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Background: The hormonal manipulation 5-Fluoro-uracil Epirubicin Cyclophosphamide (HMFEC) trial was developed at a time of uncertainty around the dose intensity of chemotherapy given to premenopausal patients with node positive breast cancer and to the benefits of tailored endocrine therapy in such patients., Patients and Methods: HMFEC was a multi-centre, phase III, open label, randomised controlled trial with a 2 × 2 factorial design. Eligible patients were premenopausal with node positive early breast cancer; significant cardiac disease or uncontrolled hypertension was exclusion criterion. Patients were allocated to receive either eight cycles of FE50C or FE75C (given 3 weekly) with or without hormone manipulation (HM; tamoxifen or luteinising hormone releasing hormone (LHRH) agonists according to residual hormone levels at the end of chemotherapy) irrespective of ER status. The primary end-point was disease free survival (DFS). Principal analyses were by intention to treat (ITT); however, to reflect contemporary practice, subgroup analyses according to ER status were also conducted. The mature follow-up now available from this modest sized trial enables presentation of definitive results., Results: Between 1992 and 2000 a total of 785 patients were randomised into the HMFEC trial (203 FE50C-HM, 191 FE50C+HM, 198 FE75C-HM, 193 FE75C+HM). At a median follow-up of 7.4 years, 245 DFS events have been reported (92 ER-, 153 ER+/unknown). The effects on DFS were not statistically significantly different according to epirubicin dose (hazard ratio [HR] = 0.82, 95% confidence interval [CI] 0.63-1.06; p = 0.13 FE75C versus FE50C); however, FE75C appeared to induce more alopecia and neutropenia. No statistically significant evidence was observed to support an improvement in DFS in patients allocated HM either overall (HR = 0.88, 95% CI 0.68-1.13; p = 0.32) or in patients with ER+/unknown disease (HR = 0.85, 95% CI 0.62-1.17; p = 0.32) although effect sizes are consistent with worthwhile clinical effects. Overall, there was no evidence of a difference in survival between any of the four treatment groups of the trial., Conclusion: Higher doses of epirubicin cause more adverse events in the absence of clear improvement in overall survival. Endocrine therapy with either tamoxifen or goserelin provided no significant added benefit to cytotoxic chemotherapy in this group of patients., Trial Registration Number: ISRCTN98335268., (Copyright © 2016 Elsevier Ltd. All rights reserved.)

Objective: The purpose of the present investigation was to assess sexual function among middle-aged women and determine related risk factors (personal and partner) for sexual dysfunction., Methods: In this cross-sectional study, women aged 40-59 years were requested to fill out the Female Sexual Function Index (FSFI) and a general demographic questionnaire containing personal and partner data., Results: A total of 409 women with a mean age of 47 +/- 5.3 years were surveyed. Of these, 42.1% were premenopausal, 24.4% perimenopausal and 33.5% postmenopausal. At the time of survey, 10.5% of women were hysterectomized, 1.5% used psychotropic drugs, and 9.8% were on hormone therapy (HT) for the menopause; 28.1% had less than 12 years of schooling and 80.4% had only one partner at the moment of survey. Among their male partners, 7.3% abused alcohol, 10.3% had erectile dysfunction, 11.2% premature ejaculation and 63.83% were faithful partners. Mean (+/- standard deviation) scores for the FSFI domains were: desire (3.7 +/- 1.2), arousal (3.1 +/- 2.5), lubrication (3.3 +/- 2.6), orgasm (2.6 +/- 2.3), satisfaction (4 +/- 1.7), and pain/dyspareunia (3.2 +/- 2.6). The mean total FSFI score was 20.1 +/- 12.4 (median 24.7). In this series, the prevalence of female sexual dysfunction (FSFI score

Serum levels of prolactin (PRL), luteinizing hormone (LH), and follicle-stimulating hormone (FSH) were measured in normally cycling women and normal men before and after oral admiministration of 1 mg of clebopride, a derivative of procainamide used in the treatment of gastrointestinal diseases. Clebopride produced a significant increase (P < 0.001) in serum PRL to a 6-fold peak as compared with basal levels. After 240 minutes the levels remained significantly higher (P < 0.05) than the mean basal level at -30 and 0 minutes. No significant effects of clebopride were noted upon the circulating levels of LH and FSH. The peak PRL response to clebopride was unaffected by pretreatment with 100 mg of nomifensine, although the secretory area from 120 to 210 minutes after clebopride was greater (P < 0.05) in the nomifensine-treated group than in the control experiment. When 5 mg of bromocriptine were given before clebopride, the PRL response was completely abolished as compared with the control experiment (P < 0.001). Our data provide new evidence that dopaminergic receptors of the adeylate cyclase system are involved in the regulation of PRL secretion, acting at the pituitary level rather than acting on the hypothalamus. The PRL-releasing activity of clebopride could be the explanation for the occasional menstrual disorders and galactorrhea registered in some cases of long-term treatment.

