Progesterone Aggravates Lung Fibrosis in a Mouse Model of Systemic Sclerosis

BackgroundGender-related factors have explained the higher prevalence of autoimmune diseases in women. Sex hormones play a key role in the immune system and parenchymal cells function; therefore, these hormones can be important in the pathogenesis of autoimmune diseases as a risk or beneficial factor. Lung fibrosis is the main cause of mortality in systemic sclerosis, a female predominant autoimmune disease. The objective of this study was to examine the effect of progesterone on lung fibrosis in a mouse model of systemic sclerosis.MethodsMice with bleomycin-induced lung fibrosis treated with progesterone subcutaneously for 21 and 28 days. Blood was collected for hormone and cytokine measurement at the end of treatment then, skin and lung tissues were harvested for histological assessment, gene expression, cytokine, hydroxyproline, and gelatinase measurement.ResultsTrichrome staining and hydroxyproline measurements showed that progesterone treatment increased the content of collagen in fibrotic and normal lung tissues. Progesterone increased α-SMA (P < 0.01), TGF- β (P < 0.05) and decreased MMP9 (P < 0.05) in fibrotic lung tissues. Also progesterone treatment decreased the gene expression of Col1a2 (P <0.05), Ctgf (P <01), End1 (0.001) in bleomycin- injured lung tissues. The serum level of TNF-α was decreased, but the serum level of cortisol was increased by progesterone treatment in fibrotic mice (P< 0.05).ConclusionOur results showed that progesterone aggravates lung fibrosis in a mouse model of systemic sclerosis.

Effect of Nonionizing Radiation on Progesterone Treatment in Endometrial Hyperplasia: An Experimental Rat Study

<b><i>Objectives:</i></b> The aim of the study was to evaluate the negative effect of nonionizing radiation on the treatment of endometrial hyperplasia (EH) with oral progesterone. <b><i>Design:</i></b> Forty oophorectomized Wistar Albino female rats were included in this experimental rat study. <b><i>Materials and Methods:</i></b> The 4 groups were planned as follows: Group A; sham group; Group B; group receiving oral estradiol hemihydrate 4 mg/kg/day; Group C; 4 mg/kg/day oral estradiol hemihydrate followed with 1 mg/day medroxy progesterone acetate (MPA) and Group D; 4 mg/kg/day oral estradiol hemihydrate followed with 1 mg/day MPA with exposure to nonionizing radiation at 1800 mHz/3 h/day. After the experimental model, uterine horns were sampled and the preparations were evaluated for pathological parameters (glandular density, epithelial cell length, and luminal epithelial cell length) via light microscopy. Nonionizing radiation was created by a signal generator and a compatible mobile phone. <b><i>Results:</i></b> Estrogen was found to increase all parameters related to EH (<i>p</i> &#x3c; 0.05). Progesterone treatment was found to decrease parameters related to EH (Group B vs. C; luminal epithelial cell length, glandular density, and epithelial length; 11.2 vs. 13.2 μm <i>p</i> = 0.007; 32.5 vs. 35.5, <i>p</i> = 0.068; and 219.9 μm vs. 285 µm, <i>p</i> &#x3c; 0.001, respectively). Final analyses revealed reduced effectiveness of progesterone treatment in the rats exposed to nonionizing radiation (Group C vs. D); luminal epithelial cell length, glandular density, and epithelial length (11.2 μm vs. 13.5 μm, <i>p</i> = 0.179; 32.5 vs. 52, <i>p</i> &#x3c; 0.001; and 219.9 μm vs. 374.1 μm, <i>p</i> = 0.001, respectively). <b><i>Limitations:</i></b> The limitations of our study are that the results of animal experiments may not be appropriate for direct adaptation to humans and the relatively low number of rats included in the study. <b><i>Conclusion:</i></b> Nonionizing radiation reduces the effect of progesterone in patients receiving treatment for EH.

Evaluation the Progesterone and Estrogen Receptor (PR & ESR) Level and Their Role in Medical Treatment of Patients with Endometriosis

Background As the endometriosis is a hormone dependent disease, this study designed to determine a cut-off point for selecting the appropriate treatment based on the hormone receptors of endometriosis lesions. Methods In this retrospective cohort study, all symptomatic endometriotic patients, between March 2017 to March 2019, was divided into two groups: responding and non-responding to hormone therapy following endometriosis surgery. Pathological slides of 72 patients were immunohistologically evaluated for progesterone (PR) and estrogen receptor (ESR) levels. Results Based on the rock curve, the presence of 70% of estrogen (P value: 0.001) and 80% of progesterone receptors (P value = 0.005), as well as 60% estrogen (P value: 0.1065) and 40% of progesterone receptors (P value: 0.1699) in the pathology sample based on H score can predict the appropriate response to hormonal treatment of dyspareunia and dysmenorrhea respectively. Dysmenorrhea in the presence of endometrioma showed the best response to OCP compared to the progesterone treatment (69.4% versus 27.8%), while the response of dyspareunia in the presence of the DIE lesions showed the best response to progesterone treatment (75% versus 27.8%). Conclusion Response to treatment of dysmenorrhea and dyspareunia is directly related to the increase of H score. Gynecologist can make the right hormonal treatment based on the specific pattern of IHC staining obtained from patients 'surgical specimens, which leads to improved quality of life and also effective pain reduction after operation as well as recurrent rate.

