The relevance of inositols treatment for PCOS before and during ART.

Polycystic ovary syndrome (PCOS) is an endo-crine disorder that occurs in 8-10% of women of reproduc-tive age. It is characterized by oligo or anovulation, hyperandrogenism and/or polycystic ovaries, but also by an increased insulin plasma level especially in overweight/obese women or in those with familial diabetes. In the last years, among the insulin sensitizers, the use of the two active isoforms of inositols (myo-inositol and d-chiro-inositol) has been spreading for the treatment of PCOS insulin resistance. Several studies have shown a positive role of inositols both on the metabolic profile of PCOS patients, but also on hormonal parameters. Hence, inositols can positively affect the infertility that characterizes many PCOS patients, acting both on ovarian function and spontaneous ovulation and during IVF procedures, in terms of oocyte quality and pregnancy rate.

Cranberry, D-mannose and anti-inflammatory agents prevent lower urinary tract symptoms in women undergoing prolapse surgery.

Objective: We assessed the effect on lower urinary tract symptoms (LUTS) of a supplement containing cranberry, D-mannose and anti-inflammatory molecules in postmenopausal women undergoing surgery for cystocele.Study design: Forty postmenopausal women were randomized 1:1 to an active group receiving the nutritional supplement twice a day for 2 weeks starting from surgery, or to a control group receiving surgery only. Primary outcomes were the effectiveness in the postoperative LUTS and urinary tract infections (UTI). LUTS were investigated by a validated questionnaire (ICIQ-FLUTS) at baseline and at week 4. Secondary outcomes were the safety and tolerability of the supplement and other perioperative outcomes.Results: No significant differences were found in perioperative outcomes and in incidence of UTI. After surgery, women treated with the supplement experienced significantly better scores on the filling domain of the questionnaire. A non-significant decrease in voiding scores was also found. No adverse events were detected.Conclusion: The use of an oral supplement containing cranberry, D-mannose and anti-inflammatory molecules decreases the perception of LUTS in postmenopausal women after anterior colporraphy. Our data suggest that perioperative use of nutritional supplements may be useful in the management of postoperative LUTS.

Oral dehydroepiandrosterone restores ß-endorphin response to OGTT in early and late postmenopause.

ß-endorphin is a neuropeptide involved in several brain functions: its plasma levels are higher in obese women and its release increases after oral glucose tolerance test (OGTT) in normal or obese women. The study included 46 healthy women and evaluated the effect of oral dehydroepiandrosterone [DHEA] (50 mg/day) in early postmenopausal women (50-55 years) both of normal weight (group A, n = 12, BMI = 22.1 ± 0.5) and overweight (group B, n = 12, BMI = 28.2 ± 0.5), and late postmenopausal women (60-65 years) both normal weight (group C, n = 11, BMI = 22.5 ± 0.6) and overweight (group D, n = 11, BMI = 27.9 ± 0.4) undergone OGTT, in order to investigate if DHEA could restore/modify the control of insulin and glucose secretion and ß-endorphin release in response to glucose load. The area under the curve (AUC) of OGTT evaluated plasma levels of different molecules. DHEA, DHEAS, and ß-endorphin plasma levels were lower in baseline conditions in older women than younger women. Considering the AUC of ß-endorphin response to OGTT, all groups showed a progressive significant increase after 3 and also after 6 months of treatment in comparison to baseline and 3 months of treatment.

Modulatory effects of alpha-lipoic acid (ALA) administration on insulin sensitivity in obese PCOS patients.

PURPOSE: To evaluate the efficacy of alpha-lipoic acid (ALA) administration on hormonal and metabolic parameters of obese PCOS patients. METHODS: A group of 32 obese PCOS patients were selected after informed consent. 20 patients referred to have first grade relatives with diabetes type I or II. Hormonal and metabolic parameters as well as OGTT were evaluated before and after 12 weeks of ALA integrative administration (400 mg per os every day). RESULTS: ALA administration significantly decreased insulin, glucose, BMI and HOMA index. Hyperinsulinemia and insulin response to OGTT decreased both as maximal response (Δmax) and as AUC. PCOS with diabetes relatives showed the decrease also of triglyceride and GOT. Interestingly in all PCOS no changes occurred on all hormonal parameters involved in reproduction such as LH, FSH, and androstenedione. CONCLUSIONS: ALA integrative administration at a low dosage as 400 mg daily improved the metabolic impairment of all PCOS patients especially in those PCOS with familiar diabetes who have a higher grade of risk of NAFLD and predisposition to diabetes.

