TY - JOUR
T1 - Pooled analysis of menstrual irregularities from three major clinical studies evaluating everolimus for the treatment of tuberous sclerosis complex
AU - Sparagana, Steven
AU - Franz, David N.
AU - Krueger, Darcy A.
AU - Bissler, John J.
AU - Berkowitz, Noah
AU - Burock, Karin
AU - Kingswood, J. Christopher
N1 - Publisher Copyright:
© 2017 Sparagana et al. This is an open access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited.
PY - 2017/10
Y1 - 2017/10
N2 - 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.
AB - 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.
UR - http://www.scopus.com/inward/record.url?scp=85031128731&partnerID=8YFLogxK
UR - http://www.scopus.com/inward/citedby.url?scp=85031128731&partnerID=8YFLogxK
U2 - 10.1371/journal.pone.0186235
DO - 10.1371/journal.pone.0186235
M3 - Article
C2 - 29023494
AN - SCOPUS:85031128731
SN - 1932-6203
VL - 12
JO - PLoS One
JF - PLoS One
IS - 10
M1 - e0186235
ER -