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Biomedical subjects

A R Genazzani

Publications and source records attributed to A R Genazzani.

At least 145 records · Page 8Linked to original sources
PubMed1998

Beta-endorphin response to oral glucose tolerance test in obese and non-obese pre- and postmenopausal women.

Beta-endorphin (beta-EP) is a neuropeptide involved in several brain functions, regulating the reproductive axis and behavioral changes. Estrogens play a modulatory role on circulating levels of beta-EP in women. Previous clinical studies have demonstrated high plasma beta-EP levels in obese subjects and increased beta-EP release after an oral glucose tolerance test (OGTT) in normal or obese women. The aim of the present study was to evaluate plasma beta-endorphin levels in response to an OGTT in pre- and postmenopausal obese and non-obese women, in order to investigate if the decrease in gonadal steroid levels at menopause could modify in a different manner the control of beta-endorphin release in response to glucose administration. A group of 24 normal women (age range 45-55 years) were included in the study. The patients were subdivided in four groups of six subjects each: group A, premenopausal women with body mass index (BMI) < 25 (control); group B, premenopausal women with BMI > 25 (obese); group C, post-menopausal women with BMI < 25 (control); group D, postmenopausal women with BMI > 25 (obese). All women were studied between 8.30 and 9.00 am, after overnight fasting, and underwent an OGTT. In obese premenopausal women, basal plasma beta-EP levels were significantly higher than in non-obese women (p < 0.01). In postmenopausal women, regardless of body weight, low basal plasma beta-EP levels were found. A significant increase in plasma beta-EP levels, at 30 and 60 minutes after oral glucose ingestion, was shown in control premenopausal women. No significant modifications to OGTT were shown in plasma beta-EP levels in the other three groups of women. In conclusion, while in premenopausal women the response of plasma beta-EP levels to OGTT is maintained, in postmenopause there is a lack of response to OGTT. This suggests that beta-EP release is dependent upon gonadal steroids, while it is only in part influenced by body weight.

Adult↗
PubMed1998

Contraception as prevention and therapy: sex steroids and the brain.

The brain is one of the specific target tissues for sex steroid hormones. Estrogens, progestins and androgens are able to induce several effects in brain areas of the central nervous system (CNS), through the binding with specific receptors. Specific receptors for gonadal steroids have been identified in the amygdala, hippocampus, basal forebrain cortex, cerebellum, locus ceruleus, midbrain rafe nuclei, glial cells, pituitary gland, hypothalamus and central gray matter. At the hypothalamic level, the principal target for sex steroids is those neurons producing the pulsatile release of the gonadotropin releasing hormone (GnRH), localized in the mediobasal hypothalamus and the arcuate nucleus. The GnRH release depends on the complex and co-ordinated interrelationships among gonadal steroids, pituitary gonadotropins and neuroactive transmitters, such as the noradrenaline, dopamine, opioid peptides (beta-endorphin), acetylcholine, serotonin, gamma-aminobutyrric acid, corticotropin releasing hormone and neuropeptide Y. The interplay of these control mechanisms is governed by peripheral feedback signals; as well as the input from higher brain centers they may modify the GnRH secretion. The anterior pituitary lobe is the best known target tissue for endogenous or exogenous sex steroid hormones, because it is possible to detect luteinizing hormone (LH) and follicle stimulating hormone (FSH) levels in blood, as the expression of the pituitary cells' activity. The synthesis and release of FSH and LH by the gonadotropic cells depend upon the peripheral control of gonadal hormones and the GnRH hypothalamic release. In summary, during a woman's reproductive life, the interaction between neurotransmitters, neuropeptides and gonadal hormones modulates the hypothalamo-pituitary-gonadal axis by acting selectively on the synthesis and release of GnRH and of pituitary gonadotropic hormones. The increased use of oral contraceptives in the last 30 years and, in general, of sex steroid hormone derivative therapies, has led to the study of the biochemical and metabolic properties of the different progestin molecules available in hormonal therapies by focusing attention on the interactions between estrogens and progestins in the modulation of the hypothalamo-pituitary-gonadal axis. The different kinds of estrogen and progestin molecules used in oral contraceptives inhibit the ovulatory process and may interfere with other sex steroid hormone receptors, thus exerting multiple effects in each target tissue.

