Effects Of Progestins Research Articles

Investigation the functions of membrane progesterone receptors using their selective ligands

Progesterone plays a key role in reproductive processes in the female body and has effects in the central nervous system and other tissues. Progestins are widely used clinically in contraception and hormonal therapy. The classical effects of progesterone are mediated through nuclear receptors, which are ligand-dependent transcription factors. Since 2003, membrane progesterone receptors (mPRs) of the adiponectin receptor family of five subtypes have been in the spotlight. Their role in many normal and pathological processes in the body remains unclear. Determining the mechanisms of action of progesterone is complicated by the fact that activation of different types of receptors can cause opposite effects. The search for selective ligands of mPRs is an important task, since the use of such compounds makes it possible to differentiate the effects of progestins mediated by different types of receptors. The review analyzes the action of three selective ligands of mPRs, described and studied at present. One of them is widely used in international research, the other two have been identified and used in our work. The advantages and defects of these three compounds and the studies of mPRs functions conducted using them are considered. In conclusion, the prospects for creating new selective mPRs ligands are assessed, taking into account the structural features of their ligand-binding pocket. We found that the 3-keto group of progesterone and its derivatives, which is fundamentally required for binding to nuclear steroid receptors, is not important for interaction with mPRs. Our conclusion was confirmed in a study published in 2022 using modeling techniques and mutational analysis. It is this structural feature that will further serve as the basis for the development of the synthesis of compounds that are effective and selectively interact with mPRs.

Efficacy and safety of different progestogens in women with first threatened miscarriage: A network meta-analysis.

Threatened miscarriage is defined as early vaginal bleeding before 12 weeks of gestational age and can occur in any pregnancy regardless of maternal age, race, comorbidities, lifestyle, or socioeconomic status, and about one-quarter of threatened miscarriages proceed to complete miscarriage. To assess the relative effectiveness and safety of different progestogens in women with first threatened miscarriage, using a network meta-analysis. A systematic search was conducted in PubMed, EMBASE, and Cochrane Library databases from inception to April 2023. Randomized controlled trials (RCTs) assessing the effectiveness or safety of placebo or different progestogens for the treatment of threatened miscarriage were eligible for inclusion, including dydrogesterone (oral), progesterone (oral, vaginal, rectal), and 17-α-hydroxyprogesterone (intramuscular). A Bayesian network meta-analysis with Markov chain Monte-Carlo simulation was performed in this study. A pairwise meta-analysis was carried out by synthesizing studies that compared the same interventions using a fixed-effects model. The primary outcome was the percentage of miscarriage (defined as delivery before 24 weeks of gestation) and preterm birth (defined as birth before 37 weeks of gestation), and the secondary outcomes were live birth rate, congenital abnormalities, neonatal outcomes (low birth weight <2500 g), and adverse events. The risk of bias was assessed by using the Cochrane Risk of Bias Tool. In total, 18 RCTs with six different interventions were included. Oral dydrogesterone can reduce the risk of miscarriage compared with both placebo (odds ratio [OR] 0.5, 95% confidence interval [CI] 0.32-0.76) and vaginal progesterone (OR 0.57, 95% CI 0.36-0.89) in women with first threatened miscarriage. In women with first threatened miscarriage, oral progesterone also reduced the risk of miscarriage compared with placebo (OR 0.61, 95% CI 0.39-0.93). However, from the available evidence, there was no statistically significant difference between progestogens and placebo in preterm birth, congenital abnormality, and live birth rate. Oral dydrogesterone was safe and better at reducing miscarriage than vaginal progesterone and placebo for women with first threatened miscarriage, and better at reducing miscarriage compared with placebo for women with threatened miscarriage.

RELATO DE CASO: HIPERPLASIA MAMÁRIA EM FELINO MACHO

Feline mammary fibroepithelial hyperplasia (FMFH) is a benign, non-neoplastic condition that primarily affects young female cats, usually less than two years old. It is characterized by the proliferation of mammary duct epithelium and periductal connective tissue, associated with the hormonal effects of endogenous and exogenous progestogens. Although more common in females during pregnancy, pseudopregnancy, or early estrus, it can also occur in males after prolonged treatment with progestogens. This report describes the case of an uncastrated male cat in which two small nodules were found in the abdominal region, and subsequently, five more nodules were detected in the mammary region via ultrasound. These nodules underwent fine-needle aspiration cytology, revealing well-differentiated epithelial and mesenchymal cells, suggestive of fibroadenomatous mammary hyperplasia. The animal then underwent castration and, the next day after the procedure, the nodules completely disappeared.

