DISSOCIATION BETWEEN TSH AND PROLACTIN DYNAMICS IN TREATED THYROTOXICOSIS

TSH and prolactin secretory patterns in thyroid disease have generally been reported as concordant. We studied TSH and prolactin responses to TRH infusion (500 mug) in euthyroid individuals previously treated for thyrotoxicosis with 131I or antithyroid drugs. The 131I-treated group (seven men, twenty women) had been clinically and biochemically euthyroid (normal serum thyroxine and triiodothyronine levels) for 6 months to 4-5 years (kappa +/- SD = 17-1 +/- 4-1 months). Based on maximal TSH increment (deltaTSH), three patient groups were identified: Group 1 [normal deltaTSH, n = 6]: delta prolactin was normal in two, blunted in one and exaggerated in three. Group 2 (exaggerated TSH response, n = 8): delta prolactin was normal in two, blunted in one and exaggerated in five. Group 3 (TSH nonresponders, n = 13): delta prolactin was normal in five, blunted in three, and exaggerated in five. Eleven patients (three men, eight women) were studied after 6 months antithyroid-drug treatment. All were clinically and biochemically euthyroid. All but one showed a blunted TRH-TSH response. All three men showed an exaggerated delta prolactin as did four of eight women. Three women showed a blunted delta prolactin and in one, delta prolactin was normal. Thus, TRH-induced TSH and prolactin response patterns in treated thyrotoxicosis are not uniformly concordant, and, while a blunted or absent TSH response commonly persists long after euthyroidism has been restored, this is most frequently accompanied by a normal or exaggerated prolactin response.     

Depressed levels of dehydroepiandrosterone sulphate in postmenopausal women with rheumatoid arthritis but no relation with axial bone density.

The sex hormones dehydroepiandrosterone sulphate (DHEAS), oestradiol, and sex hormone binding globulin (SHBG) were measured in 185 postmenopausal women (aged 45-65 years) with rheumatoid arthritis (RA) and related to assessments of bone mineral density at the spine and proximal femur. Compared with 518 postmenopausal control women (aged 45-65 years), DHEAS levels were below normal in the 120 patients with RA who had never taken corticosteroids and levels were further depressed in 39 patients currently using steroids. Twenty six patients who had completed steroid treatment also had lower DHEAS levels, suggesting a delayed recovery of adrenal androgen secretion. Oestradiol and SHBG levels were similar in all groups. There was no correlation between sex hormones and disease activity. Oestradiol correlated with bone mineral density at all sites. Although oestradiol correlated with DHEAS, there was no relation between DHEAS and bone mineral density. The cause of below normal levels of DHEAS in RA is unclear, whether a consequence of chronic illness, immune dysfunction, or a defect of adrenal androgen synthesis.     

Cabergoline in the long-term therapy of hyperprolactinemic disorders.

The efficacy and safety of the new long-acting dopamine agonist cabergoline were evaluated in 127 hyperprolactinemic patients (124F and 3M; 71 with microprolactinoma, 14 with macroprolactinoma, 5 with operated macroprolactinoma and 37 with idiopathic disorder) who were treated with the drug for from 3 to 52 months (median, 14 months). Cabergoline was administered orally at dose levels ranging between 0.2 and 3.5 mg per week, given once weekly in 92 patients, twice weekly in 22, thrice weekly in 9 and daily in 4. Serum prolactin and progesterone levels, hematology, blood chemistry and electrocardiograms were frequently evaluated throughout treatment. CT or MR imaging of the pituitary was repeated during treatment in patients with macroprolactinoma and in 38 with microprolactinoma. After drug discontinuation, serum prolactin and gonadal function were evaluated monthly for three months in 65 patients and for up to two years in 12. Serum prolactin levels were normalized in 114 patients (90%). Of 56 women with amenorrhea, 52 resumed menses (with presumptive evidence of ovulation in 49); 17 women became pregnant; and sexual potency was restored in the 3 men. Evidence of tumor shrinkage was obtained in 13 of the 14 patients with macroprolactinoma and in 28 of 38 with microprolactinoma; complete disappearance of the tumor image was achieved in 2 macro and 14 microprolactinomas. A total of 48 adverse events was reported by 29 patients (23%), almost all typical of the pharmacological class and mild to moderate; no patient withdrew from treatment due to adverse events. Safety parameters did not change. Following cabergoline discontinuation, prolactin levels increased slowly, being still markedly lower than pretreatment values after three months; 10 patients out of 32 had persistently normal prolactin levels during one year of follow-up.(ABSTRACT TRUNCATED AT 250 WORDS)     

