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Biomedical subjects

R Fabbri

Publications and source records attributed to R Fabbri.

At least 19 recordsLinked to original sources

Longitudinal evaluation of the different gonadotropin pulsatile patterns in anovulatory cycles of young girls.

We studied 13 adolescents (mean gynecological age 29.2 +/- 14.1 months) with anovulatory cycles and 7 women with ovulatory cycles (mean gynecological age 33.1 +/- 15.3 months) as a control group. Adolescents with anovulatory cycles were grouped on the basis of mean plasma LH values: group 1 (n = 7) with high LH values, and group 2 (n = 6) with normal LH values. In all women plasma gonadotropin concentrations were measured at 10-min intervals for 8 h on day 4 of the cycle. Pulsatile gonadotropin secretion was also studied in each subject a second time 40 months later, to establish the outcome of the different pulsatile patterns. Group 1 had more frequent and greater LH pulses than the other two groups (which were similar) and had the highest plasma 17 beta estradiol, testosterone, androstenedione, and 17 hydroxyprogesterone concentrations. Longitudinal control showed that: in group 1, three subjects out of seven acquired ovulatory cycles and there was a fall in mean LH plasma levels (30 +/- 5 vs. 9 +/- 4 IU/L; P less than 0.01), number of pulses (8.3 +/- 1.5 vs. 5 +/- 0; P less than 0.025), mean amplitude (13 +/- 3 vs. 5 +/- 2 IU/L; P less than 0.02) and an increase in interpulse interval (56 +/- 10 vs. 91 +/- 6 min; P less than 0.01). In four subjects anovulatory cycles persisted and the LH pulsatile profile remained unchanged. In group 2, five subjects out of six acquired ovulatory cycles, but there were no significant changes in the number of pulses (6 +/- 1 vs. 6 +/- 2; P = NS), interpulse interval (97 +/- 30 vs. 85 +/- 30 min; P = NS), or amplitude (5 +/- 2 vs. 4 +/- 2 IU/L; P = NS). The results indicate that: 1) anovulatory young women with early normal plasma LH values have an adequate GnRh pulsatile pattern which will easily lead to ovulation; 2) anovulatory young women with high LH plasma values may have a reproductive system blocked in a pathological condition, similar to that observed in polycystic ovary syndrome; 3) only few subjects with high plasma LH values are able to achieve ovulation and normalize LH pulsatile pattern as a consequence of a new mode of GnRh release.

Adolescent

The relative contribution of androgens and insulin in determining abdominal body fat distribution in premenopausal women.

To investigate the relative contribution of insulin and sex hormones in determining the abdominal pattern of fat distribution in premenopausal women, five groups of age-matched subjects were examined: Group 1 consisted of 14 normal weight eumenorrheic women (NO); Group 2 of 9 obese eumenorrheic women (OB); Group 3 of 14 normal weight hyperandrogenic women with polycystic ovary syndrome (NO-HA); Group 4 of 10 obese hyperandrogenic women with polycystic ovary syndrome (OB-HA) and, finally, Group 5 of 10 obese hyperandrogenic women with polycystic ovary syndrome and acanthosis nigricans (OB-HA-AN). Both the two normal weight groups and the three obese groups were matched for body mass index values. Sex hormone pattern showed significantly higher LH and testosterone levels in hyperandrogenic women with respect to NO and OB women but obese hyperandrogenic groups (OB-HA and OB-HA-AN) presented significantly lower LH concentrations than NO-HA. Fasting and glucose-stimulated insulin levels were significantly higher in OB than NO, in OB-HA and OB-HA-AN than in OB and NO-HA, and in OB-HA-AN than in OB-HA, without any significant difference between OB and NO-HA. Body fat distribution, expressed by the waist to hip ratio (WHR), showed progressively higher values (p less than 0.01) from NO to OB, NO-HA, OB-HA and, particularly, OB-HA-AN women. Determination coefficients r2 obtained from simple regression analysis showed that the sum of insulin values during the glucose tolerance test and testosterone levels had a more significant power in determining WHR variability.(ABSTRACT TRUNCATED AT 250 WORDS)

Abdomen

Effect of obesity and body fat distribution on sex hormones and insulin in men.