Resolution of the I Ukrainian forum on miscarriages

Today, there is an urgent need to develop and implement a regulatory document on abortion. This is due to the catastrophic state of reproduction of the Ukrainian population – the annual decrease in the number of labor, birth rates and the demographic crisis in Ukraine in general. Pregnancy loss not only causes obstetric complications, but also causes significant damage of the mental health of the woman and her partner, including depression and post-traumatic stress disorder.This resolution is a joint position of the leading specialists of Ukraine on the issue of miscarriages based on domestic experience, results of randomized controlled trials and meta-analyses, as well as clinical recommendations of scientific societies of the world. The presented information is designed to help improve clinical approaches to the management of miscarriage in today’s conditions, in order to save every pregnancy and to not lose a baby.During the Forum, the practical issues of diagnosis and treatment of miscarriage, modern management of threatened and habitual miscarriage, hormonal support of pregnant women and the use of progestogens, the influence of the first half of pregnancy on the birth of a healthy child, the impact of liver diseases on the choice of therapy in a pregnant woman, and others issues were considered.World clinical experience has convincingly proven the high effectiveness of progestogens in the therapy of threatened and repeated miscarriages. However, not all progestogens are equally effective in reducing the risk of miscarriage and live birth in case of threatened miscarriage. Micronized progesterone and dydrogesterone are the most effective. Dydrogesterone differs from progesterone in its mechanism of action and affinity for progesterone receptors. A strong evidence base has been accumulated about a high profile of effectiveness and a low frequency of maternal and fetal complications for dydrogesterone, the use of which is approved by leading foreign associations.Drug interactions and their effects on the liver should also be taken into account. Drugs that are indicated for pregnant women should be prescribed in the smallest therapeutic dose, which should be effective.

12330 Progestogen Experience And Perception Among Transfeminine Adults - A National Survey

Abstract Disclosure: J.J. Chang: None. N. Khai Tran: None. A. Flentje: None. M.E. Lubensky: None. J. Obedin-Maliver: Consulting Fee; Self; Ibis Reproductive Health, Hims, Incorporated, Folx, Incorporated, Upstream, Incorporated. M.R. Lunn: Consulting Fee; Self; Hims, Incorporated, Otsuka Pharmaceutical Development and Commercialization, Inc., American Dental Association. D. Ariel: None. Background: Current guidelines recommend estradiol with consideration of anti-androgens for gender-affirming hormone therapy (GAHT) in transfeminine adults. Many individuals also seek progestogens as part of feminizing GAHT, particularly to enhance breast development. Though progestogen use seems common, few studies describe its use, reported benefits, and side effects. SpecificAims: 1) To describe progestogen use in feminizing GAHT among transfeminine individuals in the U.S. 2) To evaluate reasons for progestogen initiation and perceived physical and emotional impact; 3) To investigate side effects and adverse events. Materials and Methods: In this cross-sectional study, participants were recruited from The PRIDE Study, a U.S.-based longitudinal cohort study of LGBTQIA+-identifying adults. Included participants were assigned male sex at birth and had a feminine/transfeminine or non-binary gender identity. Those assigned female sex at birth (AFAB) or born with 1 or more ovaries were excluded. Descriptive statistics were used to describe socio-demographic characteristics, progestogen use patterns, initiation reasons, perceived physical and mental impacts, side effects, adverse events, and care satisfaction. Results: 543 participants were eligible and completed the study. Mean age was 43.2 years (standard deviation: 14.9). Of 310 progestogen users, the most common progestogen forms were micronized progesterone (58.4% oral; 10.6% rectal) and medroxyprogesterone acetate (7.7% oral). Median progestogen use duration was 2 years (interquartile range: 1-4). Breast development (85.2%) and mimicking the hormone pattern of those AFAB (58.1%) were the two most reported reasons for progestogen initiation. Most progestogen users reported improved breast development (79.7%); none reported worsening. Sex drive, sleep, and concentration did not change with progestogen use in 46.5%, 51.3%, and 73.9% of participants, respectively. Adverse events included lower extremity deep vein thrombosis (n = 6) and pulmonary embolism (n = 4). The most common side effects were breast pain (28.7%), mood fluctuation (21.9%), fatigue (19.7%), and weight gain (19.0%). Most users expressed satisfaction with progestogens (71.9%) and would recommend to others (73.5%). Among 68 former progestogen users, 20.6% reported stopping progestogens due to negative side effects, and 32.4% stopped due to lack of perceived efficacy. Conclusions: In the largest study describing progestogens in GAHT to date, over half of transfeminine adults used progestogens, particularly for breast development. Most reported improvement with breast development and overall satisfaction. However, perceived impacts on other effects were variable. Future prospective studies are needed to investigate the effects of progestogens versus other components of feminizing GAHT. Presentation: 6/1/2024