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.     

BROMOCRIPTINE TREATMENT OF SEVEN WOMEN WITH PRIMARY AMENORRHOEA AND PROLACTIN-SECRETING PITUITARY TUMOURS

Seven women with primary amenorrhoea and hyperprolactinaemia were treated with bromocriptine. All the women had started to develop secondary sex characteristics at normal age but pubertal development stopped and menarche did not occur. Radiological signs of a pituitary tumour were found in all the women. Before the pituitary tumour was diagnosed, four women had been given longterm cyclical oestrogen replacement therapy. Three women had received primary tumour therapy with surgery and/or irradiation but had persistent hyperprolactinaemia. The basal luteinizing hormone (LH) levels were low in four of the women while all the women had normal basal levels of follicle-stimulating hormone (FSH) and normal or exaggerated gonadotrophin responses to luteinizing hormone-releasing hormone (LHRH). None of the women had evidence of endogenous oestrogen production before treatment. Bromocriptine treatment normalized the raised serum prolactin levels (46-2900 microgram/l) in all but one woman, in whom the prolactin level decreased from 160 to 38 microgram/l. Regular ovulatory menstrual cycles appeared in four women, one of whom had previously been treated by transsphenoidal adenomectomy followed by external irradiation. Two other women with persistent hyperprolactinaemia after previous surgical and/or irradiation treatment of large pituitary tumours did not menstruate after more than one year of treatment with bromocriptine. One infertile patient with a microadenoma conceived at the first ovulation on therapy and developed symptoms and signs of tumour growth during pregnancy.     

THE DYNAMICS OF PROLACTIN SECRETION DURING THE PUERPERIUM IN WOMEN

This study deals with serum prolactin concentrations during various conditions in the early puerperium in an attempt to investigate some characteristics of the mechanisms responsible for the regulation of the lactotrophes. In nursing, in non-nursing, non-medicated and in non-nursing, bromocriptine-treated women prolactin and 17β-oestradiol were measured during the early puerperium. In the first and the third group this was repeated during and after challenge with oestradiol-benzoate. The pituitary responsiveness to TRH was also determined in these two groups, challenged and unchallenged with oestradiol-benzoate. Nursing women had higher prolactin levels than the non-nursing groups, while bromocriptine decreased prolactin to very low levels. Non-nursing non-medicated women had prolactin values between those of nursing and those of bromocriptine-treated mothers. The already elevated prolactin levels in nursing women were not influenced by chronic oestradiol administration. In non-nursing puerperal women treated with bromocriptine, exogenous oestradiol caused a significant rise in plasma prolactin. The prolactin response to TRH in nursing women was clearly reduced in comparison with the normal menstrual cycle. In the bromocriptine-treated group the basal concentration of prolactin and its response to TRH stimulation was similar to normal non-pregnant women. In nursing and in non-nursing women treated with bromocriptine prolactin responses to TRH were increased after oestradiol challenge.     

