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Stem cells are recruited to the uterus where they differentiate into endometrial cells and have been suggested as potential therapy for uterine injury such as Asherman's syndrome. However, it is unknown whether local intrauterine injection may result in better stem cell engraftment of the uterus compared with systemic administration, and whether uterine-derived cells (UDCs) may confer an advantage over BM-derived cells (BMDCs). Mice underwent local injury to a single uterine horn. Green fluorescent protein (GFP)-expressing BMDCs, UDCs or saline (control) were injected either intravenously or locally (uterine lumen) into wild-type recipients. Two or 3 weeks post-transplant, uterine tissues were collected for fluorescence-activated cell sorting (FACS) and immunohistochemistry/immunofluorescence studies. Mice injected intravenously with BMDCs or UDCs had increased GFP + cells recruitment to the non-injured or injured uterus compared to those injected locally. No significant differences were noted in GFP + cell recruitment to the injured versus non-injured horn. In addition, systemic injection of BMDCs led to greater recruitment of GFP + cells at 2 weeks and 3 weeks compared with UDCs. Immunohistochemical staining demonstrated that GFP + cells were found in stroma but not in epithelium or blood vessels. Immunofluorescence analysis revealed that GFP + cells were mostly CD45-negative, and negative for CD31 and cytokeratin, confirming their stromal identity. In conclusion, the systemic route of administration results in better recruitment of BMDCs or UDCs to the injured uterus than local injection. In addition, BMDCs recruitment to the uterus is greater than UDCs. These findings inform the development of stem cell-based therapies targeting the uterus., (© 2017 The Authors. Journal of Cellular and Molecular Medicine published by John Wiley & Sons Ltd and Foundation for Cellular and Molecular Medicine.)

Objective: To determine the prevalence of undiagnosed uterine leiomyosarcoma (LMS) in women undergoing hysterectomy or myomectomy for suspected benign leiomyomas., Study Design: Retrospective, single-centre, cohort study. Information for all gynaecological procedures for suspected benign leiomyomas between 1993 and 2016 was extracted from the hospital database. The prevalence of LMS was calculated by surgery type and age group., Results: The prevalence of LMS was 1.7/1000 [one in 603 women; 95% confidence interval (CI) 0.8-3.4] for all procedures combined. The prevalence of LMS was 1.1/1000 (one in 875 women; 95% CI 0.4-2.9) for all hysterectomies combined and 4.2/1000 (one in 240 women; 95% CI 1.4-12.2) for all myomectomies combined. For women aged <50years, the prevalence of LMS was 5.4/1000 (one in 187 women; 95% CI 1.8-15.6) for abdominal hysterectomies, 1.0/1000 (one in 1040 women; 95% CI 0.2-5.4) for laparoscopic hysterectomies, 5.2/1000 (one in 191 women; 95% CI 0.9-29.1) for abdominal myomectomies, 3.0/1000 (one in 332 women; 95% CI 0.5-16.9) for laparoscopic myomectomies and 8.6/1000 (one in 116 women; 95% CI 1.5-47.2) for hysteroscopic myomectomies., Conclusions: Occult LMS is a rare malignant disease. This study found that the prevalence of LMS was higher in women undergoing myomectomy compared with women undergoing hysterectomy. The highest prevalence of LMS was found in women undergoing hysteroscopic myomectomy., (Copyright © 2017 Elsevier B.V. All rights reserved.)

RA is the most common chronic systemic autoimmune disease, with a higher prevalence in women, suggesting female hormonal factors play a role in the development of the disease. However, many controversies still exist. The aim of this review was to appraise data from recent research concerning female hormonal factors and their association with RA disease development. The study of female hormonal factors is challenging because serum levels may differ throughout a woman's lifetime and interact with various environmental, immunological, genetic and endocrine factors influencing the development of autoimmunity. As some female hormonal factors may be potentially modifiable, understanding their impact on RA development is clinically relevant and may result in specific preventive interventions in high-risk populations., (© The Author 2016. Published by Oxford University Press on behalf of the British Society for Rheumatology. All rights reserved. For Permissions, please email: journals.permissions@oup.com.)

Objective: Different types of vaginal fistulas is a relatively uncommon condition in the Western world but very frequent in developing countries. In the past, conventional vaginography was the radiological examination of choice for exploring this condition. CT and MRI are now both used for this purpose. Our objective was to test the feasibility and to explore the potential role of a new CT imaging technique implementing vaginal introitus obstruction and opacification of the vagina with iodine contrast agent, to show patency of a fistula., Methods: We describe the technical protocol of CT-vaginography as performed in Geneva University Hospitals, including vaginal catheterization with a Foley catheter and obstruction of the introitus by inflating the balloon of the catheter. We also report three cases of patients with suspected vaginal fistula who underwent CT-vaginography., Results: The examinations were technically successful. In one patient, it revealed the presence of fistulous pathways from the vaginal fornix along the bilateral infected surgical prostheses. In a second patient, it showed a fistula between the vagina and the necrotic cavity of a recurrent cervical cancer. In a third patient, it proved the absence of a suspected vaginal fistula., Conclusion: CT-vaginography is a technically feasible CT protocol that provides anatomical and functional information on clinically suspected vaginal fistulas. Advances in knowledge: After the abandon of conventional vaginography in the era of transaxial imaging, the current modalities of imaging vaginal fistulas provide excellent anatomical detail but less functional information concerning the permeability of a vaginal fistulous pathway. We propose the use of CT-vaginography, a technical protocol that we describe in detail.

Preeclampsia (PE) results in placental dysfunction and is one of the primary causes of maternal and fetal mortality and morbidity. During pregnancy, estrogen is produced primarily in the placenta by conversion of androgen precursors originating from maternal and fetal adrenal glands. These processes lead to increased plasma estrogen concentrations compared with levels in nonpregnant women. Aberrant production of estrogens could play a key role in PE symptoms because they are exclusively produced by the placenta and they promote angiogenesis and vasodilation. Previous assessments of estrogen synthesis during PE yielded conflicting results, possibly because of the lack of specificity of the assays. However, with the introduction of reliable analytical protocols using liquid chromatography/mass spectrometry or gas chromatography/mass spectrometry, more recent studies suggest a marked decrease in estradiol levels in PE. The aim of this review is to summarize current knowledge of estrogen synthesis, regulation in the placenta, and biological effects during pregnancy and PE. Moreover, this review highlights the links among the occurrence of PE, estrogen biosynthesis, angiogenic factors, and cardiovascular risk factors. A close link between estrogen dysregulation and PE occurrence might validate estrogen levels as a biomarker but could also reveal a potential approach for prevention or cure of PE., (Copyright © 2017 Endocrine Society.)

Sexual health is a critical aspect of quality of life and is also influenced by medical conditions and health care interventions, particularly when gynaecological disorders are involved. Dyspareunia is a common symptom of endometriosis, a cause of personal distress and a main raison for seeking treatment. Endometriosis negatively affects different domains of sexual function and specific biopsychological variables (chronic pain, recurrence, infertility) may further worsen quality of sexual function and relationship. Consequences of endometriosis treatment on global sexual functioning have not been featured prominently in the available literature, assuming wrongly that sexual pain improvement was always translated into a recovered sexual health., Competing Interests: Les auteurs n’ont déclaré aucun conflit d’intérêts en relation avec cet article.

