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Biomedical subjects

A R Genazzani

Publications and source records attributed to A R Genazzani.

At least 55 records · Page 3Linked to original sources
PubMed2001

Hormone replacement therapy: the benefits in tailoring the regimen and dose.

Despite the clear benefits of long-term hormone replacement therapy (HRT), the majority of patients tend to undergo short-term treatment. The cyclical bleedings induced by the sequential progestogen administration are often unacceptable namely in the elderly postmenopausal women. At the standard doses HRT preparations can also induce annoying hormone-related side effects, both in sequential and continuous combined regimens. Lower HRT schedules are reported to be highly effective in the relief of climacteric symptoms, inducing minimal endometrial stimulation with high rates of amenorrhea. Continuous administration of low doses of progestins is safe for endometrium protection and minimizes progestin-related side effects. Indeed, it has been demonstrated that low dose HRT can prevent the increase in bone turnover and the consequent bone loss in postmenopausal women. The choice of lower HRT dosages can also be useful for the number of potential disadvantages of standard HRT doses, mainly for long-term treatments. Low dose regimens should be considered as a starting dose to minimize the occurrence of side effects, improving compliance and, therefore, HRT effects on the prevention of long-term consequences of estrogen deprivation.

Drug Administration Schedule↗
PubMed2001

Prospective evaluation of body weight and body fat distribution in early postmenopausal women with and without hormonal replacement therapy.

AIMS: In order to assess the effects of menopause and hormonal replacement therapy (HRT) on body weight and body fat distribution (determined by dual energy X-ray), early postmenopausal women were given either oral calcium (500 mg/day, control group, n=13) or HRT, a combination of estradiol valerate (EV, 2 mg/day for 21 days) with cyproterone acetate (CPA, 1 mg/day in the last 10 days of the treatment cycle, n=18; Climen, Schering). RESULTS: There were no differences in basal body weight and body fat distribution in the two groups before the study. In control group, a significant (P<0.05) increase in body weight (from 63.5+/-2.0 to 68.7+/-2.0 kg after 36 months) paralleled a shift to a prevalent central, android fat distribution with a slight but significant (P<0.05) increase in total body fat mass (from 23.4+/-2.1 to 29.1+/-2.1 kg), an increase in trunk (from 10.1+/-0.4 to 12.7+/-0.4 kg, P<0.05), arms (from 2.4+/-0.2 to 2.9+/-0.2 kg, P<0.05) and legs (from 6.5+/-0.4 to 7.8+/-0.4 kg, P<0.05) fat. In the HRT group total body bone mineral showed a significant increase (from 1086+/-21 to 1128+/-19 mg/cm(2), P<0.05) increase after 36 months, with no significant increase in body weight (from 62.6+/-1.8 to 65.0+/-1.9 kg), and no modifications in trunk (from 10.0+/-0.2 to 10.1+/-0.2 kg) and arms (from 2.4+/-0.1 to 2.6+/-0.1 kg) fat, but a significant increase in legs fat (from 6.9+/-0.3 to 9.9+/-0.4 kg, P<0.05). CONCLUSION: Present results demonstrate that menopause is associated with an accelerated increase in body weight and body fat, with a prevalent central, android fat distribution, that can be counteracted at least in part by oral HRT.

Absorptiometry, Photon↗
PubMed2001

A 12-month clinical investigation with a 24-day regimen containing 15 microg ethinylestradiol plus 60 microg gestodene with respect to hemostasis and cycle control.