Efficacy of human leukocyte interferon-alpha treatment in elderly patients with hepatitis-C virus-related chronic liver disease

Sixty-seven aged patients (mean age 69, age range 67-73 years) with hepatitis C virus (HCV)-related chronic liver disease were treated with human leukocyte interferon-alpha at a dose of 9 mU/week for 9 months and then followed up for other 6 months. At the end of treatment, 39 patients (58.2%) showed normalization of alanine aminotransferase (ALT) levels; however, 24 responders (61.5%) had a relapse of the disease in the following 6 months. Fifteen out of 39 responders (38.5%) had a sustained response. Of these, 9 (60%) showed clearance of HCV-RNA from serum. Similar rates were observed in a group of younger patients (mean age 48, age range 17-58 years) treated with the same schedule. In both groups, the most important predictor of response appeared to be the degree of fibrosis at liver histology, rather than the patients' age. These data suggest that interferon-alpha treatment may be as much useful in elderly patients as it may be in younger patients, provided that liver injury is not advanced too much.     

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.     

Serum leptin and longevity

There are changes in the ability to regulate energy balance and caloric intake with aging. Consequently, we investigated whether human aging modifies the levels of serum leptin, a novel hormone implicated in the regulation of energy balance. We studied 268 Caucasian men and women aged 22-85 years, and divided them into groups with mean ages of 30, 40, 50, 65, 75, 80 and 85 years. Fasting serum leptin concentrations were determined by radioimmunoassay. Subjects aged 65 or older were followed for five years after the blood sampling. There were no statistically significant differences in fasting serum leptin concentrations across different age groups in females (p = 0.090). Fasting serum leptin concentrations were also similar in different age groups in males, except that males in the 30-year age group had lower serum leptin levels than males in the 75-year age group (p = 0.042). Leptin levels were 2-3 fold higher in females than in males in each age group (p < 0.005 except p = 0.063 in the 75-year age group). Elderly women, who lived longer, had 47% higher (p < 0.05) serum leptin concentrations, and 17% higher (p < 0.001) BMI than the women who died within five years of blood sampling. Leptin levels were not statistically different in these women after adjusting for BMI. Thus, aging has no apparent effect on serum leptin levels in women or men, and the gender differences in leptin is present also in the older age groups. Higher leptin concentrations in the females who live longer may reflect a better nutritional status, and a greater adipose tissue mass rather than a primary factor for survival.     

HORMONE PROFILE IN PREMENSTRUAL TENSION: EFFECTS OF BROMOCRIPTINE AND DIURETICS

Plasma levels of prolactin, FSH, LH, progesterone and 17-beta-oestradiol in twenty women with premenstrual tension were compared with those in twenty controls. The former group was studied also during treatment with bromocriptine. The mean prolactin level in the PMT group was lower in the follicular phase than in the luteal phase (P less than 0.01), but there was no difference between the PMT and control group in the luteal phase. No differences were found between the controls and the PMT group in FSH,LH, 17-beta-oestradiol and progesterone levels in the luteal phase. Bromocriptine suppressed prolactin concentrations (P less than 0.01), but had no effect on the FSH, LH, 17-B-oestradiol or progesterone levels.     

Inequalities in Chronic Dialysis and Transplantation in Sweden

ABSTRACT We studied the chance of receiving dialysis and transplantation in Sweden and Stockholm based on age and sex. The number of patients accepted for chronic dialysis, divided into men and women or five age groups, were set in relation to the number of patients who died of ESRD (end-stage renal disease) in the same groups. The transplanted patients were likewise related to patients waiting on chronic dialysis. Although older patients were increasingly accepted for treatment, age is still strongly inversely correlated to acceptance. Thus in 1985, young patients aged 16–39 years had an 85% chance of being dialyzed, but patients over age 70 had only a 17% chance. Of potential male candidates, 44% received dialysis, but only 38% of women received it. Similar age, but less sex inequality, existed in the selection of patients for transplantation. In Sweden, age and sex influence the selection of patients for dialysis and transplantation.     

