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Background: The aetiology of bacterial vaginosis (BV) is still unclear but it is currently considered to be a synergistic polymicrobial syndrome. BV can often arise as a chronic or recurrent disease. The reason for such recurrences is not well elucidated. Previous studies have suggested that vaginal vitamin C may be a useful treatment in reducing recurrence rate, by increasing vaginal acidification and thereby making up for the decrease in hydrogen peroxide that results from a reduction in the number of lactobacilli present. Based on the above-mentioned consideration, a study was performed that aimed to evaluate the effect of vitamin C in the prophylaxis of BV relapses. Methods: This was a randomised, double-blind, placebo-controlled, parallel-group clinical trial. One hundred and forty-two women, after having been cured from a recent episode of BV by either metronidazole or clindamycin, were randomised to receive vitamin C (74 patients) or placebo (68 patients) as prophylaxis for six monthly cycles, starting within 24 hours of the determination of ‘ BV cure ’ . The patients applied one vaginal tablet once a day for 6 consecutive days per month after menses. Results: The rate of BV recurrence during the first 3 months was considerably lower in the vitamin C group (6.8%) than in the placebo (14.7%) group. Considering a 6-month treatment period, the recurrence rate in the vitamin C group (16.2%) was significantly lower (P = 0.024) than in the placebo group (32.4%). Moreover, at the same time point, the survival analysis of Kaplan Meyer was significant in favour of the vitamin C group compared with the placebo group (P = 0.029). Conclusions: The study showed that regular use of 250 mg ascorbic acid vaginal tablets on 6 days per month for 6 months after successful treatment of bacterial vaginosis halves the risk of recurrence from 32.4% to 16.2% (P = 0.024). doi: http://dx.doi.org/10.4021/jocmr1489w

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.

Introduction Primary headaches are common in women and impact on their quality of life and psychosocial functioning. Few data are available on sexuality in female headache sufferers. Aim An observational pilot study was conducted to assess sexual function and distress in women treated for primary headaches in a tertiary university center. Methods From a total of 194 women consecutively observed over a 3‐month period, 100 patients were recruited. Migraine with and without aura, and tension‐type headache, both episodic and chronic (CTTH), were diagnosed according to the International Classification of Headache Disorders. A detailed pharmacological history was collected, and anxiety and depression were assessed using validated scales. The Female Sexual Function Index (FSFI) and Female Sexual Distress Scale‐Revised were administered. Main Outcome Measures The main outcome measures are sexual symptoms and distress in women treated for primary headaches. Results More than 90% of the women had a median FSFI full‐scale score under the validated cutoff, while 29% reported sexual distress. Hypoactive sexual desire disorder (HSDD) was diagnosed in 20% of the women and the pain domain score (median 2, score range 0–6) was highly affected by the head pain condition. However, the FSFI domain and full‐scale scores did not significantly differ by headache diagnosis. The women with CTTH displayed a high rate of sexual distress (45.5%) and a strong negative correlation between desire, arousal, and full‐scale FSFI score and number analgesics/month ( r : −0.77, P = 0.006; r : −0.76, P = 0.006; and r : −0.68, P = 0.02, respectively). Depression was positively correlated with sexual distress ( r : 0.63, P = 0.001) only in the women with CTTH. Conclusion Women treated for primary headaches were found to display a high rate of sexual symptoms and distress. Both migraine and tension‐type headache were associated with sexual pain and HSDD, but women with CTTH seem to be more prone to develop sexual distress. Nappi RE, Terreno E, Tassorelli C, Sances G, Allena M, Guaschino E, Antonaci F, Albani F, and Polatti F. Sexual function and distress in women treated for primary headaches in a tertiary university center. J Sex Med 2012;9:761–769.

Menopause is often associated with vaginal atrophy and related symptoms, such as vaginal dryness, burning, itching, and dyspareunia, decrease in libido and in general a decrease in the quality of life. The common treatment up to the 1990's has been the oral hormone replacement therapy (HRT), but this treatment has been consequently re-considered due to its adverse effects. Topical estrogenic products have been subsequently developed to minimize the systemic adverse effects of the oral HRT, but they are still considered at risk in case of prolonged use. As an alternative, two clinical trials were performed to investigate the effects of a medical device in the form of a gel, containing hyaluronic acid, liposomes, phytoestrogens from Humulus lupulus extract, and Vitamin E, with the aim of testing its safety and efficacy in post-menopausal women with urogenital atrophy. The first pilot study confirmed in 10 women the good safety profile, both locally and systemically, of the device applied on the external genitals at the dose of 1-2 g/day for 30 days. The second study was carried out, according to a multicenter, open, non-controlled design, in 100 post-menopausal women assigned to the vaginal application of 2.5 g of gel/day for 1 week followed by two applications/week for 11 weeks. The primary end-point was the evaluation of vaginal dryness assessed by a Visual Analogue Scale both by the investigator and the subject. Secondary endpoints were the evaluation of all other symptoms and signs associated with atrophic vaginitis (itching, burning, dyspareunia, vaginal inflammation/oedema and rash assessed by a 4-point scale and presence of vaginal abrasions and disepithelialisation), and the recording of adverse events during the study. At the end of the treatment, an overall judgment on the efficacy and safety of the device was made by the investigator and a judgment on the acceptability of the treatment was made by the subjects. The results showed a marked effect of the tested product on the vaginal dryness and on all other symptoms and signs with statistically significant reductions since the first week of treatment. No treatment-related adverse events were complained by the subjects and the treatment course showed a high level of acceptability by the subjects. This device could be considered an effective and safe alternative treatment of genital atrophy in post-menopausal women, especially when HRT is not recommended.