[The putative role and use of DHEA and its association with the hormone replacement therapy]. / Dall'uso del solo DHEA alla sua associazione con la terapia ormonale sostitutiva.

The putative role and use of dehydroepiandrosterone (DHEA) as replacement therapy for menopausal women has been under consideration during the latest years. DHEA is one of the main adrenal hormones that progressively reduces its plasmatic levels from the beginning of ageing. This phenomenon implies not only the reduction of the plasmatic androgens but also the decrease of a peculiar category of hormones, named neurosteroids, in particular one: allopregnanolone. This review aims to elucidate the peculiar aspects of DHEA administration and its putative use as substitutive/integrative hormonal treatment alone or in combination with the traditional hormone replacement therapy.

Advances in neurosteroids: role in clinical practice.

The steroidogenic endocrine glands and local synthesis both contribute to the pool of steroids present in the central nervous system and peripheral nervous system. Although the synthesis of neurosteroids in the nervous system is now well established, the spectrum of respective functions in regulating neuronal and glial functions remains to be fully elucidated. From the concept of neurosteroids derives another treatment strategy: the use of pharmaceutical agents that increase the synthesis of endogenous neurosteroids within the nervous system. This approach has so far been hampered by lack of knowledge concerning the regulation of the biosynthetic pathways of neurosteroids and their relationship with sex steroids produced by the peripheral gland or with exogenous steroids. The present review summarizes some of the available clinical and experimental findings supporting the critical role of neurosteroids during fertile life and reproductive aging and their relationship with endogenous and exogenous sex steroids. The brain metabolism of synthetic progestins and the implications of DHEA treatment in postmenopausal women will also be discussed.

Endocrine and clinical effects of myo-inositol administration in polycystic ovary syndrome. A randomized study.

OBJECTIVE: To evaluate the effects the administration of myo-inositol (MYO) on hormonal parameters in a group of polycystic ovary syndrome (PCOS) patients. DESIGN: Controlled clinical study. SETTING: PCOS patients in a clinical research environment. PATIENTS: 50 overweight PCOS patients were enrolled after informed consent. INTERVENTIONS: All patients underwent hormonal evaluations and an oral glucose tolerance test (OGTT) before and after 12 weeks of therapy (Group A (n»10): MYO 2 g plus folic acid 200 mg every day; Group B (n»10): folic acid 200 mg every day). Ultrasound examinations and Ferriman-Gallwey score were also performed. MAIN OUTCOME MEASURES: Plasma LH, FSH, PRL, E2, 17OHP, A, T, glucose, insulin, C peptide concentrations, BMI, HOMA index and glucose-to-insulin ratio. RESULTS: After 12 weeks of MYO administration plasma LH, PRL, T, insulin levels and LH/FSH resulted significantly reduced. Insulin sensitivity, expressed as glucose-to-insulin ratio and HOMA index resulted significantly improved after 12 weeks of treatment. Menstrual cyclicity was restored in all amenorrheic and oligomenorrheic subjects. No changes occurred in the patients treated with folic acid. CONCLUSIONS: MYO administration improves reproductive axis functioning in PCOS patients reducing the hyperinsulinemic state that affects LH secretion.

Actin cytoskeleton remodelling by sex steroids in neurones.

