Linzagolix with and without hormonal add-back therapy for the treatment of symptomatic uterine fibroids: two randomised, placebo-controlled, phase 3 trials.

Background: Uterine fibroids are common non-cancerous neoplasm that cause heavy menstrual bleeding and other signs. Linzagolix is an oral gonadotropin-releasing hormone receptor antagonist taken once per day that dose-dependently suppresses gonadal steroids and might reduce uterine-fibroid-associated signs. Two phase 3 trials were conducted to confirm the efficacy and safety of linzagolix at full-suppression (200 mg) and partial-suppression (100 mg) doses with or without hormonal add-back therapy (1 mg oestradiol and 0·5 mg norethisterone acetate) compared with placebo for the treatment of symptomatic uterine fibroids.

Uterine Adenomyosis Treated by Linzagolix, an Oral Gonadotropin-Releasing Hormone Receptor Antagonist: A Pilot Study with a New 'Hit Hard First and then Maintain' Regimen of Administration.

(1) Background: The aim of the present pilot study was to study the effect of a new oral gonadotropin-releasing hormone antagonist on adenomyosis. (2) Methods: Eight premenopausal women, aged between 37 and 45 years, presenting with heavy menstrual bleeding, pelvic pain, and dysmenorrhea due to diffuse and disseminated uterine adenomyosis, confirmed by magnetic resonance imaging (MRI), received 200 mg linzagolix once daily for a period of 12 weeks, after which they were switched to 100 mg linzagolix once daily for another 12 weeks. The primary efficacy endpoint was the change in volume of the adenomyotic uterus from baseline to 24 weeks, evaluated by MRI.

Treatment of symptomatic uterine adenomyosis with linzagolix, an oral gonadotrophin-releasing hormone antagonist: a pilot study.

Research Question: Does a once-daily regimen of linzagolix, a new oral gonadotrophin-releasing hormone (GnRH) antagonist, given at a fully suppressive dose (200 mg) for 12 weeks, followed by a partially suppressive dose (100 mg) for a further 12 weeks, reduce adenomyotic uterine size and associated symptoms?

Design: Eight women (aged 37-45 years) with adenomyosis confirmed by magnetic resonance imaging (MRI) were enrolled in a single-centre, open-label pilot study. The primary efficacy end-point was the change in uterine volume on MRI at 24 weeks. Secondary efficacy end-points included serum oestradiol, overall pelvic pain, dysmenorrhoea, non-menstrual pelvic pain, dyspareunia, dyschezia and quality of life (QoL).

Gonadotropin-Releasing Hormone Receptor Antagonist Mono- and Combination Therapy With Estradiol/Norethindrone Acetate Add-Back: Pharmacodynamics and Safety of OBE2109.

Context: OBE2109 is a potent, oral gonadotropin-releasing hormone receptor antagonist being developed for the treatment of sex-hormone-dependent diseases in women.

Objective: We assessed the pharmacodynamics and safety of OBE2109 alone and combined with estradiol (E2)/norethindrone acetate (NETA) add-back therapy on E2 levels and vaginal bleeding.

Design, Setting, And Participants: This was a single-center, open-label, randomized, parallel-group study in 76 healthy premenopausal women.

Long-term medical management of uterine fibroids with ulipristal acetate.

Objective: To investigate the efficacy and safety of repeated 12-week courses of 5 or 10 mg daily ulipristal acetate for intermittent treatment of symptomatic uterine fibroids.

Design: Double-blind, randomized administration of four 12-week courses of ulipristal acetate.

Setting: Gynecology centers.

Contribution to More Patient-Friendly ART Treatment: Efficacy of Continuous Low-Dose GnRH Agonist as the Only Luteal Support-Results of a Prospective, Randomized, Comparative Study.

Background. The aim of this pilot study was to evaluate intranasal buserelin for luteal phase support and compare its efficacy with standard vaginal progesterone in IVF/ICSI antagonist cycles. Methods.

Efficacy and safety of repeated use of ulipristal acetate in uterine fibroids.

Objective: To investigate the efficacy and safety of repeated 12-week courses of 5 or 10 mg daily of ulipristal acetate for intermittent treatment of symptomatic uterine fibroids.

Design: Double-blind, randomized administration of two 12-week courses of ulipristal acetate.

Setting: Gynecology centers.

Recombinant human luteinizing hormone to trigger ovulation: randomized, controlled, dose-finding pilot study in ovulation induction.

Objective: To evaluate recombinant human luteinizing hormone (r-hLH) versus urine-derived human chorionic gonadotropin (u-hCG) to trigger ovulation in women (aged 20-40 years) with WHO Group II anovulatory infertility undergoing ovulation induction (OI) with recombinant human follicle-stimulating hormone (r-hFSH) (150 IU/day starting dose).

Study Design: For this Phase II, open-label, dose-finding pilot study, patients were randomized to doses of 825, 2,750, 5,500, 11,000, or 22,000 IU r-hLH or u-hCG (5,000 IU). Primary endpoints were ovulation and ratio of ruptured follicles/follicle > or = 15 mm (day of r-hLH/ u-hCG administration).

