Endocrine,neuroendocrine and behavioral effects of oral dehydroepiandrosterone sulfate supplementation in postmenopausal women

Aging in women and men is characterized by a progressive decline of circulating dehydroepiandrosterone (DHEA) levels and its sulfate ester (DHEAS). The improvement of wellbeing described in postmenopausal women treated with DHEA suggests that this steroid may exert specific actions on the central nervous system (CNS). The postmenopausal period is associated with several neuroendocrine modifications. The decrease of circulating levels of β-endorphin is considered a hormonal marker of those changes. The aim of the present study was to investigate neuroendocrine and behavioral effects of three months of DHEAS supplementation in postmenopausal women.

Postmenopausal women (n = 22) were divided in three groups: the first group was treated with oral DHEAS (n = 8) (50 mg/day) ,the second treated with the same dose of oral DHEAS + transdermal estradiol (n = 8) (DHEAS) 50 mg/day ,estradiol 50 μg/patch) and the third with transdermal estradiol alone (n = 6) (50 μg/day). Before and after 1 ,2 and 3 months of therapy ,the following circulating steroid and protein hormone levels were evaluated: DHEA ,DHEAS ,androstenedione ,testosterone ,estrone ,estradiol ,17-hydroxyprogesterone ,sex hormone-binding globulin (SHBG) ,follicle-stimulating hormone (FSH) ,luteinizing hormone (LH) ,β-endorphin ,growth hormone (GH) and Cortisol ,and a Kupperman score was performed. Before and after treatments ,plasma β-endorphin levels were evaluated in response to three neuroendocrine tests: (a) clonidine ,an a₂-presynaptic adrenergic agonist (1.25 mg IV); (b) naloxone ,an opioid receptor antagonist (4 mg IV) and (c) fluoxetine ,a serotonin selective reuptake inhibitor (30 mg PO).

In both groups of women treated with DHEAS ,mean basal serum DHEA ,DHEAS ,androstenedione ,and testosterone levels significantly increased after treatment ,while no changes were shown in the group receiving estradiol alone. Serum estradiol ,estrone ,GH and plasma β-endorphin levels significantly increased progressively for the three months of treatment ,with higher levels for estrone and estradiol in subjects receiving estradiol alone or plus DHEAS. Serum SHBG ,Cortisol ,and 17-hydroxyprogesterone did not show significant variations under any treatment. Serum LH and FSH levels showed a significant decrease in groups treated with estradiol alone or plus DHEAS at the second and third months. The Kupperman score showed that all treatments were associated with similar and progressive improvement. Before therapy clonidine ,naloxone and fluoxetine stimuli failed to modify circulating β-endorphin levels. After each of the treatments ,the β-endorphin response was completely restored and was similar ,independent of the kind of therapy.

Restoration of the β-endorphin response to specific stimuli suggests that DHEAS and/or its active metabolites modulates the neuroendocrine control of pituitary β-endorphin secretion ,which may support the therapeutic efficacy of the DHEAS on behavioral symptoms.     

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 Problem The aim of this study was to verify whether anti‐thyroid antibodies are present in the follicular milieu of euthyroid infertile women with thyroid autoimmunity undergoing in vitro fertilization (IVF) and whether IVF outcome is different in affected women with respect to negative controls. A secondary endpoint was to check whether there are changes in thyroid hormone levels during the IVF cycle. Method of study Anti‐thyroglobulin and anti‐thyroperoxidase levels were measured in both follicular fluid and serum on the day of oocyte retrieval in women with thyroid autoimmunity. Serum TSH, FT3, and FT4 levels were measured in all patients before treatment initiation, on the day of oocyte retrieval and of pregnancy test. IVF outcome parameters were recorded in all women. Results Oocyte fertilization, grade A embryos, and pregnancy rates were lower in women with thyroid autoimmunity than in negative controls, while early miscarriage rate was higher. Anti‐thyroid antibodies were measurable in follicular fluid in all affected women and were strongly correlated with serum levels. No significant changes in thyroid hormone levels were recorded in any women. Conclusion The presence of anti‐thyroid antibodies in ovarian follicles, as demonstrated for the first time in this study, may play a critical role in female infertility related to thyroid autoimmunity.     

Melt-Versus Solution-Extrusion Additive Manufacturing of Poly(methyl methacrylate) Medical Implant Prototypes

The development of tailored additive manufacturing (AM) approaches is resulting in novel strategies for engineering the macro/microstructural details of potential medical devices made of biocompatible polymers. The aim of this work is the employment of a multifunctional AM machine for fabricating poly(methyl methacrylate) (PMMA) constructs with a predefined shape and porous architecture, by either melt- or solution-extrusion AM. In particular, PMMA porous scaffolds are manufactured by employing fused filament fabrication (FFF) or computer-aided wet-spinning (CAWS). The comparative characterization of the two developed PMMA implant prototypes demonstrates significant differences in terms of porous structure, polymer surface topography, material composition, glass transition temperature, and mechanical properties. As a consequence, FFF-printed PMMA samples support a faster in vitro proliferation of a murine fibroblast cell line in comparison to PMMA scaffolds by CAWS. The results achieved encourage further research on the developed processing protocols, aimed at the development of tailored PMMA implants for personalized surgery applications.