Efficacy of quinagolide in resistance to dopamine agonists: results of a multicenter study. Club de l'Hypophyse

OBJECTIVE: A retrospective French multicenter analysis was carried out to assess changes in tumor volume and plasma prolactin concentration in order to evaluate the efficacy of quinagolide (Norprolac) in patients with prolactinoma resistant to ergot dopamine agonists. PATIENTS AND METHODS: One hundred seven patients (46 men and 61 women) from 27 centers were included in the statistical analysis. All had previously been treated with a dopamine agonist (bromocriptine). Fifty-five patients had undergone surgery before being administered quinagolide: 17 of the patients had also received radiotherapy (before and after the initiation of treatment with quinagolide in 14 and 3 cases respectively). Quinagolide was given at doses ranging from 75 to 750 microg daily and continued for more than one year for 84 patients. RESULTS: The prolactin level returned to normal after a mean interval of 9.8 1.6 months (1-48) in 47 of the 107 patients (44%) using a mean dose of quinagolide of 259 32.7 microg/d (75-750). The plasma prolactin concentration had already been normalized using bromocriptine in three patients. The variation in tumor volume was assessed in 82 patients since 8 had no residual tumor post-operatively and 17 had received radiotherapy: at least partial regression of the tumor was noted in 25 (30.8%), including 16 (19.5%) with a more than 50% decrease in the remaining tumor. The mean time taken to observe the anti-tumoral effect was 16.8 3.1 months (3-78) using a mean dose of quinagolide of 255.4 37.8 microg/d d (75-750). The following predictive indicators were identified concerning the efficacy of quinagolide: a pre-quinagolide prolactin level of<300 ng/ml in the group of patients whose plasma prolactin concentration was normalized, and a mean decrease in prolactin of 619 ng/ml in the group of patients showing a reduction in tumor volume treated with quinagolide for 3 months. Side effects (nausea, vomiting, hypotension) were generally mild and were observed in 51 patients (47.6%). Only 11 (10.2%) of patients had to discontinue treatment because of adverse reactions. CONCLUSION: An anti-tumoral effect was noted in 30.8% of patients and occurred within an interval of less than 2 years in 80% of cases at a dose of 300 microg/d. Normalization of the plasma prolactin concentration was obtained in 44% of cases and occurred in less than one year in 80% of patients at a dose of 300 microg/d. Quinagolide is a useful drug and from now on should be prescribed as first-line treatment for patients presenting with bromocriptine-resistant prolactinoma.     

EFFECT OF ORAL CONTRACEPTIVES ON SERUM PROLACTIN: A LONGITUDINAL STUDY IN 126 NORMAL PREMENOPAUSAL WOMEN

A prospective longitudinal study was carried out in 126 normal premenopausal women aged 18-34 years to determine the effect of oral contraceptives containing less than 50 micrograms of oestrogen on serum prolactin concentration. The mean prolactin concentration in patients receiving oral contraceptives (n = 80) rose from a control level of 8.9 ng/ml to 10.2 ng/ml at 3 months (P less than 0.05) and 10.9 ng/ml at 12 months (P less than 0.001). In a parallel group of patients (n = 46) who used intrauterine devices for contraception, no significant change in serum prolactin concentration was observed over the same period. It is concluded that currently available oral contraceptives have a small but significant stimulatory effect on prolactin secretion in normal women.     

Heart failure in the "oldest old": clinical and echocardiographic insights

While the incidence and prevalence of heart failure (HF) increase markedly with age, few studies have included data on a large series of patients aged 85 years and older. Clinical and echocardiographic data from 533 patients admitted to a tertiary care hospital for acute HF were obtained. Data from the oldest old (>or=85 years; n=252; mean age, 91.9+/-3.6 years) were compared with data from those aged 65 to 74 years (n=123; mean age, 70.1+/-2.8 years) and 75 to 84 years (n=158; mean age, 79.4+/-2.9 years). Echocardiographic data were consistent with hypertensive remodeling. The proportion of patients with HF and a preserved left ventricular ejection fraction was greatest in the oldest patients (61%) in comparison to patients aged 65 to 74 years (48%) and 75 to 84 years (48%). Approximately three-fourths of the oldest patients were women, and two-thirds of women had a left ventricular ejection fraction >or=50%.     