Cell morphology and its interaction with the extracellular environment are integrated processes involving a number of intracellular controllers orchestrating cytoskeletal proteins and their interaction with the cell membrane and anchorage proteins. Sex steroids are effective regulators of cell morphology and tissue organisation, and recent evidence indicates that this is obtained through the regulation of the actin cytoskeleton. Intriguingly, many of these regulatory actions related to cell morphology are achieved through the rapid, nonclassical signalling of sex steroid receptors to kinase cascades, independently from nuclear alteration of gene expression or protein synthesis. The identification of the mechanistic basis for these rapid actions on cell cytoskeleton has special relevance for the characterisation of the effects of sex steroids under physiological conditions, such as for the development of neurone/neurone interconnections and dendritic spine density. This is considered to be critical for gender-specific differences in brain function and dysfunction. Recent advancements in the characterisation of the molecular basis of the extranuclear signalling of sex steroids help to clarify the role of oestrogen and progesterone in the brain, and may turn out to be of relevance for clinical purposes. This review highlights the regulatory effects of oestrogens and progesterone on actin cytoskeleton and neurone morphology, as well as recent progresses in the characterisation of these mechanisms, providing insights and working hypotheses on possible clinical applications for the modulation of these pathways in the central nervous system.

Acetyl-L-carnitine (ALC) administration positively affects reproductive axis in hypogonadotropic women with functional hypothalamic amenorrhea.

BACKGROUND: Hypothalamic amenorrhea (HA) is characterized by neuroendocrine impairment that, in turn, negatively modulates endocrine function, mainly within the reproductive axis. HA presents with hypo-LH, hypoestrogenism and, until now, a definite therapeutic strategy has not yet been found. The aim of the following study was to test the efficacy of acetyl-L-carnitine (ALC) administration in HA-affected subjects. POPULATION: Twenty-four patients affected by stress-induced HA were divided into two groups according to LH plasma levels: group A, hypo-LH (LH≤3 mIU/ml; no.=16), and group B, normo-LH (LH>3 mIU/ml; no.=8), were treated with ALC (1 g/day, per os) for 16 weeks. DESIGN: Patients underwent baseline hormonal assessment, pulsatility test (for LH and FSH), naloxone test (for LH, FSH and cortisol) both before and after 16 weeks of treatment. RESULTS: Under ALC administration hypo-LH patients showed a significant increase in LH plasma levels (from 1.4±0.3 to 3.1±0.5 mIU/ml, p<0.01) and in LH pulse amplitude (p<0.001). No changes were observed in the normo-LH group. LH response to naloxone was restored under ALC therapy. Maximal LH response and area under the curve under naloxone were significantly increased (p<0.05 and p<0.01, respectively). No changes were observed in the normo-LH patients. CONCLUSIONS: Our data support the hypothesis of a specific role of ALC on counteracting the stress-induced abnormalities in hypo-LH patients affected by hypothalamic amenorrhea.

[Effects of Klamath Algae extract on psychological disorders and depression in menopausal women: a pilot study]. / Effetti degli estratti di Alga Klamath sul tono dell'umore e la depressione in menopausa: studio pilota.

AIM: Menopause transition is able to induce a significant change in the quality of life of women and a growing demand for alternative treatments to hormonal therapy of the psychological and somatic/vasomotor symptoms related to menopausal transition has been observed in these last years. In this study we aimed to investigate the effect of a two-month supplementation period with the Klamath algae extract Klamin® on the general and psychological well-being of a group of 30 menopausal women, free from any hormonal therapy. METHODS: Patients were randomly subdivided in 2 groups (15 patients each) and each of them was treated with Algae Klamath extract (Klamin®, Nutrigea, Urbino, Italy) (1600 g/day) or with placebo (vanilla tablets) for 8 weeks. Patients were evaluated both for the hormonal and psychological profiles (Symptom Rating Scale - Italian version [SRT] and Zung Self-Rating Scale) before and after the treatment interval. RESULTS: Both groups of patients were similar in baseline conditions but significant changes were observed after the treatment interval in the group administered with Algae Klamath extracts. Though no hormonal changes occurred after the treatment interval in both groups, only patients under Klamin administration showed both SRT and Zung scales significantly improved, thus reporting a consistent change in their quality of life, for mood, anxiety and depressive attitude. CONCLUSION: Since the Klamath extract did not show steroid-like effects on the hormonal parameters, it could be proposed as valid integration for those women seeking for alternative treatment to hormonal therapy so that to overcome many of the menopausal symptoms.

Hypothalamic amenorrhea: from diagnosis to therapeutical approach.

