Treatment of moderate and severe hirsutism with a gonadotrophin-releasing hormone agonist.
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Female↗
Biomedical subjects
L Falsetti
Publications and source records attributed to L Falsetti.
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↗
Vasoactive intestinal polypeptide loses its prolactin-releasing activity in menopausal women.
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Adult↗
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↗
Development of pituitary adenoma in women with hyperprolactinaemia: clinical, endocrine, and radiological characteristics.
Sixty eight women referred for treatment of hyperprolactinaemia entered a three year follow up study to determine the clinical and endocrine course of the disease and its association with microadenoma of the pituitary. Details recorded before treatment included medical history, gonadotrophin and ovarian hormonal concentrations, and release of prolactin in response to protirelin (thyrotrophin releasing hormone), benserazide, cimetidine, and nomifensine. Sellar tomography was then performed yearly for three years in all women, 54 of them also undergoing computed coronal and sagittal tomography. At baseline evaluation 27 women showed radiological evidence of pituitary adenoma; at the end of the follow up period the number had increased to 41. Amenorrhoea, steady and raised serum prolactin concentrations, a low ratio of luteinising hormone to follicle stimulating hormone, a longer duration of disease, and low serum progesterone concentrations were more common in women with a final diagnosis of pituitary adenoma than in those whose sella remained normal. Tests for release of prolactin had yielded abnormal results from the outset in all 41 women with radiological evidence of pituitary adenoma and in about half of those whose sella had remained radiologically normal. Response to medical treatment (metergoline in 20 patients, bromocriptine in 21) was similar and showed no difference between patients with tumorous and non-tumorous hyperprolactinaemia. These findings suggest that a large proportion of women with hyperprolactinaemia may harbour a prolactin secreting pituitary adenoma which becomes apparent over a relatively short period. Amenorrhoea and steady and raised serum prolactin concentrations are more common in these women. Tests for release of prolactin are of predictive value in identifying women who will develop a pituitary adenoma.
Adenoma↗
Metergoline in the management of normoprolactinemic secondary amenorrhea. A multicentric controlled trial.
In a multicentric study, the effect of the antiserotoninergic agent metergoline was evaluated in the management of patients with idiopathic normoprolactinemic secondary amenorrhea (NSA). The awareness that psychological factors might lead to a spontaneous reappearance of menses was also taken into account, and all the patients, after physical, gynecological and laboratory examinations, and the performance of the progesterone withdrawal bleeding test (100 mg i.m.) and the clomiphene citrate test (100 mg p.o./day for 5 days), were treated for 60 days with placebo; only patients showing no menses during placebo administration were later treated with metergoline. 108 patients entered the trial: of these, 48 experienced menses on admission or during placebo administration, and were withdrawn. Of the 60 patients not responding to placebo, 50 were treated for 90 days with metergoline (4 mg t.i.d.), and 23 had menses, ovulatory in 68.4% of cases. A new placebo treatment was accompanied, in the majority of cases, by recurrence of amenorrhea. These results indicate that many patients with NSA may experience a spontaneous disappearance of the disease: in cases more seriously affected metergoline might be a useful therapeutic agent.
Amenorrhea↗
Metergoline and bromocriptine in the management of tumoral and idiopathic hyperprolactinemia.
59 patients affected by amenorrhea or anovulation, 37 of whom also with galactorrhea, and with hyperprolactinemia of unknown origin (idiopathic hyperprolactinemia, 24 patients) or due to a pituitary microadenoma (tumoral hyperprolactinemia, 35 patients) were treated with metergoline (4-12 mg/day) or with bromocriptine (2.5 to 10 mg/day) for 90 days. The effectiveness of the two treatments was assessed on clinical grounds and by evaluating at monthly intervals serum progesterone levels, during the presumed luteal phase, and serum prolactin levels. The success rate with the two drugs was superimposable in terms of disappearance of galactorrhea and return of menses, normalization of prolactin levels and induction of ovulation. Also the number of pregnancies obtained (7 with metergoline, 9 with bromocriptine) was similar. With both drugs, the majority of patients responded to the treatment within the first month.
Adenoma↗
Treatment of hyperprolactinaemia with metergoline for periods up to 5 years: clinical and biological tolerability.