Adult stem cells have a major role in endometrial physiology, remodeling, and repair, but they also have a critical role in the development and progression of endometriosis. Bone marrow-derived stem cells (BMDSCs) engraft eutopic endometrium and endometriotic lesions, showing stromal and epithelial fate. Nevertheless, circulating BMDSCs are in limited supply, and the presence of endometriosis depletes stem cells from the blood circulation, preventing their homing in the uterus. Furthermore, stem cells migrate from endometriotic lesion into the uterus, leading to a dysfunctional endometrium. Stem cell trafficking is a central feature of endometriosis. Understanding molecular mechanisms regulating cell mobility and engraftment in endometriosis may reveal new targets for treatment., (© The Author(s) 2016.)

Background: Sexual function is an important aspect of health and quality of life and is influenced by both medical conditions and health-care interventions, especially when gynecologic disorders are involved. Coital pain is among the main factors that affect sexual functioning, and this symptom is reported by almost half of women suffering from endometriosis. However, sexuality is a complex phenomenon driven by social, psychological and biological/hormonal factors and the presence of endometriosis might further affect domains of sexual function and the quality of a sexual relationship., Objective and Rationale: The objective of this report is to review the current state of knowledge on the impact that endometriosis and its treatments have on the sexual function of women and their sexual partners., Search Methods: A systematic literature search was performed to identify studies evaluating sexual function in endometriosis patients, and a narrative analysis of results is presented. The review discusses relevant quantitative and qualitative studies analyzing the effect of endometriosis and its hormonal and surgical treatments on measures of sexual function and quality of sexual relationship., Outcomes: Endometriosis negatively affects different domains of sexual function, and the presence of dyspareunia is not the only determinant of sexual health in these women. Chronic pelvic pain, advanced stages of disease and the presence of physical and mental comorbidities affect sexual function, as well as personality traits and women's expectations. Although a number of studies have evaluated the effect of surgery and hormonal treatment on deep dyspareunia, overall sexual function and quality of the relationship with the partner are often under-investigated., Wider Implications: Multiple clinical and personal determinants affect sexual function in women with endometriosis, with potentially negative consequences on the sexual function of partners and quality of the relationship. Additional prospective and longitudinal investigations are warranted using specific instruments to analyze biopsychosocial variables of sexual pain in endometriosis patients and the effects that actual treatments have on measures of quality of sexual function and relationship., (© The Author 2016. Published by Oxford University Press on behalf of the European Society of Human Reproduction and Embryology. All rights reserved. For Permissions, please email: journals.permissions@oup.com.)

Bone marrow (BM)-derived cells (BMDCs) contribute to endometrial regeneration. Our objective was to develop a nongonadotoxic mouse BM transplant (BMT) model using 5-fluorouracil (5-FU) for investigating BMDCs trafficking in reproduction. Female C57BL/6J mice received either single (CTX-1) or paired (CTX-2) 5-FU (150 mg/kg) dose, or single (CTX-1+SCF) or paired-dose (CTX-3+SCF) 5-FU with stem cell factor (SCF). Control mice received BMT only or saline. BM cells (20 × 10 6 ) from transgenic green-fluorescent protein (GFP) mice were injected iv. For fertility experiment, mice were mated on day 28 after BMT. Alternatively, mice were killed 1 month after BMT and BMDCs recruitment to the uterus was determined. Mice receiving 5-FU ± SCF showed intact ovarian function and fertility. CTX-3+SCF resulted in greatest BM donor chimerism at 1 month (∼45%). Flow cytometry analysis demonstrated that 6.6% of total uterine cells in CTX-3+SCF mice were GFP+ BMDCs. Remarkably, this was about 40- and 80-fold greater than BMDCs in uterus of CTX-1 or BMT only mice (6.6% vs 0.16% vs 0.08%, respectively, P < .001). Immunohistochemical analysis showed that BMDCs in the uterus were mostly localized to the endometrial stroma (71.8%). The majority of endometrial BMDCs colocalized with the pan-leuokocyte CD45 marker (58.5%), but 41.5% were CD45-negative. Cytokeratin and CD31 staining showed that the GFP+CD45- cells were not epithelial or endothelial, confirming their stromal identity. We demonstrate that paired-dose 5-FU regimen results in efficient BM donor chimerism while maintaining ovarian function and fertility. This model could be used for studying BMDCs trafficking to the uterus in various reproductive physiological and pathological conditions.

Progesterone and allopregnanolone have crucial and different roles in brain development, function and recovery after injury. Pregnancy is characterized by an increased synthesis of progesterone and its neuro-active metabolites by the placenta, maternal and fetal brain. This supports the critical role of these steroids in maternal brain adaptation during pregnancy and development of the fetal brain. Moreover, allopregnanolone may play a brain-protective role during complications of pregnancy, complications of pregnancy, such as preterm delivery or intrauterine growth restriction (IUGR), by reducing the impact of hypoxia and excitotoxic brain damage or impairment myelination. Behavioral consequences of altered progesterone/allopregnanolone fetal brain programming have also been hypothesized, although further evidence is needed. New potential applications of allopregnanolone as a treatment strategy have also been proposed, addressing unmet clinical needs in perinatal care.

Background: The role of growth hormone (GH) in female reproduction has become a topic of increasing interest over the last decade. The replacement of GH for ovulation induction in women with hypopituitarism remains controversial. The role of GH in the human endometrium is still largely unknown. To the best of our knowledge, this study represents the first case report showing evidence that GH might play a role not only for ovulation induction, but also for the development of endometrial thickness in women with hypopituitarism., Case: A 32-year-old hypophysectomized. woman, known for primary infertility, experienced multiple IVF/embryo transfer failures with inadequate endometrial development. The use of GH replacement therapy followed by conventional controlled ovarian hyperstimulation enabled endometrial development and better ovarian response to gonadotropins, leading to a successful ongoing pregnancy., Conclusion: The substitution with GH resulted in fewer days of ovarian stimulation, an acceptable endometrium, and a twin pregnancy delivered at 38 weeks' gestation.

Endometriosis is a chronic disease of unknown etiology that affects approximately 10% of women in reproductive age. Several evidences show that endometriosis lesions are associated to hormonal imbalance, including estrogen synthesis, metabolism and responsiveness and progesterone resistance. These hormonal alterations influence the ability of endometrial cells to proliferate, migrate and to infiltrate the mesothelium, causing inflammation, pain and infertility. Hormonal imbalance in endometriosis represents also a target for treatment. We provide an overview on therapeutic strategies based on innovations of classical hormonal mechanisms involved in the development of endometriosis lesions. The development phase of new molecules targeting these pathways is also discussed. Endometriosis is a chronic disease involving young women and additional biological targets of estrogen and progesterone pharmacological manipulation (brain, bone and cardiovascular tissue) need to be carefully considered in order to improve and overcome current limits of long-term medical management of endometriosis.

