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Peer-reviewedCC BY-NC-NDNature medicine

Population-scale reconstruction of menopause dynamics reveals a physiological cliff at the final menstrual period.

  • Glen Pridham1
  • