LEI (Lack of tEstosterone Impact) survey in a clinical sample with surgical menopause.

OBJECTIVES: To assess perception of sexuality and awareness of the impact of testosterone on sexual desire in a clinical sample of Italian women with surgical menopause. METHODS: In the present cross-sectional study, a structured interview on sexuality-related menopausal symptoms, attitudes towards sexuality and menopausal profile was administered to 568 women (age range 35-69 years) with bilateral oophorectomy with and without hysterectomy for benign conditions. RESULTS: The majority of women (58% yes; 36% most of the time) reported they were satisfied with their sexual life before surgical menopause. After oophorectomy, 79.3% noted the appearance/worsening of vaginal dryness, whereas the reduction of sexual desire was reported by 78.7%. Women with low sexual desire (n = 436) were significantly distressed (59.7%) and reported an impairment (24.8% yes/yes, very much) in the relationship with their partner. Sexual reactions of the partner reported by women included reduced sexual desire (17.8%), sexual dysfunction (5.1%) and fears of giving pain/lack of pleasure (28.3%). A high number of women (88.2%) would be willing to discuss sexual matters with their doctors and would consider therapeutic options. Only 36.8% were aware that a lack of testosterone might impact on sexual desire but 71% would like to know more about the role of testosterone. Hormone replacement therapy was used by 38.4% of the women. CONCLUSIONS: These data suggest that women experience significant vaginal dryness and low sexual desire and report a significant distress in the relationship with their partner after surgical menopause. Sexual counseling is mandatory in order to discuss potential therapeutic strategies, including testosterone use.

Local estrogens for quality of life and sexuality in postmenopausal women with cardiovascular disease.

Urogenital aging and female sexual dysfunction (FSD) are significant problems following menopause. Estrogen decline is one of the key factors contributing to sexual functioning because of its crucial role for genital arousal (vasocongestion and lubrication) and other domains of the sexual response. Several common medical conditions, including cardiovascular disease (CVD), may interfere with women's sexual response across the aging process. FSD is one of the most common CVD-related quality-of-life complications with a major impact on patients' and their sexual partners' life. There is no evidence that FSD may represent an early indication of cardiovascular risk in postmenopausal women. In spite of the high prevalence, FSD remains largely under-recognized and sexual counseling is an important consideration for the proper management of postmenopausal women with CVD. Many local estrogen products are available (creams, tablets, suppositories, pessaries and rings) and are equally effective for treatment of vaginal atrophy. When a history of CVD is present, local estrogens may be safely used to treat urogenital atrophy with a significant improvement of sexual health and quality of life.

[Aging and sexuality in women]. / Invecchiamento e sessualità nelle donne.

A large number of biological, psycho-relational and socio-cultural factors are related to women's sexual health and they may negatively affect the entire sexual response cycle inducing significant changes in sexual desire, arousal, orgasm and satisfaction during the entire reproductive life span. In spite of the high prevalence of sexual problems with increasing age, sexual retirement is not an inevitable consequence of the passage of time and a high proportion of men and women remains sexually active well into later life, a result of changing attitudes toward sexuality and the availability of effective treatments for sexual dysfunction. Population-based studies reported an age-related decline of sexual functioning and an additional adverse effect of menopausal status. Ageing per se interferes with the level of sexual performance, but sexual behaviour of midlife and older women is highly dependent on several factors such as general physical and mental well-being, quality of relationship and life situation. Sex hormones, mainly low levels of estradiol, are relevant for the lack of sexual awareness and vaginal receptivity in naturally menopausal women. Even diminished levels of androgens, as it more frequently occurs in surgically menopausal women, has a negative impact on desire and sexual responsiveness. Several hormonal treatments have been used locally or systemically to alleviate sexual symptoms, especially by using estrogen plus androgen preparations and tibolone, with noticeable results on drive, enjoyment, lubrication, ability to reach orgasm and initiation of sex. However, sexual counseling and individualized management is mandatory to obtain meaningful and long-lasting results in clinical practice.