Aims: To present preliminary data of single-access laparoscopic surgery with a new device for the treatment of benign adnexal pathologies., Methods: Ten women with benign adnexal pathologies underwent salpingectomy (n = 4) and ovarian/para-ovarian cyst enucleation (n = 6) using a laparo-endoscopic single-port approach with an innovative advanced multiport reusable trocar inserted transumbilically through a small wound retractor. Trocar introduction time, operative time, estimated blood loss, conversion to standard laparoscopy, peri- and postoperative complications, hospital stay and Visual Analog Scale score (as assessment of pain and cosmesis) were analyzed., Results: Port placement was successful in all patients. Mean trocar introduction time was 4.4 min (range 3.4-5.3 min) and no intra or postoperative complication occurred. The mean operating time was 50.0 ± 9.2 min and mean blood loss was 28.5 ± 8.8 ml. The mean hospital stay following surgery was 1.6 ± 0.5 days and convalescence was complete in 1 week. Neither scores for postoperative incisional pain nor cosmesis side effects have been observed in any subjects., Conclusion: We concluded that adnexal single-port surgery performed with this innovative advanced surgical instrumentation is a feasible, safe, and effective technique that drastically reduces postoperative pain and does not compromise cosmetic appearance. The isolation of the operative field by means of the drape prevents the contamination of the port site that occurs frequently, and mainly in adnexal pathologies of uncertain etiology. In addition, the ease of insertion and the conformation of the new port access also make the procedure feasible in obese patients., (© 2016 S. Karger AG, Basel.)

Objective: Endometriosis-associated abdominal wall cancer (EAAWC) is rare, and few reports are available. This article provides a review of reports in the literature on the pathology, diagnosis, management, and outcome of patients with EAAWC., Method: We performed a review of existing reports in the English language literature on cancer arising from abdominal wall endometriosis. MEDLINE and EMBASE searches were conducted for articles published from September 1986 to August 2014 using combinations of medical subject heading terms., Results: We identified 26 articles reporting on EAAWC and added 1 patient who was treated at our institution. In all of these patients, EAAWC was described after uterine surgery (mostly cesarean section). The delay between the first surgery and the diagnosis of malignant disease was more than 20 years. Clear cell carcinoma was the most common histology, followed by endometrioid carcinoma. Death was described in 44% of women within a few months of diagnosis., Conclusions: Endometriosis-associated abdominal wall cancer is rare and aggressive. It seems to be associated with cesarean section, and it shows poor prognosis. The mainstay of treatment remains extensive surgery and chemotherapy.

Purpose: Hysterectomy is the most common surgical procedure performed in gynecology and, in over 95% of the cases, does not necessarily require the removal of the uterine cervix to be completed successfully. In clinical practice, however, less than 20% of gynecologists offer patients the possibility to express a personal preference concerning the choice between total laparoscopic hysterectomy (TLH) and laparoscopic subtotal hysterectomy (LSH). The aim of this study is to compare patients who have undergone TLH versus LSH for benign uterine diseases in terms of intra-operative/peri-operative surgical outcomes and short-term recovery of sexual function., Methods: We performed an observational, retrospective study on 478 women who underwent hysterectomy for benign uterine disease at Gyn/Ob Clinic, Department of Women's and Children's Health of Padua University between January 2003 and December 2012. Surgical data were recorded. We investigated and compared outcomes between the two groups of patients (TLH vs LSH) in terms of the following: surgical complications rate, post-operative therapy, women satisfaction and sexual activity recovery., Results: We found that operating time and length of hospital stay were significantly lower in patients who underwent LSH. A higher rate of post-operative fever was reported in the TLH treatment group although antibiotic prophylaxis was implemented in a similar fashion for both groups. At 60-70 days following surgery, women of LSH group reported a greater ease in recovery of sexual function as opposed to those who underwent TLH., Conclusions: The advantages and potential drawbacks of both procedures need to be discussed with women presenting with benign disease. LSH is a reasonable option for women, representing both an excellent minimally invasive approach in a proper clinical setting and an appropriate procedure for those women who prefer conservative surgery.

Objective: The role of endometritis on infertility is still controversial. The aim of our prospective controlled study was to select infertile couples and to analyze: hysteroscopic findings of endometritis, bacterial endotoxin level in the menstrual blood, histological pattern of endometrial biopsy and to determine the effect of antibiotic therapy on endometritis resolution., Methods: 100 infertile couples of University Hospital waiting for in vitro fertilization program. We evaluated the incidence of endometritis in infertile population by hysteroscopy, endometrial biopsy and bacterial endotoxin levels in the menstrual samples. Moreover, we verified the effectiveness of antimicrobial treatment on the endometritis resolution by hysteroscopic control., Results: Out of 100 women enrolled, 15 showed hysteroscopic evidence of endometritis and 12 of these patients presented higher bacterial endotoxin in the menstrual samples. The histological results were positive for endometritis in 9 cases, 1 woman had no adequate samples and 5 patients had negative result. After antibiotic therapy, 9 patients had a complete hysteroscopic endometritis resolution, 4 patients had an improvement and in 2 cases there was no endometrial change. Concerning histological findings after therapy, we had negative results in 12 patients and persistent inflammatory findings in 2 patients., Conclusion: Our study demonstrated a high incidence of endometritis in infertile couples (15%). The endometrial biopsy was in agreement with the hysteroscopic findings in 60% of the cases, and the bacterial endotoxin level in the menstrual samples was higher in 12 patients with suspected endometritis, then its measurement can be helpful to confirm an endometrial infection but its influence must be confirmed with further researches. The antibiotic therapy can improve the hysteroscopic endometrial inflammatory aspect in over 80% of cases.

Background: Brain-derived neurotrophic factor (BDNF) is strongly related to hormonal networks and is modulated by hypothalamic activity., Objective: To evaluate plasma BDNF concentration in patients with functional hypothalamic amenorrhea (FHA), with reference to the BDNF circadian rhythm and its relation with the cortisol (F) rhythm, and to assess whether the duration of amenorrhea might influence the BDNF:F ratio in FHA., Design: This was an observational study evaluating 36 amenorrheic and 30 eumenorrheic women., Setting: Basal values of BDNF and hormones were examined in blood samples collected from 7:00 to 9:00 h in all the women. Basal BDNF and F levels were determined in blood samples collected in 12 subjects from each group at 8:00, 12:00, 16:00, 20:00, and 24:00 h., Results: BDNF plasma levels are significantly lower in amenorrheic women (p < 0.001) than in the follicular phase of eumenorrheic women. There are no correlations between BDNF values (p > 0.05), sex steroids, and F in FHA. Low plasma BDNF levels in FHA are not significantly correlated with duration of amenorrhea. The 24-hour variation of BDNF in amenorrheic women is significantly lower when compared to the control group, and normal daily variations of BDNF disappeared in FHA patients. F preserved its circadian rhythm in both groups., Conclusions: Interactions between BDNF, the hypothalamus-pituitary-adrenal axis, and sex steroids might be critical in clinical conditions of modified homeostasis/adaptation, such as FHA., (© 2015 S. Karger AG, Basel.)

