Oral Progesterone Research Articles

Efficacy of Vaginal and Oral Progesterone After Tocolytic Therapy in Threatened Preterm Labor: A 3-Arm Parallel- Group Randomized Controlled Trial

Background: Progesterone has established roles in preventing preterm labor in women with history of spontaneous preterm labor and short cervix, but there is little evidence to support its use to prevent preterm delivery in women with threatened preterm labor. Objective: To evaluate clinical efficacy of oral and vaginal progesterone on prevention of preterm delivery before 34 and 37 weeks in threatened preterm labor. Materials and Methods: The present study was a 3-arm randomized control trial, 231 singleton pregnancies of 28- to 33-weeks-6-days who had threatened preterm labor were recruited and randomized to three groups,1) 200 mg/day vaginal micronized progesterone, 2) 30 mg/day oral dydrogesterone and 3) control group with no progesterone. All groups received identical standard treatment for threatened preterm labor. Comparison of primary outcomes, which is the preterm delivery before 34 and 37 weeks, across groups were performed using chi-square test. Secondary outcomes, which are latency period, cervical change, maternal morbidity, neonatal morbidity, and mortality, were also compared. Results: Proportion of preterm delivery before 34 weeks was not significantly different across the three treatment groups at 16.0%, 12.0%, and 5.2% in control, oral progesterone, and vaginal progesterone groups, respectively (p=0.098). Concerning pairwise comparison, vaginal progesterone was more efficacious in preventing preterm delivery before 34 weeks than the control group (p=0.030), while oral progesterone was similarly effective to the control group (p=0.638). Proportion of preterm delivery before 37 weeks was not significantly different across the three treatment groups at 41.3%, 45.3%, and 31.2% in control, oral, and vaginal progesterone groups, respectively (p=0.182). Latency period differed across three treatment groups with a median latency of 36.5, 42.0, and 43.0 days in control, oral, and vaginal progesterone groups, respectively (p=0.041). Changes in cervical length and Bishop scores were not different across treatment groups. Conclusion: Vaginal progesterone could prevent preterm delivery before 34 weeks and prolong latency period in women with threatened preterm labor. Keywords: Preterm labor, Progesterone efficacy, Threatened preterm labor, After tocolysis

Comparison of the efficacy of different progesterone regimens in blastocyst frozen-thawed embryo transfer cycles

Aim: The progesterone’s optimal route for luteal phase support (LPS) in frozen-thawed embryo transfer (FET) cycles is controversial. This study investigates the effect of three treatment regimens of progesterone: vaginal, oral, and subcutaneous form for LPS in FET cycles.
 Material and Method: Blastocyst cryopreserved FET cycles utilizing vaginal, subcutaneous, or oral forms of progesterone between December 2018 and May 2020 were included. The main outcome was to compare clinical pregnancy rates (CPR), ongoing pregnancy rates (OPR), and live birth rates (LBR) in different progesterone groups. 
 Results: A total of 434 cycles were included, of which 200 utilized vaginal, 124 utilized subcutaneous, and 110 utilized oral forms. Demographic and cycle characteristics were similar between all three groups. Compared to cycles utilizing vaginal, subcutaneous, and oral forms, CPR, OPR, and LBR differ significantly between the three groups (p-value = 0.000). Miscarriage was calculated according to the number of days after embryo transfer, and it was shown that the subcutaneous group had the lowest rate of miscarriage with 11 cases (8.8%). The highest OPR was associated with the subcutaneous group with 67 (54%), followed by the vaginal group with 92 (46%). The highest LBR was in the subcutaneous group, with 59 (47.6%) cases. The oral group was significantly less successful 29 ( 26.4%) than the subcutaneous and vaginal groups. 
 Conclusion: Our study results showed that subcutaneous and vaginal progesterone performed better than oral progesterone for LPS in patients undergoing FET. All three forms of progesterone administration were safe and well-tolerated.

