Ulipristal Research Articles

Advantages, disadvantages and optimization of organ-sparing methods for uterine fibroids treatment

Introduction. Uterine fibroids (UF) are benign monoclonal hormone-depended tumors originating from smooth myocytes of cervix or body uterus affecting up to 29 % of women aged 15–45 years worldwide. Taking into account the current demographic situation and annually increasing tendency for pregnancy planning at older reproductive age, an organ-sparing strategy is becoming a first-priority approach for UF treatment.Aim: to investigate efficiency of selective progesterone receptors modulators (SPRM) for UF treatment in women of reproductive age.Materials and Methods. A prospective cohort study involved 40 patients with UF at average age of 39.3 ± 5.8 years. Using simple randomization, the patients were divided into 2 groups per 20 subjects in each. The average age of the patients was comparable and comprised 38.15 ± 5.65 and 40.5 ± 5.8 years in groups 1 and 2, respectively (p = 0.203). In both groups, after assessing liver function tests in accordance with the instructions, a treatment course with SPRM group drug (ulipristal acetate) was used at a daily dose of 5 mg for 84 days (1 course) with an interval until the onset of second menstruation after drug withdrawal. Group 1 and group 2 subjects received 2 and 3 therapy courses, respectively. After each course, patients underwent control ultrasound examinations (UE) by analyzing uterus volume and diameter of dominant myomatous node along with liver tests. A temporal quantitation of the difference between UF and dominant node two sizes as well as the maximum uterine volume size and effect size assessment was expressed as the difference of means (Δ) with a 95 % confidence interval (CI).Results. Based on UE data, the uterus size in group 1 was enlarged to an average of 129.49 ± 75.57 cm3, the maximum size of dominant node was 38.9 ± 17.38 mm; in group 2, the uterus was as large as 294.83 ± 161.37 cm3 with maximum size of the dominant node of 53.33 ± 25.48 mm. After therapy in group 1, dominant node size was significant regressed: after therapy course 1 an effect size of quantitated difference between UF two sizes and the dominant node (Δ) was 8.70 (4.11; 13.29) mm (p < 0.001). After therapy course 2 vs. therapy course 1, a size stabilization (Δ) was noted comprising 1.00 (–1.39; 3.39) mm (p = 0.390); the total effect (Δ) was 9.67 (–14.59; –4.75) mm (p <0.001). In group 2, after therapy course 1, the dominant node also regressed, with effect size (Δ) of 9.49 (7.08; 11.89) mm (p = 0.001). The effect (Δ) after therapy course 2 vs. therapy course 1 in group 2 was more prominent reaching 10.74 (5.86; 15.61) mm (p = 0.001). However, after therapy course 3, a larger node size was observed compared to therapy course 2 – (Δ) 8.25 (0.67; 15.83) mm (p = 0.329). Despite the lack of pronounced negative dynamics, based on medical indications 9 patients in group 2 underwent uterine artery embolization to prevent disease relapse.Conclusion. SPRM therapy can be used both as an independent means for MM therapy and in combination with surgical interventions. Such an approach allows for some women to become pregnant without preceding myomectomy, whereas for those approaching age-related menopause to avoid surgical treatment and gently enter natural postmenopause. Currently, conservative and surgical treatment methods for leiomyomas should complement each other to achieve the best clinical outcomes.

White matter integrity upon progesterone antagonism in individuals with premenstrual dysphoric disorder: A randomized placebo-controlled diffusion tensor imaging study

BackgroundPremenstrual dysphoric disorder (PMDD) is a depressive disorder triggered by fluctuations of progesterone and estradiol during the luteal phase of the menstrual cycle. Selective progesterone receptor modulation (SPRM), while exerting an antagonistic effect on progesterone and maintaining estradiol on moderate levels, has shown beneficial effects on the mental symptoms of PMDD. Progesterone is also known for its neuroprotective effects, while synthetic progestins have been suggested to promote myelination. However, the impact of SPRM treatment on white matter microstructure is unexplored. MethodsDiffusion tensor imaging was employed to collect data on white matter integrity in patients with PMDD, before and after treatment with ulipristal acetate (an SPRM) or placebo, as part of a double-blind randomized controlled-trial. Tract based spatial statistics were performed to investigate SPRM treatment vs. placebo longitudinal effects on fractional anisotropy (FA), mean diffusivity (MD), radial diffusivity (RD), and axial diffusivity (AD), on the whole white matter skeleton. ResultsVoxel-wise analyses indicated no change over time in any white matter microstructure metrics in individuals treated with SPRM versus placebo. Improvement in PMDD symptoms did not correlate with changes in white matter microstructure. In secondary, exploratory, cross-sectional comparisons during treatment, the SPRM group displayed lower FA and higher MD, RD, and AD in several tracts. ConclusionThe main findings suggest that SPRM treatment did not impact white matter microstructure compared with placebo. However, secondary exploratory analyses yielded between-group differences after treatment, which call for further investigation on the tracts potentially impacted by progesterone antagonism. Clinical trial registrationEUDRA-CT 2016–001719-19; “Selective progesterone receptor modulators for treatment of premenstrual dysphoric disorder. A randomized, double-blind, placebo-controlled study.”; https://www.clinicaltrialsregister.eu/ctr-search/trial/2016-001719-19/SE