The effects of a 24-day regimen containing 15 microg ethinyl estradiol (EE) plus 60 microg gestodene on cycle control and on hemostasis, were evaluated in 58 healthy women (age 19-47 years). All women received the pill for 12 months. Withdrawal bleeding at every cycle during the tablet-free interval was experienced by 84.5% of the women. The overall incidence of irregular bleedings was 19.3%. Hemostasis was evaluated in 20 women. No changes in plasma fibrinogen concentrations, nor in prothrombin fragment F1+2 were observed. A slight increase in thrombin-antithrombin III complexes was observed after 6 and 12 months of oral contraceptive use. Antithrombin III activity significantly increased after one-year of pill intake. The concentrations of tissue plasminogen activator and plasminogen activator inhibitor, both antigen and activity, did not change. These results show that very low doses of EE, such as 15 microg, do not impair hemostasis in healthy females. However, the reduction for the EE dose is responsible of some of the effects on cycle control.

Adolescent↗
PubMed2001

Genotype distribution of estrogen receptor-alpha gene polymorphisms in Italian women with surgical uterine leiomyomas.

OBJECTIVE: To explore a possible association between estrogen receptor-alpha (ER-alpha) gene polymorphisms and development of uterine leiomyomas. DESIGN: Case-control study. SETTING: University teaching hospital. PATIENT(S): 119 women with clinically and surgically diagnosed uterine leiomyomas. INTERVENTION(S): Therapeutic hysterectomy. MAIN OUTCOME MEASURE(S): Frequency and distribution of ER-alpha gene polymorphisms. RESULT(S): No statistically significant differences between controls and patients in the allele frequency and genotype distribution were found when Pvu II and Xba I restriction polymorphism sites were analyzed separately. When the two ER-alpha gene polymorphisms were analyzed in combination, five major genotypes were recognized in controls or patients; the frequency differed slightly but not significantly between groups. CONCLUSION(S): The Pvu II and Xba I polymorphisms in the ER-alpha gene do not produce different risks of developing uterine leiomyomas.

Alleles↗
PubMed2001

Vascular endothelial growth factor and interleukin-8 in ovarian cystic pathology.

OBJECTIVE: To determine the levels of the angiogenic factors vascular endothelial growth factor (VEGF) and interleukin (IL-8) in ovarian cysts. DESIGN: Prospective descriptive study. SETTING: University hospital. PATIENT(S): One hundred women, of whom 9 had ovarian carcinomas, 38 had ovarian endometriomata, 43 had serous ovarian cysts, and 10 had follicular ovarian cysts. INTERVENTION(S): Sampling of serum and ovarian cystic fluid before and during surgery. MAIN OUTCOME MEASURE: Levels of VEGF and IL-8 in cystic fluid and serum. RESULT(S): Levels of both VEGF and IL-8 were found to be significantly higher in the cystic fluid of ovarian carcinomas and endometriomata than in serous and follicular cysts. In endometriomata fluid, levels of VEGF and IL-8 were found to be directly correlated (r = 0.68; P=.0074). Serum levels of VEGF were significantly higher in women with ovarian carcinomas and endometriomata than in those with serous and follicular cysts. Ovarian cancers and endometriomata were similar in terms of cystic concentrations of VEGF and IL-8 and in serum levels of VEGF. CONCLUSION(S): An increase in angiogenic factors that differentiate ovarian carcinomas and endometriomata from other kinds of ovarian pathology is demonstrated.

Carcinoma↗
PubMed2001

Oral dehydroepiandrosterone supplementation modulates spontaneous and growth hormone-releasing hormone-induced growth hormone and insulin-like growth factor-1 secretion in early and late postmenopausal women.