Endocrine disorders play a major role in approximately 8% to 12% of recurrent pregnancy loss (RPL). Indeed, the local hormonal milieu is crucial in both embryo attachment and early pregnancy. Endocrine abnormalities, including thyroid disorders, luteal phase defects, polycystic ovary syndrome, hyperprolactinaemia and diabetes have to be evaluated in any case of RPL. Moreover, elevated androgen levels and some endocrinological aspects of endometriosis are also factors contributing to RPL. In the present article, we review the significance of endocrine disease on RPL.

Objective: To compare the initial surgical outcomes of robotic and laparoscopic myomectomy in patients with symptomatic uterine myomas., Study Design: Retrospective chart review of 86 patients undergoing robotic (RM) (n = 43) or laparoscopic (LM) (n = 43) myomectomy. Data included fibroid characteristics (number, weight, location) layers of uterine reconstruction, operating time, blood loss, complications, and postoperative hospital stay., Results: No significant differences were noted between RM and LM for fibroid number and weight and mean operating time, although the number of patients receiving at least a double-layer uterine reconstruction was higher in RM than LM. Blood loss was higher after LM, while no differences resulted in hospital stay., Conclusion: RM may have some additional advantages compared with LM in terms of bleeding and uterine suturing without compromising operation duration, at least when surgeons were at the beginning of their experience of endoscopic treatment of symptomatic uterine myomas., (Copyright © 2013 John Wiley & Sons, Ltd.)

Introduction: Robotic single-site surgery (RSS) represents the latest innovation for clinical use of single incision surgery. Several applications have been reported in urology, general surgery and gynecology with potential application in benign cases as well as in oncology., Presentation of Case: To further explore potential applications of RSS, we present the first case reported in the literature of combined cholecystectomy and total hysterectomy using the da Vinci Si single-port platform (Intuitive Surgical Inc., Sunnyvale, CA)., Discussion: A critical description of the procedure with potential advantages and limitations of the current platform for combined surgical procedure is provided., Conclusion: Robotics may facilitate the widespread diffusion of single incision surgery, overcoming current laparoscopic and LESS limitations. However, the available robotic platform still has technical features that will limit its uptake amongst surgeons and further technological development is needed for a wider diffusion of single incision surgery., (Copyright © 2014 The Authors. Published by Elsevier Ltd.. All rights reserved.)

Androgens play a primary role in female physiopathology. The age-related reduction in the production of ovarian and adrenal androgens may significantly affect women's health. The decline of circulating androgens results from a combination of two events: reduced ovarian production and aged-related decline in adrenal androgen synthesis. The relative androgen deficiency in pre- and postmenopausal women may induce impairment of sexual function, libido, well-being, energy and may contribute to reduced cognitive functions. Whether androgen deficiency also affects cardiovascular or bone biology in women during reproductive aging is still controversial. Both in the central nervous system and peripheral tissues, there are multiple ways whereby androgens target their specific actions through a particular tropism of the brain areas that are involved in sexual function, behavior and cognition. Among circulating available androgens that are involved in several domains of sexual response, adrenal androgens seem to be related to some sexual symptoms as well as diminished cognitive function in postmenopausal women. The possibilities of treating low sexual desire/hypoactive sexual desire disorder are multifaceted and should include the combination of both pharmacological treatments able to maximize biological signals that drive the sexual response as well as individualized psychosocial therapies to overcome personal and relational difficulties. Transdermal testosterone has been proved to be effective but the use of additional treatment like oral or vaginal dehydroepiandrosterone is still controversial, despite many evidences support it. The decision to treat premenopausal or postmenopausal women with signs/symptoms of androgen insufficiency is mainly based on the clinical judgment, together with estrogens co-administration and following informed consent related to the unknown long-term risks.

Background: The field of laparoscopy has undergone several changes to improve the morbidity and cosmesis of laparoscopic surgery. The robotic single-site surgery is the inevitable hybridization of robotic technology with laparoendoscopic single-site surgery., Methods: Perioperative information of 12 robotic single-site hysterectomies (R-SSH) were collected to evaluate the surgical feasibility and the possible influence of the body mass index (BMI) and the uterine weight on operative times., Results: The mean operative time was 85 ± 33 min (range, 355 to 149 min), the mean docking time was 9 ± 3 min, and the mean console time was 76 ± 33 min. The mean blood loss was 80 ± 18 mL, and the median weight of resected uteri was 220 ± 45 g. No serious postoperative complications occurred. The CUSUM learning curve was observed to consist of two different phases: phase 1 (the initial 6 cases) and phase 2 (the last 6 cases) with significant reduction in operative and console time observed between the two phases. For BMI, no correlation was found with operative times, console times, and docking times, and no correlation was found between uterine weight and operative time., Conclusions: This series, identifying two different phases of the learning curve and suggesting that the initial learning phase for the procedure can be achieved after six cases, confirms the feasibility and safety of a robotic approach for single-site hysterectomy. However, the limits of this study mainly rely on the limited casuistic and short follow-up, although the preliminary results appear promising. Larger series and prospective studies comparing R-SSH hysterectomy with standard robotic multiport hysterectomy are necessary to define properly the role of this innovative surgical technique.

Objective: The feasibility and safety of robotic surgery have been demonstrated by numerous comparative studies. The aim of our study was to compare several parameters related to robotic surgical procedures in uterine pathology, and to analyse clinico-biological parameters that may influence the post-operative evolution of the patients., Study Design: Retrospective analysis of 100 patients with uterine pathology who had undergone robotic-assisted laparoscopic surgery at the Santa Chiara Hospital, Pisa, Italy, between 2008 and 2010., Results: Duration of surgery, docking, hysterectomy, uterine suture, blood loss, and days of hospitalisation significantly improved in parallel with the increasing experience of the surgical team. Paradoxically, the length of myomectomy increased in the same time interval, probably due to operating on more complex clinical cases with this procedure as the surgical team's experience grew. None of the robotic surgeries was converted to laparotomy. No intra- or post-operative complications were noted., Conclusion: Since robotic-assisted laparoscopic surgery is becoming the preferred surgical technique for uterine pathology treatment, more clinical studies and development of protocols are essential to increase the quality of surgical treatment., (Copyright © 2013 Elsevier Ireland Ltd. All rights reserved.)

Brain-derived neurotrophic factor (BDNF) is a neurotrophin abundantly expressed in several areas of the central nervous system (CNS) and is known to induce a lasting potentiation of synaptic efficacy, to enhance specific learning and memory processes. BDNF is one of the key molecules modulating brain plasticity and it affects cognitive deficit associated with aging and neurodegenerative disease. Several studies have shown an altered BDNF production and secretion in a variety of neurodegenerative diseases like Alzheimer's and Parkinson's diseases but also in mood disorders like depression, eating disorders and schizophrenia. Plasma BDNF is also a biomarker of impaired memory and general cognitive function in aging women. Gonadal steroids are involved in the regulation of several CNS processes, specifically mood, affective and cognitive functions during fertile life and reproductive aging. These observations lead many scientists to investigate a putative co-regulation between BDNF and gonadal and/or adrenal steroids and their relationship with gender difference in the incidence of mental diseases. This overview aims to summarize the current knowledge on the correlation between BDNF expression/function and both gonadal (progesterone, estrogens, and testosterone) and adrenal hormones (mainly cortisol and dehydroepiandrosterone (DHEA)) with relevance in clinical application., (Copyright © 2013 IBRO. Published by Elsevier Ltd. All rights reserved.)