Impact of Regulatory Interventions on Ulipristal Acetate 5 mg (Esmya) Use in Spain: An Interrupted Time-Series Analysis.

Since late 2017, the use of ulipristal acetate 5 mg (UPA; Proprietary name: Esmya) has been under review in the European Union, due to an emerging hepatic risk. In February 2018 and in July 2018, the Spanish Agency of Medicines and Medical Devices and the marketing authorization holder put two risk minimization measures (RMM) in place, in order to inform about new safety information and to mitigate this risk. This study aims to assess RMM effectiveness in Spain, by performing an interrupted time-series (ITS) analyses, between 2014 and 2019. Two quasi-experimental ITS analyses to examine the use of UPA before and after the RMM release were performed: (a) an ecological study using aggregated data from a drug consumption database; and (b) a study using primary healthcare data gathered from electronic clinical records. Regulatory interventions were associated with an immediate and significant decrease level of DID (the number of DDD dispensed per 100 000 inhabitants and day) and incidence. The DID was 70% less than expected 12 months after the interventions. This value was 59% for the incidence. However, a change in the slope was not observed and the use started rising again in the last segment of the study period. Despite RMM had an immediate strong impact on UPA use, the last segment upward trend in the long-term might have been affected by the lack of comparable therapeutic alternatives. Further studies should be performed to confirm the increase trend observed and analyze subsequent measures and additional data.

Double dosing ulipristal acetate emergency contraception for individuals with obesity: a randomised crossover trial

ObjectiveTo determine whether increasing the dose of ulipristal acetate (UPA)-containing emergency contraception (EC) improves pharmacodynamic outcomes in individuals with obesity.Study designWe enrolled healthy, regularly-cycling, confirmed ovulatory, reproductive-age individuals with body...

Decision-making Process During Pharmaceutical Consultation when Dispensing Emergency Contraception with Ulipristal Acetate

Decision-making Process During Pharmaceutical Consultation when Dispensing Emergency Contraception with Ulipristal Acetate

In Vitro Human Endometrial Cells and In Vivo Rat Model Studies Suggest That Ulipristal Acetate Impacts Endometrial Compatibility for Embryo Implantation

Ulipristal acetate (UPA) and levonorgestrel are used as emergency hormonal contraceptives. Although both are highly effective in preventing pregnancy, UPA shows efficacy even when taken up to 120 h after unprotected sexual intercourse. To investigate whether the mechanism of UPA's contraceptive action involves post-fertilization effects. In vitro and in vivo studies using cultured human endometrial cells and a pre-clinical rat model. Endometrial cells treated with UPA showed changes in the expression of receptivity gene markers and a significant decrease in trophoblast spheroids attached to the cultured cells. In addition, administration of UPA to female unmated rats decreased the expression of implantation-related genes in the endometrium and inhibited the number of implantation sites in the mated group compared to the non-treated group. These results support that UPA as an emergency contraceptive might have post-fertilization effects that may affect embryo implantation.

Advancements and Emerging Therapies in the Medical Management of Uterine Fibroids: A Comprehensive Scoping Review.