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.

Estradiol supplementation modulates neuroendocrine response to M-chlorophenylpiperazine in menstrual status migrainosus triggered by oral contraception-free interval.

BACKGROUND: Migraine triggered by oral contraception (OC)-free interval is very common and may be extremely severe, long-lasting and poorly responsive to analgesics (status migrainosus). The serotoninergic (5-HT) system is crucially involved in pain threshold and it is sensitive to estradiol (E2). Therefore, we aimed to assess neuroendocrine correlates of OC status migrainosus in response to the direct central 5-HT agonist meta-chlorophenylpiperazine (m-CPP) and to test the effect of transdermal E2 supplementation of the OC-free interval. METHODS: Clinical investigative protocol, single-blinded placebo-controlled treatment. Oral m-CPP (0.5 mg/kg body weight) challenge test was performed in 10 patients with status migrainosus occurring within 48 h of the discontinuation of a monophasic pill (30 microg of ethinyl estradiol and 150 microg of desogestrel) and in six healthy women assuming the same OC as controls. In a consecutive menstrual cycle, patients with OC status migrainosus underwent to the same test after they were blindly treated with 2.0 g of percutaneous E2 gel or placebo daily during the pill-free interval. Plasma prolactin and cortisol levels and clinical characteristics of migraine attacks were evaluated. RESULTS: Women with OC-status migrainosus showed a derangement of prolactin release (F = 4.8; P < 0.01) and a lack of cortisol response (F = 5.8; P < 0.001) after m-CPP in comparison with controls. Transdermal E2 during the pill-free interval significantly restored prolactin (F = 2.8; P < 0.01) and cortisol responses (F = 18.9; P < 0.001) against placebo and positively affected the duration (P < 0.001), the number of hours in which pain intensity prohibits daily activity (P < 0.001), the episodes of vomiting (P < 0.001) and the consumption of analgesics (P < 0.001). CONCLUSIONS: Status migrainosus triggered by OC-free interval is associated with impaired prolactin and cortisol responses following m-CPP challenge. Transdermal E2 supplementation is able to restore neuroendocrine response to this specific 5-HT agent, exerting a positive clinical effect on the course of menstrually related migraine.

Role of testosterone in feminine sexuality.

Gonadal steroids play a crucial role in maintaining the anatomical and functional integrity of all the structures involved in feminine sexual response. While the role of estrogens on the activity of neuroendocrine circuitries and on the trophism of genital organs has been well established, the contribution of androgens to female physical and mental well-being is still a matter of debate. Recent studies reconsidered the sources, production rates, circulating concentrations and regulatory mechanism of the major androgen precursors and androgens in women throughout the reproductive life span, as well as the wide variety of actions at the target tissues. Collectively, these reports support the therapeutic use of androgens in women, mainly to cure sexual dysfunctions, one of the consequences of menopause.

Course of migraine during pregnancy and postpartum: a prospective study.

The aim of this study was to investigate prospectively the course of migraine during pregnancy and postpartum. Of all the pregnant women consecutively attending an obstetrics and gynaecology department for a routine first-trimester antenatal check-up, 49 migraine sufferers--two were affected by migraine with aura (MA) and 47 by migraine without aura (MO)--who had experienced at least one attack during the 3 months preceding pregnancy were identified, enrolled in the study and given a headache diary. Subsequent examinations were performed at the end of the second and third trimesters and 1 month after delivery. Migraine was seen to improve in 46.8% of the 47 MO sufferers during the first trimester, in 83.0% during the second and in 87.2% during the third, while complete remission was attained by 10.6%, 53.2%, and 78.7% of the women, respectively. Migraine recurred during the first week after childbirth in 34.0% of the women and during the first month in 55.3%. Certain risk factors for lack of improvement of migraine during pregnancy were identified: the presence of menstrually related migraine before pregnancy was associated with a lack of headache improvement in the first and third trimesters, while second-trimester hyperemesis, and a pathological pregnancy course were associated with a lack of headache improvement in the second trimester. Breast feeding seemed to protect from migraine recurrence during postpartum.