Among secondary amenorrheas, hypothalamic amenorrhea (HA) is the one with no evidence of endocrine/systemic causal factors. HA is mainly related to various stressors affecting neuroendocrine control of the reproductive axis. In clinical practice, HA is mainly associated with metabolic, physical, or psychological stress. Stress is the adaptive response of our body through all its homeostatic systems, to external and/or internal stimuli that activate specific and nonspecific physiological pathways. HA occurs generally after severe stressed conditions/situations such as dieting, heavy training, or intense emotional events, all situations that can induce amenorrhea with or without body weight loss and HA is a secondary amenorrhea with a diagnosis of exclusion. In fact, the diagnosis is essentially based on a good anamnestic investigation. It has to be investigated using the clinical history of the patient: occurrence of menarche, menstrual cyclicity, time and modality of amenorrhea, and it has to be excluded any endocrine disease or any metabolic (i.e., diabetes) and systemic disorders. It is necessary to identify any stressed situation induced by loss, family or working problems, weight loss or eating disorders, or physical training or agonist activity. Peculiar, though not specific, endocrine investigations might be proposed but no absolute parameter can be proposed since HA is greatly dependent from individual response to stressors and/or the adaptive response to stress. This chapter aims to give insights into diagnosis and putative therapeutic strategies.

Efficacy on menopausal neurovegetative symptoms and some plasma lipids blood levels of an herbal product containing isoflavones and other plant extracts.

OBJECTIVES: To assess the efficacy of a product containing isoflavones and other plant extracts (BIO) on whole menopausal symptomatology and plasma lipids profile. METHODS: Multicentre, randomized, double blind, placebo controlled clinical investigation on 125 menopausal women randomly assigned to two groups treated for 6 months with placebo or one tablet daily of an herbal product containing 72 mg/dose of isoflavones of different plants origin and other plant extracts (BIO). Primary end-point: Kupperman Menopause Index (KI) variations; secondary end-point: activity on plasma lipids profile and clinical global impression (CGI) on efficacy and tolerability by investigators and patients. The usual parametric test (paired Student t test) was performed to evaluate the significance. In case of non-applicability of parametric tests, the non-parametric Mann-Whitney U test was used. The differences where considered significant at p<0.05 level. RESULTS: At the end of treatment in both groups KI showed a significant decrease (p<0.001). However, in the BIO group the KI reduction was significantly higher (p=0.0265) than in the placebo group after 4 and 6 months of treatment. In the BIO treated patients the LDL cholesterol showed a borderline but not significant reduction compared to placebo (p=0.0608) and triglyceride (TG) a significant (p=0.0151) decrease compared to placebo. The investigator's and patient's CGI on BIO group where superior as compared to placebo. Clinical tolerability was good in booth groups. CONCLUSION: On the basis of positive effects on KI and lipids profile as well as of good clinical tolerability, BIO can be considered one of the possible alternative therapy for conventional HRT.

Influence of endogenous and exogenous sex hormones on plasma brain-derived neurotrophic factor.

BACKGROUND: Brain-derived neurotrophic factor (BDNF) is a mediator of neuronal plasticity and influences learning, memory and cognitive behaviour. The aim of this study is to assess plasma BDNF variations according to hormonal status. METHODS: A total of 60 subjects were included: 20 fertile ovulatory women, 15 amenorrhoeic women and 25 postmenopausal women. Blood samples were collected after overnight fasting. For 5 out of the 20 fertile women, samples were collected every 2 days throughout the whole menstrual cycle. Following basal evaluation, 10 out of 25 postmenopausal women were administered a hormone replacement therapy (HRT) and reevaluated after 6 months of treatment. Plasma BDNF concentrations were measured by enzyme-linked immunosorbent assay. In fertile women, estradiol (E(2)), progesterone and gonadotrophins were also assessed. RESULTS: In fertile women, luteal phase levels of plasma BDNF were significantly higher than follicular phase levels (P < 0.001). BDNF increased from early follicular phase up to Day 14 of the cycle, reaching a pre-ovulatory peak, similar to E(2). A second rise took place during mid-luteal phase, with a peak on Day 24. Amenorrhoeic subjects, as well as postmenopausal women, showed significantly lower plasma BDNF levels compared with fertile females (P < 0.001). BDNF was positively correlated with E(2) and progesterone and negatively correlated with menopausal age. HRT restored BDNF levels to those present in fertile women during the follicular phase. CONCLUSIONS: Plasma BDNF levels are influenced by hormonal status. Modifications in BDNF circulating levels during the menstrual cycle suggest a potential role for gonadal sex hormones (E(2) and progesterone) in regulating neurotrophin expression.