Androgens↗
PubMed1997

Neuroendocrine effects of different estradiol-progestin regimens in postmenopausal women.

OBJECTIVE: New regimens and routes of administration of hormonal replacement therapy (HRT) in climateric women are becoming available. Since there is no information on the neuroendocrine effects of sequential combined treatment with 17 beta-estradiol and a progestin, the present study evaluated the neuroendocrine, clinical vasomotor and psychological changes before and after different sequential combined HRT regimens (17 beta-estradiol plus nomegestrol acetate, or cyproterone acetate, or vaginal progesterone). Vasomotor and behavioral effects were evaluated by using the Kupperman score, while changes in plasma endorphin (beta-END) levels were used as marker of neuroendocrine effects. METHODS: Postmenopausal women (n = 30) were randomly divided into three groups (ten women for each group); all women received continuous 17 beta-estradiol (50 mg, transdermal) and each group was sequentially treated with different progestins for 12 days/month: group A, cyproterone acetate (5 mg p.o.); group B, nomegestrol acetate (5 mg p.o.); and group C, progesterone (100 mg, vaginal cream). A group of healthy fertile women (n = 8) served as control. Before and after 6 months of HRT, postmenopausal women underwent an evaluation of subjective Kupperman score and two neuroendocrine tests: (a) naloxone (4 mg i.v.) and (b) clonidine (1.25 mg i.v.). Plasma beta-END levels were measured before and at 15, 30, 45, 60 and 90 min after drug injection. Control women were studied by administering the two neuroendocrine tests only once. RESULTS: Postmenopausal women before HRT showed a pathological Kupperman and no changes of plasma beta-END levels in response to the clonidine and naloxone tests score. On the contrary the increase was significant in healthy women. In each of the three groups of treated women both naloxone and clonidine tests induced a significant increase in plasma beta-END levels (P < 0.01). After 6 months of HRT, an improvement of vasomotor and psychological symptoms was shown by a decrease of Kupperman score. CONCLUSIONS: The present study indicates that sequential treatment with transdermal 17 beta-estradiol and progestin, no matter which progestin was used, restores the beta-END release, improves vasomotor and psychological symptoms.

Administration, Cutaneous↗
PubMed1997

Preoperative D-dimer plasma assay is not a predictor of clinical outcome for patients with advanced ovarian cancer.

D-dimer (DD) plasma levels are significantly higher in patients with ovarian cancer than in those with benign ovarian masses. The aim of this paper is to assess whether preoperative DD plasma assay has a prognostic relevance for 35 patients with advanced ovarian cancer receiving platinum-based chemotherapy. Preoperative DD levels ranged from 162 to 3720 ng/ml. The 25, 50, and 75% quartiles of DD levels were 1600, 1894, and 2069 ng/ml, respectively. Preoperative DD levels correlated neither with the common clinicopathological prognostic variables nor with the disease status at the end of first-line chemotherapy. Survival was related to residual disease after initial surgery (> or =2 cm vs <2 cm, P = 0.003), but not to preoperative DD levels. In conclusion, the present data seem to show that preoperative DD plasma assay is not a predictor of clinical outcome for patients with advanced ovarian cancer.

Adult↗
PubMed1997

Ipriflavone prevents the loss of bone mass in pharmacological menopause induced by GnRH-agonists.

In a double-blind, placebo controlled study, ipriflavone (600 mg/day, T.D.D.) or identical placebo tablets were given with 500 mg/day of calcium to patients treated with the gonadotropin hormone-releasing hormone agonist (Gn-RH-A) leuproreline acetate, 3.75 mg every 30 days for 6 months. In placebo-treated subjects (n = 39), urinary hydroxyproline excretion and plasma osteocalcin levels showed a significant (P < 0.01 and P < 0.05, respectively) increase, whereas spine bone density and total body bone density significantly (P < 0.001 and P < 0.05, respectively) decreased after 3 and 6 months of GnRH-A administration. Conversely, in the ipriflavone-treated group (n = 39), no significant difference in bone markers and bone density was evidenced. These data indicate that ipriflavone can restrain the bone remodeling processes and prevent the rapid bone loss that follows medically induced hypogonadism.