Implantation failure is common in assisted reproduction techniques (ART). The role of low-molecular-weight heparin (LMWH) is a matter of debate as a potential factor to improve implantation. Aim: To evaluate the pregnancy rate in patients with or without heparin administration. Materials & methods: We performed a retrospective observational analysis of patients with at least two IVF/intracytoplasmic sperm injection cycles with implantation failure, screened for inherited thrombophilia and submitted to further ART cycles with or without administration of LMWH. A total of 265 patients fulfilled the enrollment criteria. Of these 149 (56%) were primary infertile and 116 (44%) were secondary infertile. Their mean age was 36.3 ± 3.6 years. We analyzed basal FSH, smoking habit, gene variants for inherited thrombophilia (i.e., MTHFR C677T, prothrombin G202A10G and factor V Leiden). The patients underwent 569 new ART cycles: 512 (90%) without and 57 (10%) with LMWH. Results: In total 105 clinical pregnancies were observed in 569 cycles (18.8%). The pregnancy rate was 17.19% (88/512) in patients not treated with LMWH and 29.52% (17/57) in the LMWH-treated group (p = 0.006). In women over 36 years of age the pregnancy rate was 15.53% (50/322) in nontreated versus 35.71% (10/28) in treated cycles (p = 0.007), while no difference was found in younger women. No statistical difference was found between the presence of inherited thrombophilia and pregnancy rate in treated and untreated cycles. Discussion: significantly higher pregnancy rate in patients with previous ART implantation failures was observed with LMWH. Our results confirm no relation among inherited thrombophilia and pregnancy rate in patients with previous IVF implantation failures. These findings should be confirmed by randomized controlled trials before use of LMWH for ART cycles is recommended.

Among primary headaches, migraine is the form more sensitive to the ovarian hormonal milieu. Migraine without aura (MO) benefits from the hyperestrogenic state of pregnancy and the lack of hormonal fluctuations, while migraine with aura (MA) presents distinctive features. Indeed, a very strong improvement of MO has been documented across gestation, and only a minority of pregnant women still suffers during the third trimester. On the other hand, fewer women with MA report improvement or remission, and new onset of aura may be observed during pregnancy. After delivery, breastfeeding exerts a protective action on migraine recurrence. The persistence of migraine during gestation seems to affect neonatal outcomes, and several studies indicate a link between migraine and an increased risk of developing gestational hypertension/preeclampsia and other vascular complications.

Migraine with aura (MA) is a contraindication to the use of combined oral contraceptives (COCs) because of the increased risk of ischemic stroke. Progestogen-only contraceptive pill (POP) is a safe alternative to COCs and it is preferable in women with cerebrovascular diseases or risk factors for stroke.Prospective diary-based pilot study. Thirty women with MA (n = 15 who have never used COCs and n = 15 who had previously used COCs were diagnosed according to the International Headache Society criteria. The observational period lasted 9 months during which women filled in a diary with the clinical characteristics of headache attacks. After a 3-month run-in period, each subject received an estrogen-free desogestrel (DSG) (75 mcg/day)-containing OC (Cerazette(®); Schering-Plough, formerly NV Organon, Oss, The Netherlands). Follow-up evaluations were planned at the end of the third and sixth month of treatment.The number (mean±S.D.) of migraine attacks was significantly reduced both in previous COCs users (from 3.9±1.0 to 2.9±0.8; p.001) and nonusers (from 3.2±0.9 to 2.6±1.3; p.02) following 6 months of POP use in comparison with the run-in period. Duration of headache pain did not differ significantly in both groups throughout the study. Interestingly enough, a beneficial POP effect on the duration (mean±S.D.) of visual aura (from 16.3±9.5 to 11.4±5.6 min) and on the total duration (mean±S.D.) of neurological symptoms (from 33.6±23.3 to 18.6±18.0 min) was only significantly reported by previous COCs users (p.001, for both) by the end of the study period. The POP was well tolerated by each woman and the bleeding pattern was variable with a tendency towards infrequent bleeding.The present study supports the use of the POP containing desogestrel in a population of women with MA and underlines a positive effect on symptoms of aura, especially in MA sensitive to previous use of COCs.

The present short review underlines the role of testosterone (T) in the motivational and satisfaction components of women's sexuality and critically discusses the strategies to treat hypoactive sexual desire disorder (HSDD), a condition of low desire associated with personal and/or interpersonal difficulties, which is more common in surgical menopausal women. There are multiple ways androgens target the brain regions (hypothalamic, limbic and cortical) involved in sexual function and behaviour. Even though circulating available androgens have been implicated in several domains of sexual response, they seem to be related weakly to symptoms, such as low sexual desire, poor sexual arousal, orgasm and diminished well-being in postmenopausal women. The possibilities of treating low sexual desire/HSDD are multifaceted and should include the combination of pharmacological treatments able to maximize biological signals driving the sexual response, and individualized psychosocial therapies in order to overcome personal and relational difficulties. Transdermal T has been shown to be effective at a dose of 300 µg/day both in surgically and naturally menopausal women replaced with estrogen or not, without any relevant side-effects. However, the decision to treat postmenopausal women with HSDD with T is mainly based on clinical judgement, after informed consent regarding the unknown long-term risks.

