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.

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.

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.

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.

[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.

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.

Vasopressin and oxytocin receptors in vagina, myometrium, and oviduct of rabbits.

In view of the presence of distinct oxytocin (OT) and vasopressin (VP) receptors in the male genital tract (porcine) we have reexamined the receptors for OT and AVP in the classical OT target tissue, female genital tract (rabbit). Neurohypophysial hormone receptors have been investigated in vagina, myometrium, and oviduct using quantitative ligand binding, adenylate cyclase, and contractility studies. Our results clearly indicate the presence of distinct OT and V1 VP receptors in the myometrium, while only the latter was detected in vagina and oviduct. In myometrium, estrogen treatment increases the density of OT and AVP receptors, while progesterone administration inhibits the estrogen effect. At the time of spontaneous delivery a dramatic (17-fold) increase was observed for the OT sites, while the AVP sites were unchanged. AVP receptors in vagina were sensitive to sex steroid administration and were reduced during pregnancy and delivery. Isometric contractility studies suggest that not just OT, but AVP can stimulate uterine strips, an effect that is partially reversible by the V1 antagonist d(CH2)5TyrMeAVP. In vagina only AVP is effective in inducing contractions at nanomolar concentrations. These results suggest a role for AVP as well as OT in regulation of the motility of female genital tract.

Luteinizing hormone (LH) secretory burst duration is independent from LH, prolactin, or gonadal steroid plasma levels in amenorrheic women.

The possible presence of LH pulsatile secretion has been studied in patients with hypothalamic amenorrhea [LH plasma levels, less than 3 (n = 35) or greater than 3 IU/L (n = 18)], amenorrhea associated with hyperandrogenemia (n = 31), or hyperprolactinemia (n = 10). Patients were sampled every 10 min for 4 h, and LH plasma concentrations were determined by the use of an immunofluorimetric assay. The program Detect was used for both pulse detection and data deconvolution, i.e. for instantaneous secretory rate computation, on LH time series. The presence of episodic LH secretion was observed in all patients, and LH pulse frequency ranged between 3.5 +/- 0.3 and 3.8 +/- 0.2 peaks/4 h among the four groups. LH pulse amplitude was significantly reduced in patients affected by hypothalamic amenorrhea with LH plasma levels lower than 3 IU/L (0.7 +/- 0.1 IU/L; P less than 0.01) and significantly increased in patients with hyperandrogenic amenorrhea (6.8 +/- 0.3 IU/L; P less than 0.01) compared to levels in the other groups under study. Instantaneous secretory rate computation permitted the optimal resolution of the secretory events and demonstrated that the duration of gonadotrope secretory bursts ranged from 22.8 +/- 1.4 to 26.8 +/- 2.3 min in amenorrheic patients and did not depend on LH, PRL, or sex steroid plasma levels. In conclusion, the present study shows the presence of significant LH pulsatile release in amenorrheic patients, suggesting that in amenorrheic, as in normally cycling, women the secretory bursts from the gonadotropes have the same duration, despite the plasma LH, PRL, or steroid hormone levels.

Effect of corticotropin-releasing factor-binding protein on prostaglandin release from cultured maternal decidua and on contractile activity of human myometrium in vitro.

Human placenta and uterine tissues are sites of production and local action of corticotropin-releasing factor (CRF). The recent evidence that CRF-binding protein (CRF-BP), a protein that blocks CRF-induced pituitary ACTH release, is produced by placental tissues suggested the present study to investigate the effects of CRF-BP on prostaglandin release and contractile activity of myometrial strips. Primary cultures of decidual cells were prepared using tissue collected from healthy women undergoing cesarean delivery at term. Mechanical and enzymatic cell dispersions were carried out, and experiments were performed 24-28 h after cell plating. The prostaglandin E2 (PGE2) concentration in cultured medium was measured by RIA. Myometrial strips were obtained from the upper edge of the uterine incision during elective cesarean section at term. Dissected free of connective tissue, strips were mounted in a 30-mL two-chamber organ bath containing oxygenated Tyrode's buffer (37 C) and connected to a two-channel isometric smooth muscle transducer. Cultured decidual cells collected at term significantly increased the release of PGE2 in the presence of CRF (P < 0.01). The addition of CRF-BP did not significantly modify PGE2 release, but completely reversed the effect of CRF. When human myometrial strips were incubated in the presence of CRF and PGF2 alpha, a significant increase in contractile activity was observed (P < 0.01); preincubation with CRF-BP prevented the increased contractile activity induced by CRF. The present data show that CRF-BP is able to counteract the biological effect of CRF on human pregnancy endometrium and myometrium and suggest that CRF-BP may be a regulatory protein that plays a role in the local function of uterine tissues during pregnancy.