Absorptiometry, Photon↗
PubMed1997

A long-term treatment with gonadotropin-releasing hormone agonist plus a low-dose oral contraceptive improves the recovery of the ovulatory function in patients with polycystic ovary syndrome.

OBJECTIVE: To evaluate the hormonal and clinical follow-up after the suspension of a longterm therapy with GnRH-agonist (GnRH-a) plus oral contraceptive (OC) in comparison to OC alone in patients with polycystic ovary syndrome (PCOS). DESIGN: Hormonal (plasma LH, FSH, sex steroid levels) and clinical (Ferriman-Gallwey score and ultrasound) parameters were monitored at various moments during the 6 months of treatment and during the 6 months after treatment suspension. SETTING: Physiopathology of Human Reproduction, University of Modena, Italy. PATIENT(S): Thirty patients with PCOS were enrolled and randomly subdivided in two groups of 15 each. INTERVENTION(S): Group A was treated with 3.75 mg IM GnRH-a plus OC. Group B was treated only with OC. RESULT(S): Both therapeutical regimens were effective in reducing androgenic milieu, Ferriman-Gallwey score, and ovarian volume within the 6th month of treatment. However, only patients treated with GnRH-a + OC showed a normal LH:FSH ratio, adequate plasma E2 and P levels, and ovulatory cycles during the 6 months of the after treatment follow-up. Patients treated with OC alone showed no beneficial effect after the 3rd month of the follow-up. CONCLUSION(S): These data support the evidence of a higher efficacy of the combined regimen (GnRH-a + OC) than OC alone in the treatment of patients with PCOS. In addition, the former regimen is associated with recovery of normal ovulatory cycles.

Androgens↗
PubMed1997

An increased vulnerability to stress is associated with a poor outcome of in vitro fertilization-embryo transfer treatment.

OBJECTIVE: To evaluate the association between the vulnerability to stress and the treatment outcome of couples undergoing IVF-ET. DESIGN: Controlled, prospective clinical study. SETTING: The Assisted Reproduction Unit of the Department of Obstetrics and Gynecology, University of Modena. PATIENT(S): Forty-nine infertile women consecutively admitted to standard superovulation treatment. Mean age was 33.9 years, duration of infertility was 6.3 years. Reasons for assisted reproduction were mechanical factor in 22 cases, sperm problem in 9 cases, and endocrine disorder in 6 cases. In 12 cases, infertility was unexplained. More than 55% already had an IVF-ET attempt. INTERVENTION(S): The day of oocyte pick-up, subjects were submitted to Stroop Color and Word test, a task measuring the ability to cope with a cognitive stressor, involving attentional and sympathoadrenal systems. Systolic (SBP) and diastolic blood pressure, as well as heart rate (HR) were measured at baseline, during the test, and 10 minutes after the end of testing. MAIN OUTCOME MEASURE(S): The evidence of a biochemical pregnancy (beta-hCG value 12 days after ET) define the success and failure groups. RESULT(S): Sixteen women (33%) had a biochemical pregnancy, 12 also had ultrasound evidence. Eight gave birth to healthy infants. Age, education, causes, and duration of infertility were similar in the success and failure groups. The latter were more involved in a job outside home than the former. Moreover, they had a lower number of both fertilized oocytes and transferred embryos. In response to the Stroop test, every subject reported an increase of cardiovascular parameters. However, women becoming pregnant showed a lower response of both SBP and HR than women who failed. CONCLUSION(S): Both a major cardiovascular vulnerability to stress and working outside home are associated to a poor outcome of IVF-ET treatment.

Adult↗
PubMed1997

Middle cerebral artery velocimetry: different clinical relevance depending on umbilical velocimetry.