Hypoactive sexual desire disorder (HSDD) is a common multidimensional condition which is characterized by a decrease in sexual desire that causes marked personal distress and/or interpersonal difficulty. There are a number of potential causes and contributing factors to HSDD and a balanced approach comprising both biological and psycho-relational factors is mandatory for accurate diagnosis and tailored management in clinical practice. It is clearly evident that sex hormones play a crucial role in modulating sexual response during the entire reproductive life span of women. On the other hand, a better understanding of the neurobiological basis of sexual desire supports the idea that selective psychoactive agents may be proposed as non-hormonal treatments to restore the balance between excitatory and inhibitory stimuli leading to a normal sexual response cycle. However, there are currently no approved pharmacological treatments for premenopausal women with HSDD, while transdermal testosterone is approved in...

In this review, we underline the importance of linking migraine to reproductive stages for optimal management of such a common disease across the lifespan of women. Menopause has a variable effect on migraine depending on individual vulnerability to neuroendocrine changes induced by estrogen fluctuations and on the length of menopausal transition. Indeed, an association between estrogen ‘milieu’ and attacks of migraine is strongly supported by several lines of evidence. During the perimenopause, it is likely to observe a worsening of migraine, and a tailored hormonal replacement therapy (HRT) to minimize estrogen/progesterone imbalance may be effective. In the natural menopause, women experience a more favourable course of migraine in comparison with those who have surgical menopause. When severe climacteric symptoms are present, postmenopausal women may be treated with continuous HRT. Even tibolone may be useful when analgesic overuse is documented. However, the transdermal route of oestradiol administration in the lowest effective dose should be preferred to avoid potential vascular risk.

Introduction Estrogen is relevant to women's well-being including sexual functioning. Aim The goal of this Continuing Medical Education article was to provide a comprehensive review of the effect of exogenous estrogen use on women's sexual function. Main Outcome Measures We present a literature review. Methods The medical literature was accurately searched (1990–2008) with regard to estrogen therapy in menopausal women by using several terms related to and including the terms “estrogen” and “sexual function.” Results A review of the studies most useful to guide menopausal practice. Conclusions Estrogen decline is one of the key factors contributing to sexual functioning during menopausal transition and beyond. Systemic estrogen treatments are associated with significant benefits in some domains of menopausal sexual function, especially when estradiol is delivered transdermally, whereas local estrogens are effective in preventing urogenital aging. Even tibolone, a selective tissue estrogenic activity regulator, displays positive effects in postmenopausal women with sexual complaints. However, a tailored approach to the individual woman is always needed. Nappi RE, and Polatti F. The use of estrogen therapy in women's sexual functioning. J Sex Med 2009;6:603–616.

Riassunto Premesse La sindrome premestruale (PMS) comprende un’ampia varieta di sintomi ciclici e ricorrenti di natura fisica, emozionale, comportamentale e cognitiva che insorgono durante la fase luteale del ciclo mestruale e che vanno in remissione rapidamente con l’inizio della mestruazione. La non univocita degli strumenti diagnostici ha portato negli anni a conclusioni differenti sul piano epidemiologico, eziopatogenetico e clinico. Il disturbo disforico della fase luteale (PMDD) e la forma piu severa e debilitante di disordine premestruale che si verifica nel 3-8% dei casi e che comprende sempre almeno un sintomo della serie disforica. Talvolta, rappresenta un’esacerbazione premestruale di un disturbo della serie depressiva/ansiosa. Discussione e conclusioni PMS/PMDD rappresentano un modello del compromesso psiconeuroendocrino ciclico che i sistemi adattativi femminili mettono in atto mensilmente in risposta alle fisiologiche fluttuazioni degli steroidi ovarici. La complessita della sindrome sembra ricondursi alla peculiare soglia di vulnerabilita di ciascuna donna, modulata nell’arco della vita fertile da numerosi fattori non soltanto di natura biologica, ma anche di origine psicosociale. Da cio derivano, pertanto, la poliedricita sintomatologica, la mancanza di marcatori biochimici e il non sempre agevole approccio terapeutico, che puo beneficiare di associazioni estroprogestiniche con azione contraccettiva.

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.

The primary objective of this randomized, double-blind, controlled study was the assessment of the pH-lowering effect of three different formulations of a vaginal device each containing 250 mg vitamin C. Overall, 39 women with vaginal pH >or=5, without evidence of vaginal infections, were randomly assigned to receive one of the three formulations for 6 days. The primary parameter assessed was vaginal pH, performed by the physician at the baseline and final visits and by the subjects each day during the application period; secondary parameters included the acceptability and safety profile of the tested devices. A decrease in pH to the normal range in all groups was observed following the first application, with stable low values during the whole study period. No statistically significant differences were seen among the three groups, while statistically significant within-group differences were observed. Acceptability and tolerability were rated as very good/good in most cases. The study results confirm that the vaginal application of vitamin C has an effective and long-lasting vaginal pH-lowering effect.

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 (E(-2)). 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 E(-2) 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 µg of ethinyl estradiol and 150 µg 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 E(-2) 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 E(-2) 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 E(-2) 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. (authors)

Problem: In order to investigate the role of amniotic fluid cells (AFC) in the establishment of feto–maternal immune relationship, we evaluated their phenotype and capacity to produce cytokines. Methods of study: CK 7–8, human leukocyte antigen (HLA)-I, HLA-DR, HLA-G, CD1d, CD34, CD45, CD14 surface antigens expression and the intracellular production of IL-4, IL-6, IL-8, IL-10, IL-12, interferon-γ and tumor necrosis factor-α were studied in cultured AFC and in eight samples immediately after amniocentesis using flow cytometry. IL-6 and IL-8 were detected by ELISA in all amniotic fluids and in all culture supernatants. Moreover, IL-6 and IL-8 mRNA were tested in nine samples. Results: Cultured AFC express HLA-I, HLA-G and CK 7–8 and are able to produce IL-6 and IL-8, confirmed by presence of their mRNA. We quantified IL-6 and IL-8 levels in all amniotic fluids and in all supernatants. Conclusion: Surface antigen expression of AFC are not specific of immune cells, but AFC are able to produce cytokines and we can postulate that they may participate in mechanisms involved in normal as well as pathological pregnancy.