Hormone supplementation differently affects migraine in postmenopausal women.

OBJECTIVE: To evaluate the effects of three schemes of oral hormone replacement therapy (HRT) on migraine course in postmenopausal women. METHODS: Thirty-eight patients presenting for clinical evaluation of menopausal status and suffering from migraine were enrolled. The observational period lasted 7 months, during which women filled in a daily diary with the clinical features of headache attacks and analgesic use. We evaluated climacteric symptoms, anxiety and depression. After a 1-month run-in period, women were assigned to one of three regimens of HRT: estradiol hemihydrate 1 mg/day plus norethisterone 0.5 mg/day for 28 days, in a continuous combined scheme; oral conjugated estrogens 0.625 mg/day for 28 days plus medroxyprogesterone acetate 10 mg/day in the last 14 days, in a sequential continuous scheme; and estradiol valerate 2 mg/day for 21 days plus cyproterone acetate 1 mg/day from day 12 to 21 in a sequential cyclical scheme. Follow-up evaluations were performed at 3 and 6 months. RESULTS: During the run-in period, the three subgroups of patients were similar as far as the features of migraine are concerned. Overall, a progressive increase in attack frequency (from 2.2 +/- 1.0 to 3.8 +/- 1.3, P<.001), days with headache (from 3.4 +/- 1.3 to 4.9 +/- 1.9, P<.001), and analgesic consumption (from 3.4 +/- 1.3 to 5.6 +/- 2.2, P<.001) was observed after 6 months. Duration of attacks decreased (from 18.1 +/- 7.4 to 13.6 +/- 4.2 hours, P =.005), whereas severity worsened (from 1.9 +/- 0.2 to 2.1 +/- 0.2, P<.001). The increase in number of days with headache and number of analgesics used was smaller in the group receiving the continuous combined regimen than in the other two groups. CONCLUSION: Although HRT typically will lead to some worsening of headache syndrome, estradiol hemihydrate plus norethisterone given in a combined continuous scheme was the regimen best tolerated by our patients.

Decline of maternal hepatitis A virus antibody levels in infants.

UNLABELLED: Hepatitis A is a common viral infection causing substantial morbidity and mortality. The anti-hepatitis A virus (HAV) vaccination in infants would guarantee control of the infection. However, the immunogenicity of the HAV vaccine in infants could be impaired by the presence of passively acquired maternal HAV antibodies. This study evaluated the prevalence of HAV antibodies in 103 women at delivery and in their babies in the first year of life. Eighteen mothers (17.5%) had anti-HAV serum level >10 mIU ml(-1). In their infants the anti-HAV level was still positive in 11 out of 18 (61.1%) at 12 mo. Two out of 85 infants born to anti-HAV-negative mothers and anti-HAV negative at birth were found to be positive at 5 mo of age. CONCLUSION: It is proposed that all women be screened at delivery for anti-HAV antibodies. Children born to anti-HAV-negative mothers could be vaccinated early during the first year of life, whereas vaccination could be postponed in children born to anti-HAV-positive mothers, if necessary.

Climacteric complaints, female identity, and sexual dysfunctions.

Forty early menopausal women seeking relief from sexual symptoms within a long-term marital relationship and 40 matched women seeking relief of climacteric complaints completed questionnaires concerning three subject: vasomotor and psychosocial symptoms, sexual dysfunctions, and female identity. Results showed that women with sexual dysfunctions were more likely to suffer from vasomotor and psychosocial complaints and their feminine identity was based mainly on ideals of motherhood and beauty. In addition, sexual desire disorders were present significantly in those women with higher psychosocial symptoms, while sexual arousal disorders were particularly evident in women suffering more vasomotor symptoms.