44. Abnormal Uterine Bleeding during Pubertal Induction with Transdermal Estrogen in Turner Syndrome: Experience from a Large Turner Syndrome Center

<h3>Background</h3> More than 80% of girls with Turner syndrome (TS) experience primary ovarian failure prior to the onset of menarche. Hormone replacement therapy (HRT) is recommended to start between 11-12 years of age, followed by titration to adult dosing over 18-24 months. Current guidelines recommend that HRT starts with transdermal estradiol, followed by the addition of oral progesterone once breakthrough bleeding occurs or after 18-24 months of unopposed estrogen therapy, whichever occurs first. In our TS population, several individuals have experienced abnormal uterine bleeding (AUB) while undergoing pubertal induction with transdermal estradiol. The objective of this study was to identify risk factors associated with and evaluate the management practices of AUB during pubertal induction among females with TS. <h3>Methods</h3> A retrospective case series of 45 TS females seen between January 2007 and June 2019 . Among these, 64% (n=29) served as controls and 55% (n=16) experienced AUB. <h3>Results</h3> Several risk factors for the development of AUB were identified: frequency of progestin cycling less than monthly (56.5% for cases vs. 0% for control), prolonged duration of unopposed estrogen (median of 21 months for cases vs. 17 months for controls), low dose (<200 mg) of progestin (50% of cases vs. 13.5% of control), and noncompliance with HRT (18.8%). Of the patients who experienced AUB, 3 received an additional 10 day course of progestins, 7 were treated by increasing their progestin dose, 6 were switched to another method of HRT (e.g. IUD or OCP), 6 increased cycling frequency to monthly, 4 required hospitalization, 2 required iron supplementation, and 2 required a transfusion with blood products. <h3>Conclusions</h3> Based on our experience, we recommend the following to prevent AUB during pubertal induction with transdermal estrogen in TS girls: 1) Cycle with progestins monthly, 2) Introduce progestins at the onset of breakthrough bleeding or at 18 months, whichever occurs first, 3) Use progestin dosing at the upper end of the recommended range (e.g. 200 mg for micronized progesterone) 4) Counsel all patients regarding the risk of AUB, 5) Monitor all patients regularly during pubertal induction, 6) Monitor with heightened surveillance those patients who show rapid development of secondary sex characteristics on low dose estrogen.

Evaluating Progestogens for Preventing Preterm birth International Collaborative (EPPPIC): meta-analysis of individual participant data from randomised controlled trials

Preterm birth is a global health priority. Using a progestogen during high-risk pregnancy could reduce preterm birth and adverse neonatal outcomes.We did a systematic review of randomised trials comparing vaginal progesterone, intramuscular 17-hydroxyprogesterone caproate (17-OHPC), or oral progesterone with control, or with each other, in asymptomatic women at risk of preterm birth. We identified published and unpublished trials that completed primary data collection before July 30, 2016, (12 months before data collection began), by searching MEDLINE, Embase, CINAHL, the Maternity and Infant Care Database, and relevant trial registers between inception and July 30, 2019. Trials of progestogen to prevent early miscarriage or immediately-threatened preterm birth were excluded. Individual participant data were requested from investigators of eligible trials. Outcomes included preterm birth, early preterm birth, and mid-trimester birth. Adverse neonatal sequelae associated with early births were assessed using a composite of serious neonatal complications, and individually. Adverse maternal outcomes were investigated as a composite and individually. Individual participant data were checked and risk of bias assessed independently by two researchers. Primary meta-analyses used one-stage generalised linear mixed models that incorporated random effects to allow for heterogeneity across trials. This meta-analysis is registered with PROSPERO, CRD42017068299.Initial searches identified 47 eligible trials. Individual participant data were available for 30 of these trials. An additional trial was later included in a targeted update. Data were therefore available from a total of 31 trials (11 644 women and 16185 offspring). Trials in singleton pregnancies included mostly women with previous spontaneous preterm birth or short cervix. Preterm birth before 34 weeks was reduced in such women who received vaginal progesterone (nine trials, 3769 women; relative risk [RR] 0·78, 95% CI 0·68-0·90), 17-OHPC (five trials, 3053 women; 0·83, 0·68-1·01), and oral progesterone (two trials, 181 women; 0·60, 0·40-0·90). Results for other birth and neonatal outcomes were consistently favourable, but less certain. A possible increase in maternal complications was suggested, but this was uncertain. We identified no consistent evidence of treatment interaction with any participant characteristics examined, although analyses within subpopulations questioned efficacy in women who did not have a short cervix. Trials in multifetal pregnancies mostly included women without additional risk factors. For twins, vaginal progesterone did not reduce preterm birth before 34 weeks (eight trials, 2046 women: RR 1·01, 95% CI 0·84-1·20) nor did 17-OHPC for twins or triplets (eight trials, 2253 women: 1·04, 0·92-1·18). Preterm premature rupture of membranes was increased with 17-OHPC exposure in multifetal gestations (rupture <34 weeks RR 1·59, 95% CI 1·15-2·22), but we found no consistent evidence of benefit or harm for other outcomes with either vaginal progesterone or 17-OHPC.Vaginal progesterone and 17-OHPC both reduced birth before 34 weeks' gestation in high-risk singleton pregnancies. Given increased underlying risk, absolute risk reduction is greater for women with a short cervix, hence treatment might be most useful for these women. Evidence for oral progesterone is insufficient to support its use. Shared decision making with woman with high-risk singleton pregnancies should discuss an individual's risk, potential benefits, harms and practicalities of intervention. Treatment of unselected multifetal pregnancies with a progestogen is not supported by the evidence.Patient-Centered Outcomes Research Institute.

