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. 2022 Feb 18:4:798983.
doi: 10.3389/frph.2022.798983. eCollection 2022.

Expanding Our Knowledge of Menstrual Irregularities Reported by Females With Tuberous Sclerosis Complex

Kate Mowrey  1 , Hope Northrup  1 , Syed Shahrukh Hashmi  2 , David Rodriguez-Buritica  1
Affiliations

Expanding Our Knowledge of Menstrual Irregularities Reported by Females With Tuberous Sclerosis Complex

Kate Mowrey et al. Front Reprod Health. .

Abstract

Purpose: The purpose of our study is to expand the knowledge regarding intrinsic reproductive dysfunction in females with TSC and to explore the impact of mTOR inhibitors (mTORi) on menstrual irregularity in the Tuberous Sclerosis Complex (TSC) community.

Methods: An electronic survey composed of author-designed questions set out to evaluate reproductive history, presence of menstrual irregularities, mTORi use, as well as maternal reproductive history among females with TSC.

Results: Of the 68 responses from females with TSC regarding age of menarche, the average age was 12.3 years. 56.5% (n = 48) of respondents reported irregular menstrual cycles and noted a total of 102 menstrual irregularities. There was a cohort of 35 women with a reported history of mTORi use. Of these women, 68.6% (n = 24) reported irregular menstrual cycles after taking mTORi. In comparison, among the females with no history of mTORi use (n = 50) only 48% reported irregular menstrual cycles (n = 24).

Conclusions: Our data expands the knowledge regarding intrinsic menstrual dysregulation present in women with TSC, demonstrates a rate of menstrual irregularities among females taking mTORi, and identifies a tendency toward early menarche that may be a previously unrecognized feature of TSC.

Keywords: mTOR dysregulation; mTOR inhibitors; menstrual irregularity; reproductive health; tuberous sclerosis complex.

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Conflict of interest statement

The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest.

Figures

Figure 1
Figure 1
Breakdown of menstrual irregularities between females with a history of mTOR inhibitor (mTORi) use and without a history of mTORi use. Furthermore, the females that had a history of mTORi use had their menstrual irregularities further broken down to those present before and after starting mTORi therapy.
Figure 2
Figure 2
Comparison of the menstrual irregularities present in individuals with and without the use of oral contraceptive pills (OCPs) and mTOR inhibitors (mTORi) with further subcategorization of before and after the initiation of mTORi.
See this image and copyright information in PMC

References

    1. Northrup H, Krueger DA, International Tuberous Sclerosis Complex Consensus Group. Tuberous sclerosis complex diagnostic criteria update: recommendations of the 2012 International Tuberous Sclerosis Complex Consensus Conference. Pediatr Neurol. (2013) 49:243–54. 10.1016/j.pediatrneurol.2013.08.001 - DOI - PMC - PubMed
    1. Northrup H, Koenig MK, Pearson DA, Au KT. Tuberous sclerosis complex. In Adam MP, Ardinger HH, Pagon RA, Wallace SE, Bean LJH, Gripp KW, editors. GeneReviews® [Internet], Seattle, WA: University of Washington, Seattle (1993–2021). Available online at:https://www.ncbi.nlm.nih.gov/books/NBK1220/ (Jul 13, 1999; Updated Apr 16, 2020).
    1. Au KS, Williams AT, Roach ES, Batchelor L, Sparagana SP, Delgado M .R., et al. . Genotype/phenotype correlation in 325 individuals referred for a diagnosis of tuberous sclerosis complex in the United States. Genet Med. (2007) 9:88–100. 10.1097/GIM.0b013e31803068c7 - DOI - PubMed
    1. Castro AF, Rebhun JF, Clark GJ, Quilliam LA. Rheb binds tuberous sclerosis complex 2 (TSC2) and promotes S6 kinase activation in a rapamycin-and farnesylation-dependent manner. J Biol Chem. (2003) 278:32493–6. 10.1074/jbc.C300226200 - DOI - PubMed
    1. Van Slegtenhorst M, Nellist M, Nagelkerken B, Cheadle J, Snell R, van den Ouweland A, et al. . Interaction between hamartin and tuberin, the TSC1 and TSC2 gene products. Hum Mol Genet. (1998) 7:1053–7. 10.1093/hmg/7.6.1053 - DOI - PubMed