Pituitary LH reserve suggests high risk of bulimia in amenorrheic women.

The present study was aimed at investigating a) the risk of having bulimia in a heterogeneous population of secondary amenorrhea; b) the LH and FSH secretion under basal and stimulated conditions (GnRH challenge) according to the presence of bulimic risk in our study population; c) the clinical and endocrine factors predictive of the bulimic risk in amenorrheic women. Amenorrheic women (n=73; age: 23.1+/-4.8 yrs; BMI:20.2+/-2.2 kg/m2) filled in a self rating scale for bulimia (BITE) and were classified accordingly, as being at low risk (score <10), at medium risk (score between 10 and 24), and at high risk (score > or =25) of having bulimia. In each subject basal mean plasma LH levels were calculated over one hour, sampling every 10 minutes, while in a subgroup of 45 patients the area under the curve (AUC) of plasma LH and FSH levels following a challenge with two doses of GnRH (10+10 microg, every two hours), sampling every 15 minutes, was also evaluated. High risk of bulimia was present in 12.3% of the population whereas 45.2% showed a low risk and 42.5% were at medium risk of developing the disorder. Mann-Whitney U test revealed that basal LH values were differently distributed with significantly lower levels (P<0.046) in amenorrheic women at high risk of bulimia in comparison with amenorrheic women at low risk. The AUC of LH secretion following the first challenge of GnRH was significantly higher in amenorrheic women with a high risk of bulimia in respect with both groups of women at low (P<0.034) and medium (P<0.009) risk. A similar result was found with FSH AUC following the first GnRH challenge (P<0.04 high risk vs low risk and P<0.014 high risk vs medium risk). In a multiple regression analysis, the best model predicting the risk of bulimia (BITE total score) included both the LH response to GnRH challenge and BMI. In conclusion, when facing secondary amenorrhea at first consultation, long before a precise pathophysiologic diagnosis of the disease, low basal plasma LH levels and LH response to GnRH challenge may allow one to suspect the presence of abnormal eating pattern of bulimic type.

Factors associated with nucleic acids related to human immunodeficiency virus type 1 in cervico-vaginal secretions.

OBJECTIVE: To assess HIV-related nucleic acids in cervico-vaginal secretions and the factors associated with them. DESIGN: Observational study. SETTING: Department of Obstetrics and Gynaecology, University of Pavia, Italy. POPULATION: HIV-positive patients attending a cytology service. METHODS: Paired blood and cervico-vaginal lavage samples were obtained from 122 known HIV-seropositive patients during periodic visits for cytologic screening for lower genital tract neoplasia. Vaginal specimens for the diagnosis of bacterial vaginosis, trichomonas vaginalis and candida infection were also obtained. HIV-1-RNA in plasma, proviral HIV-1-DNA, cell associated and cell-free HIV-1 RNA in cervico-vaginal secretions were quantitatively evaluated by competitive polymerase chain reaction (c-PCR) and reverse transcriptase PCR (cRT-PCR). MAIN OUTCOME MEASURE: Prevalences of HIV related nucleic acids in cervico-vaginal secretions and their univariate and multivariate associations with clinical variables. RESULTS: Proviral HIV-1 DNA, cell-associated and cell-free HIV-1 RNA were detected in 50% (61/122), 37.7% (46/122) and 32.8% (40/122) of the patients, respectively. In logistic regression analysis, the presence of HIV-1 RNA in blood was the factor which correlated best with the detection of HIV-1 DNA (OR = 5.48, 95% CI = 2.28-13.20), cell-associated (OR = 4.85; 95% CI = 1.89-12.45) and cell-free HIV-1 RNA (OR = 4.63, 95% CI = 1.74-12.33) in cervico-vaginal samples. However, between 20% and to 35% of patients who tested negative for blood HIV-1 RNA were positive for either HIV-1 DNA or HIV-1 RNA detection in cervico-vaginal lavages. Bacterial vaginosis was associated with an increased prevalence of cell-associated (OR = 3.58, 95% CI = 1.22-10.54) and cell-free HIV-1 RNA (OR = 2.94, 95% CI = 1.0-8.7) detection in cervico-vaginal secretions. Additional factors associated with increased prevalence of HIV-1 RNA detection were advanced stage of HIV disease and vulvovaginal candidiasis. CONCLUSIONS: Although the presence of HIV-1 RNA in blood is the factor which correlates best with the detection of HIV-related nucleic acids in cervico-vaginal secretions, the shedding of HIV in the genital tract can occur in 20-30% of non-viremic subjects. Bacterial vaginosis and candida infection could have a facilitating role in local HIV viral replication and shedding.