Delta-5 androgen therapies seem to enhance the sexual response in experimental animal models and in clinical trial. This study analyzed the influence of dehydroepiandrosterone (DHEA) administration on receptive and proceptive components of female rat sexual behavior. Ovariectomized (OVX) adult rats were divided in six groups submitted to the following treatments for 4 weeks: DHEA 0.5 and 5 mg/kg, by oral gavage, alone or in combination with estradiol benzoate 3 µg/rat; EB 3 and 10 µg/rat as control groups. All animals received progesterone (500 µg/rat) 4 h before the behavioral tests. All animals were tested for the following: receptivity and proceptivity weekly for 4 weeks; partner preference and paced mating behavior at the end of the treatments. Oral administration of DHEA at 5 mg/kg in EB primed rats was able to significantly increase proceptive behaviors, already after 1 week of treatment. The increase was more marked after 3 and 4 weeks of treatment. Behavioral changes were associated to modifications of circulating and brain level of allopregnanolone and beta-endorphin, although circulating hormonal levels were within a physiological range. Hormonal treatment using physiological doses of delta-5 androgens (DHEA) positively affects sexual motivation in OVX rats.

Purpose: The goal of this study was to determine the accuracy of three-dimensional (3D) MRI reconstructions obtained with segmentation technique in the preoperative assessment of deep infiltrating endometriosis (DIE) and in particular to evaluate rectosigmoid and bladder wall involvement., Materials and Methods: Institutional review board approval for this study was obtained, and each patient gave written informed consent. Fifty-seven consecutive patients with diagnosis of DIE who had undergone pelvic MRI at 1.5 T before surgery between 2007 and 2011, were retrospectively evaluated and 3D post-processed in order to obtain a detailed mapping of DIE. A blinded reader interpreted images. MRI results were compared with surgical findings and were scored by using a four-point scale (0&#95;3 score)., Results: 36/57 patients with symptomatic DIE underwent surgery: 18/36 had endometriotic nodules infiltrating the rectouterine pouch, 12/36 the vesicouterine pouch, and 6/36 the rectovaginal pouch. The sensitivity of MRI and 3D MRI vs. surgery was, respectively, 64% vs. 83%; diagnostic accuracy of 3D MRI respect to MRI alone was 86% vs. 67% for localization; 86% vs. 67% for dimension; 79% vs. 58% for rectosigmoid infiltration; 92% vs. 75% for bladder infiltration., Conclusions: In this preliminary study, 3D MRI reconstructions obtained with semi-automatic method of segmentation provided encouraging results for staging DIE preoperatively. In fact, the addition of 3D MRI reconstructions improved diagnostic accuracy and staging of DIE providing the exact volume of the lesions and enabling a precise mapping of these before surgery.

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

Premenstrual syndrome (PMS) is characterized by a cluster of psychological and somatic symptoms that begin during the late luteal phase of the menstrual cycle and disappear after the onset of menses. Since PMS might be caused by an alteration in the cyclical hormonal modifications and ovarian steroids are directly involved in the regulation of mood, affective and cognitive functions and influence neurotrophins expression, in particular the brain-derived neurotrophic factor (BDNF), we aimed to evaluate whether plasma BDNF levels in women with PMS differ from those of normally menstruating women without PMS. Sixty-two women were divided into two groups: one group of women (n=35) with PMS and one group (n=27) composed by normally menstruating women. Plasma samples were collected at day 7 (follicular phase) and day 21 (luteal phase) of the menstrual cycle. Plasma BDNF of the control group significantly increased (p<0.001) from the follicular phase (402.90±74.41pg/ml) to the luteal phase (1098.79±146.49pg/ml). On the other hand, in the PMS group plasma BDNF levels significantly decreased (p<0.001) from the follicular phase (412.45±78.35pg/ml) to the luteal phase (233.03±75.46pg/ml) Luteal BDNF levels of the PMS women were significantly lower than those of the control group (p<0.001). In women with PMS, plasma BDNF followed a decreasing trend during the ovarian cycle, in opposition to the increasing trend observed in women without PMS. The lower luteal BDNF levels of the PMS women might be a consequence of an altered hormonal response and might play a role in the onset of the symptoms PMS related., (Copyright © 2010 Elsevier Ltd. All rights reserved.)

In the aftermath of the Women's Health Initiative studies, both the clinical and basic science communities had to sort out divergent results among experimental findings, observational data and randomized controlled trials in order to establish a shared analysis. The scientific community formally debates the role of different HRT formulations, hormone doses, time of treatment initiation since the menopause and the age of treated women. Basic scientists demonstrated that the multiple neuroprotective effects of estrogen on brain cells may induce a differential biological response according to the time of treatment. Progesterone (but not all synthetic progestins) also has pivotal neuroactive functions in animal models of reproductive aging. Additionally, epidemiological surveys provide information regarding the detrimental role of hypogonadism on mental well-being. The present article briefly summarizes current evidence supporting the neuroactive role of estrogen, with reference to the clinical finding sustaining the intriguing hypothesis of the early female brain senescence as a highly responsive period to estrogen treatment.

Study Objective: To assess the roles of instrument diameter (5.0- or 3.5-mm external sheath), uterine distention medium (carbon dioxide [CO(2)] or saline solution), and hysteroscopist experience in diagnostic hysteroscopy., Design: Prospective, randomized, multicenter trial (Canadian Task Force classification I)., Setting: Two university medical centers in Italy., Patients: One hundred eighty-four women attending an infertility clinic., Interventions: Patients were randomly assigned to undergo conventional hysteroscopy (group 1, n = 92) or minihysteroscopy (group 2, n = 92) with CO(2) or saline solution as distention medium. The procedures were performed by hysteroscopists with varying degrees of experience. Patient discomfort was analyzed using the visual analog score. Procedure complications and patient satisfaction rate were also recorded., Measurements and Main Results: Independent of hysteroscopist experience, less pain, fewer complications, and higher satisfaction rates were observed with minihysteroscopy. In addition, procedures in which saline solution was used resulted in less pain and fewer complications than those in which CO(2) was used, but only when performed by inexperienced hysteroscopists., Conclusion: Instrument diameter and hysteroscopist experience, but not the distention medium, seem to be the primary variables that affect the perception of discomfort during office hysteroscopy., (Copyright 2010 AAGL. Published by Elsevier Inc. All rights reserved.)