Female precocious puberty, obesity and polycystic-like ovaries.

OBJECTIVE: To evaluate the characteristics of obese girls with gonadotropin releasing hormone-dependent precocious puberty with and without polycystic-like ovaries. METHODS: Forty-seven overweight (> 75(th) centile of the Italian reference data) girls with a diagnosis of isosexual precocious puberty underwent auxological analysis, hormonal assay and utero-ovarian sonographic and Doppler evaluation. On the basis of sonography the patients were subdivided into two groups, girls presenting normal ovaries (Group I; n = 31) and those with polycystic-like ovaries (Group II; n = 16). RESULTS: The mean body weight was significantly higher (P = 0.003) in Group II than it was in Group I. In addition, the patients with polycystic-like ovaries fell within our definition of superobese (> or = 97(th) centile of the Italian reference data) in 44% of cases. The uterine and ovarian volumes were significantly greater in Group II compared with Group I patients. The Doppler evaluation showed intraparenchymal ovarian vascularization and low downstream impedance to flow in all patients in Group II. CONCLUSIONS: Girls with precocious puberty and polycystic ovaries, compared with those without polycystic ovaries, have a higher incidence of body weight exceeding the 85(th) centile of the Italian reference data (obesity).

Tibolone, transdermal estradiol or oral estrogen-progestin therapies: effects on circulating allopregnanolone, cortisol and dehydroepiandrosterone levels.

The aim of the present study was to evaluate, in healthy postmenopausal women, the impact of tibolone (2.5 mg), transdermal estradiol (50 microg) (TE) and different oral estrogen-progestin regimens, conjugated equine estrogens (0.625 mg) plus medroxyprogesterone acetate (5 mg) (CEE + MPA) and estradiol (2 mg) plus norethisterone acetate (1 mg) (E2 + NETA) on circulating estradiol, progesterone, allopregnanolone, cortisol and dehydroepiandrosterone (DHEA) levels. Blood samples were collected before and after 1, 3, 6 and 9 months of treatment in 85 postmenopausal women. Estradiol levels increased (p < 0.001) in the TE, CEE + MPA and E2 + NETA groups after 1 month of therapy, but did not change in the tibolone group during the entire follow-up period. Both E2 + NETA and tibolone treatments induced an increase in progesterone levels (p < 0.05) after 1 year of therapy. Allopregnanolone levels showed an increase in all estrogen-based groups, being significant after 3 months of treatment (p < 0.01). Patients receiving tibolone showed a significant increase in allopregnanolone levels at 3 months (p < 0.05), but lower than in the other groups. Cortisol levels decreased significantly in the TE and CEE + MPA groups after 6 months and 12 months of treatment, respectively. Neither tibolone nor E2 + NETA treatments modified circulating cortisol levels. DHEA levels significantly (p < 0.05) decreased after 6 months of TE or estrogen-progestin therapies independently of the presence or the type of progestin used. In contrast, DHEA remained stable throughout the 12 months of treatment with tibolone. The increase of allopregnanolone, a steroid with sedative and anxiolytic properties, in response to these different treatments could underlie, at least in part, the central effects that hormone replacement therapy and tibolone have on anxiety, mood and behavior. Unlike estrogen-based therapy, tibolone treatment did not reduce the DHEA milieu in the menopause, and thus did not enhance the androgen deficiency syndrome in postmenopausal women.

Different concentrations of interleukins in the peritoneal fluid of women with endometriosis: relationships with lymphocyte subsets.

The present study explored the possible relationships between immune cell subsets and interleukin (IL)-12 or IL-13 levels in the peritoneal fluid of patients with and without endometriosis. Peritoneal fluid samples were obtained from 80 women while they were undergoing laparoscopy for pain, infertility, tubal ligation or re-anastomosis. The American Fertility Society scoring system was used to determine the extension of endometriosis. The peritoneal fluid mononuclear cells were analyzed for immunophenotyping using cytometry, whereas peritoneal fluid concentrations of interleukins were measured using two ultrasensitive commercially available enzyme-linked imnunosorbent assay kits. Significantly higher peritoneal fluid IL-12 levels were found in women with moderate or severe endometriosis (stages III and IV) than in healthy controls (p < 0.01). Conversely, subjects with endometriosis showed remarkably lower peritoneal fluid IL-13 concentrations than controls, independent of the severity of the disease (p < 0.05). Considering immune system effectors, patients with endometriosis presented a significantly higher peritoneal fluid CD8+/CD4+ ratio when compared with healthy controls. Moreover, the number of peritoneal fluid CD8+ and CD4+ activated T cells was significantly lower in the former than in the latter group, independent of the endometriosis stage. Connections were observed between peritoneal fluid interleukins and peritoneal fluid T cells: both patients with endometriosis and controls presented an inverse correlation between peritoneal fluid activated T cells and IL-13 levels, and a direct correlation between peritoneal fluid T cells and IL-12 concentrations. These data seem to suggest that a reciprocal modulation exists between peritoneal fluid cytokines and T lymphocyte subsets in patients with endometriosis.

Long-term low-dose dehydroepiandrosterone replacement therapy in aging males with partial androgen deficiency.

Dehydroepiandrosterone (DHEA) and dehydroepiandrosterone sulfate (DHEAS) age-related withdrawal is very likely to be involved in the aging process and the onset of age-related diseases, giving rise to the question of whether preventing or compensating the decline of these steroids may have endocrine and clinical benefits. The aim of the present trial was to evaluate the endocrine, neuroendocrine and clinical consequences of a long-term (1 year), low-dose (25 mg/day) replacement therapy in a group of aging men who presented the clinical characteristics of partial androgen deficiency (PADAM). Circulating DHEA, DHEAS, androstenedione, total testosterone and free testosterone, dihydrotestosterone (DHT), progesterone, 17-hydroxyprogesterone, allopregnanolone, estrone, estradiol, sex hormone binding globulin (SHBG), cortisol, follicle stimulating hormone (FSH), luteinizing hormone (LH), growth hormone (GH) and insulin-like growth factor 1 (IGF-1) levels were evaluated monthly to assess the endocrine effects of the therapy, while beta-endorphin values were used as a marker of the neuroendocrine effects. A Kupperman questionnaire was performed to evaluate the subjective symptoms before and after treatment. The results showed a great modification of the endocrine profile; with the exception of cortisol levels, which remained unchanged, DHEA, DHEAS, androstenedione, total and free testosterone, DHT, progesterone, 17-hydroxyprogesterone, estrone, estradiol, GH, IGF-1 and beta-endorphin levels increased significantly with respect to baseline values, while FSH, LH and SHBG levels showed a significant decrease. The Kupperman score indicated a progressive improvement in mood, fatigue and joint pain. In conclusion, the present study demonstrates that 25 mg/day of DHEA is able to cause significant changes in the hormonal profile and clinical symptoms and can counteract the age-related decline of endocrine and neuroendocrine functions. Restoring DHEA levels to young adult values seems to benefit the age-related decline in physiological functions but, however promising, placebo-controlled trials are required to confirm these preliminary results.

Adrenal function under long-term raloxifene administration.