OBJECTIVE: To evaluate the effects of dehydroepiandrosterone (DHEA) supplementation on the growth hormone-releasing hormone-growth hormone (GHRH-GH) axis in lean and obese postmenopausal women. DESIGN: Prospective study. SETTING: Postmenopausal women in a clinical research environment. PATIENT(S): Thirty-one postmenopausal women were divided in two groups by age (50 to 55 and 60 to 65 years). Within each group, lean and obese patients were considered. INTERVENTION(S): All patients underwent hormonal evaluations before and at the third and sixth month of therapy (50 mg of DHEA orally each day) and a GHRH test (1 microg/kg) before and at the sixth month of treatment. Ultrasound and bone mass density (BMD) examinations were performed before and after the sixth month of therapy. MAIN OUTCOME MEASURE(S): Plasma dehydroepiandrosterone (DHEA), dehydroepiandrosterone sulfate (DHEAS), E1, E2, androstenedione (A), testosterone (T), osteocalcin, GH, insulin-like growth factor 1 (IGF-1) concentrations. RESULT(S): The levels of all of the steroids that derived from DHEA metabolism (E1, E2, A, T, DHEAS) and osteocalcin were increased in plasma under DHEA supplementation. The supplementation protocol also increased the levels of GH and IGF-1. However, GHRH-induced GH and IGF-1 responses were not modified by DHEA supplementation. CONCLUSION(S): Administration of DHEA significantly affects several endocrine parameters in early and late postmenopausal women independently from body mass index. Our data support the hypothesis that DHEA treatment acts similarly to estrogen-progestin replacement therapy on the GHRH-GH-IGF-1 axis. This suggests that DHEA is more than a more than a simple "diet supplement" or "antiaging product"; rather it should be considered an effective hormonal replacement treatment.

Administration, Oral↗
PubMed2001

Serum allopregnanolone in women with postpartum "blues".

OBJECTIVE: To relate serum allopregnanolone and progesterone levels postpartum to maternity "blues." METHODS: Forty primiparous, healthy, married women (24-39 years of age; at least 13 years of education) who delivered healthy neonates in the Department of Obstetrics at the University of Pavia entered the present study. Blood samples were drawn at 8:30 AM on postpartum day 3 for measurements of serum allopregnanolone, progesterone, cortisol, prolactin, and estradiol. On the same day, every woman was interviewed using the Hamilton Rating Scale for Depression for psychometric testing and completed a self-administered version of the Stein Questionnaire for symptoms of the "blues." RESULTS: Eighteen of 40 women (45%) experienced maternity "blues" (12 who delivered vaginally and six who delivered by cesarean). Serum allopregnanolone levels were significantly lower in those women experiencing postpartum "blues" with respect to euthymic women (1.1 +/- 0.4 versus 2.3 +/- 1.0 nmol/L; P <.001), whereas progesterone levels did not differ significantly (11.6 +/- 5.6 versus 19.1 +/- 15.6 nmol/L; P >.058). Allopregnanolone and progesterone levels correlated significantly in euthymic women (r =.648; P =.001) but not in those with postpartum "blues" (r =.317; P =.199). There was a significant negative correlation between the Hamilton score and levels of serum allopregnanolone (r = -.62; P =.001) and progesterone (r = -.36; P =.024). CONCLUSION: Serum allopregnanolone levels were detectable postpartum and were significantly decreased in women with maternity "blues."

Adult↗
PubMed2001

Increased adrenal steroid secretion in response to CRF in women with hypothalamic amenorrhea.

