti-ovine prolactine antibody. At the ultra structural level, many granulations and vacuolated dense bodies can be observed.

With the use of an in vivo tritiated thymidine [( 3H]dThd) nuclear labeling followed by autoradiography, the effects at different times before sacrifice of prolactin (PRL) and/or 17 beta-estradiol (E2) were studied in C57BL X DBA/2f)F1 mice given transplants of the MXT hormone-sensitive mammary tumor whose growth was previously shown to be influenced by E2 and/or progesterone. Uteri were chosen as controls for the methodology. Experiments were conducted on ovariectomized mice submitted to endocrine manipulation to achieve plasma PRL modifications. In addition to E2, the proliferation of cancer cells, assessed by the measurement of thymidine labeling indices (TLIs), was demonstrated to be enhanced by ovine prolactin (oPRL) and Sulpiride and strongly slowed down by castration and 2-bromo-alpha-ergokryptin treatment, thus emphasizing the great importance of PRL in mammary cancer development. Moreover, a pulse of 1 mg oPRL/animal produced a marked TLI rise in tumors, lasting from the 6th to the 48th hour after its injection and reaching a maximum at 24 hours. PRL had no proliferative effect on the uterine luminal epithelium. When PRL and E2 were injected concomitantly, the profile of stimulation was quite similar to that obtained with E2 alone; i.e., a maximum stimulation was observed at the 24th and 36th hours after hormonal pulse. From these data it is concluded that, in spayed mice, not only E2 but also PRL is of major importance leading to enhanced proliferation of MXT mammary neoplastic cells. Further investigations are needed to throw light on the cellular events presiding over the action of PRL and E2 at the cancer cell level.

Chronic hyperprolactinaemia was induced in 10 women since the onset of a cycle for 2 or 3 consecutive cycles by administration of sulpiride (3 X 50 mg/day) or tiapride (100-200 mg/day). The resulting perturbations of the menstrual cycle included short luteal phase cycles, anovulatory cycles and amenorrhoea. The analysis of the hormonal profiles under treatment, as compared to the control cycles, indicate an impact of hyperprolactinaemia both preferentially at the hypothalamic (alteration of the secretion or endogenous LRH) and accessorily at the ovarian (lack of progesterone secretion by the near mature follicle) levels.

The effects of Pergolide, a potent dopamine agonist, on exercise-induced plasma prolactin (PRL) changes were studied in normal men. Exercises consisted of a graded bicycle ergometer test and of a 20-km endurance run. In both circumstances, treatment with Pergolide, when compared with placebo or control values, resulted in a significant suppression of basal PRL (P less than 0.001) as well as of exercise-induced PRL increase (P less than 0.01). From these experiments it was concluded that augmented levels of PRL in plasma, as seen during or after muscular exercise, are caused by increased pituitary secretion, rather than decreased elimination.

PRL and TSH were measured by radioimmuno-assay in 14 persons wth myxoedema aged 16 to 65 years. Three of them had galactorrhea. In 13 patients the circadian rhythm of PRL was studied, and in 8 patients PRL was measured after TRH administration. All these patients have a high value of serum TSH, with a mean value +/- SEM of 29,4 (24,3 - 35,6) mU/ml. Values of serum PRL were comprised in normal ranges with a mean value +/- SEM of 126(196 - 238) mU/ml. The circadian rhythm of PRL is not altered, since mean values of serum PRL are more elevated at 4 am than 8 am with highly statistical significance. After THR administration the PRL response is normal or exaggerated.

Four normally cycling women received an iv injection of 20 mg Premarin (conjugated estrogens equivalent to 20 mg estrone sulfate) on the seventh day of two consecutive cycles; the second experiment was performed under sulpiride-induced hyperprolactinemia (mean PRL level = 906 microU MRC standard 71/222 per ml; significantly 7.8 times greater than mean control level of 115 microU MRC standard 71/222 per ml, P less than 0.001). In comparison to the control experiment, sulpiride-induced hyperprolactinemia prevented the occurrence of any gonadotropin peak within the 84 h of estrogen administration; the negative feedback effect of estrogen on gonadotropin secretion was maintained and was even potentiated. These alterations of feedback mechanisms of estrogen were considered to be related to hyperprolactinemia itself rather than to sulpiride. Five other normally cycling women received iv injections of 100 microgram LRH on the 22nd day of a cycle under sulpiride-induced hyperprolactinemia since the onset of menstruation. Their mean LH response was somewhat greater (although not statistically significant) and their mean FSH response was considerably greater (P less than 0.001 at all times) than those of a control group of 10 women tested in their luteal phase. The results of these LRH tests under sulpiride-induced hyperprolactinemia give some support to the concept that hyperprolactinemia interferes at the hypothalamic or higher level with cyclic release of indogenous LRH.