12330 Progestogen Experience And Perception Among Transfeminine Adults - A National Survey

Abstract Disclosure: J.J. Chang: None. N. Khai Tran: None. A. Flentje: None. M.E. Lubensky: None. J. Obedin-Maliver: Consulting Fee; Self; Ibis Reproductive Health, Hims, Incorporated, Folx, Incorporated, Upstream, Incorporated. M.R. Lunn: Consulting Fee; Self; Hims, Incorporated, Otsuka Pharmaceutical Development and Commercialization, Inc., American Dental Association. D. Ariel: None. Background: Current guidelines recommend estradiol with consideration of anti-androgens for gender-affirming hormone therapy (GAHT) in transfeminine adults. Many individuals also seek progestogens as part of feminizing GAHT, particularly to enhance breast development. Though progestogen use seems common, few studies describe its use, reported benefits, and side effects. SpecificAims: 1) To describe progestogen use in feminizing GAHT among transfeminine individuals in the U.S. 2) To evaluate reasons for progestogen initiation and perceived physical and emotional impact; 3) To investigate side effects and adverse events. Materials and Methods: In this cross-sectional study, participants were recruited from The PRIDE Study, a U.S.-based longitudinal cohort study of LGBTQIA+-identifying adults. Included participants were assigned male sex at birth and had a feminine/transfeminine or non-binary gender identity. Those assigned female sex at birth (AFAB) or born with 1 or more ovaries were excluded. Descriptive statistics were used to describe socio-demographic characteristics, progestogen use patterns, initiation reasons, perceived physical and mental impacts, side effects, adverse events, and care satisfaction. Results: 543 participants were eligible and completed the study. Mean age was 43.2 years (standard deviation: 14.9). Of 310 progestogen users, the most common progestogen forms were micronized progesterone (58.4% oral; 10.6% rectal) and medroxyprogesterone acetate (7.7% oral). Median progestogen use duration was 2 years (interquartile range: 1-4). Breast development (85.2%) and mimicking the hormone pattern of those AFAB (58.1%) were the two most reported reasons for progestogen initiation. Most progestogen users reported improved breast development (79.7%); none reported worsening. Sex drive, sleep, and concentration did not change with progestogen use in 46.5%, 51.3%, and 73.9% of participants, respectively. Adverse events included lower extremity deep vein thrombosis (n = 6) and pulmonary embolism (n = 4). The most common side effects were breast pain (28.7%), mood fluctuation (21.9%), fatigue (19.7%), and weight gain (19.0%). Most users expressed satisfaction with progestogens (71.9%) and would recommend to others (73.5%). Among 68 former progestogen users, 20.6% reported stopping progestogens due to negative side effects, and 32.4% stopped due to lack of perceived efficacy. Conclusions: In the largest study describing progestogens in GAHT to date, over half of transfeminine adults used progestogens, particularly for breast development. Most reported improvement with breast development and overall satisfaction. However, perceived impacts on other effects were variable. Future prospective studies are needed to investigate the effects of progestogens versus other components of feminizing GAHT. Presentation: 6/1/2024

The effect of Norethisterone acetate on the uterus of albino rats: histological, histochemical and ultrastructure study

BackgroundNorethisterone acetate (NETA), also known as norethindrone acetate is a progestogens medication that is widely used in birth control pills, menopausal hormone therapy, and for the treatment of gynecological disorders as abnormal uterine bleeding and endometriosis. There is a lack of detailed histological information regarding the effects of NETA on the uterine structure. So, the present study focuses on the uterine histological, histochemical and ultrastructure changes following the exposure to NETA in the albino rats. To do this aim, fourteen adult female albino rats were used. They were randomly divided into two equally groups: Control group and NETA treated group. Albino rats of control group were administered daily food, water and orally distilled water only, while rats of NETA treated group were administered daily orally 20 µg of NETA dissolved in 2 ml distilled water, food, and water. The experiment was continued for three weeks.ResultsThe findings of the present work indicated that the use of NETA has negative effects on the endometrial epithelium (proliferation, autophagy and apoptosis), glands (necrotic, apoptotic or pseudosecretory glands) and stromal and myometrial reactions (granulocytes, connective tissue remodeling, apoptosis, myocytes hypertrophy).ConclusionThis work revealed that NETA has desynchronized progestogenic effect on the uterine tissues of the albino rat and thereby prevent implantation and pregnancy.