OBJECTIVE: To evaluate adrenal steroid hormone secretion in response to corticotropin-releasing factor (CRF) or to adrenocorticotropin hormone in women with hypothalamic amenorrhea. DESIGN: Controlled clinical study. SETTING: Department of Reproductive Medicine and Child Development, Section of Gynecology and Obstetrics, University of Pisa, Italy. PATIENT(S): Fifteen women with hypothalamic amenorrhea were enrolled in the study. Eight normal cycling women were used as control group. INTERVENTION(S): Blood samples were collected before and after an injection of ovine CRF (0.1 microg/kg iv bolus) or after synthetic ACTH (0.25 mg iv). MAIN OUTCOME MEASURE(S): Plasma levels of ACTH, 17-hydroxypregnenolone (17OHPe), progesterone (P), dehydroepiandrosterone (DHEA), 17-hydroxyprogesterone (17OHP), cortisol (F), 11-deoxycortisol (S) and androstenedione (A). RESULT(S): Basal plasma concentrations of ACTH, cortisol, 11-deoxycortisol, DHEA and 17OHPe were significantly higher in patients than in controls, whereas plasma levels of progesterone and 17-OHP were significantly lower in patients than in controls. In amenorrheic women the ratio of 17-OHPe/DHEA, of 17-OHPe/17-OHP and of 11-deoxycortisol/cortisol were significantly higher than in controls, while a significant reduction in the ratio of 17-OHP/androstenedione, of 17-OHP/11-deoxycortisol was obtained. In response to corticotropin-releasing factor test, plasma levels of ACTH, cortisol, 17-OHP, 11-deoxycortisol, DHEA and androstenedione were significantly lower in patients than in controls. In response to adrenocorticotropin hormone, plasma levels of 17-OHP, androstenedione and androstenedione/cortisol were significantly higher in patients than in controls. CONCLUSIONS: Patients suffering for hypothalamic amenorrhea showed an increased activation of hypothalamus-pituitary-adrenal (HPA) axis, as shown by the higher basal levels and by augmented adrenal hormone response to corticotropin-releasing factor administration. These data suggest a possible derangement of adrenal androgen enzymatic pathway.

17-alpha-Hydroxypregnenolone↗
PubMed2001

Effects of low-dose continuous combined conjugated estrogens and medroxyprogesterone acetate on menopausal symptoms, body weight, bone density, and metabolism in postmenopausal women.

OBJECTIVE: The purpose of this study was to determine the effects of a low dose of conjugated equine estrogens and medroxyprogesterone acetate plus calcium supplementation on bone density, metabolism, body weight, and symptoms in young postmenopausal women. STUDY DESIGN: Sixty postmenopausal women, aged 45 to 56 years, were randomized in an open-label, 2-year trial that compared treatment with low-dose continuous combined hormone replacement therapy that contained 0.3 mg of conjugated equine estrogens and 2.5 mg of medroxyprogesterone acetate plus 1000 mg of calcium per day or treatment with 1000 mg of calcium per day alone. Menopausal symptoms were evaluated for the first 12 weeks of the study; bleeding profiles, bone mineral density, bone turnover, and body weight were assessed for 24 months. RESULTS: After 24 months, we evaluated 15 subjects in the control group (with a 50% drop-out rate) and 23 patients (with a 23% drop-out rate) in the low-dose continuous combined hormone replacement therapy group. Low-dose continuous combined hormone replacement therapy was effective in reducing menopausal clinical symptoms and provided a favorable bleeding profile and minimal side effects. In comparison with basal values, bone mineral density significantly (P <.05) increased by 2.72% +/- 0.3% in the low-dose continuous combined hormone replacement therapy group and decreased by 7.9% +/- 0.8% (P <.05) in the control group after 24 months, with parallel changes in bone metabolism marker action. In the control group, body mass index significantly (P <.05) increased from baseline value with a weight gain of 3%; in the low-dose continuous combined hormone replacement therapy group, the body mass index did not change after 24 months of treatment, and the 1.3% gain in body weight was not significant. CONCLUSION: Low-dose continuous combined hormone replacement therapy can alleviate subjective symptoms and minimize body transformations that are associated with early menopause and provide an effective protection against the activation of bone turnover and osteoporosis.

Body Weight↗
PubMed2001

In-vitro evidence of autocrine secretion of vascular endothelial growth factor by endothelial cells from human placental blood vessels.

