Pooled analysis of menstrual irregularities from three major clinical studies evaluating everolimus for the treatment of tuberous sclerosis complex
| Autor: | Karin Burock, J. Christopher Kingswood, Steven Sparagana, Noah Berkowitz, John J. Bissler, Darcy A. Krueger, David Neal Franz |
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| Jazyk: | angličtina |
| Rok vydání: | 2017 |
| Předmět: |
0301 basic medicine
Pediatrics Physiology Peptide Hormones lcsh:Medicine Drug research and development Biochemistry Giant Cells Menstruation Follicle-stimulating hormone 0302 clinical medicine Endocrinology Clinical trials Tuberous Sclerosis Reproductive Physiology Animal Cells Medicine and Health Sciences Multicenter Studies as Topic Prospective cohort study Child lcsh:Science Neurological Tumors Menstruation Disturbances Multidisciplinary Incidence Middle Aged Phase III clinical investigation Oncology Neurology Genetic Diseases Research Design 030220 oncology & carcinogenesis Menarche Amenorrhea Female medicine.symptom Cellular Types Infertility Female Phase II clinical investigation medicine.drug Research Article Adult medicine.medical_specialty Adolescent Clinical Research Design Astrocytoma 03 medical and health sciences Clinical Trials Phase II as Topic medicine Humans Everolimus Menstrual Cycle Gynecology Clinical Genetics Pharmacology Subependymal giant cell astrocytoma Endocrine Physiology business.industry lcsh:R Biology and Life Sciences Cancers and Neoplasms Cell Biology Luteinizing Hormone medicine.disease Hormones Research and analysis methods Irregular menstruation 030104 developmental biology Clinical Trials Phase III as Topic Clinical medicine lcsh:Q Adverse Events Follicle Stimulating Hormone business |
| Zdroj: | PLoS ONE, Vol 12, Iss 10, p e0186235 (2017) PLoS ONE |
| ISSN: | 1932-6203 |
| Popis: | Objectives To determine the impact of everolimus on female fertility, including menstrual irregularities, secondary amenorrhea, and luteinizing and follicle stimulating hormone levels in female patients. Design A pooled analysis from 3 prospective studies consisting of a core phase (≥6 months) and a long-term follow-up open-label extension. Setting One phase 2 single-center and two phase 3 multicenter studies. Participants Data were obtained from female participants, restricted to those between 10 and 55 years of age, during 1 of 3 of the described clinical trials of everolimus. Patients had received ≥ 1 dose of everolimus. Main outcome measures Incidence of fertility events. Results A total of 43/112 patients (38.4%) experienced at least 1 menstrual irregularity. The most common events were amenorrhea (24.1%) and irregular menstruation (17.0%). Seven patients (6.3%) experienced grade 3/4 amenorrhea. When only the longest duration period of amenorrhea for each patient was considered, the median duration was 291 days. Fifteen patients attained menarche during the treatment period in any of the pooled studies. The mean age of menarche for this group was 12.4 years, similar to that of patients who were postmenarche at study entry (12.2 years). A total of 19/92 patients (20.7%) who were postmenarche at baseline or during the study experienced an irregular menstruation event. An increased luteinizing hormone level was reported as an adverse event in 3/112 patients (3%), and follicle-stimulating hormone levels were within normal limits for these patients. Conclusions No new safety concerns emerged regarding endocrine function and menstruation in female patients with tuberous sclerosis complex–associated subependymal giant cell astrocytoma or angiomyolipoma, who were receiving everolimus. Trial registration ClinicalTrials.gov NCT00411619, NCT00789828, NCT00790400 |
| Databáze: | OpenAIRE |
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