Neuroendocrine changes in luteal function in patients with premenstrual syndrome.

The present study evaluates the luteal progesterone (P) and LH secretions in 14 patients affected by premenstrual syndrome (PMS) and in 14 asymptomatic controls through the evaluation of their episodic release. PMS was prospectively confirmed in two consecutive menstrual cycles using Moos' Menstrual Distress Questionnaire. A pulsatility study was performed during the luteal phase. Blood samples were drawn every 10 min for 12 h, beginning at 0800 h. Statistically significant pulses were detected using the Detect program, and the degree of concordance of LH and P pulses was estimated. Similar mean 12-h P levels were found in controls (mean +/- SD, 13.9 +/- 9.3 nmol/L) and patients (14.2 +/- 10.1). LH levels were also similar in the two groups. Patients showed a higher P pulse frequency (13.4 +/- 1.8 vs. 11.4 +/- 2.3; P < 0.02) and a reduced amplitude of secretory episodes (126.5 +/- 61.6% vs. 187.1 +/- 126.7%; P < 0.03) than controls. Similarly, PMS patients showed pulsatile LH release of increased frequency and reduced amplitude than controls. A significant degree of concordance between LH and P pulses was observed in both groups, with a time lag of 0-10 min; that is, P secretory episodes follow LH with a delay of 0-10 min. These findings demonstrate that despite the fact that integrated P levels in PMS patients are similar to those in control subjects, the episodic secretion of the hormone is characterized by pulses of increased frequency and reduced amplitude. This phenomenon is temporally related to LH secretion, thus reinforcing the concept of PMS as a neuroendocrine disorder.

Naloxone administration does not affect gonadotropin secretion in agonadal men either basally or during testosterone treatment.

Naloxone administration has no effect on plasma gonadotropin levels of agonadal men. The present study was designed to evaluate whether testosterone replacement therapy could restore LH responsiveness to naloxone in such men. We measured plasma LH and FSH levels at 15-min intervals during naloxone infusion (8 mg in 1 min followed by 12 mg in 3 h) and for the following 3 h in a group of agonadal men both before and after at least 2 months of three different schedules of testosterone replacement therapy: 1) testosterone undecanoate, 40 mg three times a day by mouth; 2) testosterone enanthate 200 mg im every 2 weeks; and 3) testosterone enanthate 100 mg im once a week. Mean plasma gonadotropin levels as well as LH pulse frequency did not vary during naloxone infusion vs. placebo either basally or during each testosterone regimen. These results suggest that long term testosterone therapy does not affect the altered opioid modulation of gonadotropin secretion which is present in agonadal men.

Inhibin and activin modulate human monocyte chemotaxis and human lymphocyte interferon-gamma production.

Inhibin and activin are referred to as gonadal glycoprotein hormones whose function is the control of FSH release from the pituitary gland. However, several observations indicate that inhibin and activin are produced in various organs and serve multiple functions. Because bone marrow and spleen produce inhibin and activin, our aim was to evaluate their possible effect on cell-mediated immune function. For this reason we studied 1) monocyte chemotaxis, 2) lymphocyte interferon-gamma production, 3) phytohemagglutinin-induced lymphocyte proliferation, and 4) nonmajor histocompatibility complex-restricted and lymphokine-activated lymphocyte cytotoxicity. All studies were performed on human peripheral blood cells in the absence or presence of various doses of inhibin, activin, or inhibin plus activin. A significant dose-related increase in monocyte chemotaxis was induced by inhibin. Activin increased the migrational activity of monocytes, but via random, not directed, migration. Inhibin significantly decreased interferon-gamma production, and its effect was reversed by activin. Inhibin and/or activin had no significant effect on either phytohemagglutinin-induced lymphocyte proliferation or lymphocyte cytotoxic capability. The present demonstration that inhibin and activin may affect some immune parameters suggests a possible involvement of these hormones in regulating cell-mediated immune function.