Effect-directed analysis of endocrine and neurotoxic effects in stormwater depending discharges

The investigation of pollutant inputs via stormwater runoff and subsequent effects in receiving waters is becoming increasingly urgent in view of climate change with accompanying extreme weather situations such as heavy rainfall events. In this study, two sampling areas, one urban and one rural but dominated by a highway, were investigated using effect-directed analysis to identify endocrine and neurotoxic effects and potentially responsible substances in stormwater structures and receiving waters. For this purpose, a transgenic yeast cell assay for the simultaneous detection of estrogenic, androgenic, and progestogenic effects (YMEES) was performed directly on high-performance thin-layer chromatography (HPTLC) plates. Concomitantly, estrogens were analyzed by GC–MS/MS and other micropollutants typical for wastewater and stormwater by LC-MS/MS. Discharges from the combined sewer overflow (CSO) contribute a large portion of the endocrine load to the studied water body, even surpassing the load from a nearby wastewater treatment plant (WWTP). An effect pattern similar to the CSO sample was shown in the receiving water after the CSO with lower intensities, consisting of an estrogenic, androgenic, and progestogenic effect. In contrast, after the WWTP, only one estrogenic effect with a lower intensity was detected. Concentrations of E1, 17α-E2, 17β-E2, EE2, and E3 in the CSO sample were 2000, 410, 1100, 560, and 2700 pg/L, respectively. HPTLC-YMEES and GC–MS/MS complement each other very well and help to elucidate endocrine stresses. An Acetylcholinesterase (AChE) inhibitory effect could not be assigned to a causative compound by suspect and non-target analysis using LC-HRMS. However, the workflow showed how information from HPTLC separation, effect-based methods, and other meta-information on the sampling area and substance properties can contribute to an identification of effect-responsible substances. Overall, the study demonstrated that effect-based methods in combination with HPTLC and instrumental analysis can be implemented to investigate pollution by stormwater run-off particularly regarding heavy rain events due to climate change.

The effect of oral progestogens on the intestinal microbiota composition in patients with endometriosis: pilot study

The effect of oral progestogens on the intestinal microbiota composition in patients with endometriosis: pilot study

O-089 Association of pituitary suppression method with euploid blastocyst yield in preimplantation genetic testing for aneuploidy (PGT-A) cycles

Abstract Study question Do progestin primed ovarian stimulation (PPOS) cycles have lower euploidy yield compared to pituitary suppression with gonadotropin releasing hormone (GnRH) antagonists? Summary answer The choice of pituitary suppression method has no bearing on euploid retrieval per blastocyst tested. What is known already Progestin primed ovarian stimulation cycles are an alternative to GnRH antagonists when fresh embryo transfer is not a priority. While the two approaches have been shown to be similar in terms of conventional stimulation outcomes such as mature oocyte retrieval, and blastulation rates, there is still some lingering controversy regarding cumulative pregnancy rates and the effects of progestins on embryo genetic constitution. Study design, size, duration This was a multicenter retrospective cohort study including data from two tertiary-level treatment centers. Participants/materials, setting, methods Infertile women undergoing ovarian stimulation with either progestin primed or GnRH antagonist pituitary suppression with the intention of transfer after PGT-A embryo testing with next-generation sequencing. The main outcome parameter was euploid embryo count per blastocyst tested and was modeled with mixed-effects log-binomial regression models. Results were adjusted for patient age and laboratory performing the PGT-A tests while they were not adjusted for embryo quality to avoid collider bias. Main results and the role of chance A total of 1425 PGT-A tested blastocysts from 383 cycles of 365 patients were included in the analysis. 243 cycles (63.4%) received GnRH antagonists for pituitary suppression while 140 (36.5%) received progestins. The overall euploidy rates per blastocyst tested in the GnRH antagonist and PPOS groups were 38.8% vs. 31.1%, 30.2% vs. 29.4%, 27.0% vs. 25.2%, and 13.8% vs. 14.5% for the age categories &amp;lt;35, 35-37, 38-40, and &amp;gt;40, respectively. After adjusting for the effect of female age at testing and the laboratory performing the PGT-A test, the type of pituitary suppression was not significantly associated with euploid retrieval per blastocyst tested (adjusted risk ratio: 0.94, 95% CI: 0.70 - 1.28, P = 0.701). After testing, 191 women received 233 embryo transfers. Human chorionic gonadotropin (hCG) positivity per transferred embryo was not significantly different between progestin primed and GnRH antagonist cycles (RR: 0.89, 95% CI: 0.71 – 1.08, P = 0.268). Limitations, reasons for caution This is a retrospective study with data from multiple centers with a non-standardized selection of blastocysts to be tested. In addition, the sample size and retrospective nature of the data may have biased the estimates. Wider implications of the findings The choice of pituitary suppression method does not appear to have a significant effect on euploid embryo retrieval rates or hCG positivity per transfer. The choice of medication can be based on the needs of the individual case without concern for suboptimal PGT-A outcomes. Trial registration number Not Applicable