Vascular endothelial growth factor (VEGF), a highly specific mitogen for vascular endothelial cells, is involved in placental vascular growth and remodelling. The aim of this study was to investigate whether placental endothelial cells secrete VEGF in an autocrine manner and if this secretion is correlated with endothelial cell growth. Blood vessels, excised from the apical surface of three human placentae, were sectioned into 40 fragments per placenta and cultured in fibrin gel matrix for 27 days. Immunohistochemical detection of placental endothelial cells was performed by positive staining with anti-human factor VIII-associated antigen and negative staining with anti-human alpha-actin and desmin. To investigate the production and autocrine action of VEGF, VEGF concentrations in culture media were measured and the effect of an anti-VEGF neutralizing antibody on endothelial cell growth was observed. The results demonstrate that soluble VEGF is secreted by placental endothelial cells reaching a plateau from day 24 (68.74 +/- 7.52 pg/ml) to day 27 (67.20 +/- 6.28 pg/ml). Furthermore, VEGF concentrations in media collected on days 6, 12, 18, 21 and 27 of culture were found to be directly correlated to the sprouting parameter of endothelial cells, as calculated by image analysis on the same day ( P < 0.001, r (2) = 0.95 ). The use of 10 and 100 ng/ml of a neutralizing antibody against human VEGF suppressed cell proliferation, compared to that observed in the untreated controls, by 74.8 +/- 7.3 and 89.4 +/- 3.9% respectively. In conclusion, this study reports the first evidence of autocrine secretion of VEGF by human placental endothelial cells and demonstrates the involvement of VEGF in endothelial cell growth within a fibrin gel culture.

Autocrine Communication↗
PubMed2001

Serum activin A levels in males and females during pubertal development.

Activin A is a dimeric protein composed of two beta A-subunits protein of the transforming growth factor-beta (TGF-beta) family. This protein is synthesized by a variety of organs. A sensitive and specific assay for bioactive dimeric activin A has recently been developed, to measure circulating levels in adult women and men, giving a new insights into the possible physiological role of this protein in the reproductive axis and/or in other functions. The aim of the present study was to evaluate serum dimeric activin A levels in boys and girls during pubertal development. The study was performed on a group of children (n = 54) aged between 6 and 18 years at different Tanner stages. Serum levels of activin A were measured using a specific and sensitive two-site ELISA. Serum activin A levels were not significantly different at various Tanner stages (Tanner I, 0.36 +/- 0.02 ng/ml; Tanner II, 0.33 +/- 0.02 ng/ml; Tanner III, 0.35 +/- 0.03 ng/ml; Tanner IV, 0.41 +/- 0.04 ng/ml; Tanner V, 0.35 +/- 0.05 ng/ml; p > 0.01). No difference between male and female children was observed. In conclusion, the lack of significant differences in activin A serum levels according to the Tanner stages or to gender demonstrates that this protein is not involved in the endocrine modifications during pubertal development and that its measurement may not provide a sensitive new tool for determining gonadal maturity at puberty.

Activins↗
PubMed2001

Expression and prognostic significance of urokinase and plasminogen activator inhibitor type-1 in endometrial hyperplasia and cancer.

Proteolytic enzymes, like urokinase (uPA) and plasminogen activator inhibitor type-1 (PAI-1), are involved in remodelling tissues during invasion and metastasis of tumor cells. The purpose of the study is to evaluate the expression and the prognostic significance of these enzymes in endometrial hyperplasia and cancer. We used immunohistochemical staining to localize uPA and PAI-1 antigens and evaluate their expression, and the enzyme-linked immunosorbent assay (ELISA) to measure their levels during the progression of endometrial carcinoma. The results show that the levels of uPA and PAI-1 detection are systematically weak in simplex hyperplasia and are moderate in complex hyperplasia. In the endometrial carcinoma a very strong reaction was observed in the most aggressive variant of epithelial tumors. A positive signal for uPA was found only in the cytoplasm of normal and hyperplastic cells while, in tumors, uPA was present also in the cellular areas surrounding the neoplastic glands and at the apex of the malignant cells. The PAI-1 immunoreactivity was weak to moderate in 95.4% of carcinomas, with a diffuse signal mostly distributed in the cytoplasm of neoplastic cells and tumor stroma. UPA antigen concentrations were significantly higher in endometrial carcinoma than in endometrial hyperplasia (p<0.05) and in normal endometrium (p<0.001). PAI-1 antigen concentrations in carcinoma samples were significantly higher than in normal endometrium (p=0.002), but the difference was not statistically significant with respect to that in endometrial hyperplasia. We did not find any correlation between uPA and PAI-1 concentrations and the standard prognostic parameters for evaluating endometrial carcinoma. In conclusion, this study demonstrates that in hyperplastic endometria and in endometrial carcinoma there is a progressive increase in expression of uPA and PAI-1 than in normal endometrial tissue. In carcinoma tissues, the high expression of uPA is unregulated in the surrounding stroma tissue, particularly in the most aggressive histopathologic variants. UPA and PAI-1 may be factors associated with invasive behavior in endometrial carcinoma independent of other clinicopathological parameters.

