Search

Context Women with Turner syndrome (TS) suffer from hypergonadotropic hypogonadism, causing a deficit in gonadal hormone secretion. As a consequence, these women are treated with estrogen from the age of 12 years, and later in combination with progesterone. However, androgens have been given less attention. Objective To assess sex hormone levels in women with TS, both those treated and those nontreated with hormone replacement therapy (HRT), and investigate the impact of HRT on sex hormone levels. Methods At Aarhus University Hospital, 99 women with TS were followed 3 times from August 2003 to February 2010. Seventeen were lost during follow-up. Control group 1 consisted of 68 healthy age-matched control women seen once during this period. Control group 2 consisted of 28 young, eumenorrheic women sampled 9 times throughout the same menstrual cycle. Serum concentrations of follicle-stimulating hormone (FSH), luteinizing hormone (LH), 17β-estradiol, estrone sulfate, DHEAS, testosterone, free androgen index, androstenedione, 17-OH progesterone, and sex hormone–binding globulin (SHBG) were analyzed. Results All androgens, 17-OH progesterone, and sex hormone–binding globulin (SHBG) were 30% to 50% lower in TS compared with controls (P < 0.01). FSH, LH, and estrone sulfate were more than doubled in women with TS compared with controls (P < 0.02). Using principal component analysis, we describe a positive correlation between women with TS receiving HRT, elevated levels of SHBG, and decreased levels of androgens. Conclusion The sex hormone profile in TS reveals a picture of androgen deficiency, aggravated further by HRT. Conventional HRT does not normalize estradiol levels in TS.

Este artículo se encuentra disponible en la siguiente URL: https://www.mdpi.com/2306-7381/9/12/663 The objective of this investigation was to determine the ovarian response, fertility, and prolificacy of nulliparous sheep when compared to multiparous sheep after a short-term (7 days) CIDR/eCG treatment which was administered during the non-breeding season. All the multiparous sheep, whereas only 54% of the nulliparous ewes, showed signs of estrus. However, 81.8% of the multiparous sheep and 100% of the nulliparous ewes ovulated. Fertility was also low after short-term progesterone treatments during the anestrous season in maiden sheep (30.8 vs. 72.7% in multiparous ewes). Such results indicate significant differences in the response to CIDR/eCG protocols for induction and synchronization of estrus and ovulation between nulliparous and multiparous sheep during the non-breeding season.

Esta tesis doctoral pertenece al Programa en Medicina Traslacional de CEINDO - CEU Escuela Internacional de Doctorado. Contiene 3 artículos: 1. Alambiaga-Caravaca, A.M., Domenech-Monsell, I.M., Sebastián-Morelló, M., Miranda, M., Balaguer-Fernández, C., Calatayud-Pascual, A., Rodilla, V., López-Castellano, A. (2021). HPLC-UV analytical validation of a method for quantification of progesterone in ex vivo trans-corneal and trans-scleral diffusion studies. Journal of Pharmaceutical and Biomedical Analysis, vol. 193, art. 113749. 2. Alambiaga-Caravaca, A.M., Calatayud-Pascual, M.A., Rodilla, V., Concheiro, A., López-Castellano, A., Álvarez-Lorenzo, C. (2020). Micelles of progesterone for topical eye administration: interspecies and intertissues differences in ex vivo ocular permeability. Pharmaceutics, vol. 12, pp. 1?18. 3. Alambiaga-Caravaca, A.M., Domenech-Monsell, I.M., Sebastián-Morelló, M., Calatayud-Pascual, Merino, V., Rodilla, V., López-Castellano, A. (2021). Development, characterization, and ex vivo evaluation of an insert for the ocular administration of progesterone. International Journal of Pharmaceutics, vol. 12, art. 120921. Tesis - CEINDO - CEU Escuela Internacional de Doctorado, Universidad CEU Cardenal Herrera (Valencia), Facultad de Ciencias de la Salud, Departamento de Farmacia, leída el 08-04-2022.

