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Biomedical subjects

L Falsetti

Publications and source records attributed to L Falsetti.

At least 19 recordsLinked to original sources

Dose-dependent suppression of serum prolactin by cabergoline in hyperprolactinaemia: a placebo controlled, double blind, multicentre study. European Multicentre Cabergoline Dose-finding Study Group.

OBJECTIVE: Dopamine agonists have a well established place in the treatment of hyperprolactinaemic disorders but their use is associated with a high incidence of adverse effects. We have investigated the biochemical efficacy and side-effect profile of a range of doses of the novel, long-acting dopamine agonist, cabergoline, in suppressing prolactin (PRL) in hyperprolactinaemic women. DESIGN: Multicentre, prospective, randomized, placebo controlled and double blind. PATIENTS: One hundred and eighty-eight women with hyperprolactinaemia secondary to microprolactinoma (n = 113), idiopathic disease (n = 67), empty sella syndrome (n = 7) or following failed surgery for a macroprolactinoma (n = 1). MEASUREMENTS: Weekly assessment of adverse symptoms, blood pressure and pulse, serum PRL, blood count, liver and renal function. RESULTS: Patients received either placebo (n = 20) or cabergoline 0.125 (n = 43), 0.5 (n = 42), 0.75 (n = 42) or 1.0 mg (n = 41) twice weekly for 4 weeks. The five treatment groups were comparable in age (mean 31.8, range 16-46 years), diagnosis, previous therapy, and pretreatment serum PRL. PRL was suppressed to below half the pretreatment level in 5, 60, 90, 95 and 98% and normalized in 0, 30, 74, 74 and 95% of patients taking placebo or cabergoline 0.125, 0.5, 0.75 or 1.0 mg twice weekly respectively (Armitage's test, chi 2 = 39.3, P < 0.01). Cabergoline therapy (all doses) restored menses in 82% of the amenorrhoeic women not previously treated with dopamine agonists. Adverse events were recorded in 45% of patients in the placebo group and in 44, 50, 50 and 58% of those taking 0.125, 0.5, 0.75 and 1.0 mg cabergoline twice weekly (Armitage's test, P > 0.05). Over 95% of reported symptoms were relatively trivial, most frequently transient nausea, headache, dizziness, fatigue and constipation. More severe adverse events, interfering significantly with the patients' lifestyle, occurred in 13 (7.7%) patients taking cabergoline; treatment withdrawal was necessary in only one case. No adverse effects were detected on blood pressure or haematological or biochemical parameters. CONCLUSIONS: We have shown a linear dose-response relationship for cabergoline in the treatment of hyperprolactinaemia in the range 0.125-1.0 mg twice weekly, with normalization of PRL in up to 95% of cases and acceptable tolerability throughout the dose range.

Adolescent

Requirement of oestrogens for the sensitivity of prolactin cells to vasoactive intestinal peptide in rats and man.

Vasoactive intestinal peptide (VIP) is a prolactin-releasing hormone which is involved in the multifactorial modulation of prolactin secretion in mammals. Intravenous injection of VIP (1 microgram/kg) to fertile women increased plasma prolactin levels and heart rate and reduced diastolic pressure. The same treatment to menopausal women caused similar cardiovascular effects but did not modify plasma prolactin levels. In contrast, TRH (200 micrograms, i.v.) induced a significant increase in plasma prolactin levels in both fertile and menopausal women. The relevance of oestrogens in affecting VIP-stimulated prolactin secretion was evaluated in vitro by measuring prolactin release from pituitary cells of control and ovariectomized rats. The sensitivity of rat mammotrophs to VIP, but not to TRH, was completely suppressed 3 or 4 weeks after ovariectomy. Furthermore, implantation of rats with a silastic capsule containing oestradiol-17 beta during ovariectomy, preserved the cell responsiveness to VIP. The prolactin-releasing property of VIP was also restored when pituitary cells from ovariectomized rats were cultured for 3 days in the presence of 10 nmol oestradiol-17 beta/l before being used for prolactin release experiments. The present study shows that the ability of prolactin-secreting cells to respond to the stimulatory action of VIP requires high levels of circulating oestrogens, both in man and rats.

Adult

Weight loss and menstrual cycle: clinical and endocrinological evaluation.

This study explores the clinical and endocrine implications of weight loss. The frequency of menstrual abnormalities was found to be greatly influenced by reduction in body weight. The occurrence of amenorrhea appeared to be proportional to the rate of weight loss, while regular cycles and luteal phase deficiency were inversely correlated to weight loss. Endocrine variations were noted. Significant decreases in luteinizing hormone and follicle stimulating hormone levels occurred only in amenorrheic patients with a weight loss higher than 20%. The estradiol level decreased in proportion to the reduction in body weight. Cortisolemia increased in all patients, with higher values apparent in amenorrheic women presenting with a weight loss higher than 20%. The prolactin values were normal except in amenorrheic patients who had lower levels. A reduction of insulin levels occurred in all groups, with a significant difference found only in amenorrheic women in Group C (weight loss higher than 20%). The data suggest that weight loss in young women causes alterations in the menstrual cycle mainly through two mechanisms involving both the hypothalamic-pituitary-adrenal axis and ovarian steroidogenesis together with estrogen catabolism.