Role of progestogens in women at risk for spontaneous preterm birth: the final word?

Preterm birth is defined by WHO as delivery before 37 weeks of gestation. 1 WHO: recommended definitions, terminology and format for statistical tables related to the perinatal period and use of a new certificate for cause of perinatal deaths, modifications recommended by FIGO as amended October 14, 1976. Acta Obstet Gynecol Scand. 1977; 56: 247-253 PubMed Google Scholar It is one of the most common pregnancy complications, with an estimated global rate of 10·6% in 2014, equating to an estimated 14·84 million live preterm births. 2 Chawanpaiboon S Vogel JP Moller AB et al. Global, regional, and national estimates of levels of preterm birth in 2014: a systematic review and modelling analysis. Lancet Glob Health. 2019; 7: 37-46 Summary Full Text Full Text PDF PubMed Scopus (962) Google Scholar Preterm birth considerably increases risk of neonatal morbidity and mortality, including long-term sequelae, and can result in long-term health and financial implications for families. 3 Goldenberg RL Culhane JF Iams J Romero R The epidemiology and etiology of preterm birth. Lancet. 2008; 371: 75-84 Summary Full Text Full Text PDF PubMed Scopus (4622) Google Scholar Evaluating Progestogens for Preventing Preterm birth International Collaborative (EPPPIC): meta-analysis of individual participant data from randomised controlled trialsVaginal progesterone and 17-OHPC both reduced birth before 34 weeks' gestation in high-risk singleton pregnancies. Given increased underlying risk, absolute risk reduction is greater for women with a short cervix, hence treatment might be most useful for these women. Evidence for oral progesterone is insufficient to support its use. Shared decision making with woman with high-risk singleton pregnancies should discuss an individual's risk, potential benefits, harms and practicalities of intervention. Full-Text PDF

Oral versus Vaginal Micronized Progesterone for the Treatment of Threatened Miscarriage.

Objectives:This study was planned with an aim to find out the effectiveness of oral versus vaginal micronized progesterone for the treatment of threatened miscarriage.Methods:This randomized controlled trial was conducted at The Department of Obstetrics and Gynaecology, Nishtar Hospital Multan, from August 2019 to January 2020. A total of 136 pregnant women, aged 18 to 45 years having vaginal bleeding were included and divided into two groups (68 women in each group). Participants in the Group-A were given oral micronized progesterone as 200mg twice a day while Group-B participants were given vaginal progesterone suppository 400mg once a day. All women were followed up until 20th week of their pregnancy. Outcome was labeled as prevention of miscarriage if woman had no bleeding per vagina and pregnancy went beyond 20th weeks of gestation.Results:In a total of 136 women enrolled, mean age was noted to be 30.85+3.34 years. Overall, mean gestational age was noted to be 9.3+2.7 weeks. A total of 98 women (49 in each group) completed the follow up and were included in the final analysis regarding outcome. Among Groups-A, 45 (91.8) had prevention of miscarriage while 4 (9.2%) had miscarriage in comparison to 36 (73.5%) in Group-B had prevention of miscarriage whereas 13 (26.5%) had miscarriage and this difference was statistically significant in between the both study groups as women in Group-A had significantly better outcome in terms of prevention of miscarriage. (P value = 0.0164).Conclusion:The use of oral micronized progesterone was found to be significantly more effective than vaginal progesterone in women with threatened miscarriage.

Fixed-time artificial insemination protocols on brazilian locally adapted breed gilts on ovulatory response and embryo production.