The aim of the present cross-sectional study was to investigate the frequency of self-reported sexual symptoms in women (n = 355; age range 46–60 years) attending menopausal clinics in Italy and to relate them to other vasomotor, psychological, physical, and genital complaints. Each subject completed a visual scale for sexual symptoms and for other complaints frequently occurring at menopause. Pain during sexual intercourse (29.8%) and low libido/lack of arousal (22%) were significantly more frequent with age (χ2 = 8.0, p < 0.02; χ2 = 6.2, p < 0.04, respectively) and years since menopause (χ2 = 13.0, p < 0.005; χ2 = 11.3, p < 0.01, respectively). Reduction of sexual pleasure/satisfaction (45.9%) was common with age, but was more frequent with longer time since the menopause (χ2 = 19.9, p < 0.001). By examining the intensity of sexual symptoms according to the presence of other complaints, we found that physical, psychological, and genital well-being significantly affects components of sexual response after the menopause. For example, loss of fitness, urogenital symptoms, a negative self-image (increase of facial hair), and depressive symptoms were more common in women with sexual complaints. Given the concomitant role of hormonal and aging determinants, a comprehensive approach to female health is needed when facing climacteric sexual dysfunction.

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.

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 (χ2 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.

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.

To relate serum allopregnanolone and progesterone levels postpartum to maternity "blues."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."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).Serum allopregnanolone levels were detectable postpartum and were significantly decreased in women with maternity "blues."

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 begining 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.

Background. We sought to evaluate the long-term safety and efficacy of cyclic combined estradiol valerate and cyproterone acetate. Methods. A six-year, single center, open study was performed of forty-eight recently postmenopausal women. We evaluated biochemical markers of bone turnover, bone mineral content, bone mineral density, serum lipids, climacteric symptoms, and bleeding throughout the six-year period. Ultrasound evaluation of the endometrium was performed yearly for the first two years. Results. Markers of bone turnover were decreased over the study period, while bone mineral content and density remained unchanged. High density lipoprotein cholesterol levels were increased with unchanged blood pressure over the six years. Menopausal symptoms showed significant improvements within 6 months. Endometrial scan results never required hysteroscopic evaluation. Conclusion. Sequentially combined estradiol valerate and cyproterone acetate can be used for an indefinite number of years in women with recent natural menopause. Cyproterone acetate provides adequate endometrial protection and cycle control while allowing estradiol valerate to exert its positive effects on lipid profile, bone metabolism, and climacteric symptoms.

Estrogens are known to act selectively on some components of memory, exerting beneficial effects on cognitive performances. However, there are few data on the long-term effect of the lack of estrogen in postmenopausal women. Therefore, we investigated attentive and verbal memory performances in physiological and surgical menopause, drawing attention to the impact of age at menopause, and we compared a well-known aging and estrogen-dependent index, the entity of bone mass loss to memory functioning. No significant differences were found in the mean scores of attentive and psychomotor performances between physiological and surgical menopause, whereas a lower number of recalled words (recency effect = PS2) was found in surgical menopause (p < 0.001) in comparison to physiological menopause. In addition, both the age at the time of ovariectomy (r = 0.47; p = 0.014) and the years since surgery (r = –0.64; p = 0.000) correlated to short-term verbal memory performance (PS2) with better scores when surgery occurred later in women’s lives. Surgical menopause is able to affect short-term verbal memory more than physiological menopause and seems to represent a critical negative event within the female brain, in particular when it occurs prematurely.

A prospective study has been designed to investigate bone metabolism in young women taking an oral monophasic contraceptive formulation (ethinylestradiol 20 micrograms + desogestrel 0.150 mg) over 5 years. Healthy women (n = 200) between 19 and 22 years of age were divided into two groups. Group A received oral contraception, Group B did not receive any treatment. All the subjects underwent a bone mass density (BMD) evaluation at spinal level L2-L4 with Dexa (Norland XR-26) and a measurement of the serum alkaline phosphatase levels and urinary excretion of OH-proline at baseline and every 12 months over 5 years. Our results demonstrated that Group A did not show any significant BMD change after 5 years of oral contraceptive treatment, while Group B demonstrated a significant increase (p0.01) in the bone mass content at the end of the time of observation (+7.8% after 5 years). No significant changes were found in serum alkaline phosphatase levels and in urinary excretion of OH-proline at the end of the study in comparison with basal levels in both groups. Our data suggested that long-term treatment with an oral monophasic contraceptive formulation (ethinylestradiol 20 micrograms + desogestrel 0.150 mg) did not modify the BMD but prevented the occurrence of the physiologic peak of bone mass in young women.Between June 1988 and March 1989 in Italy, health workers enrolled 200 women aged 19-23 attending obstetric-gynecology clinics in and around Pavia into a five-year study of the effects of an oral contraceptive (OC) with 20 mcg ethinyl estradiol and 0.15 mg desogestrel on bone mass. They were able to follow 76 of the 100 women using the OC and 71 of the 100 women using no OC for five years. Health workers conducted a bone mass density (BMD) evaluation at spinal level L2-L4 with Dexa (Norland XR-26). They measured serum alkaline phosphatase levels and urinary excretion of hydroxyproline (OH-proline) at baseline and every 12 months for five years. Neither urinary excretion of OH-proline levels nor alkaline phosphatase levels differed significantly in the two groups during the five years from baseline levels. Over the five years, the BMD of OC users did not change significantly while the BMD of the controls increased 7.8% from baseline (p 0.01). These findings suggest that this monophasic OC prevented or delayed the physiologic peak bone mass. Even though the low dosage of ethinyl estradiol (20 mcg) may have contributed to the prevention of bone mass loss, it could not achieve the peak bone mass. More studies are needed to understand the effect of long-term OC treatment on bone mineral content.