Background: Plasma brain-derived neurotrophic factor (BDNF) levels are associated with the hormonal status of women. Moreover, the suprachiasmatic nucleus appears to be implicated in the modulation of BDNF central levels. We aimed to investigate whether BDNF circadian rhythms exist in women and if there is a relationship with cortisol circadian rhythmicity. Moreover, we aimed to establish whether the hormonal status influences BDNF diurnal variations., Methods: A total of 30 women were studied: 10 fertile ovulatory women, 10 women undergoing oral contraceptive (OC) therapy and 10 post-menopausal women. Basal BDNF and estradiol levels were assayed in blood samples collected after overnight fasting at regular intervals (08:00, 12:00, 16:00, 20:00, 24:00). BDNF and cortisol levels were measured in samples collected during the follicular and luteal phases in ovulatory women and once a month in OC and post-menopausal women., Results: Luteal BDNF levels were significantly higher than follicular levels in fertile women (P < 0.001). In OC women, BDNF levels were similar to the follicular BDNF levels, whereas in post-menopausal women, they were significantly lower (P < 0.001). BDNF showed a diurnal rhythm in the follicular phase and in women undergoing OC, although the diurnal rhythm was blunted in the luteal phase. In post-menopausal women, BDNF and cortisol levels significantly decreased during the day., Conclusions: BDNF has a diurnal variation in women that is somewhat analogous to cortisol variation; however, the amplitude of the variation in BDNF levels appears to be influenced by ovarian function. Interactions between BDNF, the hypothalamus-pituitary-adrenal axis and sex steroids might play a critical role in the human homeostasis and adaptation.

The aim of the present study was to evaluate the potential action of Nestorone (alone or in combination with estradiol valerate) on the level of allopregnanolone and of the opioid beta-endorphin in selected brain areas. Wistar ovariectomized rats were given 0.05 mg/(kg day) of estradiol valerate (E2V) or subcutaneous Nestorone at three dose levels: low dose (10 microg/(kg day)), antiovulatory dose (50 micro/(kg day)) and high dose (250 microg/(kg day)) with and without E2V. E2V therapy reversed the reduction of allopregnanolone and beta-endorphin induced by ovariectomy anywhere was analyzed except for the adrenal gland. Nestorone showed no effect on allopregnanolone concentration in serum or any part of the brain tissue when given alone while it had a synergistic increasing effect in allopregnanolone concentration in some parts of the brain (hippocampus, hypothalamus, anterior pituitary and serum) when given at high dose of 250 microg/(kg day) in combination with E2V. At lower doses it possesses a synergistic effect with E2V only in the hippocampus (at 50 microg/(kg day)) and in the anterior pituitary (at 10 and 50 microg/(kg day)). Nestorone administered alone at any dose led to significant increase in beta-endorphin levels in the hippocampus only while, in the high dose group, there was a significant increase in endorphin levels in anterior pituitary and hypothalamus in addition to hippocampus as compared to ovariectomized control rats. In addition, only the highest dose of Nestorone added to estrogen increased beta-endorphin levels of hippocampus and plasma. Thus the lower doses of Nestorone alone or in combination with estrogen do not seem to exert any great effect on both allopregnanolone and beta-endorphin. It is only the highest dose of Nestorone that increases allopregnanolone and beta-endorphin levels in selected brain areas, which are the hippocampus, the hypothalamus, the anterior pituitary and serum/plasma. This suggests that Nestorone at the antiovulatory dose levels may not alter the positive effects of estrogen treatment on mood and behaviour.

Background: Synthetic progestins may have different biological actions depending on the target tissue, the dose administered or the coadministration of an estrogen molecule. The purpose of the present study was to evaluate the neuroendocrine effect of chlormadinone acetate (CMA) administration, analyzing the brain content of allopregnanolone (ALLO), an endogenous neurosteroid gamma-aminobutyric acid agonist with anxiolytic properties, and the brain level of beta-endorphin (beta-END), an endogenous opioid implicated in pain mechanism, emotional state and autonomic control., Study Design: Seven groups of Wistar ovariectomized (OVX) rats received one of the following treatments: oral CMA at a dose of 0.1, 0.5 or 1 mg/kg per day; estradiol valerate (E(2)V) at a dose of 0.05 mg/kg per day; CMA plus E(2)V (CMA 0.1 or 0.5 or 1 mg/kg per day + E(2)V 0.05 mg/kg per day) for 14 days. One group of fertile rats and one group of OVX rats were used as controls., Results: CMA increased ALLO content in the hippocampus and, when it was administered with E(2)V, also in the hypothalamus and anterior pituitary, evidence of a synergic effect with estrogens only in selective brain areas. beta-END content increased in the neurointermediate lobe and anterior pituitary after CMA administration, and it did not antagonize the positive, estrogen-induced increase of beta-END level., Conclusion: CMA is effective in increasing ALLO and beta-END in selective brain areas showing a specific pattern of interaction with brain function, different compared to progesterone or to other synthetic progestins. In particular, CMA action on part of the limbic system (hippocampus and hypothalamus) and on the anterior pituitary support the hypothesis that this progestin might affect cognitive function, emotional state and autonomic control.

Cornual pregnancy is an infrequent pathological condition with severe prognosis if not adequately recognized. Ipsilateral salpingectomy represents a unique risk factor for this clinical entity. This article reports a laparoscopically treated spontaneous cornual pregnancy after homolateral salpingectomy for an earlier tubal pregnancy in a condition of hemodynamic instability as a result of cornual rupture. We include a review of the literature, underlining the feasibility of a laparoscopic approach and new treatment options combining medical and surgical tools with specific attention to their impact on future fertility and on risk of uterine rupture in a future pregnancy.

Aims: The present study aims at evaluating the effect of a 2-week treatment with testosterone (T), dihydrotestosterone (DHT) and estradiol valerate (E(2)V) on brain and plasma beta-endorphin (beta-END) concentrations in gonadectomized rats of both sexes., Methods: Eight groups of female and 8 groups of male Wistar rats were included. For each sex, 1 group of gonad-intact and 1 group of gonadectomized rats were employed as controls (placebo). The other groups received subcutaneous T at the doses of 10 and 100 microg/kg/day (female rats) or 1 and 5 mg/kg/day (male rats). Subcutaneous DHT was administered at the doses of 1, 10, 100 microg/kg/day (female rats) or 0.1, 1 and 5 mg/kg/day (male rats). E(2)V was administered subcutaneously at 0.05 mg/kg/day. beta-END levels were measured in different brain areas and plasma., Results: Ovariectomy (OVX) induced a significant decrease in beta-END in all brain areas analyzed as well as in plasma. Orchidectomy (OCX) reduced opioid concentration in the hypothalamus, anterior pituitary and neurointermediate lobe. In OVX rats, T replacement as well as E(2)V significantly increased beta-END concentration in all brain areas and in plasma. In the OCX group, T and E(2)V did not influence beta-END concentrations in different hypothalamic areas. However, they produced a significant rise in beta-END levels in the hypothalamus, neurointermediate lobe, anterior pituitary and plasma. Conversely, DHT replacement did not affect beta-END levels at any dose administered, either in males or females., Conclusions: The sensitivity of the endogenous opiatergic system to T administration seems to be sex-related. This effect is particularly evident in the brains of female animals where this endogenous endorphin elicits a much greater response than it does in males that have undergone gonadal steroid depletion and subsequent T replacement., (Copyright 2009 S. Karger AG, Basel.)