Maternal plasma and placental immunoreactive corticotrophin-releasing factor concentrations in infection-associated term and pre-term delivery.

The present study aimed to investigate whether microbial invasion of the amniotic cavity affects maternal plasma or placental immunoreactive corticotrophin releasing factor (ir-CRF) concentrations in pregnant women with pre-term or term labour. A cross-sectional study was conducted collecting blood samples in: (1) women with pre-term labour and intact membranes (25-36 weeks), with or without microbial invasion of the amniotic cavity (subdivided into three groups: 1A, no microbial invasion of the amniotic cavity, delivery at term, n = 54; group 1B, delivery < 48 h, no microbial invasion of the amniotic cavity, n = 10; group 1C, delivery < 48 h, microbial invasion of the amniotic cavity, n = 8); (2) women at term, not in labour and without microbial invasion of the amniotic cavity (n = 15); (3) women in spontaneous active labour at term without (A) (n = 55) or with (B) (n = 16) microbial invasion of the amniotic cavity; and (4) healthy women not in labour at 25-36 weeks of gestation (n = 25). Specimens of trophoblast tissue were collected from pregnant women with pre-term labour (no microbial invasion of the amniotic cavity, n = 6; microbial invasion of the amniotic cavity, n = 4) or delivering at term (no microbial invasion of the amniotic cavity, n = 8; microbial invasion of the amniotic cavity, n = 4). A specific radioimmunoassay on acidic extracts of plasma or placental specimens was used.(ABSTRACT TRUNCATED AT 250 WORDS)

Long-term GnRH-agonist administration revealed a GnRH-independent mechanism stimulating FSH discharge in humans.

The present study evaluated the FSH and LH episodic discharge in different physiopathological conditions undergoing chronic GnRH-agonist administration. Four girls with true precocious puberty and five postmenopausal women were administered GnRH-agonist (3.73 leuprolide acetate every 4 weeks; Takeda Italia, Rome, Italy) for at least 4 months. Plasma LH and FSH secretory profiles were assessed before and under GnRH-agonist administration (after 21 and 120 days). Pulsatility studies were conducted for 4 h in the girls and for 6 h in postmenopausal women, with blood sampling intervals of 10 min. Pubertal and postmenopausal patients showed the distinct episodic co-secretion of LH and FSH before GnRH-agonist administration; this co-secretion disappeared in both groups after 21 and 120 days of treatment. Moreover, while LH concentrations decreased to almost undetectable levels and LH episodic release disappeared, FSH plasma levels were only partially reduced and FSH episodic secretion was detectable in both groups. In conclusion, this study demonstrated that long-term GnRH-agonist administration blocked LH but not FSH episodic release. These data enforce the hypothesis that FSH episodic discharge might be dependent not only on hypothalamic GnRH, but also on a GnRH-independent stimulatory pathway.

Episodic secretion of activin A in pregnant women.

The aim of the present study was to determine the characteristics of activin A secretion in women with normal and abnormal pregnancy. With this purpose, a prospective study was done to evaluate the putative pulsatile pattern of serum activin A in serial specimens of blood collected during a certain amount of time (every 15 min for 3 h). A group of pregnant women (N = 24) participated in a cross-sectional study. They were subdivided into three groups: healthy pregnant women (N = 8), patients with preterm labor (N = 8) and patients with gestational diabetes (N = 8) before and after insulin therapy. Secretory pulses of serum activin A were determined in all patients with a specific frequency and amplitude by using two different computerized analyses, i.e. DETECT and CLUSTER. Mean +/- SEM values of serum activin A were significantly higher in patients with preterm labor and gestational diabetes than in controls (p < 0.01), showing a significant decrease following insulin therapy in diabetic patients (p < 0.01). Specific pulses of serum activin A levels were observed in all women. The mean pulse frequency did not change significantly between healthy controls and the different pathological groups. Patients with gestational diabetes after insulin therapy showed a pulse frequency that was significantly higher than in controls (p < 0.05). When the mean peak amplitude of activin A pulses was evaluated, patients with preterm labor or gestational diabetes showed values that were significantly higher than in healthy pregnant women (p < 0.01) A significant, inverse correlation between pulse frequency and amplitude was found both in healthy pregnant women (p < 0.05) and in patients with gestational diabetes (p < 0.001). The present study showed that circulating activin A levels in pregnant women change in a pulsatile pattern whose pulse amplitude is modified in the presence of gestational diseases, such as preterm labor or gestational diabetes.