To investigate the relationship between body fat distribution, sex hormones, and hyperinsulinemia in male obesity, we examined 52 obese men (body mass index [BMI], 35.0 +/- 6.1, mean +/- SD) and 20 normal-weight controls. Their waist to hip circumference ratio (WHR), which was used as an index of fat distribution, was 0.985 +/- 0.052 and 0.913 +/- 0.061 (P less than .005), respectively. Compared with controls, obese men presented significantly lower levels of total (357 +/- 132 v 498 +/- 142 ng/dL; P less than .005) and free testosterone (14.2 +/- 2.9 v 17.1 +/- 2.6 pg/mL; P less than .05) and sex hormone-binding globulin (SHBG; 41.7 +/- 31.9 v 66.2 +/- 18.6 nmol/L; P less than .001) without any significant difference on the other sex steroid or on gonadotropin concentrations. Fasting and glucose-stimulated insulin and C-peptide levels were significantly higher in obese than in controls, and in obese with the WHR value greater than 0.97 (corresponding to the distribution median) than in those with WHR lower or equal to 0.97. BMI was negatively correlated with testosterone (P less than .005), free testosterone (P less than .01), and SHBG (P less than .001) and positively with fasting (P less than .001) and glucose-stimulated (P less than .005) C-peptide concentrations, whereas no relationship was found between these variables and WHR values. On the contrary, WHR was significantly correlated with fasting and post-glucose insulin levels (P less than .05), but not with those of sex steroids.(ABSTRACT TRUNCATED AT 250 WORDS)

Adipose Tissue

Comparison of monoclonal immunocytochemical and immunoenzymatic methods for steroid receptor evaluation in breast cancer.

The production of monoclonal antibodies against estrogen receptor (ER) and progesterone receptor (PR) has permitted the development of the enzyme immunoassay (EIA) and immunocytochemical assay (ICA) for steroid receptor determination. The results obtained with these two techniques, using the same monoclonal antibodies, were compared in a large series of breast carcinomas (187 for ER and 100 for PR). The correlation between these methods was significant for ER (rs = 0.54) and PR (rs = 0.55) (P less than 0.001) but was lost when the receptor concentrations determined by EIA were less than or equal to 15 and less than or equal to 30 fmol/mg protein for ER and PR, respectively. When these values are considered as cutoffs, the concordance between the two methods was 84.5% for ER and 73% for PR. An analysis of discordant results revealed that low epithelial cellularity generally was present in ICA-positive, EIA-negative specimens, whereas only focal positivity with ICA, or positivity of only normal peripheral mammary ducts and lobules, frequently was found in ICA-negative, EIA-positive tumors. In conclusion, there is good correlation between the results obtained by EIA and ICA methods for detection of ER and PR. The authors suggest that biochemical and histochemical methods for steroid receptors could be considered complementary and used together for the analysis of breast cancer.

Adult

Ketoconazole therapy for women with acne and/or hirsutism.

The effects of ketoconazole, a synthetic imidazole derivate, were evaluated in 42 women affected by acne (17 cases) and/or hirsutism (36 cases) treated with 400 mg/day for 3-6 months. Androstenedione, total and free testosterone, 5 alpha dihydrotestosterone and dehydroepiandrosterone levels progressively dropped during treatment while 17 alpha hydroxyprogesterone, estradiol, ACTH, cortisol, LH and FSH levels increased. Dehydroepiandrosterone sulfate decreased only towards the end of treatment, while estrone, sex hormone binding globulin, and PRL remained unchanged. Daily mean +/- SD rate of hair growth, measured by a special image analysis processor, decreased within 3 months of therapy from 0.258 +/- 0.058 to 0.184 +/- 0.039 mm/day (P less than 0.02) and mean +/- SD hair diameter from 0.123 +/- 0.015 to 0.110 +/- 0.013 mm (P less than 0.05) together with decreasing hormone levels. The therapeutic effects of ketoconazole on hirsutism was evident at 6 months in only 14 subjects, while no significant change in hirsutism score was recorded in 22 women who failed to complete the therapy. Acne improved in all cases. Several side effects and complications arose during treatment, such as headache, nausea, loss of scalp hair, hepatitis, and biochemical changes. Even though ketoconazole improves hyperandrogenism, only selected patients are eligible for treatment as scrupulous monitoring is required.