Effect of progestin on thyroid function in female Wistar rats.

To characterize the influence of female-specific hormones on women's thyroid function, the study investigated the influence of extra progestin from oral contraceptives on inducing thyroid dysfunction. Sixty female Wistar rats were divided into six groups based on levonorgestrel or desogestrel administration as the main active agents: control, low (0.0039 mg*20-fold), medium (0.0039 mg*100-fold), high (0.0318 mg*100-fold) levonorgestrel (pure product); and low (0.0083 mg*20-fold) and high (0.0083 mg*100-fold) desogestrel (pure product). Progestin was administered by gavage every 4 days for 1 month. Statistical analysis was performed using one-way analysis of variance and the Kruskal-Wallis test. Following levonorgestrel gavage, serum free T4 and thyroidstimulating hormone levels were significantly lower in the experimental group than that in the control group (p=0.013 and 0.043). After desogestrel gavage, the serum free T4 and free T3 levels were lower in the experimental group than that in the control group (p=0.019 and 0.030). Thyroid hormone antibody concentrations were lower in rats administered levonorgestrel and desogestrel than that in control rats. Moreover, exposure to progestin upregulated the expression of the thyroid-stimulating hormone receptor and sodium iodide symporter in thyroid. Progestin stimulation enhanced the proliferation of follicular epithelial cells in rat thyroid tissues. Progestin exposure could cause thyroid dysfunction by upregulating the transcription of thyroid-stimulating hormone receptor and sodium iodide symporter in thyroid, thus inducing pathomorphological changes in rats' thyroid.

High enrichment factors in chemical analysis of progestins and in bioassays: insights beyond trace levels.

Concerns are growing about adverse effects of progestins on biota, even at ultra-trace concentrations. The enrichment factor (EF) from extraction of analytes in environmental samples that is needed for sample pre-concentration can affect not only performance of the analytical method but also the matrix effect. Therefore, the present study aimed to assess the influence of high sample EF on performance of the high-performance liquid chromatography with atmospheric pressure chemical ionization and photoionization coupled with high-resolution mass spectrometry (HPLC-APCI/APPI-HRMS) method for analysis of progestins in waste water treatment plant (WWTP) effluents and surface waters and analysis of (anti-)progestogenic activities measured by (anti-)PR-CALUX bioassays. The results showed that HPLC-APCI/APPI-HRMS coupled with solid-phase extraction and a high EF (33,333 Lwater/Lextract) enabled the detection of more compounds compared to samples with lower sample EF (10,000 Lwater/Lextract). The matrix effect did not increase proportionally compared to lower EFs (10,000 and 16,666 Lwater/Lextract), and lower limits of quantification were achieved in WWTP effluents and surface waters. The results of bioassays have shown that relative EF of 25 Lwater/Lbioassay appears high enough to detect progestogenic activity in treated waste water. Our study is one of the first to provide insights into sample pre-concentration in analysis of progestins and progestogenicity in aquatic environments.

Enhancement of southern flounder (Paralichthys lethostigma) sperm velocity and fertility by direct activation of sperm epidermal growth factor and adenylyl cyclase signaling pathways