Intrinsic secretory characteristics of luteinizing hormone and prolactin episodic release during pubertal development.

The intrinsic characteristics of LH and prolactin (PRL) episodic secretion were evaluated in a group of 18 children (8M and 10F). The children were divided into two groups according to the Tanner stage: Group A (Tanner < or = 1, N = 7, 3M and 4F, 6-10 years of age) and group B (Tanner 2-3, N = 11, 5M and 6F, 9-11 years of age). A pulsatility study of 4 h, sampling every 10 min, was carried out in all children. LH and PRL plasma levels were assayed by IFMA and RIA respectively. LH and PRL secretory episodes were then identified on plasma determinations using the program DETECT. Instantaneous secretory rates (ISR) were then computed for both LH and PRL using the specific algorithm within the DETECT program. Plasma LH levels were different between the two groups of children. Group A children showed undetectable LH plasma levels (below the minimal detectable dose of 0.1 mIU/ml), while group B demonstrated LH plasma levels in the normal range of values for age and sexual development (1.5 +/- 0.3 mIU/ml, mean +/- SEM). LH pulse frequency for group B was 3.2 +/- 0.4 peaks/4 h. No significant differences in mean plasma PRL levels, pulse frequency and pulse amplitude were observed between the two groups of children. Computation of ISR for LH (group B only) and PRL (both groups) identified the intrinsic episodic characteristics of the two hormones. No significant differences in LH and PRL pulse frequencies were observed when comparing the results estimated on ISR with those estimated on plasma concentrations.(ABSTRACT TRUNCATED AT 250 WORDS)

Allopregnanolone and dehydroepiandrosterone response to corticotropin-releasing factor in patients suffering from Alzheimer's disease and vascular dementia.

OBJECTIVE: Neurosteroids have been suggested to be involved in the regulation of cognitive performances. A major neurosteroid gamma-aminobutyric acid (GABA) agonist is allopregnanolone: the main source of circulating allopregnanolone is the adrenal cortex. Studies indicated that a disturbance of the central regulation of the hypothalamic-pituitary-adrenocortical axis occurs in both senile (Alzheimer's disease: AD) and vascular dementia (VD). DESIGN: The aim of the present study was to evaluate the levels of circulating allopregnanolone, dehydroepiandrosterone (DHEA) and cortisol and their response to corticotropin-releasing factor (CRF) test in AD and VD. METHODS: Three groups of 12 subjects were included in the study: AD, VD and age-matched control subjects. CRF test was performed in all subjects and allopregnanolone, DHEA and cortisol levels were measured every 15min for 2h. RESULTS: Mean +/- s.e.m. allopregnanolone and DHEA basal levels were significantly lower in AD and VD than in controls, while cortisol levels were significantly higher than in controls (P<0.01). Allopregnanolone and DHEA levels increase in response to CRF test in all subjects but the area under curve (AUC) in patients was significantly lower than in controls (P<0.01). Cortisol secretion appeared to be very sensitive in response to CRF stimulation: in fact, cortisol response to CRF test in AD and VD subjects was higher (both as AUC and as % max increase) than in controls (P<0.01). CONCLUSIONS: The present study firstly showed that allopregnanolone levels are reduced both in AD and in VD and that dementia has a preserved stimulated response of allopregnanolone to CRF. Overall, however, the total response of allopregnanolone to CRF remains reduced in respect to controls. Further studies are necessary for a better understanding of the role of neurosteroids in the regulation of cognitive function.