Acne Vulgaris

Endocrine and ovarian parameters at various frequencies of ovulation in adolescents.

We assessed ovarian and endocrine function in 86 adolescents over a six month period. Postmenstrual estrone (E1) and estradiol-17 beta (E2) levels, premenstrual FSH levels and pre- and postmenstrual LH, testosterone (T) and androstenedione (A) levels decreased as the frequency of ovulation increased, while premenstrual E2, progesterone (P) and 17 alpha-hydroxyprogesterone levels increased. Both right and left ovarian volume and the per cent of multifollicular ovaries decreased with an increase in the frequency of ovulation. In the premenstrual phase P values correlated significantly with frequency of ovulation for FSH (r = -0.43: P less than 0.001), LH (r = -0.36: P less than 0.01), T (r = -0.31: P less than 0.05) and A (r = -0.26: P less than 0.05). Our data suggest that in the postmenarcheal period the progressive loss of immature endocrine and ovarian characteristics (high LH, FSH, and androgen levels and enlarged, multifollicular ovaries) is linked to an increasing number of ovulations. Progesterone plays a major role in the development of cyclic function characteristic of adult maturity.

17-alpha-Hydroxyprogesterone

Uterine development and endocrine relationships after menarche.

Uterine volume and ovarian/uterine ratio during the first 6 postmenarchal years in 143 women were compared with an adult control group. Plasma gonadotropins and sex steroids were also correlated with uterine volume in adolescents. Uterine volume increased progressively and correlated positively with advancing postmenarchal (r = 0.24; p less than 0.05) and chronologic (r = 0.23; p less than 0.05) age. However, normal adult uterine volume was not yet reached by the highest postmenarchal (6 years) and chronologic (18 years) age. The ovarian/uterine ratio decreased gradually with increasing postmenarchal age but was always higher (0.22) than that of control subjects (0.12). Uterine volume correlated positively with plasma estradiol (r = 0.25; p less than 0.05) and dehydroepiandrosterone (r = 0.22; p less than 0.05) and its sulfate (r = 0.22; p less than 0.05) levels. This study indicates that the uterus continues to grow after menarche in conjunction with increasing hormone levels.

Adolescent

Recurrent familial brachial plexus palsies as the only clinical expression of 'tomaculous' neuropathy.

Two familial cases of recurrent brachial plexus are described and similar episodes were noticed in other members of the family. Electrophysiological investigations found impaired motor and sensory nerve conduction velocity in affected and nonaffected members. Tomaculous neuropathy was found at biopsy of peripheral nerve in more than 40% of dissected fibers. In addition, two affected members showed a reduced interpupillary distance, i.e. the most common dysmorphic feature found in the hereditary neuralgic amyotrophy (HNA). A literature review showed only two other instances of recurrent familial brachial plexus palsies as the only manifestation of tomaculous neuropathy (hereditary neuropathy with liability to pressure palsy, HNPP). The dysmorphic feature found in our cases in addition to the clinical, electrophysiological and anatomical data support the hypothesis that these cases of HNPP and the HNA may represent the same disease.

Adult

Clinical and hormonal characteristics of obese amenorrheic hyperandrogenic women before and after weight loss.