Development of southern flounder commercial aquaculture is limited by poor sperm motility and fertility, but the underlying causes and mechanisms regulating sperm motility are unknown. In vitro treatment of southern flounder sperm with progestin hormones rapidly increases velocity (swimming speed), a major component of sperm motility, and also fertility through membrane progestin receptor alpha (mPRα) and increases in Acy (adenylyl cyclase)/cAMP signaling. The progestin-induced increase of Atlantic croaker sperm velocity is also mediated through epidermal growth factor receptor (Egfr) transactivation resulting in extracellular-regulated kinase 1/2 (Erk1/2) signaling, but its role in regulating southern flounder sperm velocity is unknown. The hypotheses that Egfr transactivation and Erk1/2 signaling mediates progestin-induced increases in sperm velocity and calcium levels in southern flounder, and that direct stimulation of sperm Egfr/Erk1/2 and Acy/cAMP pathways increases sperm fertility in strip spawning trials were tested in the present study. Golf, Egfr, Erk1/2, and protein kinase A were detected on southern flounder sperm by immunocytochemistry. Involvement of Egfr/Erk1/2 signaling in increasing sperm velocity and calcium levels was investigated by preincubating sperm with two EGFR inhibitors, AG1478, and AG825, a matrix metalloproteinase inhibitor, Ilomastat, and two ERK1/2 inhibitors, PD98059, and U0126, for 30 min prior to 1 min treatment with progestins. Sperm swimming speed was observed under a microscope after activation with a hyperosmotic medium and recorded for 1 min. Whereas treatment with the inhibitors did not alter basal sperm velocity and calcium levels, all of them significantly attenuated velocity and calcium increases in response to progestins. Treatment in vitro for 1 min with the Egfr agonist, recombinant human EGF (0.1 nM and 100 nM), mimicked the stimulatory effects of progestins on sperm velocity, the increase in calcium, and also fertility in a strip spawning trials with ovulated southern flounder eggs. The results suggest Egfr/Erk1/2 signaling is involved in sperm velocity and fertility responses to progestins in southern flounder. Direct in vitro treatment with the Acy activator, forskolin (10 μM) for 1 min mimicked the stimulatory action of progestins on sperm calcium levels, velocity, and fertility, suggesting that Acy/cAMP signaling also mediates increased sperm swimming speed and fertility. Importantly, both EGF and forskolin also directly stimulated southern flounder sperm velocity and fertility at the end of the reproductive season when sperm were no longer responsive to progestins. The results suggest that EGF and forskolin could potentially be used as pharmacological agents to enhance reproductive performance of male southern flounder broodstock.

Long-Term Maintenance of Viable Human Endometrial Epithelial Cells to Analyze Estrogen and Progestin Effects.

There are fewer investigations conducted on human primary endometrial epithelial cells (HPEECs) compared to human primary endometrial stromal cells (HPESCs). One of the main reasons is the scarcity of protocols enabling prolonged epithelial cell culture. Even though it is possible to culture HPEECs in 3D over a longer period of time, it is technically demanding. In this study, we successfully established a highly pure, stable, and long-term viable human conditionally reprogrammed endometrial epithelial cell line, designated as eCRC560. These cells stained positive for epithelial markers, estrogen and progesterone receptors, and epithelial cell-cell contacts but negative for stromal and endothelial cell markers. Estradiol (ES) reduced the abundance of ZO-1 in a time- and dose-dependent manner, in contrast to the dose-dependent increase with the progestin dienogest (DNG) when co-cultured with HPESCs. Moreover, ES significantly increased cell viability, cell migration, and invasion of the eCRC560 cells; all these effects were inhibited by pretreatment with DNG. DNG withdrawal led to a significantly disrupted monolayer of eCRC560 cells in co-culture with HPESCs, yet it markedly increased the adhesion of eCRC560 to the human mesothelial MeT-5A cells. The long-term viable eCRC560 cells are suitable for in vitro analysis of HPEECs to study the epithelial compartment of the human endometrium and endometrial pathologies.

Progestogens in women with threatened miscarriage or recurrent miscarriage: A meta-analysis.