The aim of this study was to use estrus synchronization protocols to favor fixed-time artificial insemination and consequently fixed-time embryo collection, and increase embryo production using eCG, in gits. In a cross over design, nine Piau breed gilts were subjected to 18 days of oral progesterone; P4 group did not receive any further; GnRH group received 25µg of GnRH 104 hours after the final application of P4; and eCG+GnRH group received 1000IU of eCG 24 hours after the final P4 in addition to GnRH for subsequent embryo collection, that was performed six days after first AI, by laparotomy. Artificial insemination was performed after 12 and 24 hours of estrus in P4 group, and 128 and 144 hours in GnRH and eCG+GnRH groups. The number of CL (8.6±3.9; 8.3±2.1; 26.7±15.0) and anovulatory follicles (4.3±3.7; 3.9±3.9; 17.2±9.5) was higher in the eCG+GnRH gilts (P<0.05). However, the use of 1000 IU of eCG reduced (P<0.05) the number of total structures (5.2±3.6; 5.1±3.1; 1.7±2.7), viable embryos (5.0±3.5; 4.8±3.3; 0.4±0.7), freezable embryos (3.6±3.4; 3.3±3.8; 0.1±0.3) and recovery rate (63.7±38.9; 58.6±24.7; 5.38±9.5). P4 and GnRH protocols were effective in the production and recovery of embryos. However, the use of 1000 IU of eCG, 24 hours after P4, was not effective in promoting the production of embryos, although the animals had superovulated.

Bioidentical Oral 17β-Estradiol and Progesterone for the Treatment of Moderate to Severe Vasomotor Symptoms of Menopause

To review the efficacy, safety, and available literature regarding the novel combination bioidentical product Bijuva, or 17β-estradiol/progesterone (17β-E/P), for the treatment of moderate to severe menopausal symptoms in cisgender females with an intact uterus. Literature searches of both PubMed (1966 to October 2020) and Google Scholar were conducted using search terms including bioidentical, estradiol, progesterone, menopause, E2/P4, TX-001HR, and Bijuva. All articles with studies conducted in cisgender human females and in the English language were considered for review; 18 publications were included. In 1 phase 3 clinical study, 17β-E/P was proven to be effective at reducing the frequency and severity of vasomotor symptoms (VMS) at 12 weeks compared with placebo, and no cases of endometrial hyperplasia were observed over the 52-week safety study period. Menopausal women with an intact uterus were included in the study population. Concerns over content and safety of compounded bioidentical hormones have been raised by several professional societies. As women experience VMS of menopause, a desire for a Food and Drug Administration-regulated bioidentical combination product for the treatment of moderate to severe menopausal symptoms may be desirable. Given as a once-daily oral capsule at the dose of 1 mg estradiol/100 mg progesterone, 17β-E/P is approved for the treatment of VMS associated with menopause. 17β-E/P is a novel bioidentical product that is the first of its kind in the treatment of moderate to severe menopausal symptoms.

Management of gynecological cancers in the COVID-19 era: a survey from Turkey

Objective:This study aimed to investigate how gynecologic oncologists modified their patient management during Coronavirus disease-2019 (COVID-19) in Turkey.Material and Methods:An online survey was sent to gynecologic oncology specialists and fellows in Turkey. It included management questions about strategies for newly diagnosed or recurrent endometrial, cervical, ovarian and vulvar cancer during the pandemic. Participants were asked if treatment of these cancers can be delayed or not and, if yes, the duration of delay.Results:32.9% of surgeons prescribed oral or intrauterine progesterone for early stage, low-grade endometrial cancer. Conversely, 65.7% and 45.7% of the most surgeons did not change their management for early stage high-grade and advanced stage endometrial cancers respectively, as they perform surgery. 58% and 67.1% of the surgeons continued to prefer standard surgical treatment for microinvasive and early stage cervical cancers, respectively. Radiotherapy was preferred administered with hypofractionated doses for locally advanced cervical cancer (57.1%). While 67.1% of surgeons operated early stage ovarian cancer patients, 50% administered neoadjuvant chemotherapy (NACT) to all advanced stage ovarian cancers and 50% administered more cycles of NACT in preference to interval debulking surgery. 93.7% of the surgeons responded that treatment should not be delayed beyond eight weeks.Conclusion:Most Turkish gynecologic oncologists modified their management of gynecologic cancers due to the COVID-19 pandemic. While chemotherapy was preferred for ovarian cancer, postponement of the surgery, with or without non-surgical options, was considered for early stage, low-grade endometrial cancer. Treatment of gynecologic cancers should be decided on a case by case basis, taking into account local COVID-19 infection rates and availability of health facilities. Prognosis is also an important consideration if delay is contemplated. Standard treatment and normal time-frames should be used if possible. If not, a postponement for a maximum of eight weeks or referral to another center were acceptable alternatives.