We studied a group of obese hyperandrogenic amenorrheic women to determine the effects of weight loss on anthropometry, hormonal status, menstrual cycles, ovulation, and fertility. Fourteen women had polycystic ovaries, two the hyperandrogenism-insulin resistance-acanthosis nigricans syndrome, one hirsutism of adrenal origin, and three idiopathic chronic anovulation. The duration of amenorrhea before the study ranged from 3-17 months [mean, 8.6 +/- 4.5 (+/- SD)]. All women ate a hypocaloric diet for a period of 8.0 +/- 2.4 months. Weight loss ranged from 4.8 to 15.2 kg (mean, 9.7 +/- 3.1 kg; 1.35 +/- 0.56 kg/month) and the waist to hip ratio, which was used as a measurement of body fat distribution, decreased from 0.86 +/- 0.1 to 0.81 +/- 0.06 (P less than 0.0001). The women's mean plasma testosterone and LH concentrations decreased significantly (P less than 0.001 and P less than 0.005, respectively). A significant positive correlation was found between the decreases in plasma testosterone levels and the decreases in glucose-stimulated insulin levels. Moreover, the decreases in the waist to hip ratio correlated positively with the decreases in glucose-stimulated insulin levels and inversely with the decreases in plasma 17 beta-estradiol. No relationships were found between weight loss and the changes in plasma insulin, steroid, and gonadotropin concentrations. The responsiveness to the weight reduction program was evaluated by comparing the number of menstrual cycles during the study period with the number reported before it. Eight women had significantly improved menstrual cyclicity (responders), while 12 did not (nonresponders). The clinical characteristics and hormone values were similar in responder and nonresponder women. In the group as a whole, 33% of the menstrual cycles during the study were ovulatory, and 4 pregnancies occurred. Hirsutism improved significantly in more than half of the women, as did acanthosis nigricans when present. We conclude that weight loss is beneficial in all obese hyperandrogenic women regardless of the presence of polycystic ovaries, the degree of hyperandrogenism, and the degree and distribution of obesity.

Adult

Weight loss and sex steroid metabolism in massively obese man.

To evaluate the effect of weight loss and diet therapy on plasma sex hormone behavior in male obesity, 9 men with a BMI of 43.4 +/- 6.3 participated in an 8-week semistarvation program [whose energy content ranged from 320 to 500 k calorie/day (proteins 44 to 60 g and carbohydrates 54 to 81 g per day)] followed by a two-week hypocaloric (1000 k calorie/day) refeeding. In basal conditions, obese patients presented higher estrogen and lower dehydroepiandrosterone sulphate, testosterone (total and free) and sex-hormone binding globulin concentrations with respect to a group of control normal-weight subjects. Cumulative weight loss was 23.9 +/- 3.6 kg after semistarvation and 24.4 +/- 4.8 kg after refeeding (p = NS). A significant increase in testosterone, free testosterone and dehydroepiandrosterone sulfate was observed throughout the study, irrespective of dietary intake. A transient increase occurred in estrone levels while 17B-estradiol did not change. Gonadotropins and sex-hormone binding globulin values remained unaltered. No relationship was found between sex hormones and dietary energy content or composition. Daily urine free cortisol, which was used as a parameter of adrenal function, fell approximately 50% during semistarvation but returned to baseline values after refeeding. These results show that in massively obese patients weight loss per se may partially reverse sex hormone abnormalities but not sex-hormone binding globulin concentrations. It remains to be determined whether the return to "normal weight" can normalize steroid metabolic derangements in the obese man.

Adult

Episodic pulsatile secretion of FSH, LH, prolactin, oestradiol, oestrone, and LH circadian variations in polycystic ovary syndrome.