As bacterial vaginosis (BV) is a potential cause of obstetric complications and gynecological disorders, there is substantial interest in establishing the most effective treatment. Standard treatment - metronidazole or clindamycin, by either vaginal or oral route – is followed by relapses in about 30% of cases, within a month from treatment completion. This inability to prevent recurrences reflects our lack of knowledge on the origins of BV. Atopobium vaginae has been recently reported to be associated with BV in around 80% of the cases and might be involved in the therapeutic failures. This review looks at the potential benefits of nifuratel against A. vaginae compared to the standard treatments with metronidazole and clindamycin. In vitro, nifuratel is able to inhibit the growth of A. vaginae, with a MIC range of 0.125-1 µg/mL; it is active against G. vaginalis and does not affect lactobacilli. Metronidazole is active against A. vaginae only at very high concentrations (8-256 µg/mL); it is partially active against G. vaginalis and also has no effect on lactobacilli. Clindamycin acts against A. vaginae with an MIC lower than 0.125 µg/mL and is active on G. vaginalis but it also affects lactobacilli, altering the vaginal environment. These observations suggest that nifuratel is probably the most valid therapeutic agent for BV treatment.

Objective The aim of the present observational, cross-sectional study was to examine the effects of hormonal and psycho-relational variables on sexual function during menopausal transition and at early postmenopause in women with hot flushes. Study design The sample comprised 138 women referred to a clinic for the treatment of hot flushes. They were categorised according to their stage of menopausal transition using the STRAW criteria: early menopausal transition (EMT) if their menstrual cycle was 7 or more days different from normal; late perimenopause (LMT) if they had experienced 60 days or more of amenorrhoea; and early postmenopause (EPM) if their amenorrhoea had lasted for at least 12 months but less than 4 years. Main outcome measures Sexual function was measured by using the Female Sexual Function Index (FSFI), while anxiety (state and trait), depression, eating disorder and marital adjustment were evaluated by validated self-report questionnaires. Levels of free testosterone (FT), dehydroepiandrosterone sulfate (DHEAS) and estradiol (E2) were also measured. Results Overall sexual function varied significantly with stage of menopause, with total FSFI score less in EPM than in EMT ( p = .009). A similar pattern was evident on FSFI sub-scales for sexual desire ( p = .02), arousal ( p = .01) orgasm ( p = .01) and also pain ( p = .02), but not for lubrication and satisfaction. Ratings for anxiety, depression and eating disorder did not differ across the menopausal sub-groups, and neither did ratings of marital adjustment. Both FT ( p = .01) and DHEAS ( p = .03) levels were slightly reduced at EPM in comparison with EMT, as were E2 levels ( p = .001 EMT versus LMT; p = .0001 LMT versus EPM). In multiple regression analyses, plasma FT level was the only factor to predict FSFI full score ( β = .48; p = 0.004) in women at EMT, while in women at LMT the depression score was the only factor to do so ( β = −.62; p = 0.0001). The best model predicting FSFI full score at EPM included levels of DHEAS and E2 levels and state anxiety score. Conclusions Hormonal and some psychological variables are relevant to sexual function in symptomatic women during menopausal transition and at early menopause but their role differs with the specific stage of reproductive ageing.

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.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.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.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.

Considerable advances have been made in hormonal contraception in recent years, geared at maximizing compliance and minimizing discontinuation. In oral contraceptive (OC) formulations, the estrogenic component, generally ethinyl estradiol (EE), has been reduced significantly and newer progestins like dienogest and drospirenone (DRSP), compounds with different molecular structures, have been introduced; in addition, new regimens (extended, flexible, 24/4 formats instead of the standard 21/7 format) and innovative delivery systems (vaginal rings, transdermal patches, subcutaneous implants and intrauterine devices) are available. The multitude of choices allows hormonal contraception to be tailored to the individual woman in order to obtain non-contraceptive benefits, without significant side effects, and also a favorable risk/benefit profile for her general and reproductive health. Over the past few years, new OC formulations combining DRSP (3 mg), a unique progestin with both antimineralocorticoid and antiandrogenic activities, with estrogen (30 mcg or 20 mcg EE), in two regimens (24/4 and 21/7) of active pills in a 28-day cycle, have shown positive effects on water retention-related weight gain and physical, emotional and psychosexual well-being. It seems likely that the use of a low-dose, well-balanced OC and the shorter 4-day hormone-free interval may minimize the side effects that can impair quality of life and thus increase women's compliance with hormonal contraception therapy.

Estrogen is relevant to women's well-being including sexual functioning. Aim. The goal of this Continuing Medical Education article was to provide a comprehensive review of the effect of exogenous estrogen use on women's sexual function. Main Outcome Measures. We present a literature review.The medical literature was accurately searched (1990-2008) with regard to estrogen therapy in menopausal women by using several terms related to and including the terms "estrogen" and "sexual function."A review of the studies most useful to guide menopausal practice.Estrogen decline is one of the key factors contributing to sexual functioning during menopausal transition and beyond. Systemic estrogen treatments are associated with significant benefits in some domains of menopausal sexual function, especially when estradiol is delivered transdermally, whereas local estrogens are effective in preventing urogenital aging. Even tibolone, a selective tissue estrogenic activity regulator, displays positive effects in postmenopausal women with sexual complaints. However, a tailored approach to the individual woman is always needed.