Este artículo se encuentra disponible en la siguiente URL: https://www.mdpi.com/1424-8247/15/3/328 Este artículo pertenece al número especial "Advances in Ocular Pharmacology". Retinitis pigmentosa (RP) is an inherited eye disorder which triggers a cascade of retinal disorders leading to photoreceptor cell death and for which there is currently no effective treatment. The purpose of this research was to study whether ocular administration of a solution of progesterone (PG) in -cyclodextrins (CD) could delay photoreceptor cell death and counteract the gliosis process in an animal model of RP (rds mice). The possible effect of PG reaching the contralateral eye through the circulatory system was also evaluated. Finally, this research discusses and evaluates the diffusion of the drug from possible topical formulations for ocular administration of PG. A group of rds mice received one drop of a solution of PG in CD every 12 h for 10 days to the left eye, while the right eye was left untreated. Another group of rds mice (control) received the drug vehicle (PBS) on the left eye and, again, the right eye was left untreated. Once the treatment was finished on postnatal day 21, the animals were euthanized and histological immunofluorescence studies (TUNEL, GFAP, and DAPI staining) were carried out. Our results showed that the administration of a solution of PG in CD (CD-PG) as drops significantly decreased cell death and inflammation in the retina of the PG-treated eyes of rds mice. No effect was seen in the contralateral eye from PG that may have entered systemic circulation. In conclusion, CD-PG applied topically as drops to the eye decreases photoreceptor cell death in the early stages of RP, delaying vision loss and decreasing gliosis.

Although uterine contractions in the non-pregnant uterus have been studied extensively, the knowledge gained has not been used in general fertility treatment work-up. In this review paper, we provide an overview of the current knowledge on uterine peristalsis (UP), based on the available literature. This literature shows that UP influences pregnancy chances in both natural and artificial cycles. Although the physiological background of these contractions is not completely clear, we know that several factors can be of influence, like uterine pathologies and hormones. Several options to alter pregnancy outcome by interfering with uterine contractions have been studied. Our meta-analysis on therapeutic options shows positive results of progesterone at time of embryo transfer in IVF cycles or prostaglandins at time of intrauterine insemination, although the quality of evidence is low. These therapies are probably most beneficial in selected groups of patients with abnormal contraction patterns. The introduction of an objective and user-friendly UP measuring tool suitable for use in daily practice would make it possible to identify and monitor these patients. We suggest that future research should focus on the physiology of initiation of UP and on the development of an effective standard measuring tool.

Prospective studies comparing different durations of progesterone supplementation before transfer of vitrified-warmed blastocysts in an artificial cycle are lacking. However, in oocyte donation programmes, the sporadic available evidence demonstrates considerable differences in clinical pregnancy rates according to the duration of progesterone administration. This randomised controlled trial (RCT), included 303 patients undergoing a frozen-thawed embryo transfer (FET) of one or two vitrified-warmed blastocyst(s) in an artificial cycle. Randomisation was performed when the endometrial thickness reached ≥7 mm after oestrogen supplementation. One hundred and fifty two patients in group A received 7 d of vaginal micronised progesterone tablets and 151 patients in group B received 5 d of micronised vaginal progesterone before FET. No differences were seen in clinical pregnancy rate between both groups: 42/152 (27.6%) in group A versus 49/151 (32.5%) in group B. Although no statistically significant difference was observed in clinical pregnancy rates, our study was powered to detect an absolute difference of 16%. In this regard, we cannot exclude that smaller, clinically relevant differences might exist and our study did not have the power to detect this. Patients were also not blinded for the intervention, causing a potential bias.