HYPOTHALAMO-PITUITARY OVARIAN FUNCTION IN THIRTY-ONE WOMEN WITH CHRONIC ALCOHOLISM

A study of hypothalamo-pituitary function was carried out in chronic alcoholic women aged 29–66 years, with chronic pancreatitis or cirrhosis of the liver. Amenorrhoea was present in most of them (67%). The hormonal investigation included assessment of basal plasma steroids, gonadotrophin and prolactin values, followed by an anterior pituitary function test. Clomiphene stimulation and/or hCG tests were performed. The subjects were divided into four groups according to their oestrogen status on the one hand, and the baseline gonadotrophin concentration on the other. Results were compared with two control groups composed of twelve healthy post-menopausal women and ten normal women of reproductive age. Five different patterns of hypothalamo-pituitary ovarian activity could be distinguished: post-menopausal women (eight), perimenopausal women (eight), hypothalamic amenorrhoea (five), anovulation (four) and inadequate luteal phase (six). A normal peri- or post-menopausal hormonal profile was found in most (77%) chronic alcoholics of more than 45 years of age. In contrast, 84% of patients of reproductive age had functional hypothalamic disorders. These observations suggest that chronic alcoholism affects sexual function at the hypothalamo-pituitary level chiefly during the reproductive period. The pathogenesis of these endocrine changes is not clear. The relative importance of ethanol consumption, liver damage and non-specific factors such as nutritional status and chronic illness are discussed.     

Acquired prolactin deficiency indicates severe hypopituitarism in patients with disease of the hypothalamic-pituitary axis

OBJECTIVE: Prolactin deficiency has been the subject of many scientific studies, but there is a paucity of information regarding prolactin deficiency in humans. In this report, adults with disease of the hypothalamic-pituitary axis (HPA) were studied to determine the prevalence of severe acquired prolactin deficiency (APD) and the pathophysiological characteristics associated with it. PATIENTS AND METHODS: APD was defined as a serum prolactin level persistently below the detection limit of the assay, i.e. less than 50 mU/l (normal range: male 85-444, female 85-530). Patients with a diagnosis of acromegaly, prolactinoma or with congenital or drug induced prolactin deficiency were excluded. Three hundred and sixty-nine patients (190 women, age range 17-79 years) with disease of the HPA, meeting the specified criteria were identified. RESULTS: Twenty-two (13 women, age range 29-76 years), showed evidence of APD. Thirteen of the 22 patients with APD had been treated for Cushing's disease. In all, 62 patients treated for Cushing's disease were identified, resulting in a prevalence of APD in treated Cushing's disease of 20.97%. Excluding treated Cushing's disease, the prevalence of APD in the remainder of the cohort was 2.93%. Nineteen patients with APD (86.4%) and 183 without APD (52.7%) underwent surgery in the region of the HPA (P = 0.0042). In contrast, nine patients with APD (40.9%) and 283 without APD (80.4%) had received radiotherapy, with fields which included the HPA (P < 0.001). No patient with isolated APD was identified. All patients with APD had evidence of severe GH deficiency (GHD) with a peak GH response to provocative stimuli of < 1.6 mU/l and a median IGF-I standard deviation score (SDS) of -4.85 (quartiles -9.56 to -2.80). Of the 13 patients with APD and Cushing's disease, all were gonadotrophin and TSH-deficient, six were adrenocorticotropic hormone (ACTH)-deficient and six (46.1%) had cranial diabetes insipidus (CDI). Of the remaining nine patients with APD, total anterior pituitary hormone failure was present in all and CDI was present in two (22.2%). CONCLUSIONS: The presence of APD indicates severe hypopituitarism in adults with HPA disease. It is universally associated with severe GHD. It is more common after surgery to the HP region. It has a low overall prevalence except in patients surgically treated for Cushing's disease.     