Adolescent

Long-term treatment with the combination ethinylestradiol and cyproterone acetate in polycystic ovary syndrome.

This study evaluates the effect of therapy over a long period of time (36 cycles without interruption) with the monophasic combination containing 0.035 mg of ethinylestradiol and 2 mg of cyproterone acetate (EE35-CPA) on hormonal and clinical parameters of 66 patients with polycystic ovary syndrome (PCOS). During the administration of the pill a significant decrease in the LH/FSH ratio and in adrenal and ovarian androgens has been observed, as well as a significant increase of the Sex Hormone Binding Globulin (SHBG). The progressive decrease of the total androgenic activity explains the clinical results that have been obtained: at the 36th cycle of therapy acne disappeared in 100% of the cases, seborrea in 76.4% and hirsutism in 75%. Our results underline the need for a continuous administration without interruption of the pill with CPA in patients with clinical hyperandrogenic symptoms.

Acne Vulgaris

Ovulation induction with intravenous gonadotropin-releasing hormone.

The efficacy of ovulation induction with the use of pulsatile gonadotropin-releasing hormone (GnRH) therapy was examined in 21 infertile women. Seventeen had hypothalamic amenorrhea (HA) and 4 polycystic ovary syndrome (PCO). All patients were treated as outpatients. GnRH was infused in a pulsatile mode by means of portable auto-infusion pumps connected to an indwelling intravenous catheter inserted into a forearm vein. The doses varied from 1.8 to 5 micrograms/pulse with a frequency of 90 minutes. Ovulation occurred in 52 out of 64 cycles (81.2%). Ten (47.6%) of the 21 patients became pregnant. Seven patients had normal term deliveries and 3 aborted spontaneously. With regard to the 17 patients with HA, ovulation occurred in 93.7% of treatment cycles and 6 women became pregnant. In the case of the PCO patients, ovulation was achieved in 6 out of 15 cycles (40%) and 2 women became pregnant. There was no overstimulation or any other serious complication. In conclusion, therapy with GnRH provides an elevated probability of therapeutic success, especially in HA.

Adult

[Effects of therapy and pregnancy on hyperprolactemia caused by a pituitary adenoma. A clinical case].

A woman who presented with amenorrhea and galactorrhea with a large prolactinoma (8.5 mm) which regressed on bromocriptine therapy is described. When treatment with bromocriptine was instituted (10 mg/daily) mean serum prolactin concentration fell from 490 ng/ml to 108 ng/ml. Despite a progressive reduction in size up to disappearance of the adenoma after the first 5 years of therapy, prolactin levels remained high. Bromocriptine treatment was stopped after 6 years, when pregnancy was diagnosed. Pregnancy proceeded without complications and lactation was initiated and maintained. After 8 months of breast-feeding, menstrual function resumed spontaneously and bromocriptine therapy was no longer required. Bromocriptine can cause not only a decrease in serum prolactin levels but also a regression in the size of prolactinomas in hyperprolactinemic women. No problems associated with pregnancy and/or breast-feeding were noted in these patients.

Adult

Vasoactive intestinal polypeptide (VIP) selectively stimulates prolactin release in healthy women.

The neuropeptide, vasoactive intestinal polypeptide (VIP), is released from the hypothalamus to the portal circulation, and experiments on animals provide evidence that it might modulate hormone secretion from the pituitary. Here we report the effects of VIP on the release of different pituitary hormones, including prolactin (PRL), luteinizing hormone (LH), follicle-stimulating hormone (FSH) and thyrotropin-releasing hormone (TSH), in normal women. Seven healthy women (aged 27-32; body weight 53-60 kg), with normal menses and receiving no medication, were tested on days 20-23 of their cycle. Porcine VIP was injected i.v. as a bolus dose of 1 mcg/kg body weight. Blood samples were collected 10 minutes prior to VIP administration and 5, 15, 30, 45, 60 and 90 minutes after VIP injection. Blood pressure and heart rate were continuously monitored. Hormone levels were determined by RIA. Stress, which can stimulate PRL release, was assayed by measuring the effect of placebo on hormone release (5 controls). VIP injection induced a significant (p less than 0.01) increase in plasma PRL levels. Basal PRL was 20.25 +/- 9.14 ng/ml; 5 minutes after VIP injection PRL levels rose to 45.0 +/- 14.9 ng/ml (p less than 0.01). At 15 minutes a plateau was reached (46.0 +/- 14.5 ng/ml), then the levels slowly decreased. VIP administration did not modify the plasma concentration of LH, FSH or TSH at any time during the observation period. The present study indicates that VIP might play a physiological role as a RPL-releasing factor in human beings.