Uterine fibroids, benign tumors originating from uterine smooth muscle cells, vary in prevalence depending on patient ethnicity, hormonal exposure, and genetics. Due to their high incidence, these neoplasms pose a significant burden on healthcare systems. Current treatment strategies range from routine monitoring in asymptomatic cases to surgical procedures such as myomectomy or hysterectomy in symptomatic patients, with an increasing trend toward uterus-preserving or non-surgical alternatives. This review examines the existing medical treatments for uterine fibroids and delves into the potential of emerging therapies. A scoping review of the literature was conducted in accordance with the Preferred Reporting Items for Systematic Reviews and Meta-Analyses extension for Scoping Reviews. Medical therapies are divided into hormonal and non-hormonal treatments; however, long-term, safe, and effective treatments in the treatment of uterine fibroids are limited. In addition to established therapies, there is an increasing number of studies investigating the effect of substances such as vitamin D or green tea extract on uterine fibroids. Some studies investigate acupuncture as a possible alternative therapy. While existing treatments offer symptomatic relief and preparation for surgery, our findings point to a significant need for further research into long-term solutions, especially owing to recent limitations in the use of ulipristal acetate due to risk of liver damage. Initial studies involving vitamin D and epigallocatechin gallate are encouraging; however, additional research is required to establish definitive therapeutic roles.

Safety of Progestogen Hormonal Contraceptive Methods during Lactation: An Overview.

Breastfeeding is a process for not only nourishing infants but also for building a unique emotional bond between mother and child. Therefore, the ideal contraception during lactation should not affect lactation (milk composition, milk volume) and offspring development. This study aims to analyze the literature on the safety of progestogen hormonal contraceptive methods during lactation. We conducted a thorough search across various databases, including the National Library of Medicine (PubMed), and the Cochrane Database, Drugs and Lactation Database (LactMed). Our search utilized specific phrases such as: "lactation" and "breastfeeding" and "oral contraception" with "drospirenone" or "desogestrel", with "subcutaneous etonogestrel implant" or "etonogestrel implant", with "levonorgestrel-releasing intrauterine system", and "emergency contraception", with "levonorgestrel" or "ulipristal acetate". Based on published scientific reports, progestogen hormonal contraceptives can be considered a relatively safe solution for women desiring to continue feeding their infant with their milk while using hormonal contraception. It is important to seek guidance on selecting the best contraception method based on the latest medical knowledge, tailored to the individual needs and clinical circumstances of each woman and place of residence. A woman should always be informed of the potential risks of such a treatment and then allowed to make her own decision based on the knowledge received from a specialist.

A novel g-C3N4@La:Y2O3 nanocomposite fluorescence sensor for simultaneous determination and photocatalytic degradation of Ulipristal acetate and Tacrolimus using Doehlert design optimization

Graphitic carbon nitride nanocomposite doped with La:Y2O3 was used as a new sensor for detection and determination of two hazardous active pharmaceutical compounds, Tacrolimus and Ulipristal acetate, by fluorescence spectrophotometry. This novel nanosensor has a fantastic ability to detect these drugs quickly, accurately, and simultaneously. The effect of Tacrolimus on this nanosensor is the quenching of fluorescence emission intensity at the wavelength of 369 nm while the Ulipristal acetate increases the fluorescence emission at 433 nm. Doehlert design was used to optimize the effective factors to reach the maximum fluorescence emission intensity of the nanosensor. Factors including pH, buffer solution concentration and the ratio of La:Y2O3 dopant in the nanocomposite structure. Under optimal conditions, the limit of detection of 17 nM and the limit of qualification of 58 nM for Tacrolimus and the limit of detection of 11 nM and the limit of qualification of 36 nM for Uipristal acetate were obtained with good accuracy. The prepared g-C3N4@La:Y2O3 nanocomposite has a reasonable ability to photodegrade these two drugs. In this regard, the process of photocatalytic degradation of Tacrolimus and Ulipristal acetate was investigated under visible light irradiation. The effect of active species in photocatalytic degradation was evaluated in order to determine the exact degradation mechanism, and the effect of Fenton factors on analytes degradation was also investigated.

Pharmacist recommendations for emergency contraception in Belgium: a simulated user study