Comparison of the cardiotoxicity of ethanol in women versus men.

Subclinical left ventricular (LV) dysfunction is a common occurrence in alcoholic men but has been claimed to be absent or very rare in alcoholic women. M-mode echocardiography was performed to study LV size, mass and systolic function, and Doppler ultrasound to study LV filling in 14 chronic female alcoholics aged 24 to 48 years and in 2 age-matched control groups consisting of 17 healthy women and 22 alcoholic men. Compared with healthy women, female alcoholics had no differences in heart rate or blood pressure but a shorter LV end-diastolic diameter (mean +/- standard deviation, 46 +/- 4 vs 48 +/- 3 mm, p less than 0.05), lower fractional shortening (31 +/- 6 vs 34 +/- 3%, p less than 0.05), increased wall thickness to radius ratio (0.43 +/- 0.08 vs 0.37 +/- 0.05, p less than 0.05), reduced peak early diastolic transmitral velocity (45 +/- 11 vs 68 +/- 7 cm/s, p less than 0.001), reduced deceleration of the early diastolic velocity (-274 +/- 69 vs -572 +/- 107 cm/s2, p less than 0.001), and an increased atrial filling fraction (35 +/- 12 vs 27 +/- 5%, p less than 0.05). Although alcoholic men had a longer duration of heavy drinking than alcoholic women (median 19 vs 5 years, p less than 0.001), and a higher systolic blood pressure (140 +/- 17 vs 120 +/- 17 mm Hg, p less than 0.001), there were no statistically significant differences between the sexes either in LV diameters, wall thickness or mass normalized to body area, or in indexes of systolic or diastolic LV function.(ABSTRACT TRUNCATED AT 250 WORDS)     

Fracture thresholds in osteoporosis: implications for hormone replacement treatment.

The bone mineral densities of the lumbar spine and femoral neck were determined by dual energy chi ray absorptiometry in 110 women aged 40-82 years (average 65 years) with spinal osteoporosis who had had at least one atraumatic vertebral compression fracture and in 1026 normal women aged 40-79 years (average 52 years). The women with osteoporosis showed a significant decrease in bone mineral density (BMD) at the lumbar spine and femoral neck compared with age matched normal women (sixth decade of life -26% spine, -23% femoral neck; seventh decade -26% spine, -16% femoral neck). The fracture threshold, defined as the 90th centile of spinal BMD for women with osteoporosis, was 0.81 g/cm2 at the lumbar spine and 0.656 g/cm2 at the femoral neck. Five per cent of normal women aged 40-49 years, 20% aged 50-59 years, and 45% aged 60-69 years had a BMD below this threshold. To maintain the bones of women above the fracture threshold until the age of 70 years about 50% of postmenopausal women need hormone replacement therapy. However, if the BMD is to be kept above the fracture threshold for a women's lifetime, e.g. until the age of 80-90 years, then most women will need treatment, though for various lengths of time depending on their initial BMD. Measurements of BMD in postmenopausal women currently help in identifying the risk of osteoporotic fractures but in the lifetime assessment of risk in a single subject they may have a more important role in deciding the duration of hormone replacement therapy.     