Adult

A new low-dose estrogen oral contraceptive combination: effect on endocrine parameters and lipid status.

In this study the variations of endocrine and metabolic parameters of 39 women treated with a new oral contraceptive combination containing 20 mcg of ethinylestradiol and 150 mcg of desogestrel were examined. Gonadotropins and androgen presented a significant decrease, showing the efficiency of suppression of the pituitary-ovarian activity and of the contraceptive effect. The significant increase of SHBG and the corresponding reduction of free testosterone reflect the estrogenic environment of this pill and the low androgenicity of desogestrel. During the observation period, plasma levels of total cholesterol, trglycerides, LDL-C and HDL2-C were not altered, whereas total phospholipids, HDL-C and HDL3-C increased significantly. Besides a general positive effect on the main lipid parameters involved in atherogenic process, this pill also presented an optimal subjective tolerability.

Adult

Presurgical treatment of uterine fibroids by using gonadotropin-releasing hormone agonists.

Evaluation of clinical intra- and post-operative benefits of pre-myomectomy therapy with a Gonadotropin-Releasing Hormone Agonist (GnRH-A) (Goserelin) in anemic and non-anemic patients suffering from uterine leiomyomas. Evaluation of ultrasound, estradiol (E2) and hematological measurements before and during treatment with a GnRH-a in thirty women with uterine leiomyomas, comparing pre-treated patients operative time, total intraoperative blood loss, blood counts and febrile morbidity with of thirty-five control women. GnRH-A pre-treatment cures, iron-deficiency anemia, significantly reduces myoma and uterine volume (p < 0.01), total intra-operative blood loss (p < 0.001), decreases post-operative febrile morbidity, though it does not reduce operative time. GnRH-A pre-treatment over a period no longer than two months should be suggested in anemic patients suffering from uterine leiomyomas who have to undergo myomectomy.

Anemia

Conservative surgical treatment in infertile patients with endometriosis.

In the period 1985-1988 23 infertile patients with pelvic endometriosis underwent conservative surgery with microsurgical technique. 8.7% (only 2 women) of the patients were in 2nd stage, 43.5% in 3rd stage and 47.8% in 4th stage of the American Fertility Society classification (1985). Associated pathology was found in 52.2% of the patients. Surgical techniques and results are presented. We obtained 13 (56.5%) full term pregnancies. The postoperative birth rate was 50% in 2nd stage, 80% in 3rd stage and 36.4% in 4th stage. Associated pathology was present in 69.2% of pregnant patients. Ten women (43.5) did not conceive: 10% were at 2nd, 20% at 3rd and 70% at 4th stage. Associated disease was present in 30% of women that did not become pregnant.

Adult

Ovarian hyperstimulation syndrome (OHS): a case of severe OHS.

A 26 year old patient, who underwent an ovulation stimulation therapy (Clomiphene /UH-FSH), monitored only by ultrasound presented a severe Ovarian Hyperstimulation Syndrome (OHS). beta-HCG values confirmed conception, that outcame in an abortion. During an ovulation stimulation therapy, patient's management with the ultrasound examination, is often inadequate and it's moreover necessary to determine the 17 beta E2 levels.

Abortion, Spontaneous

Polycystic ovary syndrome: long-term evolution.

A study was made of the long-term evolution of 64 women with PCO in order to identify the clinical and/or endocrine alterations that may modify the prognosis of each case. The patients were divided into two groups: Group A, where at the conclusion of the observation period disorders were present, and Group B, where they were not. A comparison between the clinical and endocrine data obtained from the two groups at the first observation showed only one significant difference, concerning the time of onset of menstrual irregularities; these coincided with the menarche in only 57.6% of the cases in Group A, but in 94.7% of those in Group B.

Adult

Uterine fibromyoma and sterility: role of myomectomy.

The role of abdominal myomectomy with regard to surgical technique, subsequent conception and term pregnancy was evaluated. Of 30 patients undergoing myomectomy 13 conceived and 10 had a good pregnancy. It should be noted that 10 of 30 patients considered in this study had a leiomyomas associated disease, representing another cause of infertility. Thus, a preoperative evaluation of the reproductive capability of the couple would allow a selection of patients who are to undergo myomectomy resulting in a better pregnancy rate. In the present series, the ages of the patients and the size of the leiomyomas did not significantly influence the pregnancy rate. The most important correlation with subsequent fertility was the duration of infertility prior to myomectomy. The general principles of reproductive microsurgery should be kept in mind when performing myomectomy.

Adult