The aim of the present study was to evaluate the effect of long-term (12 months) administration of raloxifene hydrochloride (60 mg/day) on the steroid production of the adrenal cortex and on the hypothalamic-pituitary-adrenal axis in postmenopausal women. We performed a basal evaluation, a corticotropin releasing factor (CRF) (100 microg i.v. bolus) test and a dexamethasone (DXM) (0.25 mg) suppression-adrenocorticotropic hormone (ACTH) (10 microg i.v. bolus) stimulation test in 11 postmenopausal women, before and after 3, 6 and 12 months of raloxifene treatment. Raloxifene administration significantly modified circulating levels of adrenal steroids, decreasing cortisol (-24%), dehydroepiandrosterone (DHEA) (-36%), and its sulfate (DHEAS) (-41%), and androstenedione (-29%), and increasing circulating allopregnanolone (+39%) levels. Progesterone and 17OH-progesterone levels remained unmodified, while estradiol and estrone levels showed a significant decrease (-51% for estradiol and -61% for estrone). We also observed an increase in circulating ACTH (+58%) and beta-endorphin (+120%). No modifications in the hormonal responses to CRF were observed during the treatment. DXM significantly suppressed circulating steroids at any time with a lower suppression of cortisol from the third month and a higher suppression of DHEA at 12 months. ACTH administration was associated with a significantly blunted cortisol response from the sixth month and a significantly increased response of allopregnanolone from the third month. The present data exclude a raloxifene effect on pituitary sensitivity to CRF and demonstrate a reduced adrenal sensitivity to ACTH, sustained by the opposite changes in basal cortisol and Delta5 androgens, which were reduced, and in ACTH and beta-endorphin, which were increased, as well by the reduced response of cortisol to the direct ACTH stimulus. The reduction of circulating cortisol levels and cortisol response to the ACTH challenge suggests that raloxifene protects against the neurotoxic effects of endogenous glucocorticoids. Furthermore, the progressive increase in basal allopregnanolone and its increased response to ACTH indicate that chronic raloxifene administration exerts direct effects on the pattern of adrenal enzymes, leading to specific changes in the circulating levels of this anxiolytic progesterone metabolite. The important reduction in the circulating levels of estradiol and estrone under long-term raloxifene administration may represent a further mechanism by which this molecule may exert a protective effect against breast and endometrial malignancies.

Assessment of the QoL in Italian menopausal women: comparison between HRT users and non-users.

OBJECTIVES: The aim of this cross-sectional study was to describe QoL in a large sample of women attending menopause centres and compare untreated postmenopausal women and matched HRT users by employing the Women's Health Questionnaire (WHQ) and two generic instruments, the SF-36 and the EQ-5D. METHODS: Overall, 2906 women were recruited by 64 menopause centres throughout Italy, of whom 2160 filled in the questionnaire (1093 on HRT and 1067 not on HRT; response rate: 74%). RESULTS: HRT users tended to be younger, healthier and with shorter menopause duration as opposed to non users, while no major socio-economic differences were present. At multivariate analysis, the presence of chronic diseases, low socio-economic status and living in Southern Italy represented the most important predictors of poor QoL. Furthermore, HRT users showed a lower probability of reporting problems in usual activities and pain/discomfort (EQ-5D), role limitations due to emotional problems (SF-36) and anxiety/fears (WHQ). HRT users also showed highly significant better outcomes in those areas that are more directly attributable to hormonal changes of mid age, namely vasomotor symptoms and sexual problems. CONCLUSIONS: Although QoL is mainly influenced by socio-economic and cultural factors, HRT has the potential for improving not only symptoms, but also more general aspects of physical and psychological well-being of symptomatic postmenopausal women.

Validation of Italian version of the Women's Health Questionnaire: assessment of quality of life of women from the general population and those attending menopause centers.

OBJECTIVES: The Women's Health Questionnaire has been developed and validated in Anglo-Saxon and Swedish populations. The purpose of this study was to evaluate the Italian version of the questionnaire to determine whether cross-cultural differences exist in the perception of quality of life, and to use it to compare the quality of life in women attending menopause centers with that of women in the general population. METHODS: An Italian version of the Women's Health Questionnaire (WHQ) was produced, using the forward-backward translation method to ensure conceptual equivalence, and approved by the originator. Women were recruited by random selection from the general population and from menopause centers, those taking hormone replacement therapy being ineligible. The questionnaire was completed anonymously at home and mailed to the co-ordinating center. Psychometric evaluation included tests of item convergent and discriminant validity, internal-consistency reliability, test-retest reliability, construct validity and the discriminative properties of the questionnaire. RESULTS: The completeness of the data was good, with missing-value rates consistently low for most items. Item-scale correlations, used to evaluate internal consistency, were also good and the scaling success rate, used to measure item discriminant validity, was high for all scales. Scale scores were reliable for seven out of nine scales and test-retest reliability was excellent. There were few significant differences between the two populations of women in most of the WHQ areas. A comparison of Italian data with published data on English women showed great similarity. CONCLUSION: The Italian version of the WHO is valid and reproducible. The subjective perception of the menopause and its related problems is similar in geographically and culturally different populations.