Background Emergency contraception reduces the risk of unintended pregnancy, after unprotected sexual intercourse or contraceptive failure. In Belgium, emergency contraception is available without a prescription and pharmacists play therefore a crucial role in dispensing emergency contraception. Aim This study assesses the dispensing practices of emergency contraception by pharmacists in two regions of Belgium. Method and design Simulated patient study, using a predefined scenario, evaluating a request for emergency contraception. The scenario involves a 25-year-old woman not using contraception, who had unprotected sexual intercourse 84 h (3.5 days) ago. Her last menstrual period was 10 days ago. Population 260 pharmacies were randomly selected. Principal outcome: proportion of pharmacists who deliver the adequate emergency contraception. We considered the following responses as adequate: Prescribing ulipristal acetate or redirecting to another pharmacy, in case of unavailability, or referring for a copper IUD Results We analysed the data obtained in 216 pharmacies (216/260 = 83.1%). In 64% of cases, adequate dispensing of emergency contraception (dispensing of ulipristal acetate or referral for intrauterine device insertion) occurred. There was an association between correct dispensing and asking appropriate questions, such as the date of the last menstrual period and the date of the risky sexual intercourse. Conclusion More than one-third of visited pharmacies did not distribute appropriate emergency contraception, underlining the need for improvement. We hypothesise that this may be achieved with appropriate training, use a dispensing checklist.

Accessibility of oral emergency contraceptives in Australian community pharmacies

ObjectivesTo assess the availability of over-the-counter emergency contraceptive pills in the Australian community pharmacy setting. Study designRepresentative national telephone survey. ResultsOnly 70% of the 233 pharmacies surveyed stocked ulipristal acetate (UPA) emergency contraceptive pills, compared to levonorgestrel, which was stocked in 98%. When ulipristal acetate was stocked, it was on average $13 more expensive. ConclusionsDespite being recommended as the first-line oral emergency contraceptive, UPA is less likely to be available, and when available, it is likely to be more expensive. These findings support anecdotal reports UPA is challenging to access and less commonly used. ImplicationsStrategies are urgently required to improve equitable access to all methods of oral emergency contraception within the Australian community pharmacy setting and ensure pharmacists are aware of key differences between the available methods. This will ensure that they are prepared to facilitate shared decision making based on the individual needs of each woman.

Use of serum evaluation of contraceptive and ovarian hormones to assess reduced risk of pregnancy among women presenting for emergency contraception in a multicenter clinical trial

ObjectiveTo evaluate ovulation risk among women enrolling in an emergency contraception (EC) study by measuring contraceptive steroids and ovarian hormones. Study DesignWe used standard chemoluminescent assays to evaluate endogenous hormones [estradiol (E2), progesterone (P4), FSH, LH] and liquid chromatography-tandem triple quadrupole mass spectrometry (LC-MS/MS) to simultaneously analyze concentrations of ethinylestradiol (EE), dienogest (DNG), norelgestromin (NGMN), norethindrone (NET), gestodene (GSD), levonorgestrel (LNG), etonogestrel (ENG), segesterone acetate (NES), medroxyprogesterone acetate (MPA), and drospirenone (DRSP), in serum samples obtained at the time of enrollment in a recent study comparing oral ulipristal acetate and LNG EC in women with weight ≥ 80kg reporting no recent use of hormonal contraception. ResultsWe enrolled 532 and obtained a valid baseline blood sample from 520 women. Of these, 117 (22.5%) had detectable concentrations of a progestin [MPA (n=58, 11.2%), LNG (50, 9.6%), ENG (11, 2.1%), NET (5, 0.96%), NGMN (3, 0.06%), or DRSP (1, 0.02%)]. LNG was co-detected in all three participants with samples containing NGMN. Multiple progestins were detected in 8 other women: ENG/MPA (1); ENG/LNG (2); MPA/LNG (5). Samples from 55 (10.6%) had concentrations of one or more progestin considered above the minimum level for contraceptive [MPA ≥ 0.1ng/mL, n = 19; NGMN/LNG ≥ 0.2ng/mL, n = 31; ENG ≥ 0.09 ng/mL, n = 8; NET ≥ 0.35 ng/mL, n = 4]. We detected concentrations of serum P4 ≥ 3ng/mL, indicative of luteal phase (post-ovulation) status, in an additional 194 (37.3%) samples. ConclusionsMore than one third of enrolled in our clinical trial of oral emergency contraception had evidence of prior ovulation at the time of enrollment. Additionally, about 23% had evidence of recent use of hormonal contraception recent use of hormonal contraception. This results would have decreased the expected risk of pregnancy in the study. ImplicationsMany participants in a recent clinical trial of oral emergency contraception did not appear to be at risk for pregnancy or would not have benefited from intervention due to cycle timing. Investigators should consider the effects of these findings on expected pregnancy rates when determining sample size in future EC clinical trials, particularly when using non-inferiority designs or historical controls.Keywords

Emergency contraception for individuals weighing 80 kg or greater: A randomized trial of 30 mg ulipristal acetate and 1.5 mg or 3.0 mg levonorgestrel