Progesterone (PG) may provide protection to the retina during retinitis pigmentosa, but its topical ocular supply is hampered by PG poor aqueous solubility and low ocular bioavailability. The development of efficient topical ocular forms must face up to two relevant challenges: Protective barriers of the eyes and lack of validated ex vivo tests to predict drug permeability. The aims of this study were: (i) To design micelles using Pluronic F68 and Soluplus copolymers to overcome PG solubility and permeability, and (ii) to compare drug diffusion through the cornea and sclera of three animal species (rabbit, porcine, and bovine) to investigate interspecies differences. Micelles of Pluronic F68 (3&ndash, 4 nm) and Soluplus (52&ndash, 59 nm) increased PG solubility by one and two orders of magnitude, respectively and exhibited nearly a 100% encapsulation efficiency. Soluplus systems showed in situ gelling capability in contrast to the low viscosity Pluronic F68 micelles. The formulations successfully passed the hen&rsquo, s egg-chorioallantoic membrane test (HET-CAM) test. PG penetration through rabbit cornea and sclera was faster than through porcine or bovine cornea, although the differences were also formulation-dependent. Porcine tissues showed intermediate permeability between rabbit and bovine. Soluplus micelles allowed greater PG accumulation in cornea and sclera whereas Pluronic F68 promoted a faster penetration of lower PG doses.

Este artículo se ha publicado de forma definitiva en: https://www.mdpi.com/2076-3921/8/3/53 Este artículo pertenece al número especial "Antioxidants and Retinal Disease". Oxidative stress has been documented to be a key factor in the cause and progression of different retinal diseases. Oxidative cellular unbalance triggers a sequence of reactions which prompt cell degeneration and retinal dysfunction, both hallmarks of several retinal pathologies. There is no effective treatment, yet, for many retinal diseases. Antioxidant treatment have been pointed out to be an encouraging palliative treatment; the beneficial effects documented involve slowing the progression of the disease, a reduction of cell degeneration, and improvement of retinal functions. There is a vast information corpus on antioxidant candidates. In this review, we expose three of the main antioxidant treatments, selected for their promising results that has been reported to date. Recently, the sulforaphane, an isothiocyanate molecule, has been unveiled as a neuroprotective candidate, by its antioxidant properties. Progesterone, a neurosteroid has been proposed to be a solid and effective neuroprotective agent. Finally, the lipoic acid, an organosulfur compound, is a well-recognized antioxidant. All of them, have been tested and studied on different retinal disease models. In this review, we summarized the published results of these works, to offer a general view of the current antioxidant treatment advances, including the main effects and mechanisms described.

Este artículo se encuentra disponible en la siguiente URL: https://iovs.arvojournals.org/article.aspx?articleid=2743694 Esta comunicación se presentó en el ARVO Annual Meeting Abstract celebrado en Vancouver, Canadá entre el 28 de abril y el 2 de mayo de 2019.

Este artículo se encuentra disponible en la página web de la revista en la siguiente URL: https://www.sciencedirect.com/science/article/abs/pii/S0960076018305077?via%3Dihub This is the pre-peer reviewed version of the following article: Benlloch-Navarro, S., Trachsel-Moncho, L., Fernández-Carbonell, Á., Olivar, T., Soria, J.M., Almansa, I. et al. (2019). Progesterone anti-inflammatory properties in hereditary retinal degeneration. Journal of Steroid Biochemistry and Molecular Biology, vol. 189 (may), pp. 291-301, which has been published in final form at https://doi.org/10.1016/j.jsbmb.2019.01.007. Este es el pre-print del siguiente artículo: Benlloch-Navarro, S., Trachsel-Moncho, L., Fernández-Carbonell, Á., Olivar, T., Soria, J.M., Almansa, I. et al. (2019). Progesterone anti-inflammatory properties in hereditary retinal degeneration. Journal of Steroid Biochemistry and Molecular Biology, vol. 189 (may), pp. 291-301, que se ha publicado de forma definitiva en https://doi.org/10.1016/j.jsbmb.2019.01.007. The interactions between steroid gonadal hormones and the retina (a part of the visual system and the central nervous system (CNS)) have received limited attention and beneficial effects of these hormones in retinal diseases is controversial. Retinitis pigmentosa (RP) is the most common cause of retinal hereditary blindness and to date no treatment is available. However, results regarding the effects of progesterone on the progression of RP are promising. With the idea of demonstrating if the progesterone retinal protection in RP is related to its possible anti-inflammatory properties, we have administered orally progesterone to rd10 mice, an animal model of RP. We observed that progesterone decreased photoreceptors cell death, reactive gliosis and the increase in microglial cells caused by RP. We also examined the expression of neuronal and inducible nitric oxide synthase (nNOS and iNOS), the enzyme responsible for NO production. The results demonstrated a decrease in nNOS expression only in control mice treated with progesterone. Inflammation has been related with an increase in lipid peroxidation. Noticeably progesterone administration was able to diminish retinal malondialdehyde (MDA, a lipid peroxidation product) concentrations in rd10 mice. Altogether, we can conclude that progesterone could be a good therapeutic option not only in RP but also for other retinal diseases that have been associated with inflammation and lipid peroxidation. Preprint

Este artículo se encuentra disponible en la página web de la revista en la siguiente URL: https://www.frontiersin.org/articles/10.3389/fphar.2018.00469/full Retinitis pigmentosa (RP) is a group of inherited retinopathies characterized by photoreceptors death. Our group has shown the positive progesterone (P4) actions on cell death progression in an experimental model of RP. In an effort to enhance the beneficial effects of P4, the aim of this study was to combine P4 treatment with an antioxidant [lipoic acid (LA)] in the rd1 mice. rd1 and control mice were treated with 100 mg/kg body weight of P4, LA, or a combination of both on postnatal day 7 (PN7), 9, and 11, and were sacrificed at PN11. The administration of LA and/or P4 diminishes cell death in rd1 retinas. The effect obtained after the combined administration of LA and P4 is higher than the one obtained with LA or P4 alone. The three treatments decreased GFAP staining, however, in the far peripheral retina, and the two treatments that offered better results were LA and LA plus P4. LA or LA plus P4 increased retinal glutathione (GSH) concentration in the rd1 mice. Although LA and P4 are able to protect photoreceptors from death in rd1 mice retinas, a better effectiveness is achieved when administering LA and P4 at the same time.

Este artículo se encuentra disponible en la página web de la revista en la siguiente URL: https://www.sciencedirect.com/science/article/abs/pii/S0378432018306626?via%3Dihub This is the pre-peer reviewed version of the following article: Martinez-Ros, P., Astiz, S., Garcia-Rosello, E., Rios-Abellan, A. & Gonzalez-Bulnes, A. (2018). Effects of short-term intravaginal progestagens on the onset and features of estrus, preovulatory LH surge and ovulation in sheep. Animal Reproduction Science, vol. 197 (oct.), pp. 317-323, which has been published in final form at https://doi.org/10.1016/j.anireprosci.2018.08.046. Este es el pre-print del siguiente artículo: Martinez-Ros, P., Astiz, S., Garcia-Rosello, E., Rios-Abellan, A. & Gonzalez-Bulnes, A. (2018). Effects of short-term intravaginal progestagens on the onset and features of estrus, preovulatory LH surge and ovulation in sheep. Animal Reproduction Science, vol. 197 (oct.), pp. 317-323, que se ha publicado de forma definitiva en https://doi.org/10.1016/j.anireprosci.2018.08.046. In the present study, there was a comparison among classical long-term progestagen (fluorogestone acetate) protocols for synchronization of estrus and ovulation (14 days; group FGA14, n = 9 ewes) and short-term protocols based on 7 days of progestagen treatment plus a dose of prostaglandin F at either insertion (PG-FGA7, n = 11) or removal (FGA7-PG, n = 12). There were no significant differences in the ovulation rate and progesterone secretion among treatments. The FGA7-PG group, however, had a similar percentage of ewes expressing estrous behavior than the group FGA14 (90.9 and 100%, respectively, with a trend for a lesser percentage in the PG-FGA7 group, 63.6%) and about 90% of the ewes in the FGA7-PG group had the preovulatory surge release of LH 8 h after the onset of estrous behavior. These features may be related to a greater number of preovulatory follicles during growing phases (P < 0.05) and a greater plasma estradiol concentration (P < 0.05) in this group than in the classical 14-day group, which suggest these are more functional preovulatory follicles. In conclusion, therefore, the use of the FGA7-PG treatment may favor efficiency of progestagen-based protocols for reproductive management. Preprint

Summary points: • Meta-analysis methods combine quantitative evidence from related studies to produce results based on a whole body of research • Studies that do not provide direct evidence about a particular outcome or treatment comparison of interest are often discarded from a meta-analysis of that outcome or treatment comparison • Multivariate and network meta-analysis methods simultaneously analyse multiple outcomes and multiple treatments, respectively, which allows more studies to contribute towards each outcome and treatment comparison • Summary results for each outcome now depend on correlated results from other outcomes, and summary results for each treatment comparison now incorporate indirect evidence from related treatment comparisons, in addition to any direct evidence • This often leads to a gain in information, which can be quantified by the “borrowing of strength” statistic, BoS (the percentage reduction in the variance of a summary result that is due to correlated or indirect evidence) • Under a missing at random assumption, a multivariate meta-analysis of multiple outcomes is most beneficial when the outcomes are highly correlated and the percentage of studies with missing outcomes is large • Network meta-analyses gain information through a consistency assumption, which should be evaluated in each network where possible. There is usually low power to detect inconsistency, which arises when effect modifiers are systematically different in the subsets of trials providing direct and indirect evidence • Network meta-analysis allows multiple treatments to be compared and ranked based on their summary results. Focusing on the probability of being ranked first is, however, potentially misleading: a treatment ranked first may also have a high probability of being ranked last, and its benefit over other treatments may be of little clinical value • Novel network meta-analysis methods are emerging to use individual participant data, to evaluate dose, to incorporate “real world” evidence from observational studies, and to relax the consistency assumption by allowing summary inferences while accounting for inconsistency effects

Este artículo se encuentra disponible en la página web de la revista en la siguiente URL: https://www.publish.csiro.au/rd/RD18477 This is the pre-peer reviewed version of the following article: Gonzalez-Bulnes, A., Menchaca, A., Martin, G.B. & Martinez-Ros, P. (2020). Seventy years of progestagen treatments for management of the sheep oestrous cycle: where we are and where we should go. Reproduction, Fertility and Development, vol. 32, i. 5 (24 jan.), pp. 441-452, which has been published in final form at https://doi.org/10.1071/RD18477. Este es el pre-print del siguiente artículo: Gonzalez-Bulnes, A., Menchaca, A., Martin, G.B. & Martinez-Ros, P. (2020). Seventy years of progestagen treatments for management of the sheep oestrous cycle: where we are and where we should go. Reproduction, Fertility and Development, vol. 32, i. 5 (24 jan.), pp. 441-452, que se ha publicado de forma definitiva en https://doi.org/10.1071/RD18477. The management of the ovine estrous cycle is mainly based on the use of exogenous hormones for mimicking (progesterone and its analogues) or manipulating (prostaglandin F2α and its analogues) the activity of the corpus luteum, combined with the application of other hormones mimicking the pituitary secretion of gonadotrophins (e.g.: equine chorionic gonadotrophin, eCG). These protocols have been applied without major change for decades but, now, there are two reasons to reconsider them: i) our greatly improved knowledge of the dynamics of ovarian physiology, following the application of transrectal ultrasonography, indicates that modification of the protocols may improve the yields; ii) increasing concerns about animal health and welfare, food safety and the environmental impact of the treatments, as evidenced by public opinion and therefore market forces. Here, we offer an overview of these issues, introduce an updated protocol, and suggest ways for future improvements of the protocols. Preprint

Tesis - Universidad CEU Cardenal Herrera (Valencia), Facultad de Ciencias de la Salud, Departamento de Ciencias Biomédicas, leída el 26-06-2017.

OBJECTIVE To evaluate the effectiveness of 200 mg of daily vaginal natural progesterone to prevent preterm birth in women with preterm labour. DESIGN Multicentre, randomised, double-blind, placebo-controlled trial. SETTING Twenty-nine centres in Switzerland and Argentina. POPULATION A total of 385 women with preterm labour (24(0/7) to 33(6/7) weeks of gestation) treated with acute tocolysis. METHODS Participants were randomly allocated to either 200 mg daily of self-administered vaginal progesterone or placebo within 48 hours of starting acute tocolysis. MAIN OUTCOME MEASURES Primary outcome was delivery before 37 weeks of gestation. Secondary outcomes were delivery before 32 and 34 weeks, adverse effects, duration of tocolysis, re-admissions for preterm labour, length of hospital stay, and neonatal morbidity and mortality. The study was ended prematurely based on results of the intermediate analysis. RESULTS Preterm birth occurred in 42.5% of women in the progesterone group versus 35.5% in the placebo group (relative risk [RR] 1.2; 95% confidence interval [95% CI] 0.93-1.5). Delivery at