OBJECTIVE: To evaluate the role of cerebral velocimetry as a predictor of perinatal outcome in high-risk pregnancies. METHODS: Middle cerebral artery pulsatility index was measured in 576 high-risk pregnancies undergoing umbilical velocimetry. The results of both tests were evaluated with respect to the birth of small for gestational age (SGA) infants and adverse perinatal outcome, defined as perinatal death, cesarean delivery for fetal distress, or low Apgar score. RESULTS: Once umbilical velocimetry was taken into account, cerebral velocimetry did not improve the prediction of fetal growth restriction or adverse perinatal outcome. Neither test was able to predict adverse perinatal outcome in normally grown fetuses. As for SGA fetuses with adverse perinatal outcome, the simultaneous assessment of both umbilical and cerebral velocimetry did not improve diagnostic accuracy (kappa index 0.37 versus 0.41 for umbilical velocimetry only). However, within the group of high-risk pregnancies with abnormal umbilical velocimetry, the risk of being SGA and having an adverse perinatal outcome was doubled (relative risk 2.1, 95% confidence interval 1.1, 4.3) if cerebral velocimetry also was abnormal. CONCLUSION: The routine use of cerebral velocimetry in high-risk pregnancies adds little information beyond that obtained from umbilical velocimetry; however, it is useful in predicting SGA infants with adverse perinatal outcome when umbilical velocimetry is abnormal.

Blood Flow Velocity↗
PubMed1997

Difference of LH and FSH secretory characteristics and degree of concordance between postmenopausal and aging women.

OBJECTIVE: Several neuroendocrine changes occur at menopause and the present study aimed to verify whether the episodic release and the degree of concordance of LH and FSH differs between early and late postmenopausal women. METHODS: Postmenopausal (n = 32) women were enrolled and subdivided in two groups according to the menopausal age: group A (n = 22), patients with more than 2 but less than 5 years from the occurrence of menopause; group B (n = 10), patients with more than 15 years from the occurrence of menopause. All subjects underwent a pulsatility study (4 h, sampling every 10 min) to assess LH and FSH secretory characteristics and their degree of concordance. RESULTS: Mean +/- S.E.M. LH and FSH plasma levels were lower in older women than in postmenopausal women (P < 0.01). The secretory pattern was pulsatile for both LH and FSH and their pulse amplitudes were lower in aged women (P < 0.01). No significant difference was observed in terms of pulse frequency between the two groups. LH and FSH pulses were co-secreted in early postmenopausal women while such a concordance was lost in older women. CONCLUSIONS: Late postmenopause is characterized by the reduction of the amplitude of gonadotropin pulses in comparison to women in early postmenopause, reflecting changes of both GnRH secretion and/or pituitary responsiveness to GnRH. The age-related loss of concordance between LH and FSH pulses discloses the existence of a hidden FSH stimulating system, which drives FSH episodic release independently and more promptly than GnRH.

Aging↗
PubMed1997

Effects of combined low dose of the isoflavone derivative ipriflavone and estrogen replacement on bone mineral density and metabolism in postmenopausal women.

OBJECTIVES: To assess the pattern of biochemical markers of bone metabolism and vertebral bone mineral density in early postmenopausal women treated with combined ipriflavone and low dose conjugated estrogens. METHODS: Bone biochemical markers and vertebral bone density were evaluated in a longitudinal, comparative, 2 year study conducted in postmenopausal women treated with sole calcium supplementation (500 mg/day), or with either ipriflavone (IP) at the standard dose (600 mg/day) plus the same calcium dose, low dose conjugated estrogens (CE) (0.3 mg/day) plus calcium, or low dose IP (400 mg/day) plus low dose CE (0.3 mg/day) plus calcium. The results were analyzed by repeated measures analysis of variance, as appropriate. RESULTS: No modifications of both urinary excretion of hydroxyproline and plasma osteocalcin levels were observed in calcium and in CE-treated women, while vertebral bone density significantly decreased (P < 0.0001) in both groups. In IP or IP + CE-treated women, plasma osteocalcin did not show any modification, while urinary hydroxyproline showed a significant (P < 0.05) decrease, that paralleled a significant (P < 0.05) increase in vertebral bone density. CONCLUSION: Postmenopausal IP administration, at the standard dose of 600 mg/day, can prevent the increase in bone turnover and the decrease in bone density that follow ovarian failure. The same effect can be obtained with the combined administration of low dose (400 mg/day) IP with low dose (0.3 mg/day) CE.

Administration, Oral↗
PubMed1997

p53 alterations are predictive of chemoresistance and aggressiveness in ovarian carcinomas: a molecular and immunohistochemical study.

