Vito Cela

STEROID HORMONES AND BDNF

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 Alzheimers and Parkinsons 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.

Daily variation of brain-derived neurotrophic factor and cortisol in women with normal menstrual cycles, undergoing oral contraception and in postmenopause

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.

Female Infertility Related to Thyroid Autoimmunity: The Ovarian Follicle Hypothesis

Citation 
Monteleone P, Parrini D, Faviana P, Carletti E, Casarosa E, Uccelli A, Cela V, Genazzani AR, Artini PG. Female infertility related to thyroid autoimmunity: the ovarian follicle hypothesis. Am J Reprod Immunol 2011; 66: 108–114

Efficacy of a polyethylene oxide-sodium carboxymethylcellulose gel in prevention of intrauterine adhesions after hysteroscopic surgery.

STUDY OBJECTIVES To assess the efficacy of a polyethylene oxide-sodium carboxymethylcellulose gel (Intercoat; Gynecare, division of Ethicon, Inc., Somerville, NJ) in preventing the development of de novo intrauterine adhesions (IUAs) after hysteroscopic surgery and to rate the patency of the internal uterine ostium at 1-month follow-up diagnostic hysteroscopy. DESIGN Randomized controlled study (Canadian Task Force classification I). SETTING University hospital. PATIENTS One hundred ten patients diagnosed during office hysteroscopy as having single or multiple lesions suitable for surgical treatment or resistant dysfunctional uterine bleeding requiring endometrial ablation. INTERVENTIONS Patients were randomized to 2 groups. Group 1 underwent hysteroscopic surgery plus intrauterine application of Intercoat gel, and group 2 underwent hysteroscopic surgery only (control group). Follow-up office hysteroscopy was performed at 1 month after surgery to assess the rate and severity of IUA formation and to rate the patency of the internal uterine ostium after the surgical intervention. MEASUREMENTS AND MAIN RESULTS Compared with the group 2, group 1 demonstrated a significant reduction in the incidence (6% vs 22%; p <.05) of de-novo IUAs. Application of the gel seemed to reduce the severity of IUAs, with fewer moderate and severe IUAs at follow-up in group 1 in comparison with group 2 (33% vs 92%). Furthermore, group 1 demonstrated significant improvement in the degree of patency of the internal uterine ostium (41.9% of cases) in comparison with diagnostic office hysteroscopy performed at enrollment (p <.05). In contrast, in group 2, worsening of patency of the internal uterine ostium was recorded in 18.2% of cases (p <.05). CONCLUSIONS Intercoat gel seems to prevent de novo formation of IUAs and to improve the patency of the internal uterine ostium at follow-up hysteroscopy. However, larger studies are needed to confirm these findings.

Progestogens and brain: an update.

Each synthetic progestins 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. These actions might be particularly relevant in the central nervous system (CNS) where progesterone (P) has pivotal roles besides reproduction and sexual behavior, going from neuropsychological effects to neuroprotective functions. Growing evidence supports the idea that synthetic progestins differ significantly in their brain effects, and clinical studies indicate that these differences also occur in women. Molecular and cellular characterization of the signaling properties of synthetic progestins in brain cells is therefore required and is hoped will lead to a better clinical utilization of the available compounds, as well as to new concepts in the engineering of new molecules. The aim of the present paper is to briefly review and compare neuroendocrine effects of progestogens with special reference to P metabolism into neuroactive steroids and the opioids system.

Membrane integrity evaluation in rabbit spermatozoa

OBJECTIVES The behaviour of head and tail sperm membrane subjected to different vitality tests was evaluated, searching for possible correlations with sperm motility. STUDY DESIGN On fresh semen from seven rabbits we performed: the Eosin Exclusion Test (EET) and, with different incubation times (T(0), T(5), T(30)), a Hypoosmotic Swelling Test (HOS-test) and a combined Hypoosmotic and Eosin Test (HE-test). Kinetic parameters were determined by using the CASA system CELL-TRAK. Statistical analysis was performed by one way ANOVA and Pearsons correlation coefficient. RESULTS The HOS-test revealed significant differences between percentages of curled spermatozoa at T(0) (67.86+/-4.28) versus T(5) (72.86+/-3.28) and versus T(30) (75.14+/-6.5). Among four types of spermatozoa obtained with the HE-test, percentage of Type 1 sperm (HOS+/Eosine) at T(0) (32.3%+/-6.65), was lower than motile sperm (66.86%+/-9.72) but positively correlated. CONCLUSIONS The HE-test is a rapid instrument for predicting sperm motility, selecting spermatozoa with a high degree of membrane resistance both in the tail and the head compartment.

Follicular fluid VEGF levels directly correlate with perifollicular blood flow in normoresponder patients undergoing IVF

BackgroundIt has become increasingly clear that the follicular microenvironment of the maturing human oocyte is a determining factor for the implantation potential of an embryo deriving from that oocyte. Indeed the quality and maturity of an oocyte are influenced by the level of intrafollicular oxygen content which, in turn, is proportional to the degree of follicular vascularity. The aim of the study was to establish whether there is a relationship between follicular fluid VEGF concentrations, perifollicular vascularity and reproductive outcome in normal responders under the age of 35 undergoing IVF.Materials and methodsSixty-one consecutive patients, all at their first IVF cycle, were included in the study. All patients had primary infertility due to male factor or tubal factor. At oocyte retrieval, the perifollicular vascularity of two follicles per ovary was estimated qualitatively through power Doppler blood flow, for a total of two hundred forty-four follicles. The follicular fluid from the identified follicles was centrifuged and stored until VEGF assay. The maturity and fertilization rate of the corresponding oocytes as well as embryo quality and pregnancy rate were recorded.ResultsIn our study, we found VEGF levels to be significantly correlated with grade of perifollicular vascularity. Oocytes obtained from follicles with the higher grade of vascularization also showed a higher rate of fertilization, embryos, a better quality and higher pregnancy rates were obtained in women with highly vascularized follicles. Perifollicular blood flow doppler indices seem to predict oocyte viability and quality. Moreover, VEGF may play a potential role in the development of the perifollicular capillary network.DiscussionThe ability of a given follicle to express VEGF and develop an adequate vascular network may be inter-related in patients under the age of 35. An adequate blood supply may be fundamental important in the regulation of intrafollicular oxygen levels and the determination of oocyte quality.

Comparison of the initial surgical experience with robotic and laparoscopic myomectomy

To compare the initial surgical outcomes of robotic and laparoscopic myomectomy in patients with symptomatic uterine myomas.

Office Vaginoscopic Hysteroscopy in Infertile Women: Effects of Gynecologist Experience, Instrument Size, and Distention Medium on Patient Discomfort

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.

Androgen therapy in women: for whom and when

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.