Long-term follow-up of children exposed in-utero to progesterone treatment for prevention of preterm birth: study protocol of the AMPHIA follow-up

IntroductionPreterm birth is one of the main problems in obstetrics, and the most important cause of neonatal mortality, morbidity and neurodevelopmental impairment. Multiple gestation is an important risk factor for preterm birth, with up to 50% delivering before 37 weeks. Progesterone has a role in maintaining pregnancy and is frequently prescribed to prevent (recurrent) preterm birth and improve pregnancy outcomes in high-risk patients. However, little is known about its long-term effects in multiple gestations. The objective of this follow-up study is to assess long-term benefits and harms of prenatal exposure to progesterone treatment in multiple gestations on child development.Methods and analysisThis is a follow-up study of a multicentre, double-blind, placebo-controlled randomised trial (AMPHIA trial, ISRCTN40512715). Between 2006 and 2009 women with a multiple gestation were randomised at 16–20 weeks of gestation to weekly injections 250 mg 17α-hydroxyprogesterone caproate or placebo, until 36 weeks of gestation or delivery. The current long-term follow-up will assess all children (n=1355) born to mothers who participated in the AMPHIA trial, at 11–14 years of age, with internationally validated questionnaires, completed by themselves, their parents and their teachers.Main outcomes are child cognition and behaviourAdditional outcomes are death (perinatal and up to age 14), gender identity, educational performance and health-related problems. We will use intention-to-treat analyses comparing experimental and placebo group. To adjust for the correlation between twins, general linear mixed-effects models will be used.Ethics and disseminationAmsterdam UMC MEC provided a waiver for the Medical Research Involving Human Subjects Act (W20_234#20.268). Results will be disseminated through peer-reviewed journals and summaries shared with stakeholders, patients and participants. This protocol is published before analysis of the results.Trial registration numberNL8933.

Optimal Duration of Progesterone Treatment before Cryopreserved-Thawed Embryo Transfer

Objective: To investigate the optimal duration of progesterone therapy before cryopreserved-thawed embryo transfer and its impact on clinical pregnancy and live birth rates. Methods: Five hundreds women undergoing cryopreserved-thawed embryo transfer were included in the study. These patients had a total of 500 embryos frozen on day 3 (n = 200), day 4 (n = 100), day 5 (n = 150) and day 6 (n = 50). Artificial endometrial preparation was successfully performed in all participants. If the endometrial thickness reached a minimum of 8 mm or in the presence of a triple-line view, the patients were divided into four different groups and each group into two subgroups according to the estimated duration of progesterone treatment to be used. Group 1 (n = 200): This group consisted of patients with day 3 embryo transfer. While 100 of 200 patients received embryo transfer after 3 days of progesterone treatment, the remaining 100 patients received embryo transfer after 4 days of progesterone treatment. Group 2 (n = 100): This group consisted of patients who underwent day 4 embryo transfer. While 50 of 100 patients had embryo transfer after 4 days of progesterone treatment, the remaining 50 patients received embryo transfer after 5 days of progesterone treatment. Group 3 (n = 150): This group consisted of patients who received day 5 embryo transfer. While 75 of 150 patients received embryo transfer after 5 days of progesterone treatment, the remaining 75 patients received embryo transfer after 6 days of progesterone treatment. Group 4 (n = 50): While 25 of 50 patients received embryo transfer after 6 days of progesterone treatment, the remaining 25 patients received embryo transfer after 7 days of progesterone treatment. The primary outcome measure of our study was to evaluate clinical pregnancy rate (CPR), ongoing pregnancy rate (OPR), live birth rate (LBR) and miscarriage rate per pregnancy. Results: Clinical pregnancy rates were found in 50 of 100 (50%) cases who were given progesterone for 3 days. Of the 100 cases who were given progesterone for 4 days, 40 clinical pregnancy was detected (40%). Both OPR and LBR were found to be significantly lower in patients who received 4 days of progesterone treatment compared to those given 3 days. The rates of miscarraige (9.09%) in patients who received progesterone treatment for 4 days were significantly higher than those who received progesterone for 3 days (5.8%). In Group 2 both OPR and LBR were found to be significantly lower in patients who received 5 days of progesterone treatment compared to those given 4 days. The rate of miscarraige (25.0%) was significantly higher in patients who received progesterone treatment for 5 days compared to those who received progesterone for 4 days (33.3%). When 75 patients in group III who underwent embryo transfer on the fifth day and received progesterone treatment for 5 days and 75 patients who were given progesterone treatment for 6 days were evaluated in terms of CPR, OPR and LBR the difference was statistically significant between the two gruops. When patients in group IV were evaluated in terms of CPR, OPR and LBR the difference was statistically insignificant. Conclusions: Extending the progestereone usage period one day before embryo transfer has been found beneficial in patients who have been transferred for only fifth day.