ObjectiveTo compare the efficacy of oral emergency contraception (EC) regimens used within 72 hours of unprotected intercourse in individuals weighing >80 kg. Study DesignWe enrolled healthy women aged 18-40 years with a weight of at least 80 kg requesting EC in a multi-center, single-blind, randomized study of levonorgestrel 1.5 mg (LNG1X) and 3.0 mg (LNG2X) and ulipristal acetate 30 mg (UPA) (enrollment goal 1200). Key eligibility requirements included regular cycles, unprotected intercourse within 72 hours of enrollment, no use of hormonal contraception since last menstrual period, a negative urine pregnancy test (UPT), and willingness to abstain from intercourse until next menses. Study staff directly observed EC ingestion. To assess our primary outcome of incidence of pregnancy, participants completed home UPTs; if no menses by 2-weeks post-treatment, or a positive UPT, they returned for an in person visit with quantitative serum human chorionic gonadotropin (hCG) and ultrasound. ResultsWe enrolled and randomized 532; 44 were not dosed or not evaluable for primary end-point, leaving an analyzable sample of 488 (173 LNG1X, 158 LNG2X, 157 UPA) with similar demographics between groups [mean age 29.6 years (5.74), BMI 37.09 kg/m2 (6.95)]. Five pregnancies occurred during the study (LNG1X n = 1, LNG2X n = 1, UPA n = 3); none occurred during the highest at-risk window relative to estimated day of ovulation (day of ovulation and the 3 days prior). We closed the study prior to achieving our enrollment goal because the low pregnancy rate in all groups established futility based on an interim blinded analysis. ConclusionAlthough slow enrollment limited our study power, we found no differences in pregnancy rates between oral EC regimens among women weighing 80 kg or more. Our results are not able to refute or support differences between the three treatment arms. ImplicationsWomen weighing 80 kg or more experienced no differences in pregnancy rates between oral EC regimens but due to several significant study limitations including sample size and the lack of a study population at high risk of pregnancy, our results are not able to determine if differences in treatment effectiveness exist.

Ulipristal (UPA) effects on rat ovaries: Unraveling follicle dynamics, ovulation inhibition, and safety implications for prolonged use

Ulipristal (UPA), a selective progesterone receptor modulator, has both agonistic and antagonistic effects on progesterone receptors. UPA suppresses ovulation by inhibiting the luteinizing hormone (LH) surge from the pituitary gland; however, the direct effect of UPA on ovarian tissue remains poorly studied. In the present study, we examined the effects of UPA on the ovaries of rats. Rats were treated for 28 days with UPA, and the effects of UPA on ovarian tissue were examined histologically and the expression of antioxidant genes and cell death markers were also investigated. UPA treatment increased the number of primordial follicles at each treatment group, primordial follicles increased at all dose levels, but the size/magnitude of the effect decreased with the increasing dose. The number of primary and antral follicles tended to increase with increasing UPA levels. Furthermore, the decrease in primary follicle number could be attributed to the exhaustion of follicles, but the examination of proliferation markers, oxidative stress markers, and cell death markers revealed no remarkable toxic effects on ovarian tissues. These results suggest that UPA treatment promotes follicle development at each stage but inhibits ovulation by suppressing the LH surge, resulting in an increase in atretic follicles or unruptured luteinized cysts. These results suggest that UPA may not have both toxic effects on the ovary and a direct local effect on ovarian follicles, but we should be careful about the effects of prolonged UPA treatment in patients with uterine fibroids on their future fecundity.

White matter volume and treatment with selective progesterone receptor modulator in patients with premenstrual dysphoric disorder

Premenstrual dysphoric disorder (PMDD) is a mood disorder for which selective progesterone receptor modulator (SPRM) treatment has been demonstrated to be beneficial. The neural signatures of this treatment have been so far identified as greater fronto-cingulate reactivity during aggressive response to provocation, but no changes in terms of gray matter structure. White matter has recently been found to differ between patients with PMDD and healthy controls. The present study thus sought to investigate the relationship between white matter volume and SPRM treatment in patients with PMDD. A pharmaco-neuroimaging study was conducted on patients with PMDD participating in a randomized controlled trial. Participants underwent magnetic resonance imaging before and after treatment randomization to ulipristal acetate (an SPRM), or placebo, for three months. The interaction effect of treatment by time on white matter volume (WMV) was assessed. Voxel based morphometry analyses were performed on both a whole brain exploratory level and on regions of interest. No treatment effect was observed on WMV in any region, including the anterior thalamic radiations, cingulum, forceps minor, fornix, inferior fronto-occipital fasciculus, superior cerebellar peduncle, superior longitudinal fasciculus, and uncinate fasciculus. This is the first finding to indicate that no white matter volume alterations follow three-month progesterone antagonism, suggesting that white matter volume does not participate in symptom relief upon SPRM treatment for PMDD.