Chemotherapeutic management of ovarian cancers is a difficult task as these neoplasms show significant differences in chemosensitivity, even if they share identical clinicopathological features. The present study was undertaken to investigate the prognostic and predictive role of p53 alterations in ovarian cancer. To this end, using different technical approaches, i.e. genetic and immunohistochemical analyses, we analysed a series of 68 ovarian neoplasms including 15 low malignant potential (LMP) tumours and 53 invasive carcinomas. We never observed p53 abnormalities in LMP tumours. p53 alterations were present only in invasive ovarian carcinomas, and they were detected much more frequently in tumours characterized by high histological grade (P = 0.01) and advanced-stage disease (P = 0.006 and P = 0.05 for gene mutations and protein expression respectively). For 33 patients with invasive ovarian cancer, information was available concerning response to cisplatin-based chemotherapy. A strong correlation (P = 0.001) has emerged between p53 alterations and response to chemotherapy; only one (14%) of seven patients who had a pathological complete response to antiblastic drugs showed p53 aberrations, whereas 18 (82%) of 22 cases with partial response and all of the four non-responsive patients scored positive for p53 abnormalities. We also observed that patients with p53 mutations had a significantly shorter progression-free survival than patients with p53-negative tumours (P = 0.05). Taken together, our results strongly suggest that in epithelial ovarian malignancies tumours showing p53 aberrations are significantly less sensitive to chemotherapy and more aggressive than those with functional p53. Thus, a routine analysis of this gene could have profound implications for the treatment of ovarian cancer.

Antineoplastic Agents↗
PubMed1997

Effects of sex steroid hormones on the neuroendocrine system.

Estrogen and progesterone are the most important ovarian steroid hormones regulating female fertility. They have a profound effect on the central nervous system. Target functions of sex steroids in the brain are: pituitary and hypothalamic hormone release, thermoregulatory and cardiocirculatory activities and behavior and mood changes. Furthermore, several studies have shown a correlation between brain neurotransmitters, neuropeptides and sex steroid hormones: they influence synthesis and release of norepinephrine, dopamine, serotonin, gonadotropin releasing hormone, beta-endorphin, corticotropin releasing factor and prolactin. Thus, oral hormone contraceptives inhibit the ovulatory process by blocking the activity of the hypothalamus-pituitary-gonadal axis. This inhibitory effect seems to be due to the action of both estrogens and progestins.

Contraceptives, Oral↗
PubMed1997

Endogenous estrogen and acetylcholine-induced vasodilation in normotensive women.

Acute exogenous estrogen administration enhances endothelial function in postmenopausal women. To evaluate the effect of endogenous estrogen on endothelium-dependent vasodilation, in 10 fertile normotensive women (age range 45 to 51 years) we studied the changes in forearm blood flow (strain-gauge plethysmography) induced by intrabrachial acetylcholine (0.15, 0.45, 1.5, 4.5, 1.5 micrograms.100 mL-1.min-1), an endothelium-dependent vasodilator, or sodium nitroprusside (1, 2, 4 micrograms.100 mL-1.min-1), an endothelium-independent vasodilator, in basal conditions and within 1 month after ovariectomy. As control subjects, 10 matched healthy women were also evaluated. In basal condition, vasodilation to acetylcholine and sodium nitroprusside was similar in patients and control subjects. Ovariectomy was followed by endogenous estrogen deprivation (from 71.6 +/- 31.3 to < 12 pg/mL) and was associated with a significant (P < .01) reduction in acetylcholine-induced vasodilation compared with baseline (maximum percent increase in forearm blood flow: baseline 568.2 +/- 47.1%; ovariectomy 309.5 +/- 37.4%); the response to sodium nitroprusside was unaffected by ovariectomy (maximum percent increase in forearm blood flow: baseline 526.4 +/- 36.5%; ovariectomy 454.7 +/- 47.2%; P = NS). In 6 of 10 patients, the study was repeated after 3 months of estrogen replacement therapy (17 beta-estradiol, 50 micrograms/d by transdermal patches). Exogenous estrogen restored acetylcholine-induced vasodilation (maximum percent increase in forearm blood flow: 548.9 +/- 43.1%; P < .01 versus ovariectomy), which was no longer different from baseline, whereas the response to sodium nitroprusside was not affected (maximum percent increase in forearm blood flow: 480.2 +/- 39.3%; P = NS). These results suggest a protective role of endogenous estrogen on endothelium-dependent vasodilation in the forearm vascular bed of normotensive women.

Acetylcholine↗