Human immunodeficiency virus type 1-related nucleic acids and papillomavirus DNA in cervicovaginal secretions of immunodeficiency virus-infected women.

OBJECTIVE: To evaluate simultaneous human immunodeficiency virus (HIV)-related nucleic acids and human papillomavirus (HPV)-DNA in cervicovaginal secretions of HIV-seropositive women. METHODS: We collected 47 paired blood and cervicovaginal lavage samples from 124 known HIV-1-seropositive women. Proviral HIV-1 DNA, cell-associated, and cell-free HIV-1 RNA in cervicovaginal secretions were quantitatively evaluated by competitive polymerase chain reaction (PCR) and reverse transcription PCR. Polymerase chain reaction and subsequent restriction fragment length polymorphism analysis of PCR products were used to detect HPV types 6, 11, 16, 18, 31, 33, 35, and 56. RESULTS: Proviral HIV-1 DNA, cell-associated, and cell-free HIV-1 RNA were detected in 52.4% (65 of 124), 38.7% (48 of 124), and 33.9% (42 of 124) of lavage samples, respectively. Human papillomavirus-DNA in cervicovaginal secretions was detected in 64% (79 of 124) of participants. The rate of detection of HPV types of intermediate to high oncogenic risk was higher in HIV-positive women who tested positive for cell-associated (odds ratio [OR] 3.57, 95% confidence interval [CI] 1.17, 11.12) or cell-free (OR 4.63, 95% CI 1.42, 15.51) HIV-1 RNA in cervicovaginal secretions than their counterparts who tested negative. Logistic regression analysis showed that the association between HPV infection and the detection of HIV-1 RNA in cervicovaginal secretions persisted after adjustment for potential confounders such as CD4+ cell counts, HIV-1 RNA in plasma, use of antiretroviral drugs, vaginal infection, and regular condom use. In univariable and multivariable analysis, HPV-DNA detection was associated with amounts of cell-free and cell-associated HIV-1 RNA in cervicovaginal secretions (chi(2) for trend 10.35, and 9.84, P =.001 and.002, respectively). CONCLUSIONS: The rate of HPV detection in the genital tract of HIV-1-seropositive women is associated with the amount of cell-associated and cell-free HIV-1 RNA present in cervicovaginal secretions. The association does not appear to be attributable entirely to the effect of HIV-related immunodepression.

Course of primary headaches during hormone replacement therapy.