Background:The prevalence of venous thromboembolism (VTE) in ovarian cancer during first-line chemotherapy (CHT) ranges between 6.4% and 10.6%. Identification of the susceptible population is crucial for effective thromboprophylaxis.Methods:We performed a retrospective study of all our patients with epithelial ovarian cancer who underwent ambulatory first-line CHT between 1990 and 2004. Data were collected regarding age, body mass index (BMI), previous deep vein thrombosis, pulmonary embolism (PE), menopause status, FIGO stage, grade, histology, type of surgery, residual disease, and CHT. Univariable and multivariable regression analyses were performed to assess independent prognostic factors for VTE/PE to calculate a prognostic index (PI).Results:Of 203 patients, 16 (7.8%) had symptomatic VTE: 15 deep vein thrombosis and 1 PE. Multivariable regression analysis found that age (P = 0.01), BMI (P = 0.01), and stage (P = 0.05) were independent prognostic factors for VTE. Age, BMI, and stage were used to calculate the PI: 0.285 × age + 0.555 × BMI + 1.110 × stage. The PI was dichotomized according to its median cutoff (5.8) to define a low (3.8% at 6 months) and a high (11.3%) VTE incidence group.Conclusions:Age, BMI, and stage permit to identify ovarian cancer patients with a high risk in developing symptomatic VTE during CHT.

To assess the efficacy of a product containing isoflavones and other plant extracts (BIO) on whole menopausal symptomatology and plasma lipids profile.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 p0.05 level.At the end of treatment in both groups KI showed a significant decrease (p0.001). 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.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.

Objective: The present randomized prospective study aimed to compare the effect of tibolone (T) with conventional low-dose estrogen-progestogen therapy (EPT) administered in a combined continuous regimen on the course of primary headaches in postmenopausal women requesting hormone therapy (HT) for climacteric complaints. Design: Forty women presenting for clinical evaluation of headache (migraine without aura and episodic tension-type headache) were enrolled. The observational period lasted 7 months during which women kept a diary of the clinical characteristics of headache attacks and analgesic use. Climacteric symptoms and both anxiety and depression were also measured. After a 1 -month run-in period, women received two different HT regimens: 1 mg 17β-estradiol + 0.5 mg norethisterone acetate (EPT) or 2.5 mg T. Follow-up evaluations were planned after 3 and 6 months of treatment. Results: Although T did not affect the number of days with migraine without aura, it significantly reduced the number of hours during which pain intensity prohibited daily activities (P < 0.001) and the number of analgesics (P < 0.001) after 3 months. Conventional low-dose EPT administered in a combined continuous regimen was confirmed to have a mild, but negative, effect on the course of migraine without aura by increasing the number of days with head pain (P < 0.001) and the number of analgesics (P < 0.001). Interestingly, both treatments were effective in the management of episodic tension-type headache, significantly reducing the number of days with head pain, severity, and analgesic consumption. Conclusions: In postmenopausal headache sufferers, analgesics are more effective in alleviating severe head pain when women are treated with T in comparison with low-dose EPT for climacteric complaints.

Objective: The aim of the present pilot, randomized, study was to assess hemodynamic status of clitoral erectile tissues in postmenopausal women reporting female sexual dysfunction (FSD), namely libido and arousal disorders, under hormone therapy (HT). Vaginal health and sexual function were also investigated. Study design: Fifty patients presenting for clinical evaluation of menopausal status and suffering from FSD were randomly assigned to receive tibolone (2.5 mg) or 1 mg 17 beta-estradiol .5 mg NETA (EPT) for 6 months. The observational period lasted 7 months during which women underwent to duplex Doppler ultrasonography to obtain clitoral hemodynantic data, were evaluated by using the vaginal health score index (VHIS) and filled in the two-factor Italian McCoy female sexuality questionnaire (MFSQ). Results: Tibolone significantly increased clitoral peak systolic and end diastolic velocity (p

In order to investigate the role of amniotic fluid cells (AFC) in the establishment of feto-maternal immune relationship, we evaluated their phenotype and capacity to produce cytokines.CK 7-8, human leukocyte antigen (HLA)-I, HLA-DR, HLA-G, CD1d, CD34, CD45, CD14 surface antigens expression and the intracellular production of IL-4, IL-6, IL-8, IL-10, IL-12, interferon-gamma and tumor necrosis factor-1 were studied in cultured AFC and in eight samples immediately after amniocentesis using flow cytometry. IL-6 and IL-8 were detected by ELISA in all amniotic fluids and in all culture supernatants. Moreover, IL-6 and IL-8 mRNA were tested in nine samples.Cultured AFC express HLA-I, HLA-G and CK 7-8 and are able to produce IL-6 and IL-8, confirmed by presence of their mRNA. We quantified IL-6 and IL-8 levels in all amniotic fluids and in all supernatants.Surface antigen expression of AFC are not specific of immune cells, but AFC are able to produce cytokines and we can postulate that they may participate in mechanisms involved in normal as well as pathological pregnancy.