Introduction: Clinical and biological evidences have shown a wide range of neuroactive effects of testosterone administration., Aim: Evaluation of the effects of 2-weeks treatment with testosterone (T), Dihydrotestosterone (DHT), and estradiol valerate (E2V) on brain and serum allopregnanolone (AP) in gonadectomized rats of both sexes., Main Outcome Measures: AP levels were measured in frontal and parietal lobe, hippocampus, hypothalamus, anterior pituitary, and in serum., Methods: Eight groups of Wistar female and eight groups of Wistar male rats were included. For each sex, one group of fertile and one group of gonadectomized rats were employed as control receiving placebo. The others groups received subcutaneous T at the dose of 10 microg/kg/day and 100 microg/kg/day for female rats, and 1 mg/kg/day and 5 mg/kg/day for male rats, or DHT at the doses of 1 microg/kg/day, 10 microg/kg/day, and 100 microg/kg/day for females, and 0, 1 microg/kg/day, 1 mg/kg/day and 5 mg/kg/day for males, or E2V (0.05 mg/Kg/day)., Results: Ovariectomy (OVX) and orchidectomy (OCX) induced a significant decrease in AP in all brain areas analyzed, as well as in serum. In OVX rats, T replacement, as well as E2V, significantly increased AP content in all brain areas and in plasma. In OCX, T and E2V did not actively result in influencing AP concentration in frontal and parietal lobe, while it produced a significant rise in AP levels in the hippocampus, hypothalamus, anterior pituitary, and serum. Conversely, DHT replacement had no affect on AP levels anywhere or at any administered dose, either in males or in female rats., Conclusions: Gender difference and T therapy affect brain AP synthesis/release during the reproductive aging. This effect becomes particularly evident in the brain of ovariectomized animals, where the content of this specific neurosteroid is much more responsive than male animals to testosterone replacement.

Objective: To investigate the effects of dydrogesterone (DYD), a synthetic progestin largely used in hormone therapy, on the central nervous system by studying two markers of the neuroendocrine function: the neurosteroid allopregnanolone and the opioid beta-endorphin., Design: Experimental study on animal model., Setting: Academic research environment., Animal(s): 72 Wistar female rats., Intervention(s): One group of fertile and one of ovariectomized rats (receiving placebo) were used as control. After ovariectomy, the rats underwent a 2-week oral treatment of DYD (0.2, 0.6, or 1.0 mg/kg per day), alone or with estradiol valerate (E2V; 0.05 mg/kg per day)., Main Outcome Measure(s): Allopregnanolone and beta-endorphin, assessed in different brain areas and in circulation., Result(s): Ovariectomy decreased allopregnanolone anywhere except in the adrenal gland and reduced beta-endorphin central levels; E2V reversed the effects of ovariectomy; and DYD (1 mg/kg per day) increased allopregnanolone levels in frontal lobe, hippocampus, and hypothalamus. Combined administration of DYD at 1 mg/kg per day plus E2V determined a further increase of allopregnanolone levels in frontal lobe, hippocampus, hypothalamus, and serum. Dydrogesterone did not modify the levels of beta-endorphin induced by E2V., Conclusion(s): Dydrogesterone interacts with allopregnanolone levels (less with beta-endorphin), and it can be considered important modulator of the neuroendocrine function.

Expression and secretion of neurotrophins, including brain-derived neurotrophic factor (BDNF), are regulated also by neuronal activity. Data available in the literature suggest that BDNF central levels are influenced by light and dark. Diurnal changes of BDNF mRNA and protein contents have been demonstrated in the rat central nervous system. Based on these pieces of evidence, we investigated the hypothesis of a possible diurnal variation of BDNF circulating levels in human males. Moreover, we looked for a possible correlation with cortisol circadian rhythm, since both BDNF and cortisol are implicated in the maintenance of cerebral functions. In this study, 34 healthy young male volunteers were included. Five blood samples were drawn from each subject thrice in a month at regular 4-h intervals (0800, 1200, 1600, 2000, and 2400 h). BDNF and cortisol were measured in all samples. BDNF was determined by ELISA method. Our results show that plasma BDNF levels, as well as cortisol levels, are significantly higher in the morning when compared with the night (P<0.001), with a trend of constant decrease during the day. Furthermore, plasma BDNF and cortisol are positively correlated (Spearman index=0.8466). The present study is the first to demonstrate the presence of a diurnal rhythm of BDNF in humans. Moreover, the correlation found out between BDNF and cortisol circadian trend allows us to speculate that these two factors may be physiologically co-regulated, in order to maintain the homeostasis of integrated cerebral activities.

The aim of this study was to investigate the effects of nomegestrol acetate (NOMAc) on the central nervous system by analyzing the neurosteroid allopregnanolone and the opioid beta-endorphin (beta-endorphin). 104 Wistar female rats were used in this study; one group of fertile and one group of ovariectomized rats were used as control. The others were ovariectomized and they underwent a 2-week oral treatment of NOMAc (0.05, 0.1, 0.2, 0.5, 1mg/kg/day), alone or with 0.05 mg/kg/day of estradiol valerate (E2V). Allopregnanolone and beta-endorphin were assessed in different brain areas and in circulation. Ovariectomy decreased allopregnanolone anywhere except in the adrenal gland and E2V reversed the effects of ovariectomy. 0.5 and 1mg/kg/day of NOMAc increased allopregnanolone levels in hippocampus. Combined administration of 1mg/kg/day of NOMAc plus E2V induced a further increase of allopregnanolone levels in hippocampus, hypothalamus, and anterior pituitary. NOMAc (1mg/kg/day) decreased the adrenal content of allopregnanolone, both by itself and associated with E2V. NOMAc increased hippocampal and hypothalamic content of beta-endorphin at the highest doses, and it increased positively E2V action, at 1mg/kg/day, also in anterior pituitary and plasma. These findings reinforce the clinical data regarding the capability of NOMAc to modulate the pathways involved in mood and behaviour. In fact, due to the NOMAc action on hippocampus, hypothalamus, and anterior pituitary, our results highlight the selectivity of NOMAc on part of the limbic system and the anterior pituitary, regarding both allopregnanolone and beta-endorphin.