OBJECTIVE: The aim of the present study was to evaluate how hormone replacement therapy (HRT) could influence the course of primary headaches in postmenopausal women. METHODS: Fifty patients presenting for clinical evaluation of menopausal status and suffering from headache were enrolled. The observational period lasted 7 months during which women filled in a diary with the clinical characteristics of headache attacks (frequency, days with headache, severity) and the analgesic use (no. of analgesic/month). Climacteric symptoms and both anxiety and depression were also measured. At the first visit the patients were divided into two groups: those suffering from migraine without aura (MwA) and those suffering from episodic tension-type headache (ETTH) and separately randomized. After a month of run-in period, they received two different HRT regimen, either: (1) transdermal estradiol 50 mcg every 7 days for 28 days plus medroxyprogesterone acetate (MAP) 10 mg/day from 15th to 28th day, or (2) oral conjugated estrogens 0.625 mg/day for 28 days plus MAP 10 mg/day for the last 14 days. Follow up evaluations were planned after 1, 3 and 6 months of treatment. RESULTS: While we did not observe any significance change regarding headache parameters in ETTH patients during both transdermal and oral treatment, the course of migraine was significantly affected by the route of HRT. Both frequency of attacks (F = 8.5; P < 0.000) and days with headache (F = 6.9; P < 0.000) significantly increased during HRT in the subgroup assuming oral formulation. On the contrary, no changes in the same parameters were found in the group taking transdermal treatment. Moreover, while severity of migraine was unaffected by HRT, analgesic consumption was significantly increased in the subgroup on oral treatment (F = 6.3; P = 0.001). CONCLUSIONS: HRT significantly affects the course of headache in postmenopausal migraine sufferers. Indeed, while the clinical pattern of ETTH remained stable throughout the observational period, patients suffering from MwA worsened their symptoms within the first 3 months of treatment. In particular, the oral route of administration significantly worsened migraine in comparison to the transdermal route.

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."

Uterine myoma in postmenopause: a comparison between two therapeutic schedules of HRT.

OBJECTIVES: It is still controversial whether hormone replacement therapy (HRT) can affect the onset of uterine myomas or their growth in postmenopause. It is likely that some therapeutic schedules can influence the myometrial growth differently, due to a more potent stimulation of the uterine receptors. The aim of the present study is to evaluate the effects of two different hormonal treatment schedules on the risk of uterine myoma onset or progression. METHODS: In a 2 year prospective randomised study we compared an oral cyclic association of oestradiol valerate and cyproterone acetate versus a sequential combination of transdermal E(2) and per oral medrossiprogesterone acetate on 240 postmenopausal women with and without uterine myomas. RESULTS: Among the patients without uterine myomas treated with the transdermal-oral combination we noted the onset of myomas in 5% of cases after 24 months of treatment, while no new uterine formation was observed for the orally treated women (P<0.01). Among the patients with uterine myomas at the beginning of the study, in the group transdermally treated we found a mean increase in myoma volumes of 25.3% in the following 24 months, which was significantly different compared with the initial volume of myomas. On the other hand, women treated with the oral combination showed no significant modification of myoma volumes at the end of the study. CONCLUSIONS: Percutaneous-oral schedule of HRT seems to affect the growth of uterine myomas more than a single oral combination of oestradiol valerate and cyproterone acetate.

Stimulating effect of HIV-1 coat protein gp120 on corticotropin-releasing hormone and arginine vasopressin in the rat hypothalamus: involvement of nitric oxide.