Adenocarcinoma↗
PubMed2001

Controversial issues in climacteric medicine II. Hormone replacement therapy and cancer. International Menopause Society Expert Workshop. 9-12 June 2001, Opera del Duomo, Pisa, Italy.

Sex steroids are not known to damage DNA directly. They can stimulate or inhibit cell proliferation, and thus can modulate tumor developmental progression. Sex steroid-related tumors in women are represented by breast cancer and endometrial cancer, and a possible relationship exists between sex steroids and both ovarian and colon cancer. Among current ERT users or those who stopped use 1-4 years previously, the relative risk of having breast cancer diagnosed increases by a factor of 1.023 for each year of hormone use. This increase is comparable with the effect on breast cancer of delaying menopause, and seems to be largely limited to lean women. The breast cancers diagnosed during ERT are more likely to contain ER and are less aggressive. Some reports indicate no increase in breast cancer mortality in HRT users. Recent data suggest that an estrogen-progestin regimen may increase breast cancer risk beyond that associated with estrogen alone. However, the effect of progestogens on the breast awaits further clarification. ERT/HRT is generally considered to be contraindicated in breast cancer patients, as no firm data are yet available from randomized clinical trials. Despite the potential risks, ERT/HRT could be considered for breast cancer patients suffering from menopausal symptoms resistant to alternative treatments, after completely informed consent is given, particularly in women with ER--(hormone-resistant) cancers. Unopposed estrogen therapy is known to increase endometrial cancer risk, and is appropriate only for hysterectomized women. To negate the excess risk of endometrial hyperstimulation, an adequate progestin dose must be given in a continuous combined regimen or for an appropriate number of days in sequential regimens (10 days or more for some progestogens or 12 days or more for other progestogens). An appropriate combination of estrogen and progestin does not appear to increase, and may even decrease, the risk of endometrial cancer. HRT is generally considered to be contraindicated in endometrial cancer patients. Despite the potential risks, HRT could be considered for patients suffering from menopausal symptoms resistant to alternative treatments, after completely informed consent is given. Available data suggest a reduced risk of colorectal adenoma and colon cancer in current users of HRT, but definitive studies are still needed. There is no contraindication to HRT prescription in colon cancer survivors. Consistent epidemiological data describe a decreased incidence of ovarian cancer with oral contraceptive use during the reproductive years. Studies on HRT and risk of epithelial ovarian cancer have produced conflicting results but most data seem to exclude a strong association. While no data contraindicate HRT use in epithelial ovarian cancer survivors, current studies do not allow us to exclude the possibility that estrogens alone could stimulate ovarian cancer growth in a small fraction of patients. Additional studies are required. It is important to consider that not all estrogens and progestins are used with the same dosage, route of administration (oral, transdermal and for estradiol intranasal) and, mostly, different estrogens do not show the same bioavailability and tissue effects. The available data do not allow to discriminate for all these variables and therefore it is inappropriate to consider jointly all forms of hormonal therapy. This issue is considered as an important area for future evaluation and research. The International Menopause Society is in the process of drawing up specific recommendations for further research in the field of HRT and cancer.

Breast Neoplasms↗