The efficacy, tolerance and acceptability of a single i.m. injection of 50 mg bromocriptine retard (in polylactic acid microspheres), given within 12 h after delivery for suppression of lactation, were investigated in 47 mothers not willing to breast-feed. Slight to moderate breast discomfort was noticed during the first postpartum days in 23% of the patients but lactation was indeed prevented in all cases and no rebound lactation occurred in any case. Only six patients exhibited at least two symptoms of mammary engorgement (congestion and pain or milk let-down): in this group, blood mean PRL levels were significantly less suppressed on postpartum days 2, 6, 21 and 28 (p less than 0.05 to p less than 0.001) than in the group of mothers completely free of any mammary symptoms. Slight side-effects (mostly dizziness), as mentioned at systematic request, were recorded in 34% of the patients; only 3 patients required treatment for their side-effects. Recovery of ovarian function was evident quite early (by day 28 in 72% of the patients), thus requiring early onset of contraception.

A double-blind clinical study was conducted to compare the therapeutic activity of veralipride and placebo in menopausal sudden flushes. Comparison of final numerical rate showed a statistical significant superiority for veralipride. Tolerance was excellent and no significant difference was observed between clinical side effects, or biological parameters studied (blood counts and differential, and blood bilirubin, transaminases, glucose, cholesterol, or creatinine levels) in the two groups.

LRH tests were performed in 6 adult men with intravenous injections of 25 mug, before and one week after an intramuscular injection of 250 mg testosterone oenanthate (Testoviron Depot). One week after intramuscular injection of Testoviron the tonic secretion of LH was completely suppressed, but the reactivity or the reserve capacity of LH secretion, as tested by LRH, remained unchanged. In contrast, the tonic secretion of FSH and the reactivity of FSH secretion to LRH were both partly suppressed. Three months after the Testoviron injection, the basal levels of LH were still significantly lower than the control values, but the basal levels of FSH were identical to the control values. These data indicate that, in man, the feedback action of testosterone on gonadotrophin secretion could be exerted, at least for LH, at the hypothalamic level rather than at the pituitary level . No significant effects of LRH were noted on the circulating levels of growth hormone and sugar. There was a distinct rise in serum prolactin, which was occasionally significant, within 30 min after LRH injection; this is considered to be without physiological significance.

Four regularly menstruating volunteers were submitted to an oral treatment, for 3 consecutive cycles and starting on the first day of a cycle, with tiapride at daily doses ranging from 1 x 100 mg to 2 x 100 mg. The first and the last cycle under treatment, as well as a prior control cycle, were thoroughly studied by means of daily measurements of blood concentrations of LH, FSH, prolactin (PRL), oestradiol and progesterone. Tiapride, a benzamide derivative with dopaminergic blocking activity at the level of the lactotrophes, increased mean PRL secretion in each subject but a permanent hyperprolactinaemia above 700 uU/ml was attained only in one subject. Despite these widely fluctuating PRL levels in most subjects, the resulting overall hyperprolactinaemia induced in all cases a progressive deterioration of the function of the corpus luteum: 5 cycles showed luteal phases reduced by 2--5 days, one cycle was characterized by some slight luteinisation but questionable ovulation and the 2 remaining cycles were anovulatory. The interruption of drug intake one week after the onset of menses led thereafter to a cycle with a likely inadequate luteal phase but of normal length. It is concluded that even a non-permanent hyperprolactinaemia can impair the normal function of the hypothalamo-pituitary-ovarian axis, as well as exhibit some effects in a cycle consecutive to the normalization of PRL. With the exception of the impaired luteal progesterone secretion, the pooled hormonal data from the short luteal phase cycles under tiapride-induced hyperprolactinaemia exhibit very little significant differences, as compared to the corresponding values in the control cycles. Some delay in the onset of follicular maturation, however, should be assumed since the follicular phase had been lengthened by 1 to 31 days in 5 of the 6 cycles with luteinisation during treatment. The present results are compatible with a double impact -- both at the ovarian and the hypothalamo-pituitary levels -- of hyperprolactinaemia in its mechanisms of impaired function of the hypothalamo-pituitary ovarian axis.

Immunoreactive human serum prolactin of pituitary origin has been measured by a radioimmunoassay developed for ovine prolactin. Blood samples were collected at four-hour intervals during a 24-hour period from 12 non-pregnant women, three pregnant women, and seven adult men. A circadian periodicity was found in serum prolactin concentration, with peak values during the night, between 1 a.m. and 5 a.m. for the non-pregnant women, and at 5 a.m. for the adult men. Mean serum levels of prolactin were 1.5 times higher in non-pregnant women than in men. In women investigated during the last month of their pregnancy the mean serum prolactin levels were 2.3 times higher than in the non-pregnant women, but there was no circadian periodicity.