Pharmacodynamic evaluation of the etonogestrel contraceptive implant initiated midcycle with and without ulipristal acetate: An exploratory study

ObjectiveTo estimate the incidence of ovulation suppression within five days of etonogestrel 68 mg implant insertion in the presence of a dominant follicle with and without same-day ulipristal acetate. Study designThis single site non-masked, exploratory randomized trial recruited people age 18–35 years with regular menstrual cycles, no pregnancy risk, and confirmed ovulatory function. We initiated transvaginal ultrasound examinations on menstrual day 7–9 and randomized participants 1:1 to etonogestrel implant alone or with concomitant ulipristal acetate 30 mg oral when a dominant follicle reached ≥14 mm in diameter. We completed daily sonography and serum hormone levels for up to seven days or transitioned to labs alone if sonographic follicular rupture occurred. We defined ovulation as follicular rupture followed by progesterone >3 ng/mL. We calculated point estimates, risk ratios and 95% confidence intervals for ovulation for each group. Ovulation suppression of ≥44% in either group (the follicular rupture suppression rate with oral levonorgestrel emergency contraception), would prompt future method testing. ResultsFrom October 2020 to October 2022, we enrolled 40 people and 39 completed primary outcome assessments: 20 with etonogestrel implant alone (mean follicular size at randomization: 15.2 mm ± 0.9 mm) and 19 with etonogestrel implant + ulipristal acetate (mean follicular size at randomization: 15.4 mm ± 1.2 mm, p = 0.6). Ovulation suppression occurred in 13 (65%) of etonogestrel implant-alone participants (Risk ratio 0.6 (95% CI: 0.3, 1.1), p = 0.08) and seven (37%) of implant + ulipristal acetate participants. ConclusionsOvulation suppression of the etonogestrel implant alone exceeds threshold testing for future research while the implant + ulipristal acetate does not. ImplicationsData are lacking on midcycle ovulation suppression for the etonogestrel implant with and without oral ulipristal acetate. In this exploratory study, ovulation suppression occurred in 65% of implant participants and 37% of implant + ulipristal acetate participants. Ovulation suppression of the implant alone exceeds threshold testing for future emergency contraception research.

A Comprehensive Update on the Medical Treatment of Endometriosis-Correlated Pain Clinically with Emphasis over Pharmacokinetics, Pharmacodynamics, Biochemistry, Safety and Effectiveness of Accessible Options in a Condition not having Permanent Cure Till Date: A Narrative Review

Having comprehensively reviewed the etiopathogenesis, medical, surgical therapies in addition to revival of surgery in endometriosis, in particular circumstances earlier here our main idea is to present the update of the available medical treatments, specifically in case of pain amelioration with emphasis over Pharmacokinetics, Pharmacodynamics, Biochemistry, Safety and effectiveness of currently accessible medical treatment for Endometriosis-correlated pain. Here we conducted a narrative review utilizing search engine PubMed, Google scholar, Web of science, Embase, Cochrane review library utilizing the Mesh terms like; endometriosis; medical treatments; Non Steroidal Anti Inflammatory Drugs (NSAIDS); Combined Oral contraceptives (COC); progestins; selective estrogen receptors modulators (SERM); selective Progesterone receptors modulators (SPRMs); Aromatase Inhibitors (AI); GnRH agonists; GnRH antagonists; Levonorgestrel releasing intra uterine system (LNG-IUS) from 1993 till April 2024.We found a total of 1500 articles out of which we selected 115 articles for this review. No meta-analysis was done. Thereby we have reviewed in detail pros &cons of various NSAIDS, COC’s, SERM’s, SERM’s tamoxifen Raloxifene, Bazedoxifene (BZA) fulvestrant of which are none clinically of use SPRMs, Progestins inclusive of medroxy progesterone acetate (MPA), Norethindrone acetate (NETA) and dienogest, of GnRH agonists-Leuprolide Acetate, of oral GnRH antagonist, relugolix linzagolix, elagolix, of AI’s letrozole, anastrazole, of the SPRMs mifepristone, Asoprisnil, ulipristal acetate (UPA) Vilaprisan & Lonaprisan of which till now only mifepristonel is of little use & UPA for select few where no history of liver disease of all these NSAIDS, COC’s, progestins need to be first line with them having better tolerability, efficacy and economical overall in contrast to 2nd line GnRH agonists, GnRH antagonists or AI’s. Dependent over this, key preferences are isolation of new noncontraceptive in addition to non-hormonal’ approaches for diminishing propagation of endometriosisis, thus chances of pregnancy getting feasible.

Emergency contraception in a historic southern city: Mystery caller study in Birmingham, Alabama

BackgroundAlabama's Human Life Protection Act (the Act) signed in 2019 became law in 2022, making provision of abortion a felony offense. ObjectiveIn 2020, we assessed the accessibility of emergency contraception (EC) pills in Birmingham, Alabama prior to the Act's enactment given the probable increased need for EC access due to abortion criminalization. Study designPharmacy staff were asked about availability, price, location, and identification requirements to obtain EC. ResultsOf 69 pharmacies, 59% had levonorgestrel EC and none had ulipristal acetate EC available. ConclusionThere are persistent barriers to EC accessibility that should be addressed as abortion is increasingly restricted.

Ulipristal acetate, a selective progesterone receptor modulator, induces cell death via inhibition of STAT3/CCL2 signaling pathway in uterine sarcoma

Ulipristal acetate (UPA) is a selective progesterone receptor modulator and is used for the treatment of uterine leiomyoma (a benign tumor). Uterine sarcoma which is highly malignant cancer with a poor prognosis is clinically resembled with uterine leiomyoma. There has been no experimental research on the effect of UPA on uterine sarcoma. In this study, we examined the efficacy of UPA in uterine sarcoma with in vitro and in vivo animal models. Cytotoxicity of UPA was determined in uterine sarcoma cell lines (MES-SA, SK-UT-1, and SK-LMS-1). Apoptotic genes and signaling pathways affected by UPA were analyzed by complementary DNA (cDNA) microarray of uterine sarcoma cell lines and western blot, respectively. An in vivo efficacy of UPA was examined with uterine sarcoma cell line- and patient-derived xenograft (PDX) mice models. UPA inhibited cell growth in uterine sarcoma cell lines and primary culture cells from a PDX mouse (PDX-C). cDNA microarray analysis revealed that CCL2 was highly down-regulated by UPA. Phosphorylation and the total expression of STAT3 were inhibited by UPA. UPA also inhibited CCL2 and STAT3 in PDX-C. The inhibitory effect of UPA had not changed in the overexpression of PR and treatment of progesterone. In vivo efficacy studies with cell line-derived xenografts and a PDX model with leiomyosarcoma, a typical uterine sarcoma, demonstrated that UPA significantly decreased tumor growth. UPA had significant anti-tumor effects in uterine sarcoma through the inhibition of STAT3/CCL2 signaling pathway and might be a potential therapeutic agent to treat this disease.

Novel Approaches to Possible Targeted Therapies and Prophylaxis of Uterine Fibroids.

Uterine leiomyomas are the most common benign tumors in women of childbearing age. They may lead to problems of conception or complications during the gestational period. The methods of treatment include surgical (myomectomy and hysterectomy, embolization of arteries) and therapeutic treatment (ulipristal acetate, leuprolide acetate, cetrorelix, goserelin, mifepristone). Both approaches are efficient but incompatible with pregnancy planning. Therefore, there is a call for medical practice to develop therapeutical means of preventing leiomyoma onset in patients planning on becoming pregnant. Based on the analysis of GWAS data on the search for mononucleotide polymorphisms associated with the risk of leiomyoma, in meta-transcriptomic and meta-methylomic studies, target proteins have been proposed. Prospective therapeutic treatments of leiomyoma may be based on chemical compounds, humanized recombinant antibodies, vaccines based on markers of the uterine leiomyoma cells that are absent in the adult organism, or DNA and RNA preparations. Three different nosological forms of the disease associated with driver mutations in the MED12, HMGA2, and FH genes should be considered when developing or prescribing drugs. For example, synthetic inhibitors and vaccines based on matrix metalloproteinases MMP11 and MMP16 are expected to be effective only for the prevention of the occurrence of MED12-dependent nodules.