Preservation of white matter integrity on DTI 3 years after early menopausal hormone therapies

AbstractBackgroundThe critical‐period theory of menopausal hormone therapy (mHT) suggests that if menopausal hormone therapy begins shortly after menopause, it may have beneficial effects on brain structure and cognitive health. We investigated white matter integrity with diffusion tensor MRI (DTI) 3 years after the end of mHT trial in recently menopausal women who were randomized shortly after menopause.MethodParticipants of this study were enrolled in the Kronos Early Estrogen Prevention Study (aged 42–56 years; 5–36 months past menopause). Participants received the following treatments: 0.45 mg/d oral conjugated equine estrogen (oCEE, n=19); 50 μg/d transdermal 17β‐estradiol (tE2, n=22); or placebo (n=33) for 4 years. Oral progesterone (200 mg/d) was given to hormone therapy groups for 12 days each month. DTI was performed 3 years after the end of 4 years of hormone therapy (n=75), which corresponded to 7 years after randomization. Voxel‐based analysis was performed on DTI to evaluate fractional anisotropy (FA) and mean diffusivity (MD) differences between treatment groups (uncorrected p&lt;0.001).ResultVoxel based analysis showed higher FA, a measure of white matter integrity, in the superior corona radiata, anterior limb of the internal capsule and splenium of the corpus callosum of participants treated with oCEE compared to placebo (p &lt;0.001, Figure 1A). Furthermore, higher FA was observed in the superior corona radiata, anterior limb of internal capsule and thalamus in participants treated with tE2 compared to placebo (p &lt;0.001, Figure 1B). There were no differences in FA findings between oCEE and tE2 groups, and no MD differences between treatments groups.ConclusionA relatively higher FA in a variety of white matter regions in the oCEE and tE2 groups compared to placebo suggest that mHT may have long‐term protective effects on white matter integrity. Previously, we had shown that women in the tE2 group preserved their dorsolateral prefrontal cortex volumes better than the placebo group over 7 years. Our findings suggest that the tracts that connect the dorsolateral prefrontal cortex and the thalamus such as the superior corona radiata and the anterior limb of internal capsule may particularly benefit from mHT.

Oral dydrogesterone vs. micronized vaginal progesterone gel for luteal phase support in frozen-thawed single blastocyst transfer in good prognosis patients

ObjectiveTo investigate the efficacy of oral dydrogesterone for luteal phase support (LPS) in modified natural cycle frozen-thawed embryo transfers (mNC-FET) compared to micronized vaginal progesterone (MVP) gel. MethodsThis was a randomized, single-center, parallel controlled trial conducted at an ART and Reproductive Genetics Centre within a private hospital between January and August 2019. A total of 134 women, aged below 38, were assigned randomly to receive oral dydrogesterone (n=67) or MVP (n=67) for LPS in mNC-FET. The primary outcome was ongoing pregnancy rate (OPR) and secondary outcomes were clinical pregnancy and miscarriage rates, patients’ satisfaction and tolerability of oral and vaginal progesterone. A questionnaire was developed to compare patient satisfaction and side effect profiles. ResultsThere was no significant difference in demographic features such as female age, body mass index, AMH levels and fresh cycle characteristics between two groups (p>0.05). When mNC-FET outcomes were compared, OPR was 68.7 % in MVP gel group and 71.6 % in the dydrogesterone group respectively percentage difference, -2.99; 95 % CI: -17.96, 13.10) Biochemical and clinical pregnancy rates and biochemical and clinical miscarriage rates were also similar between two groups. A significantly higher patient tolerability score was present in the dydrogesterone arm (4.09 ± 0.96 vs 3.36 ± 1.23, p=0.001). ConclusionOur results suggest that oral dydrogesterone provides similar ongoing pregnancy rates compared to MVP gel as a LPS in mNC FET. Since dydrogesterone is an effective and easy-to-use option with fewer intolerable side effects including vaginal irritation, vaginal discharge, and preventing sexual intercourse, it can be used as LPS in mNC FET.

Transdermal Testosterone Attenuates Drug-Induced Lengthening of Both Early and Late Ventricular Repolarization in Older Men.

