Pooled analysis of menstrual irregularities from three major clinical studies evaluating everolimus for the treatment of tuberous sclerosis complex

Steven Sparagana, David N. Franz, Darcy A. Krueger, John J. Bissler, Noah Berkowitz, Karin Burock, J. Christopher Kingswood

Research output: Contribution to journalArticle

3 Citations (Scopus)

Abstract

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.

Original languageEnglish (US)
Article numbere0186235
JournalPLoS One
Volume12
Issue number10
DOIs
StatePublished - Oct 1 2017

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Tuberous Sclerosis
sclerosis
clinical trials
Follicle Stimulating Hormone
amenorrhea
Amenorrhea
menstruation
Menstruation
Therapeutics
Luteinizing Hormone
menarche
Menarche
Labels
follicle-stimulating hormone
Fertility
Clinical Studies
Everolimus
luteinization
Angiomyolipoma
female fertility

ASJC Scopus subject areas

  • Biochemistry, Genetics and Molecular Biology(all)
  • Agricultural and Biological Sciences(all)

Cite this

Pooled analysis of menstrual irregularities from three major clinical studies evaluating everolimus for the treatment of tuberous sclerosis complex. / Sparagana, Steven; Franz, David N.; Krueger, Darcy A.; Bissler, John J.; Berkowitz, Noah; Burock, Karin; Kingswood, J. Christopher.

In: PLoS One, Vol. 12, No. 10, e0186235, 01.10.2017.

Research output: Contribution to journalArticle

Sparagana, Steven ; Franz, David N. ; Krueger, Darcy A. ; Bissler, John J. ; Berkowitz, Noah ; Burock, Karin ; Kingswood, J. Christopher. / Pooled analysis of menstrual irregularities from three major clinical studies evaluating everolimus for the treatment of tuberous sclerosis complex. In: PLoS One. 2017 ; Vol. 12, No. 10.
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abstract = "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.",
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