Pulsatile secretion of LH, FSH, PRL, oestradiol and oestrone was studied in a group of 16 patients with micropolycystic ovary syndrome (PCOS) and compared with that of normal ovulatory women in the fifth to sixth day of the cycle. Hormone concentrations were measured at 10 min intervals for 8 h starting at 0930 h. In seven subjects, the study was prolonged for 24 h, with 20 min interval samples, in an attempt to evaluate the circadian rhythm of LH by cosinor analysis. Significant fluctuations occurred in the concentration of each hormone. Values shown are mean +/- SD. PCOS subjects had high LH mean values (27.9 +/- 5.9 IU/l) (P less than 0.005). LH pulse amplitude was higher than controls (11.6 +/- 3.7 IU/l versus 5.2 +/- 1.8 IU/l; P less than 0.005) while no consistent changes in frequency or interpulse interval (62.0 +/- 10.7 min versus 65.8 +/- 19.2 min; P = NS) were found. A mean of 4.8 +/- 1.2 pulses of FSH occurred in 8 h and the mean pulse amplitude was 2.68 +/- 1.11 with no differences from controls. All patients were normoprolactinaemic. A mean of 5.5 +/- 1.9 pulses occurred in 8 h, the interpulse interval was 76.1 +/- 14.4 min and the amplitude was 2.87 +/- 0.76 ng/ml and there were no significant differences from controls; 75% of PRL pulses showed a temporal relationship with LH pulses. Oestrone mean basal values were higher in PCOS (47.2 +/- 12.5 pg/ml) than controls (32.0 +/- 9.9 pg/ml; P less than 0.02), while no differences were observed as regards oestradiol. Oestradiol pulse amplitude was nearly the same as oestrone (43.6 +/- 18.8 pg/ml and 37.7 +/- 16.1 pg/ml, respectively); 6.0 +/- 2.2 pulses and 6.0 +/- 1.6 pulses occurred in 8 h with an interpulse interval of 81.1 +/- 27.1 min and 71.8 +/- 11.1 min, respectively. Sixty-five per cent of LH pulses were followed by an oestradiol and oestrone peak. The mean time of the appearance was 17 +/- 15 min and 25 +/- 23 min, respectively. In the PCOS group a consistent 24 h rhythm in mean plasma LH levels was found with the highest hormone values at 1720 h (P less than 0.05) unrelated to apparent sleep and different from that of adult women. Pulse frequency showed a significant slowing during the night with the longest interpulse interval at 0327 h (P less than 0.03) while no significant periodicity was observed in LH pulse amplitude.(ABSTRACT TRUNCATED AT 400 WORDS)

Adult

Evidence for a hypothalamic alteration of catecholamine metabolism in polycystic ovary syndrome.

The role of brain catecholamine (CA) activity in the neuroendocrine regulation of the GnRH-LH system in polycystic ovary syndrome (PCO) was investigated by high-performance liquid chromatography (HPLC) with electrochemical detector. We measured urinary dopamine (DA), noradrenaline (NA), adrenaline (A), vanillylmandelic acid (VMA), homovanillic acid (HVA), 3,4-dihydroxyphenylacetic acid (DOPAC) and total 3-methoxy-4-hydroxyphenylglycol (MHPG) levels in a group of 12 women with PCO before and during peripheral dopa-decarboxylase blockade, by carbidopa. HVA and DOPAC concentrations were significantly lower (P less than 0.001 and P less than 0.005, respectively) in PCO patients compared with twelve control subjects in early follicular phase, whereas total MHPG concentrations and MHPG/VMA ratio were significantly higher (P less than 0.005) in PCO patients. Moreover, HVA and DOPAC concentrations in PCO patients were similar to those of the control subjects in preovulatory phase, while MHPG concentrations remained higher in PCO patients (P less than 0.01). DA, NA, A and VMA concentrations were similar to those of control subjects in both phases of the cycle. During carbidopa administration the concentrations of all urinary CAs and metabolites were unchanged, except those of DA which dropped markedly (P less than 0.001). These data suggest that (1) an altered central catecholamine metabolism consisting of DA deficiency and NA excess is present in PCO, and (2) the site of DA deficiency may be located in the hypothalamus.

3,4-Dihydroxyphenylacetic Acid

Premature epiphyseal fusion and extramedullary hematopoiesis in thalassemia.

The main skeletal abnormalities in beta-thalassemia are widening of medullary spaces, rarefaction of bone trabeculae, thinning of cortical bone, and perpendicular periosteal spiculation. Premature epiphyseal fusion (PEF) and extramedullary hematopoiesis (EH) are found, though more rarely. The incidence of PEF and EH in 64 patients affected by beta-thalassemia is reported. The different incidence of such complications in thalassemia major and intermedia is reported, and a possible correlation with transfusion regimen is also considered.

Adolescent

Familial hypertrophy of masticatory muscles.

Three familial cases of idiopathic hypertrophy of the masticatory muscles are reported. The muscular enlargement was noted in late childhood or early adult life, was bilateral, insidious, painless and non-progressive. Electrophysiological and laboratory findings were normal in one case. CT examination, performed in two cases, showed homogeneous bilateral enlargement of masseter muscle bulk consistent with true hypertrophy. Two patients also showed congenital malformations. A review of the literature showed that this disorder is very rare.