Clinical practice guidelines provide inconsistent recommendations regarding progestogen supplementation for threatened and recurrent miscarriage. We conducted a systematic review and meta-analysis to assess the effectiveness and safety of progestogens for these patients. We searched Medline, Embase, and Cochrane Central Registry of Controlled Trials up to October 6, 2023 for randomized control trials (RCTs) comparing progestogen supplementation to placebo or no treatment for pregnant women with threatened or recurrent miscarriage. We assessed the risk of bias using a modified version of the Cochrane risk-of-bias tool and the certainty of evidence using the GRADE approach. Of 15 RCTs (6616 pregnancies) reporting on threatened or recurrent miscarriage, 12 (5610 pregnancies) reported on threatened miscarriage with or without a prior history of miscarriage. Results indicated that progesterone probably increases live births (relative risk (RR) 1.04, 95% confidence interval (CI) 0.99-1.10, absolute increase 3.1%, moderate certainty). Of these RCTs, three (1973 pregnancies) reporting on threatened miscarriage with a prior history of miscarriage indicated that progesterone possibly increases live births (RR 1.06, 95% CI: 0.97-1.16, absolute increase 4.4%; low certainty), while four (2540 pregnancies) reporting on threatened miscarriage and no prior miscarriage left the effect very uncertain (RR 1.02, 95% CI: 0.96-1.10, absolute increase 1.7%; very low certainty). Three trials reporting on 1006 patients with a history of two or more prior miscarriages indicated progesterone probably increases live births (RR 1.08, 95% CI: 0.98-1.19, absolute increase 5.7%, moderate certainty). Six RCTs that reported on 2979 patients with at least one prior miscarriage indicated that progesterone probably increases live births (RR 1.07, 95% CI: 1.01-1.13, absolute increase 5.0%; moderate certainty). Progesterone probably has little or no effect on congenital anomalies (RR 1.06, 95% CI: 0.76-1.48, absolute increase 0.1%; moderate certainty), and other serious adverse pregnancy events (RR 1.07, 95% CI: 0.83-1.40, absolute increase 0.2%, moderate certainty). In women at increased risk of pregnancy loss, progestogens probably increase live births without increasing adverse maternal and neonatal events. It remains possible that the benefit is restricted to those with prior miscarriages.

Progestins for pituitary suppression during ovarian stimulation in artificial reproductive technology

Background: Progestins can suppress endogenous luteinizing hormone secretion from the pituitary gland. Progestins can be used orally and are less expensive than gonadotrophin-releasing hormone (GnRH) analogs. However, early endometrial exposure to progestin precludes fresh embryo transfer (ET), but the emergence of vitrification for oocyte cryopreservation cycles allows more opportunities for using progestins for pituitary suppression.&#x0D; Objective: To assess the mechanism of pituitary suppression by progestins, the effectiveness of progestins compared with GnRH analogs, the effect of progestins on oocyte and embryo developmental potential and euploidy status, and the cost-effectiveness of progestin-primed stimulation. &#x0D; Methods: A literature search using the keywords “multiple waves of antral ovarian follicular development, In Vitro Fertilization, Ovarian stimulation ” was performed in the PubMed database.&#x0D; Results: The duration of stimulation, gonadotrophin consumption, and oocyte yield were similar in progestins and GnRH analogs. However, progestins were associated with significantly lower gonadotrophin consumption than their analogs. Overall, live birth and clinical pregnancy rates per ET were similar to those of progestins and GnRH analogs. Studies comparing medroxyprogesterone acetate, dydrogesterone, and micronized progesterone suggest similar ovarian responses and pregnancy outcomes. The euploidy status of embryos and obstetric and neonatal outcomes from progestin-primed cycles are similar to those of embryos from conventional stimulation cycles. Despite the lower cost of progestins than GnRH analogs, the mandatory cryopreservation of all embryos followed by a deferred transfer may increase the cost per live birth with progestins compared with an artificial reproductive technology cycle culminating in a fresh ET.&#x0D; Conclusion: Progestins present an effective option for women who do not contemplate a fresh ET, e.g., fertility preservation, anticipated hyper responders, preimplantation genetic testing, oocyte donors, and double stimulation cycles.

TSLP enhances progestin response in endometrial cancer via androgen receptor signal pathway.

The enriched proteins within in vitro fertilisation (IVF)-generated human embryonic microenvironment could reverse progestin resistance in endometrial cancer (EC). The expression of thymic stromal lymphopoietin (TSLP) in EC was evaluated by immunoblot and IHC analysis. Transcriptome sequencing screened out the downstream pathway regulated by TSLP. The role of TSLP, androgen receptor (AR) and KANK1 in regulating the sensitivity of EC to progestin was verified through a series of in vitro and in vivo experiments. TSLP facilitates the formation of a BMP4/BMP7 heterodimer, resulting in activation of Smad5, augmenting AR signalling. AR in turn sensitises EC cells to progestin via KANK1. Downregulation of TSLP, loss of AR and KANK1 in EC patients are associated with tumour malignant progress. Moreover, exogenous TSLP could rescue the anti-tumour effect of progestin on mouse in vivo xenograft tumour. Our findings suggest that TSLP enhances the sensitivity of EC to progestin through the BMP4/Smad5/AR/KANK1 axis, and provide a link between embryo development and cancer progress, paving the way for the establishment of novel strategy overcoming progestin resistance using embryo original factors.