Subjects with human immunodeficiency virus type 1 (HIV-1) infection display increased activity of the hypothalamo-pituitary-adrenal (HPA) axis, which may play a role in both HIV-related neurodegenerative processes and disease progression. It has been speculated that the HIV coat protein gp120 may be responsible for these changes, and previous experimental evidence in both transgenic and nontransgenic mice supports this view. We speculated that one of the effects of gp120 in the CNS is to act within the hypothalamus to affect both corticotropin-releasing hormone (CRH) and arginine vasopressin (AVP), the principal regulators of HPA axis. We therefore administered i.p. gp120 (100 ng/rat) or vehicle to male Wistar rats and then detected Fos protein (an index of neuronal activation), CRH, and AVP immunoreactivity in the cellular compartments of the hypothalamic paraventricular nucleus (PVN). In addition, we tested the direct effect of various concentrations of gp120 on the release of CRH and AVP from rat hypothalamic explants maintained in vitro. Any modulation of gp120 effects by nitric oxide (NO) pathways was also sought by coadministering i.p. to rats or adding to the hypothalamic preparations the NO synthase inhibitor N(G)-methyl-l-arginine (l-NMMA). Gp120 induced the expression of Fos protein in both the parvo- and the magnocellular PVN, which was significantly attenuated by l-NMMA 10(-6) nM/L (P < 0.001 vs gp120 alone). Double immunochemistry showed costaining for Fos protein and CRH or AVP in the PVN following gp120; the number of double-labeled CRH and AVP cells for Fos protein was markedly reduced (P < 0.001) by coadministration of l-NMMA 10(-6) nM/L. In the in vitro studies, addition of gp120 to the hypothalamic explants in the dose range of 10 pM-1 nM resulted in a clear stimulation of both CRH and AVP release (P < 0.05-0.001 compared to control); in the presence of l-NMMA at 10-fold higher concentrations the stimulatory effect of gp120 on the release of both peptides was completely lost. It would therefore appear that gp120 activates CRH and AVP-producing neurons in the hypothalamic PVN and stimulates the release of both peptides in vitro via NO-dependent mechanisms. These findings, in line with previous evidence, further suggest that the increased activity of the HPA axis associated with HIV infection may be of central origin, due to the effects of gp120 on hypothalamic CRH and AVP release.

Vertical transmission of hepatitis C virus and follow-up of newborns from infected mothers.

BACKGROUND: Aim of the study is to analyze the rate of vertical transmission of HCV and the time of clearance of maternal antibodies in non-infected babies serum. METHODS: We have studied 36 babies born to HCV-positive and HIV-negative pregnant women at the University of Pavia. All mothers underwent blood tests to evaluate the presence of anti-HCV antibodies and viral RNA during pregnancy and after delivery. All babies underwent several tests at different times to evaluate the presence of viral RNA and the clearance of maternal antibodies. RESULTS: All babies proved HCV-Ab positive at birth, but only one case (2.7%) proved infected at PCR analysis. Different patterns of HCV-Ab clearance were noted in the 35 non-infected babies. Of 24 babies from HCV-RNA-positive mothers, HCV-Ab reached zero in 24 months while in 11 babies from HCV-RNA-negative mothers, the antibodies disappeared at 12 months. A statistical difference was noted between the two groups of babies for the time of clearance of antibodies. CONCLUSIONS: The risk of vertical transmission in babies born to HCV-RNA negative mothers is very low, and the clearance of maternal antibodies is set within 12 months of follow-up. Mothers positive to HCV-RNA have a higher risk of transmitting the virus to their offspring and the time of clearance of antibodies in non-infected babies seems to be longer. A correct follow-up of these children must be no shorter than 24 months.

Bone mineral changes during and after lactation.

OBJECTIVE: To investigate variations in bone mineral density during lactation and throughout the 12 months after scheduled cessation of lactation in relation to the resumption of ovarian function. METHODS: Three hundred eight mothers who decided to lactate were scheduled to fully breast-feed for 6 months, followed by a 1-month weaning period, and then suppress lactation with cabergoline. Their bone mineral density variations were compared with those of a control group of nonlactating mothers during the first 18 months postpartum. Half the lactating women were given daily oral calcium supplements of 1 g in an open design. RESULTS: There was a significant progressive decrease in bone mineral density in lactating women over the first 6 months, followed by recovery of bone mass up to levels that at 18 months were higher than baseline. In nonlactating women, bone mineral density increased progressively after delivery, and at 18 months postpartum had increased by 1.1-1.9% compared with baseline. Compared with lactating women who resumed menstruation within 5 months of delivery, breast-feeding mothers with longer amenorrhea initially lost more bone, but they also gained significantly more bone after resumption of menses, so there were no differences at 18 months postpartum. Oral calcium supplementation decreased bone loss, but had only a transient effect. CONCLUSION: A scheduled lactation period of 6 months, followed by a 1-month weaning period, allowed bone mineral density to reach higher values compared with early postpartum, regardless of calcium supplementation and duration of postpartum amenorrhea.