Adolescent

Insulin as a factor of increased androgen production in women with obesity and polycystic ovaries.

To evaluate the possible role of moderate hyperinsulinemia on abnormal androgen secretion, we examined 4 age and weight-matched groups of obese subjects: 2 groups of women with normal menses whose fasting insulin (IRI) levels were less than or equal to 20 microU/ml (OB-I) or greater than or equal to 40 microU/ml (OB-I) and 2 groups of women with polycystic ovaries who were similarly grouped. All subjects underwent an oral glucose tolerance test, blood sex hormone determination and multiple LH determinations. Compared to OB, OB-PCO women showed significantly higher values of LH, androgen and estrogen concentrations. OB-I and OB-II showed similar hormonal patterns. On the contrary, OB-PCO-II presented significantly (p less than 0.05) higher androstenedione concentrations (348.7 +/- 129.9 ng/dl) (m +/- SD) than OB-PCO-I women (237.0 +/- 73.7 ng/dl). These differences were evident despite similar plasma LH concentrations. In conclusion, these results suggest that insulin may be a factor amplifying LH-dependent androgen secretion in hyperandrogenized women with obesity and PCO.

Androgens

Sex hormones in obese premenopausal women and their relationships to body fat mass and distribution, B cell function and diet composition.

We examined sex hormone blood concentrations in a group of 33 obese non-hirsute premenopausal women with normal menses and in 14 age-matched normal-weight controls, and evaluated their relationship with anthropometric parameters, dietary habits and insulin levels. Obese women showed lower than control sex hormone-binding globulin (24.9 +/- 14.6 vs 38.6 +/- 12.5 nmol/l; p less than 0.005) and 5 alpha-dihydrotestosterone (13.7 +/- 5.4 vs 18.2 +/- 4.8 ng/dl; p less than 0.005) values. Despite their consensual behavior, the correlation coefficient between 5 alpha-dihydrotestosterone and sex hormone-binding globulin was not significant in the obese while in controls it was 0.68 (p less than 0.01). This suggests that mechanisms operating to lower the plasma levels of these compounds may be regulated differently in obesity. Body Mass Index, per cent body fat and its distribution showed a highly significant negative correlation with sex-hormone binding-globulin and 5 alpha-dihydrotestosterone values. Insulin levels did not appear to be correlated with sex hormone values. On the contrary, in the obese women we found a highly significant correlation between dietary lipids and sex-hormone-binding-globulin levels (r = -0.54; p less than 0.005) and between dietary carbohydrates and estrone values (r = 0.47; p less than 0.005); all these relationships were independent of body weight. These results confirm that in premenopausal women obesity may be characterized by detectable changes in sex steroid metabolism and suggest a possible causal role not only of the excessive quantity of metabolically active adipose tissue but also of specific dietary factors.

Adult

Postmenarchal evolution of endocrine pattern and ovarian aspects in adolescents with menstrual irregularities.

Ninety-five adolescents with menstrual irregularities persisting since menarche were studied and the data analyzed in relation to gynecologic age. In each year, in the premenstrual phase, luteinizing hormone (LH), testosterone (T), and androstenedione (delta 4A) values were higher than those of adults. Estrone (E1), estradiol (E2), 17-hydroxyprogesterone (17-OHP), progesterone (P), and dehydroepiandrosterone (DHEA) and its sulfate (DHEAS) gradually increased up to adult values correlating with gynecologic age. By ultrasound, nearly half the ovaries were multicystic and ovarian volume was greater than that of adults in each gynecologic year. When the data were classified as ovulatory or anovulatory, ovulation appeared to be a dynamic process characterized by ovaries similar to those of adults and by increasing hormonal levels correlated to gynecologic age. By contrast, in anovulatory cycles, mean T, delta 4A, and LH values were stable in each year and constantly higher than in ovulatory cycles and adult controls. These findings suggest that, despite persistent irregular cycles, some adolescents normalize all endocrine and ovarian parameters toward maturity, while subjects with persistent irregular anovulatory cycles maintain marked hyperandrogenism, increasingly high LH values, and enlarged multicystic ovaries.

Adolescent