Tesis - Universidad CEU Cardenal Herrera (Valencia), Facultad de Ciencias de la Salud, Departamento de Ciencias Biomédicas, leída el 30-03-2015.

Tocolysis is an important treatment in the improvement of outcome in preterm labor and preterm birth, provided that its use follows clear evidence-based recommendations. In this expert opinion, the most recent evidence about efficacy and side effects of different tocolytics is being reviewed and evidence-based recommendation about diagnosis and treatment of preterm labor is given. Further aspects such as progesterone administration or antibiotic treatment for the prevention of preterm birth are included. Our review demonstrates that an individualized choice of different tocolytics and additional treatments is necessary to improve short- and long-term neonatal outcome in preterm labor and preterm birth.

Threatened miscarriage—vaginal bleeding before 20 gestational weeks—is the commonest complication in pregnancy, occurring in about a fifth of cases.w1 Miscarriage is 2.6 times as likely,1 and 17% of cases are expected to present complications later in pregnancy.2 Although general practitioners and gynaecologists often see this condition, management of threatened miscarriage is mostly empirical. Bed rest is routinely recommended, and about a third of women presenting with threatened miscarriage are prescribed drugs.w2 However, two thirds of the general practitioners recommending this do not believe it affects outcome.3 In this review, we present available evidence on the initial evaluation and management of threatened miscarriage, focusing mainly on the first trimester of pregnancy and primary healthcare settings. We searched literature in English with Medline (January 1965 to April 2004), Embase (January 1980 to April 2004), and the Cochrane database using the keywords “threatened” and “abortion” or “miscarriage” and “pregnancy” and “first trimester” or “early” and “bleeding”. We scanned abstracts and got the full text of relevant articles. We also scanned the references of retrieved articles. The more recent or randomised, prospective, or large studies focusing on women with symptoms of threatened miscarriage were primarily cited; we excluded studies on recurrent pregnancy loss or women without symptoms, unless otherwise stated. ### Evaluation Bleeding in the first trimester can originate from the uterus, cervix, or vagina, or it can be extragenital. Thorough physical examination is essential to differentiate between genital and extragenital causes. After exclusion of extragenital causes, several parameters have been associated with prognosis (table 1). View this table: Table 1. Prognostic factors in cases of threatened abortion #### History Older women are at increased risk of miscarriage in the general population.w3 A prospective study on women with threatened abortion reported that women older than 34 years had an odds ratio of 2.3 for miscarriage, however, …

To study the role of oestradiol and progesterone in the secretion of leptin, 21 normally ovulating women were recruited from those scheduled for ovariectomy plus hysterectomy performed in mid-follicular phase of the cycle. Seven of the women were used as controls and received no hormonal treatment post-operatively. Another seven women received oestradiol (oestradiol group) and the remaining seven women received oestradiol plus progesterone (oestradiol plus progesterone group). Serum leptin values showed a temporal but significant increase 24 h after the operation and were significantly correlated with the cortisol and progesterone values, which increased temporarily at 12 h. At that time a marked decline in oestradiol concentrations was seen. After the temporal increase, leptin values in the controls and the oestradiol group decreased significantly up to day 4 (P: < 0.05), while in the oestradiol plus progesterone group they increased (P: < 0.01) and were significantly higher than in the other two groups (P: < 0.05). Body mass index (BMI) was the most important variable accounting for the changes in leptin values post-operatively, but in the oestradiol plus progesterone group progesterone correlated significantly with leptin independently of BMI. These results suggest that progesterone and cortisol can stimulate leptin secretion in women regardless of oestradiol concentrations. Hum Reprod