Effect of hormone replacement therapy on age-related increase in carotid artery intima-media thickness in postmenopausal women

The aim of this study was to determine the changes in carotid artery intima-media thickness as measured by B-mode ultrasound in postmenopausal women receiving hormone replacement therapy (HRT) or not. One hundred and fifty-nine healthy postmenopausal women aged 45-65 years were recruited from our menopause clinic. All the selected women were free of cardio-vascular diseases and had no cardio-vascular risk factors. None of the women were receiving lipid-lowering or antihypertensive drugs. Because carotid artery intima-media thickness was shown to be strongly and positively correlated with age in women aged 55 years and older but not before, women were divided into four groups according to age (<55 vs. > or =55 years) and use of HRT (current users vs. never users). All the treated women received non-oral 17beta-estradiol with a non-androgenic progestin and had started HRT within the first year after menopause. Scanning of the right common carotid artery was performed with a B-mode ultrasound imager and thickness of the intima-media complex as well as luminal diameter of the artery were determined using an automated computerized procedure. Within each age group (i.e. <55 or > or =55 years), women had comparable demographic characteristics and only differed by HRT use. Long-term treated women had significantly lower total cholesterol levels than untreated women (P=0.005). Triglycerides, low-density lipids (LDL)-cholesterol and high-density lipids (HDL)-cholesterol levels, systolic and diastolic blood pressure were not significantly different between users and non-users. In women <55 years, no significant difference in carotid intima-media thickness was found between current users (mean 2.5+/-1.4 years) and non users. In older women, the mean values of carotid intima-media thickness were significantly smaller in current users (mean 6.9+/-3.3 years) than in never treated women: 0.50+/-0.05 versus 0.56+/-0.07 mm, P<0.0001. Carotid artery intima-media thickness was significantly correlated to age in never users (r=0.5, P<0.0001) but not in women who were currently receiving HRT (r=0.2, ns). These findings suggest an apparent protective effect of long-term HRT on age-related thickening of the intima-media of the right common carotid artery. This may contribute to explain the apparent cardio-protective effect of HRT after the menopause.     

Treatment of macroprolactinoma with cabergoline: a study of 85 patients

OBJECTIVE Cabergoline is now established as an effective and well-tolerated treatment for prolactinoma. However, there are relatively few published data on the treatment of macro-, as opposed to micro-, prolactinoma. We have therefore reviewed the efficacy and safety of cabergoline in the treatment of patients with prolactin-secreting macroadenomas treated on a compassionate basis. STUDY DESIGN AND PATIENTS Eighty-five patients with prolactin-secreting macroadenomas were treated with cabergoline 0.25 to 10.5 mg per week (median 1 mg) given in one to seven doses. Treatment durations ranged between 3 months and 8 years. Sixty-five patients (32 intolerant, 16 resistant) had been treated previously with other dopamine agonists. Pretreatment prolactin levels ranged between 80 and 8300 μg/l and tumour maximum diameters were between 11 and 42 mm. MEASUREMENTS Serum prolactin, visual fields if initially abnormal, occurrence of menses or return of libido and potency, blood chemistry and adverse events were assessed at 1 month and then at 3-month intervals during treatment. Pituitary computed tomography or magnetic resonance imaging was usually repeated at 3 months and 1 year, then yearly, in most patients (n=62). RESULTS Normalization of prolactin levels was achieved in 52 patients (61.2%) and a prolactin decrease of at least 75% of pretreatment values occurred in 24 others (28.2%). Of the 20 de novo patients, 17 had prolactin normalized and the remainder had at least 75% reduction. Disappearance of tumour image was found in eight of 62 evaluable patients (12.9%) and reduction of the largest diameter by at least 25% in another 33 (53.2%), with an overall success rate of 66.1%; among the 17 evaluable de novo patients the success rate was 82.3%. Fifteen of 21 patients who failed to show tumour shrinkage had previously demonstrated resistance/intolerance to other prolactin-lowering treatments. Of the 12 patients with visual field defects at baseline, six normalized and two showed an improvement. Menses resumed during cabergoline treatment in 79.5% of premenopausal women. Restoration of potency was reported by seven of eight evaluable men. Adverse events were recorded in 24.7% of cases, four of whom (4.7%) discontinued treatment. CONCLUSIONS Although the present data were not obtained in a formal study we conclude that cabergoline is an effective and well-tolerated treatment for macroprolactinoma patients.