The purpose of this study was to evaluate the effects on hormonal milieu of 1-year therapy with 10 mg/day oral dehydroepiandrosterone (DHEA) or 50 microg transdermal estradiol plus 100 mg/day oral micronized progesterone in a group of 20 healthy postmenopausal women (age=50-58 and years since menopause (ysm)=1-6) and also the effects observed by combining these two therapies in a group of 12 postmenopausal women (age=54-61 and ysm=6-10) characterized by lower baseline DHEA and DHEAS levels (<2.40 and <0.55 microg/ml, respectively). DHEA produced a significant rise in androgens levels, whereas HRT did not. Moreover, DHEA alone induced a significantly lower increase in estrogens and beta-endorphin levels and a higher decrease in cortisol levels than HRT. DHEA and HRT also produced a significant similar increase in allopregnanolone levels. DHEA plus HRT induced a significantly higher increase in testosterone and estradiol and a lower increase in allopregnanolone and beta-endorphin levels and a significantly lower decrease in cortisol levels than HRT alone treated group. A similar increase was observed in progesterone and SHBG levels in all groups. These results suggest that 10-mg DHEA seems to be the proper dose to replace androgen deficiency in subjects with reduced Delta-5 androgens plasma levels. However, the aging process and the number of years since menopause may further modulate the effects of hormone therapy on hormonal milieu.

Purpose: The aim of the study was to measure circulating BDNF levels, a neurotrophin recently identified in the ovary, in parallel with estradiol, to verify if assessing this factor could add any predictive value to the outcome of in vitro fertilization., Methods: Blood sampling for BDNF and estradiol was performed in 23 subjects undergoing IVF on day 1 (D1), day 8 (D8), day of HCG administration (DHCG) and day of oocyte retrieval.(DOR)., Results: There was a positive correlation between BDNF and estradiol throughout the stimulation cycle in all subjects. In both pregnant and nonpregnant patients, the values of BDNF grew significantly only between D8 and DHCG and remained constant until DOR. Between-group comparisons showed no statistically significant differences in both BDNF and estradiol values throughout the IVF cycle., Conclusion: Although BDNF plasma concentrations are not seemingly predictive of IVF outcome, this neurotrophin is highly correlated to estradiol levels and seems to be an important factor especially in the periovulatory period.

Several epidemiological and observational studies have investigated the role of hormone replacement therapy (HRT) in postmenopausal women. Within a few years, clinicians shifted from considering HRT as the panacea for everything to considering it a venomous poison with which women, in search of the fountain of eternal youth, could instead harm themselves. This debate is not yet settled and the unexplained discrepancy between basic science and some of the clinical trials has fueled the discussion. One of the hottest areas of discussion remains the role of progestins. For many years, progestins were considered only as necessary additions to estrogen to protect the endometrium. However, we now know that every progestin has its own specific activities on different tissues, which can vary significantly between progestins of different classes and even within the same class. Indeed, different progestins may support or oppose the effects of estrogen depending on the tissue, thereby supporting the concept that the clinical selection of progestins for HRT is critical in determining potential positive or detrimental effects. Newer progestins, such as dydrogesterone, show effects that are remarkably different from those of other agents; these actions might be particularly relevant in the central nervous system and the cardiovascular system. The aim of the present paper is to review the comparative effects of dydrogesterone and other progestins at these sites, supporting the idea that the progestin has to be clinically selected.

Steroids arriving from the gonads via the circulation modulate brain function, affecting gender differentiation and sexually differentiated behavioral responses, but also the ability of the brain to process, store and retrieve sensory information. Androgens play a pivotal neuroactive role during the "organizational/developmental" phase, mainly in the fetal-neonatal period, when participated to the formation of neuronal circuits, as well as during the aging process when it has been demonstrated to directly affect hippocampal spine synapse density, suggesting a physiopathological role for androgen in the modulation cognitive function and development of neurodegenerative disease. The present short review will focus on the neuroactive effect of androgen with particular regard to the Delta4 and Delta5 androgen replacement therapy.

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

Starting from fetal life, estrogens are crucial in determining central gender dimorphism, and an estrogen-induced synaptic plasticity is well evident during puberty and seasonal changes as well as during the ovarian cycle. Estrogens act on the central nervous system (CNS) both through genomic mechanisms, modulating synthesis, release and metabolism of neurotransmitters, neuropeptides and neurosteroids, and through non-genomic mechanisms, influencing electrical excitability, synaptic function and morphological features. Therefore, estrogen's neuroactive effects are multifaceted and encompass a system that ranges from the chemical to the biochemical to the genomic mechanisms, protecting against a wide range of neurotoxic insults. Clinical evidences show that, during the climacteric period, estrogen withdrawal in the limbic system gives rise to modifications in mood, behaviour and cognition and that estrogen administration is able to improve mood and cognitive efficiency in post-menopause. Many biological mechanisms support the hypothesis that estrogens might protect against Alzheimer's disease (AD) by influencing neurotransmission, increasing cerebral blood flow, modulating growth proteins associated with axonal elongation and blunting the neurotoxic effects of beta-amyloid. On the contrary, clinical studies of estrogen replacement therapy (ERT) and cognitive function have reported controversial results, indicating a lack of efficacy of estrogens on cognition in post-menopausal women aged >or=65 years. These findings suggest the presence of a critical period for HRT-related neuroprotection and underlie the potential importance of early initiation of therapy for cognitive benefit. In this review, we shall first describe the multiple effects of steroids in the nervous system, which may be significant in the ageing process. A critical update of HRT use in women and a discussion of possible prospectives for steroid use are subsequently proposed.

Objective: Drospirenone is the unique progestin derived from 17-spironolactone used for contraception and hormone therapy. Few data are available concerning the effects of drospirenone on the central nervous system and neuroendocrine milieu. The opioid beta-endorphin and the neurosteroid allopregnanolone are considered markers of neuroendocrine functions, and their synthesis and activity are regulated by gonadal steroids. The aim of the present study was to evaluate the effect of a 2-week oral treatment with drospirenone, estradiol valerate, and combined therapy of drospirenone + estradiol valerate on central and peripheral beta-endorphin and allopregnanolone levels in ovariectomized female rats., Design: Seven groups of Wistar ovariectomized rats received oral drospirenone (0.1, 0.5, and 1.0 mg/kg per day), estradiol valerate (0.05 mg/kg per day), or drospirenone (0.1, 0.5, and 1.0 mg/kg per day) + estradiol valerate (0.05 mg/kg per day). One group of fertile and one group of ovariectomized rats were used as controls. beta-endorphin levels were measured in frontal and parietal lobes, hippocampus, hypothalamus, anterior and neurointermediate pituitary, and plasma, and allopregnanolone content was assessed in frontal and parietal lobes, hippocampus, hypothalamus, anterior pituitary, adrenal glands, and serum., Results: Ovariectomy induced a significant decrease in beta-endorphin and allopregnanolone content in all brain areas analyzed and in circulating levels, whereas it increased allopregnanolone content in the adrenal gland. Estradiol valerate replacement increased beta-endorphin and allopregnanolone levels in all brain areas analyzed and in plasma/serum. Drospirenone treatment significantly increased beta-endorphin levels in all brain areas analyzed (with the only exception being the parietal lobe), whereas it produced no effect on allopregnanolone levels. The addition of drospirenone to estradiol valerate did not modify the effects of estradiol valerate on beta-endorphin or allopregnanolone levels. Drospirenone showed an additive and synergistic effect with estradiol in the neurointermediate lobe on beta-endorphin synthesis., Conclusions: Drospirenone significantly increases central and circulating beta-endorphin levels and does not seem to interfere with allopregnanolone production.