Reproductive life milestones were studied in 150 unselected women with idiopathic Parkinson's disease (PD) and in 300 postmenopausal healthy women (PM). Duration of reproductive life was found to be similar in the two groups. The women with PD reported significantly more premenstrual symptoms, fewer deliveries and abortions, and less use of contraception. Time and mode of menopause onset were similar in PD and PM, but the PD women reported significantly more hot flushes, less insomnia, depression, urinary incontinence and dyspareunia, and less recourse to hormone replacement therapy than the PM women. Women diagnosed with PD before the menopause reported more premenstrual symptoms and contraceptive use compared with those with postmenopausal PD onset, as well as a premenstrual worsening of PD symptoms in more than 50% of cases. Our data indicate poor adaptation of neuronal pathways to the hormonal fluctuations of reproductive life in women with PD, supporting the existence of a qualitative relationship between PD and reproductive events.

Objective: The dose-effect relationship of nifuratel (CAS 4936-47-4) + nystatin (CAS 1400-61-9, CAS 34786-70-4) (Macmiror Complex ®) in topical treatment of vulvo-vaginitis was studied. Method: Sixty patients with Trichomoniasis and/or Candidiasis were randomized to: 1) nifuratel 125 mg/nystatin 50000 IU, 2) nifuratel 250 mg/nystatin 100000 IU, 3) nifuratel 500 mg/nystatin 200000 IU. Undistinguishable ovules were intravaginally applied qd for 10 days. The dose-effect relationship was assessed by ANCOVA. Result: After 5 days the microbiological cure rate occurred in 10 % of patients in the least dose, in 40 % in the middle dose and in 85 % in the highest dose group (P=0.000). After 10 days of treat-ment, the microbiological cure rate increased to 45 %, 84 %, and 95 %, respectively (P=0.007). Clinical signs and symptoms gradually disappeared in a doseand time-dependent manner. No relapse has been observed after 10 day-follow up on 46 patients. Conclusion: The results confirmed a linear relationship between nifuratel + nystatin dose and effect. The least effective dose was nifuratel 250 mg + nystatin 100,000 IU once daily for 5 days and the best dose in terms of risk/benefit ratio was nifuratel 500 mg + nystatin 200,000 IU once daily for 5 days.

The aim of this study was to measure serum allopregnanolone levels and other hormones in women who completed the Female Sexual Function Index (FSFI; Rosen et al., 2000) during the follicular or the luteal phase of the menstrual cycle. Twenty-nine women with a regular menstrual cycle completed the FSFI during days 5-7 and days 19-21 of their menstrual cycles. We collected a blood sample on the same days so that we could determine levels of allopregnanolone (AP), dehydroepiandrosterone (DHEA), free testosterone (FreeT), androstenedione (A), and estradiol (E2); we stored serum at--20 degrees C until we assayed it. We performed statistical analyses by parametric and nonparametric comparisons and correlations, as appropriate. We found that the full FSFI score was 23 +/- 11.3 (mean +/- SD; 31% under 95% confidence interval = 18.7) in our study population. We also found a significant positive correlation between serum allopregnanolone levels and each FSFI domain, including full scale score (r = 0.47, p < 0.01), with the exception of pain. Similarly, we found a positive correlation between FreeT and each FSFI domain and full scale score (r = 0.55, p < 0.002). We found no significant correlation among FSFI scores and DHEA, A, or E2 plasma levels. It is interesting to note that FSFI full score was significantly higher (p < 0.04) in women tested in the luteal phase compared to women tested in the follicular phase. Serum allopregnanolone may be relevant to female sexuality directly or by its influence on a woman's general sense of well-being during the menstrual cycle. Further studies are required to test the hypothesis that high serum allopregnanolone levels in the luteal phase play a role in women's attitudes toward self-report questionnaires on sexual function.

We performed an open study to investigate the use of electrical stimulation (ES) on the vestibular area and vaginal introitus in women with sexual pain disorders. We recruited 29 women (age range 20-45 years) from among the patients at our Reproductive Psychobiology Unit to participate in the present study. They each experienced vestibular pain, inducing dyspareunia and vaginism. We performed ES with an ECL43400 apparatus (Elite, EssediEsse srl, Milan, Italy) once a week for 10 weeks. To evaluate the muscular activity of the perineal floor and sexual function, we employed the same apparatus with a vaginal probe for recording myoelectrical activity (muV), we employed a VAS scale for evaluating pain, and we administered the Female Sexual Function Index (FSFI; Rosen et al., 2000) before and after the study protocol. We analyzed data by parametric and nonparametric comparisons and correlations, as appropriate. Our major findings were as follows: (a) the contractile ability of pelvic floor muscles (p < 0.001), as well as the resting ability (p < 0.001), significantly improved following ES; (b) the current intensity tolerated significantly increased (p < 0.001) throughout the study, from 41.3 +/- 7.4 mA at the start of the study to 50 +/- 7.4 mA at the end of the stimulation protocol; (c) the Visual Analogic Scale (VAS) for pain significantly declined (p < 0.001), whereas FSFI pain scores (p < 0.001) and full scale scores (p < 0.001) significantly improved following ES, and 4 out of 9 women with vaginism went back to coital activity; (d) FSFI pain score and the current intensity tolerated, both before (R = .59; p < 0.006) and at the end (R = .53; p < 0.02) of the stimulation protocol, positively correlated. ES may be effective in the management of sexual pain disorders. Further controlled studies are necessary to standardize stimulation protocols according to the severity of pain and to better clarify the long-term clinical effects of ES.

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.