Hormones and thrombosis: the dark side of the moon.

The main drawback of oral contraceptives (OC) and hormone replacement therapy (HRT) is an increased risk of venous and, to a lesser extent, arterial thrombosis. This narrative, case-based review describes the effect of available estrogens and progestogens on the hemostatic system and their potential impact on the risk of thrombosis. Clinical cases are used to illustrate different options for prescribing OC and HRT in the real-word. The aim is to offer discussion topics that could be helpful to guide the choice of different hormonal treatments over a woman's lifetime and in the presence of risk factors. We describe physio-pathological changes occurring during the administration of hormonal therapies. Furthermore, we analyze the risk of venous and arterial thrombosis associated with different products, routes of administration and additional risk factors. New hormonal preparations, such as estradiol combined with dienogest, as well as non-oral hormonal therapies, are suggested to decrease thrombotic risk significantly. The availability of many products and different routes of administration allow most women to safely use contraception, as well as HRT. We encourage careful counselling instead of inflexible or fearful behavior, as expanding options and choices will allow women to make the best decisions for their health.

Intervening effects of progesterone combined with estradiol on streptozotocin-induced diabetes in ovariectomized mice and the underlying mechanisms

Background: Estrogen and progesterone are closely related to the occurrence of diabetes, and the progestogenic and estrogenic effects in the development of diabetes are related to their blood levels and the organism state, and it is not clear what effect their combination will be. The present study was to investigate the interaction between estrogen and progesterone in the development of diabetes mellitus. Methods: A model of type 1 diabetes mellitus（T1DM）was established in ovariectomized (OVX) mice by intraperitoneal injection of streptozotocin (STZ), and the levels of plasma glucose, insulin, C-peptide, progesterone, and estradiol, the changes of islet cells, the expressions of glucose transporter 4 (GLUT4), Glucokinase (Gck), Glucose-6-phosphatase (G-6-P) and phosphoenolpyruvate carboxylase (PCK) were detected after chronically injected different doses of progesterone and 17β-estradiol subcutaneously for 4 weeks. Results: Progesterone and 17β-estradiol could delay the occurrence of T1DM induced by STZ in ovariectomized mice, but there was no dose-response relationship; progesterone (2mg/kg) and 17β-estradiol (0.1mg/kg) injected separately or jointly could make the plasma concentration of estradiol and progesterone reaches the physiological dose range, which markedly inhibited the increase of the blood glucose induced by STZ, improved the glucose tolerance, protected islet cells, promoted C-peptide and insulin secretion, up-regulated skeletal muscle GLUT4 and liver Gck expressions, but significantly down-regulated the expressions of liver PCK and G-6-P mRNA. Conclusions: The physiological dose of progesterone combined with estradiol has certain synergistic effects in delaying the occurrence of diabetes, the mechanisms are probably related to the protection of islet cells, the promotion of insulin release, skeletal muscle glucose transport, and liver glucose metabolism.

Resolution of the First Ukrainian endometriosis forum “Drug treatment for endometriosis-associated pelvic pain. The quality of a woman’s life”

Endometriosis affects 10% of all women of reproductive age, i.e. 190 million patients. Ukraine currently does not gather statistics on the incidence of endometriosis, but, at a rough estimate, this number is approximately 280 thousand women and the real number may be higher. Endometriosis has known significant social, medical and economic impact. Therefore, Ukrainian leading specialists in obstetrics and gynecology focus on new treatments for endometriosis, given current scientific data and the needs of patients. The given resolution and algorithms for treatment for endometriosis are the common stand of leading specialists in gynecology in our country and were developed on the basis of modern domestic and foreign data and current clinical guidelines. This resolution aims to improve clinical approaches to the routine practice of treatment for endometriosis. The constant increase in the incidence of endometriosis and its management characteristics allows to conduct an extensive study of the effectiveness and safety profile of various progestogens. In recent years, a number of further evidence have appeared regarding dydrogesterone treatment for endometriosis. New data on the effectiveness of dydrogesterone offer another hormone-based treatment for endometriosis, which is extremely important given the need for long-term and individualized treatment for endometriosis.The Europ ean Society of Human Reproduction and Embryology (ESHRE) states that the degree of pain relief in endometriosis is the same for all hormone-based treatments, but the safety and tolerability profiles of different medicinal products differ, which must be considered. According to the obtained data on the effectiveness and metabolic safety profile of various progestogens and during the discussion, algorithms for dydrogesterone-based treatment for endometriosis were proposed.