Using a new antiserum, an enzymatic radioiodination of arginine vasopressin (AVP), and the methodology of Robertson et al. (1,2), we have developed a sensitive and specific radioimmunoassay for plasma AVP in the monkey. The sensitivity of the assay is 0.5 muU/ml, the cross reaction with oxytocin (OT), minimal. We used this assay to study the effects that variations in blood osmolality have in regulating AVP secretion in unanesthetized, chair-restrained, chamber-isolated, adult female rhesus monkeys. Under water ad lib conditions, plasma AVP and osmolality were relatively constant, averaging 1.7 +/- 0.6 (SD) muU/ml and 298 +/- 3 mosmol/kg, respectively. Water loading decreased plasma AVP and osmolality to 0.6 +/- 0.2 muU/ml and 282 +/- 6 mosmol/kg, respectively. When fluid restriction increased osmolality, plasma AVP rose progressively to twice the baseline after 1 day, and to 6 times the baseline after 3 days. The rise in plasma AVP was linearly correlated with the rise in osmolality (r = 0.93; P less than 0.001). Intravenous infusions of hypertonic saline produced significant rises in plasma osmolality and plasma AVP. There was a dose-related rise in plasma AVP that declined later at the expected rate with the infusion of physiological amounts of synthetic AVP.

Intramuscular injection of 0.2 mg methylergobasine maleate3) (Methergin, Sandoz) in women on day 3 post-partum, in regularly menstruating women and in adult men, is followed within 30 to 75 min by a 50% decrease in serum prolactin concentration: the levels remain low until 180 min and increase between 180 and 240 min. The amplitude of the decrease is the same when prolactin is measured in terms of the same serum prolactin standard by a homologous ovine assay and by a homologous human assay. However, in the case of regularly menstruating women and of men serum prolactin concentration is some three times higher when estimated by the ovine assay than when estimated by the human assay. This difference between assay results obtained by the two radioimmunoassay methods could be due to heterogeneity of serum prolactin. However, non-specific effects of serum are not excluded. In regularly menstruating women and in men, intramuscular injection of 0.2 mg methylergobasine maleate is followed within 45 to 75 min by a 50% decrease in immunoreactive serum LH concentration without concomtant change in immunoreactive FSH. The depression of LH secretion lasts for 1 to 2 h. The circulating levels of HCG in post-partum women are not modified after intramuscular injection of Methergin. In humans as in animals and in in vitro studies, inhibition of prolactin and LH release induced by ergot drugs are likely due to both an indirect effect via the hypothalamus and to a direct effect on the pituitary cells.

Physiologic and pathologic production of milk involves complex relations between the mammary glands, hormones, and the central nervous system. In all the galactorrhea syndromes there is a functional or mechanical problem at the pituitary level, with abnormal secretion or reserve of prolactin secretion. Stimulatory agents of prolactin, like thyrotropin releasing hormone (TRH), chlorpromazine, amnio acids, and insulin, can be helpful in the study of the hypothalamic pituitary functional reserve, while the osmotic tests seem to provide a clear distinction between functional and tumoral causes. The inhibitory agents of prolactin secretion, L-dopa and CB 154, permit the study of the negative control of the hormone. In addition, CB 154 appears to be an effective treatment for functional galactorrhea. Hyperprolactinemia appears to exert an inhibitory influence on gonadotropins. Clomiphene, acting on the hypothalamus, and LHRH, acting on the gonadotropes, permit the assessment of the gonadotropic hypothalamic-hypophyseal axis.

To evaluate a possible role of the amygdala (Amyg) in the neural control of arginine vasopressin (AVP) release, adult female monkeys (Macaca mulatta) with electrodes chronically implanted in the Amyg, hypothalamus and pituitary gland were given 5% dextrose and water infusions and were stimulated electrically at these sites. Immediately before and after, and at 5, 10, 15 and 30 min intervals following electrical stimulation, blood samples were withdrawn from unanesthetized monkeys, through implanted cardiac cannulae, for radioimmunoassay (RIA) of plasma AVP and for plasma osmolality determination. In the Amyg-stimulated monkeys, plasma AVP rose rapidly to peak values at the end of stimulation followed by an abrupt post-stimulation fall to control levels in 30 min. A small yet significant rise in plasma osmolality was also observed. Electrical stimulation of the hypothalamus and the pituitary gland yielded a temporal pattern of plasma AVP rise and fall identical to that seen following Amyg stimulation. Blood sampling, precisely timed to the onset and end of the stimulus train, was important in capturing the rise and fall in plasma AVP. Stimulus intensity determined the magnitude of plasma AVP elevation at each of these sites, with the highest current densities yielding the highest levels of plasma AVP. It is suggested that the Amyg may be involved in the neural triggering of AVP release from the neurohypophysis.