Long-term treatment of uterine fibroids with ulipristal acetate ☆.

Objective: To investigate the efficacy and safety of ulipristal acetate (UPA) for long-term treatment of symptomatic uterine fibroids.

Design: Repeated intermittent open-label UPA courses, each followed by randomized double-blind norethisterone acetate (NETA) or placebo.

Setting: European clinical gynecology centers.

Ulipristal acetate versus leuprolide acetate for uterine fibroids.

Background: The efficacy and side-effect profile of ulipristal acetate as compared with those of leuprolide acetate for the treatment of symptomatic uterine fibroids before surgery are unclear.

Methods: In this double-blind noninferiority trial, we randomly assigned 307 patients with symptomatic fibroids and excessive uterine bleeding to receive 3 months of daily therapy with oral ulipristal acetate (at a dose of either 5 mg or 10 mg) or once-monthly intramuscular injections of leuprolide acetate (at a dose of 3.75 mg).

Ulipristal acetate versus placebo for fibroid treatment before surgery.

Background: The efficacy and safety of oral ulipristal acetate for the treatment of symptomatic uterine fibroids before surgery are uncertain.

Methods: We randomly assigned women with symptomatic fibroids, excessive uterine bleeding (a score of >100 on the pictorial blood-loss assessment chart [PBAC, an objective assessment of blood loss, in which monthly scores range from 0 to >500, with higher numbers indicating more bleeding]) and anemia (hemoglobin level of ≤10.2 g per deciliter) to receive treatment for up to 13 weeks with oral ulipristal acetate at a dose of 5 mg per day (96 women) or 10 mg per day (98 women) or to receive placebo (48 women).

Kit ligand and the somatostatin receptor antagonist, BIM-23627, stimulate in vitro resting follicle growth in the neonatal mouse ovary.

In the mammalian ovary, kit ligand (KL), coded by a cAMP-stimulatable gene, is a protein that promotes initiation of follicle growth. The neuropeptide somatostatin (SST) is a small peptide that inhibits cAMP generation in many cell types. Consequently, SST receptor agonists might alter KL production and subsequent follicle growth.

Evaluation of estrogen treatment in an immunodeficient mouse endometriosis model.

Background/aims: Endometriosis is known to be an estrogen-dependent disease. However, only a few studies have analyzed the effect of estrogen treatment in mice xenotransplanted with human endometrium. The objective of this study was to adapt a previously developed heterologous murine model to the study of estrogens and test the impact of estrone treatment on endometriosis development.

Nonsupplemented luteal phase characteristics after the administration of recombinant human chorionic gonadotropin, recombinant luteinizing hormone, or gonadotropin-releasing hormone (GnRH) agonist to induce final oocyte maturation in in vitro fertilization patients after ovarian stimulation with recombinant follicle-stimulating hormone and GnRH antagonist cotreatment.

Replacing GnRH agonist cotreatment for the prevention of a premature rise in LH during ovarian stimulation for in vitro fertilization (IVF) by the late follicular phase administration of GnRH antagonist may render supplementation of the luteal phase redundant, because of the known rapid recovery of pituitary function after antagonist cessation. This randomized two-center study was performed to compare nonsupplemented luteal phase characteristics after three different strategies for inducing final oocyte maturation. Forty patients underwent ovarian stimulation using recombinant (r-)FSH (150 IU/d, fixed) combined with a GnRH antagonist (antide; 1 mg/d) during the late follicular phase.

Improvement in consistency of response to ovarian stimulation with recombinant human follicle stimulating hormone resulting from a new method for calibrating the therapeutic preparation.

Traditionally, therapeutic preparations of gonadotrophins are quantified with a rat in-vivo bioassay in biological international units (IU). This method was developed to cope with variability of production batch quality. The bioassay, however, presents some limitations, and differences in clinical responses when using different batches of urine-derived gonadotrophins have been reported.

Clinical evidence for an LH 'ceiling' effect induced by administration of recombinant human LH during the late follicular phase of stimulated cycles in World Health Organization type I and type II anovulation.

Background: The objective of these studies was to test the hypothesis that over-dosing with recombinant human LH (rLH) during the late follicular phase would suppress the development of follicles.

Methods: Two double-blind studies were conducted. In study A, WHO I anovulatory patients received treatment with rFSH and rLH.

Relationship of baseline ovarian volume to ovarian response in World Health Organization II anovulatory patients who underwent ovulation induction with gonadotropins.

Objective: To assess whether ovarian volume of World Health Organization II anovulatory patients in the early follicular phase predicts the response to ovulation induction with gonadotropins.

Design: Retrospective data analysis of two prospective, randomized, multicenter studies.

Setting: Clinical development unit of biotechnology company.

Efficacy and safety of recombinant human follicle-stimulating hormone in men with isolated hypogonadotropic hypogonadism.

Objective: To assess the efficacy and safety of recombinant human follicle-stimulating hormone (rhFSH; follitropin alpha) in increasing sperm concentration in 26 men with severe isolated hypogonadotropic hypogonadism (IHH).

Design: Clinical and endocrine studies using an open design.

Setting: Six university clinical sites in three European countries.