To assess the neuroendocrine correlates of menstrual status migrainosus (MSM) and menstrual migraine (MM), we evaluated the prolactin (PRL) and cortisol responses to the direct central serotoninergic (5-HT) agonist meta-chlorophenylpiperazine (m-CPP) administered orally (0.5 mg/kg) during the follicular (FP: +6, +8) and luteal phases (LP: –4, –6) of the same menstrual cycle. Ten women with MSM (migraine attacks occurring within 2 days of the onset of menstrual bleeding but lasting more than 72 h) and 9 women with MM (migraine occurring within 2 days of the onset of menstrual bleeding with a typical duration of attacks) were studied. Six healthy women served as controls. Blood samples were taken at times –30, 0 and every 30 min over 4 h. Statistical analysis was performed using MANOVA followed by Duncan’s post hoc comparisons. We found that the PRL response to the m-CPP test was significantly blunted in MSM compared with MM and controls in both phases of the menstrual cycle (F = 4.6; p < 0.001). Indeed, the PRL area under the curve (AUC) after m-CPP was higher in both MM and controls compared with MSM (F = 12.7; p < 0.001). The m-CPP-induced cortisol response was absent in MSM compared with MM and controls in both FP and LP (F = 4.1; p < 0.001). On the other hand, the pattern of the plasma cortisol response to m-CPP was similar in MM and controls throughout the menstrual cycle. In addition, the basal plasma cortisol levels were significantly higher in MSM compared with controls (p < 0.001) and MM (p < 0.001) during FP, but not in LP, and progressively decreased over time. Thus, no significant effect of the menstrual cycle phase and diagnosis on the cortisol AUC was found, while a significant diagnosis effect (F = 25.6; p < 0.001) on %Δmax plasma cortisol levels was evident and consistent with the lack of cortisol response to m-CPP in MSM during the FP and LP compared with MM and controls. A derangement in central 5-HT control of pituitary PRL, and even more so in cortisol release, is present in women with MSM, but not with MM, regardless of the phase of the menstrual cycle, suggesting the involvement of some 5-HT1 and 5-HT2 receptor subtypes in the occurrence of extremely severe migraine attacks triggered by menstruation.

The aim of the present study was to measure clitoral artery blood flow throughout the menstrual cycle and in oral contraceptive users. We recruited healthy young women (n = 19, age range: 21-28 years; body-mass index: 18-23 kg/m2) without sexual dysfunction (Female Sexual Functioning Index criteria; Rosen et al., 2000). Clitoral arterial peak systolic velocity (PSV) in at least two phases of the same ovulatory cycle or during the second week of the pill was measured by doppler ultrasonography. Clitoral arterial PSV measures (cm/s) were superimposable during the follicular and the luteal phase of the menstrual cycle (10.4 +/- 1.2 versus 10.2 +/- 1.6), whereas a slight but significant increase (12.2 +/- 1.2, f = 3.99; p < 0.04) was evident at the time of ovulation. In addition, PSV measures were significantly higher in women taking hormonal contraception compared to women studied throughout the menstrual cycle (14.2 +/- 2.7 versus 10.8 +/- 1.5; p < .001). Whether or not these preliminary data may be of any significance to female sexual arousal throughout the menstrual cycle remains to be established.

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 (score10), at medium risk (score between 10 and 24), and at high risk (scoreor =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 (P0.046) 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 (P0.034) and medium (P0.009) risk. A similar result was found with FSH AUC following the first GnRH challenge (P0.04 high risk vs low risk and P0.014 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.

The aim of the present study was to evaluate how hormone replacement therapy (HRT) could influence the course of primary headaches in postmenopausal women.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.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; P0.000) and days with headache (F = 6.9; P0.000) 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).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.

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.

Objective: Intravaginal estriol (E3) effectively improves postmenopausal genito-urinary disturbances, without stimulating endometrial proliferation. The aim of the present study was to evaluate the effect of intravaginal estriol (E3) plus nasal spray salmon calcitonin (sCT), to improve neurovegetative symptoms and to prevent the decline of bone mineral density (BMD) of postmenopausal women. Methods: Two hundred and fourteen (214) healthy postmenopausal women were treated for 12 months with: (1) E3 (0.5 mg every other day) + Ca (0.5 g/day); (2) E3 + Ca + sCT (50 IU × 2/day); (3) sCT + Ca; (4) Ca. Climacteric complaints, such as hot flushes and sweating, BMD at the distal 1 10 of the radius, analyzed by dual photon absorptiometry, urinary excretion of hydroxyproline and serum alkaline phosphatase were evaluated at baseline and every 6 months. At the same time, patient compliance and drug tolerability were evaluated. Results: E3 but not sCT, improved hot flushes and sweating. E3 blunted but not completely counteracted the BMD decline observed in women treated with only Ca, and reduced urinary hydroxyproline excretion. sCT markedly increased BMD values and reduced both urinary hydroxyproline excretion and serum alkaline phosphatase. These effects were not potentiated by E3 coadministration. All treatments were well tolerated. Conclusions: Present data indicate that the combined administration of intravaginal E3 and sCT may represent an alternative therapeutic regimen for those postmenopausal women who do not accept or have contraindications to classical hormone replacement therapy.

This study involved 912 infants born to HBsAg-negative mothers from 1 May 1991 to 30 June 1992. The subjects were randomly allocated to an accelerated (Group A) or traditional (Group B) immunization schedule and immunized with 10 μg of recombinant HBV vaccine. At the end of the vaccinal cycle 98.14% of both groups were protected against HBV with a high percentage of high responders (88.1% group B and 68% group A). Following a random plan, 345 of the initial 912 infants (144 group A and 201 group B) were serologically evaluated, 15–18 months after the booster dose, to identify the level of long-lasting specific antibody. The data obtained allowed us to identify the non-responder subjects after the seroconversion, to propose the evaluation of antibody titre after the booster dose of vaccine and, because one year after the booster dose 5.6% of the subjects responsive at seroconversion have shown undetectable anti-HBsAg titre, to propose the elevation of the antibody level considered as protective at the end of the vaccinal cycle.