Forty patients with hyperprolactinaemia were treated with metergoline (8 to 12 mg/day) for periods up to 5 years. Analysis of the results of clinical and biological tolerability showed that treatment was generally well tolerated and although 28 patients complained of drug-related side-effects of various kinds, principally nausea, these were usually mild, present at the beginning of treatment and disappeared spontaneously in spite of continued metergoline administration over a prolonged period. No patient stopped treatment because of side-effects. Laboratory parameters also stayed within normal levels and there was no evidence of any alterations in the ECG. It is concluded, therefore, that metergoline is a well-tolerated as well as an effective ergolinic compound for use in those patients in whom prolonged treatment with a prolactin-lowering drug is considered necessary.
Adenoma↗
Profiles and endocrine correlations in endometrial carcinoma.
The Authors compared the mean LH, FSH, PRL, E1, E2, Testosterone, Androstenedione plasmatic levels in a group of post-menopausal women affected by endometrial carcinoma (EK), with those of a control group presenting clinical characteristics as close as possible to those of the pathologic group. The case series was significant. They found no significant difference between the two groups' hormonal levels. On the other hand, E1 levels were found to increase along-side with obesity. In patients affected by EK, E1 plasma levels significantly increased alongside with the post-menopausal age. Conversely, in the control group, this hormonal value significantly and progressively decreased from the menopause onwards. Furthermore, the Authors studied the effects of surgical intervention on the hormonal picture in EK bearers.
Age Factors↗
A study of prolactin, follicle-stimulating hormone, and luteinizing hormone in puerperium: spontaneous variations and the effect of metergoline.
In 80 normal puerperae, serum follicle-stimulating hormone (FSH), luteinizing hormone (LH), including human chorionic gonadotropin (hCG/LH), and prolactin (PRL) levels were evaluated 6 to 29 hours after vaginal delivery. In these puerperae, PRL levels were higher and FSH levels were lower than in menstruating women; hCG/LH levels were very high, due to persisting hCG levels. The values of the three hormones showed a log-normal distribution, and no relationship was found between the three hormones considered in pairs. Thirty-six puerperae chosen from the above 80 were followed during a 5-day period: 24 were not able to breast-feed their babies and were treated with metergoline, an antiserotoninergic agent able to prevent puerperal lactation, 8 or 12 mg/day; 12 additional puerperae, nursing their babies, were evaluated as controls. In lactating women PRL and FSH levels remained steady during the observation period, while hCG/LH levels progressively decreased. Metergoline lowered PRL levels, when employed at both dosages, and FSH levels only at the higher dosage, without affecting the decline of hCG/LH levels. Since dopaminergic drugs are known to lower serum LH levels and not to affect or to increase FSH levels, our data indicate that metergoline might act through a mechanism of action different from dopaminergic drugs.
Adolescent↗
Metergoline in the management of hyperprolactinemic amenorrhea and anovulation.
84 patients with elevated serum PRL levels, ranging from 25 to 253 ng/ml, were treated with an antiserotonin agent, metergoline, at the dose of 12 mg/day for 90 days. The clinical complaint was of amenorrhea in 70 cases (plus galactorrhea in 44 cases) and of anovulation in 14 cases (plus galactorrhea in 6 cases). Hyperprolactinemia was due to a pituitary adenoma in 18 cases; in 53 cases it was of unknown origin, while in 7 cases it followed treatment with neuroleptics or with oral contraceptives and in 6 cases it followed a puerperium. In patients with amenorrhea, metergoline induced the appearance of menses in 61 cases (94%), and of ovulation in 46 cases (82%). In 13 of the 14 patients with anovulation, ovulation was restored. Galactorrhea disappeared in 40 out of 50 patients. Metergoline normalized serum PRL levels (less than 20 ng/ml) in 46 cases and significantly reduced serum PRL levels in all but 3 of the remaining patients. In spite of suggested nonhormonal contraceptive measures, 14 patients became pregnant; 2 had abortions and the remaining 12 patients completed by vaginal delivery, uneventful pregnancies. These results indicate metergoline as a safe and effective drug in the management of hyperprolactinemic amenorrhea and anovulation. 49 patients were followed for 2 additional months, receiving no treatment (24 cases) or metergoline at a reduced daily dosage (8 mg/day, 25 cases). Within 60 days, 60% of the first group had relapse of the clinical condition and a rebound elevation of serum PRL levels while only 20% of the second group experienced relapse of amenorrhea and rebound elevation of serum PRL levels (p less than 0.01).
Amenorrhea↗