We have previously reported that transdermal testosterone attenuates drug-induced QT interval lengthening in older men. However, it is unknown whether this is due to modulation of early ventricular repolarization, late repolarization, or both. In a secondary analysis of a prospective, randomized, double-blind, placebo-controlled three-way crossover study, we determined if transdermal testosterone and oral progesterone attenuate drug-induced lengthening of early and late ventricular repolarization, represented by the electrocardiographic measurements J-Tpeak c and Tpeak -Tend , respectively, as well as Tpeak -Tend /QT, a measure of transmural dispersion of repolarization. Male volunteers ≥65years of age (n=14) were randomized to receive transdermal testosterone 100mg, oral progesterone 400mg, or matching transdermal/oral placebo daily for 7days. On the morning following the seventh day, subjects received intravenous ibutilide 0.003mg/kg, after which electrocardiograms were performed serially. One subject was excluded due to difficulty in T-wave interpretation. Pre-ibutilide J-Tpeak c was lower during the testosterone phase than during progesterone and placebo (216±23 vs. 227±28 vs. 227±21ms, P=0.002). Maximum post-ibutilide J-Tpeak c was also lower during the testosterone phase (233±22 vs. 246±29 vs. 248±23ms, P<0.0001). Pre-ibutilide Tpeak -Tend was not significantly different during the three phases, but maximum post-ibutilide Tpeak -Tend was lower during the testosterone phase (80±12 vs. 89±18 vs. 86±15ms, P=0.002). Maximum Tpeak -Tend /QT was also lower during the testosterone phase (0.199±0.023 vs. 0.216±0.035 vs. 0.209±0.031, P=0.005). Progesterone exerted minimal effect on drug-induced lengthening of J-Tpeak c, and no effect on Tpeak -Tend or Tpeak -Tend /QT. Transdermal testosterone attenuates drug-induced lengthening of both early and late ventricular repolarization in older men.

Determinants of attained estradiol levels in response to oral estradiol plus progesterone therapy

Objectives Among postmenopausal women taking hormone therapy (HT), the estradiol (E2) dose and E2 levels were differentially associated with change in metabolic measures. We evaluated determinants of attained E2 levels in response to HT. Methods Postmenopausal women from the REPLENISH trial tested four formulations of oral combined E2 and progesterone compared with placebo. Mixed-effects linear models assessed characteristics associated with E2 levels among women with ≥80% HT compliance, adjusted for E2 dose and baseline E2 level. Results Among 1173 postmenopausal women with mean (standard deviation) age 55 (4.3) years and 5.2 (4.8) years since menopause, higher treated E2 levels were significantly related to younger age, more recent menopause, and current alcohol use, while lower E2 levels were related to current smoking. Both age and time since menopause were significantly inversely associated with E2 levels; time since menopause had a stronger association with E2 levels. In the final multivariable model, E2 levels were positively associated with current alcohol use, and inversely associated with time since menopause and current smoking. Conclusion Adjusting for E2 dose and baseline E2 level, on-trial E2 levels were significantly associated with time since menopause, current smoking, and current alcohol use. Practitioners should consider these factors in individual women to achieve a desirable E2 level during HT.

Association between the reproductive health of young women and cardiovascular disease in later life: umbrella review

ObjectiveTo consolidate evidence from systematic reviews and meta-analyses investigating the association between reproductive factors in women of reproductive age and their subsequent risk of cardiovascular disease.DesignUmbrella review.Data sourcesMedline, Embase, and...

Abstract 697: Improvement in quality and length of life following treatment with mifepristone in women with stage IV non-small cell lung cancer, positive for the epidermal growth factor receptor (EGFR) mutation, that previously progressed on targeted therapy

Abstract Treatment with the oral single agent progesterone receptor modulator, mifepristone, has been demonstrated to significantly increase the quality and length of life in a patient with stage IV non-small cell lung cancer (NSCLC) that progressed despite multiple rounds of chemotherapy, when no markers existed for specific targeted therapy. The purpose of the present study was to determine if mifepristone could similarly provide palliative benefits to patients with NSCLC, that were positive for EGFR mutation, who had progressed despite targeted therapies. Patient 1, a 59 year old woman presented with 6 months of upper back pain and dyspnea, was found to have innumerable tiny lung nodules (miliary pattern), bone metastases, and a single brain metastasis (left occipital lobe). The tumor was an adenocarcinoma, with an EGFR exon leu858 arg identified. The brain metastasis was treated with palliative radiation therapy and erlotinib was started. She remained stable for 1 ½ years, but then her lung nodules started to increase in size. Erolotinib was stopped, and osimertinib was started. However, she progressed 6 months later, with continued growth of pulmonary nodules bilaterally and a new brain metastasis, in the right lateral cuneus. Her dyspnea, which had improved on erlotinib, returned to pre-treatment status. She was started on oral single agent mifepristone, 200mg per day. Patient 2, a 46 year old woman, had presented with headaches, difficulty with executive function, and memory loss. She was diagnosed with stage IV NSCLC, with extensive lung lesions and brain metastases. A MRI of the brain revealed innumerable supratentorial rim enhancing lesions, with one dominant left parietal lobe lesion measuring 3 × 2.1cm (treated with palliative radiation). CT scans showed innumerable bilateral pulmonary nodules with evidence of lymphangitic spread and multiple bone lesions. Because the tumor was positive for the EGFR1 exon 19 mutations (E746/751 mutation), she was started on afatinib, which was stopped 8 months later. She then had a second course of brain radiation and 5 months after stopping afatinib she began osimertinib. After 10 months of osimertinib, it seemed to be losing effectiveness, and so 200mg oral mifepristone was added. Both women have had stable disease, with no growth of previous nodules and no new nodules, or new brain metastases after 6 months and 14 months of mifepristone therapy, respectively. More importantly they both feel much better, with no dyspnea, or pain, and remain ECOG-0. Thus, similar to small cell lung cancer and NSCLC devoid of tumor markers, or with the PD-L1 mutation, patients with advanced NSCLC with EGFR mutation also seem to respond to the progesterone receptor modulator, mifepristone. Citation Format: Jerome H. Check, Diane Check, Trina Poretta, James Aikins, Carrie Wilson. Improvement in quality and length of life following treatment with mifepristone in women with stage IV non-small cell lung cancer, positive for the epidermal growth factor receptor (EGFR) mutation, that previously progressed on targeted therapy [abstract]. In: Proceedings of the Annual Meeting of the American Association for Cancer Research 2020; 2020 Apr 27-28 and Jun 22-24. Philadelphia (PA): AACR; Cancer Res 2020;80(16 Suppl):Abstract nr 697.

Adenomyotic Cyst at Menopause Transition: A Combined Treatment

Cystic adenomyosis is a progressive, severe disease that causes medical resistant dysmenorrhea with a delay in diagnosis [1]. A 52-year-old woman presented to our clinic with a complaint of severe dysmenorrhea, an 8 on the visual analog score of pain, persisting for 1 year. Her previous menstrual cycles were regular and pain-free. There was no response to the oral progesterone therapy that she had for 6 months.

Lower extremity deep venous thrombosis and pulmonary embolism associated with an uterine leiomyoma

Deep venous thrombosis (DVT) and pulmonary embolism (PE) are rare and life-threatening complications caused by compression of inferior vena cava (IVC) and pelvic veins by large leiomyoma of the uterus. We report a 54-year-old woman presented to the Accident and Emergency (A & E) department with complaints of left leg swelling, pain and shortness of breath. She had a history of heavy menstrual bleeding and treated with oral progesterone. Her examination revealed tachypnea and 24-week size abdominopelvic mass. Imaging investigations confirmed DVT in left iliofemoral vein and PE. MRI pelvis showed a uterus containing a large intramural fundal fibroid, compressing the IVC, common iliac veins and the right ureter. The patient successfully treated by anticoagulation therapy and delayed hysterectomy. DVT and PE are life-threatening and rare complications of leiomyoma. Early diagnosis, intense monitoring, appropriate treatment for DVT, PE and timely intervention of leiomyoma are vital elements for optimal management and outcome.

Response to nicotine following overnight smoking abstinence during short-term progesterone treatment in women.

Preclinical and clinical literature suggest that sex hormones impact tobacco use behaviors in women. The goal of this double-blind crossover laboratory study was to examine the effect of oral exogenous progesterone (200 mg twice per day) versus placebo on nicotine response using measures of motor speed and cognitive function in women following overnight smoking abstinence. We hypothesized that increased progesterone would blunt the nicotine response whereby producing less change in motor speed and cognition in response to nicotine exposure. Female smokers, age 18-35, were randomized to participate in two 9-day crossover testing weeks. Participants completed a lab session following overnight abstinence where they were administered nicotine nasal spray and asked to complete measures of immediate memory (IMT), delayed memory (DMT), word recall (WR), and finger tapping speed (FT). After the first 9-day testing week, participants resumed smoking and returned the following month to complete the identical lab session in the crossover condition. Forty-seven women were included in this analysis (n = 47). We found no differences in the magnitude of response for IMT, DMT, and WR between conditions. For FT, women had a blunted response to nicotine during the placebo condition. When examining the association between hormone levels and relative performance, we found increases in DMT, WR, and FT but decreases in IMT during the progesterone condition. We observed differences between progesterone versus placebo in relative change in some measures of nicotine response following overnight abstinence. Future studies are needed to further characterize this response. (PsycInfo Database Record (c) 2020 APA, all rights reserved).

The effects of exogenous oral micronized progesterone on first trimester aneuploidy screening markers in women with threatened miscarriage: a matched case control study

Objectives To evaluate the effect of using progesterone due to early vaginal bleeding on aneuploidy screening markers in the first trimester. Material and methods This case control study includes the pregnant women who applied to our clinic in order to have a screening test for Down syndrome in the weeks of 11°/7−136/7. The patients were divided into three groups. Self reported vaginal bleeding with progesterone therapy (Bl+, Prg+, n:70), Self reported vaginal bleeding without progesterone therapy (Bl+, Prg−, n:70) and as a control group pregnant women who had no vaginal bleeding. (NoBl, NoPrg, n:70). In all patients, free beta-human chorionic gonadotrophin (β-hCG), pregnancy associated plasma protein-A (PAPP-A) levels and nuchal translucency (NT) thickness were analyzed. Mean MoMs of the markers were compared between three groups. Results In the two groups with vaginal bleeding (Bl+, Prg + and Bl+, Prg−) the free β-Hcg MoM values were statistically higher (1.22 ± 0.72, 0.98 ± 0.45, respectively) compared to the No Bleeding/No Progesterone group (0.81 ± 0.52) (p ≤ 0.001, p ≤ .01, respectively). However, no significant difference was found between the free β-hCG MoM value of women with Bl+, Prg + group (1.22 ± 0.72) and Bl+, Prg − group (0.98 ± 0.45). (p: .053, significance level limitation with Bonferroni correction p: .017). PAPP-A and NT thickness did not differ significantly between the groups. Conclusion Our data did not find an association between the use of oral progesterone and any alternations in first trimester screening parameters. Regardless of the progesterone usage, vaginal bleeding in the first trimester pregnancies increased the free β-hCG MoM values compared to pregnancies without vaginal bleeding during pregnancy.

Basket study of the oral progesterone antagonist onapristone ER in women with progesterone receptor positive (PR+) recurrent granulosa cell tumor (GCT), low-grade serous ovarian cancer (LGSOC), or endometrioid endometrial cancer (EEC).

TPS6098 Background: Onapristone extended release (ER) is a type I full progesterone antagonist that inhibits progesterone mediated PR activation and stabilizes PR association with corepressors. Onapristone has shown activity across multiple preclinical models of hormonally driven cancer. A phase I dose escalation study of onapristone ER in PR+ breast, endometrial and ovarian cancer patients found all doses tested to be well tolerated, with 50mg PO BID determined to be the recommended phase 2 dose (RP2D). GCT (98% of cases PR+), LGSOC (58% of cases PR+) and EEC (67% of cases PR+) are hormonally driven cancers which generally have poor responses to chemotherapy and limited treatment options in the recurrent setting. Methods: This is an open-label, investigator-initiated basket study of onapristone ER in patients with PR+ recurrent GCT, LGSOC, or EEC currently enrolling patients at Memorial Sloan Kettering Cancer Center in NY, USA (NCT03909152). The primary objective is to evaluate the efficacy, in terms of response rate by RECIST 1.1 criteria, within 36 weeks of treatment. Eligible patients must have received at least 1 prior line of chemotherapy, have measurable disease by RECIST 1.1 criteria, and have tumor tissue collected within 3 years prior to enrollment with PR expression ≥ 1% by IHC. Patients are allowed to have unlimited additional prior lines of chemotherapy, biologic therapy, immunotherapy or hormonal therapy. Enrolled patients are treated with onapristone ER 50mg PO BID until time of progression or intolerable toxicity. The 3 disease cohorts are currently enrolling to Stage I in parallel with expansion from stage I to stage II planned when the prespecified response criteria are met for each cohort as described in the table below. Clinical trial information: NCT03909152. [Table: see text]