A comparative prospective observational study on the use of ulipristal acetate versus mifepristone in reduction of the size of uterine leiomyoma

Background: Fibroid or uterine leiomyoma is the most common benign tumor of the uterus in the reproductive age group and found in one out of every four women. They are symptomatic in 50% of women, with the peak incidence occurring among women in their 30s or 40s. Fibroid can cause a variety of symptoms which include menstrual disturbances commonly menorrhagia and dysmenorrhea. It is a common indication of hysterectomy in Indians. An effective medical treatment option may reduce hysterectomy-associated morbidity and mortality. This study is undertaken to evaluate the efficacy and safety of medical management of myoma and contribution in the reduction of myoma size comparing the two drugs ulipristal and mifepristone. Aims and Objectives: The study was conducted to compare reduction of menorrhagia (By pictorial blood loss assessment chart score), reduction of fibroid size (using transvaginal ultrasonography), and improvement of hemoglobin (Hb) level. We are also evaluating safety or side effects using these drugs. Materials and Methods: The study includes 210 patients who are divided into two groups. Group A includes 105 patients who are treated with tablet Ulipristal Acetate 5 mg daily for 3 months and Group B includes 105 patients who are treated with tablet mifepristone 25 mg daily for 3 months. Results: Ulipristal and mifepristone both are effective in reduction of menorrhagia and improvement of Hb levels, but Ulipristal is more effective in reduction of size of uterine myoma than mifepristone after 3 months of treatment. Conclusion: Multicentric study over a larger population is required to reach a valid conclusion.

Investigation of Inherited Chromosomally Integrated Human Herpesvirus-6A+ and -6B+ in a Patient with Ulipristal Acetate-Induced Fulminant Hepatic Failure

Inherited chromosomally integrated (ici) human herpes virus 6 (HHV-6) is estimated to occur in 0.6–2.7% of people worldwide. HHV-6 comprises two distinct species: HHV-6A and HHV-6B. Both HHV-6A and HHV-6B integration have been reported. Several drugs are capable of activating iciHHV-6 in tissues, the consequences of which are poorly understood. We report herein a case of a woman with iciHHV-6A+ and iciHHV-6B+, who developed ulipristal acetate (a selective progesterone receptor modulator)-induced fulminant hepatic failure that required liver transplantation. We confirmed the presence of ~one copy per cell of both HHV-6A and HHV-6B DNA in her hair follicles using multiplex HHV-6A/B real-time PCR and demonstrated the Mendelian inheritance of both iciHHV-6A and iciHHV-6B in her family members over three generations. Because of the rarity of this presentation, we discuss herein the possible links between reactivated HHV-6 from iciHHV-6A and/or iciHHV-6B and adverse drug reactions, suggesting that iciHHV-6 could be screened before the introduction of any hepatotoxic drugs to exclude HHV-6 active disease or combined idiosyncratic drug-induced liver injury in these patients.

Emergency Contraception Access and Counseling in Metropolitan and Nonmetropolitan Pharmacies in Georgia

Background: Emergency contraception (EC) efficacy is dependent on timing of administration. Adequate pharmacy stock information and accurate patient counseling are important to ensure timely access. Objective: This study evaluates pharmacist reported availability and counseling for levonorgestrel (LNG) and ulipristal acetate (UPA), and identifies differences between caller type and pharmacies in metropolitan vs nonmetropolitan areas of Georgia. Methods: This prospective, randomized, telephone-based study included 25% of Georgia community pharmacies, stratified by geographic location. Calls were made by investigators, first posing as a mystery shopper inquiring about EC stock and efficacy, then 3–6 weeks later as a researcher inquiring about EC stock. Analysis utilized descriptive statistics, chi Square, and logistic regression. Results: Of 600 pharmacies, the mystery shopper caller reached 86%: 74% of pharmacists initially discussed LNG, 57.1% had it stocked, more often in metropolitan areas (OR 1.7, 95% CI 1.08–2.6). Ulipristal acetate was discussed by 1.9% and reported in-stock < 1%. Of those who discussed window of efficacy, 79% indicated LNG would either not work 4 days after intercourse or they were unsure. The research caller successfully completed a second call for 64% of pharmacies: 57% stocked LNG, 3% stocked UPA, and UPA was more likely to be stocked in metropolitan pharmacies. Conclusion: In Georgia, UPA availability is poor, and nonmetropolitan pharmacies were less likely to stock LNG and UPA. A minority of pharmacists correctly indicated that LNG may work up to 120 hours after intercourse. Strategies are needed to overcome barriers to EC availability in community pharmacies and support pharmacists’ EC counseling.

Ulipristal Acetate Versus Leuprolide Acetate in Medical Management of Uterine Fibroids

BACKGROUND We wanted to compare the effectiveness of the treatment and the adverse effects of ulipristal acetate and leuprolide acetate in the medical management of symptomatic uterine fibroids. METHODS This is a randomised controlled study conducted in the the Department of Obstetrics and Gynaecology in Chalmeda Anand Rao Institute of Medical Sciences from January 2019 to January 2020. 60 patients with symptomatic fibroids and excessive uterine bleeding were randomly divided. They were given daily therapy of ulipristal acetate 10 mg orally for 3 months or monthly injection leuprolide acetate 3.75 mg intramuscularly for 3 months. RESULTS Controlled uterine bleeding was observed in 98 % of patients who received oral therapy of ulipristal acetate of 10 mg, and 89 % of patients who received injections of leuprolide acetate, for differences in comparison with leuprolide acetate of 8.8 % points (95 % CI, 0.4 to 18.3) for ulipristal acetate of 10 mg. Median time of amenorrhea for those taking ulipristal acetate of 10 mg was 5 days, and 21 days for leuprolide acetate. 10 % of patients receiving ulipristal acetate reported moderateto-severe hot flashes and 40 % of patients receiving leuprolide acetate reported moderate to severe hot flashes (P < 0.0010 for each dose of leuprolide acetate vs. ulipristal acetate). CONCLUSIONS Daily therapy of 10-mg ulipristal acetate was considered non inferior when compared to monthly injections of leuprolide acetate in control of uterine bleeding, moreover ulipristal acetate therapy was also significantly less likely to cause hot flashes. KEY WORDS Ulipristal Acetate; Leuprolide acetate; Abnormal Uterine Bleeding; Leiomyoma

Ulipristal Acetate Modifies miRNA Expression in Both Superficial and Basal Layers of the Human Endometrium

(1) Background: Ulipristal acetate (UPA) is a selective progesterone receptor modulator (SPRM) widely used for emergency contraception and mid- to long-term leiomyoma treatment. The aim of this study was to identify modifications of miRNA expression in superficial and basal layers of the human endometrium at the end of the UPA treatment for at least 3 months. (2) Methods: Microarray miRNA analysis of formalin-fixed, paraffin-embedded hysterectomy tissue samples was conducted, followed by an Ingenuity Pathway Analysis. Samples were divided into three groups: women having had 3 months of UPA treatment (n = 7); and two control groups of UPA-naïve women in the proliferative (n = 8) or secretory (n = 6) phase. (3) Results: The UPA modified the expression of 59 miRNAs involved in the processes of cell cycle, carcinogenesis, and inflammation. Their expression profiles were different in the basal and superficial layers. Most of the processes influenced by the UPA in the basal layer were connected to the cell cycle and immune regulation. (4) Conclusion: Specific changes were observed in both layers of the endometrium in the UPA group. However, the miRNA expression in the basal layer was not consistent with that in the superficial layer. Other large studies analysing the long-term impact of SPRM on endometrial miRNA expression are necessary.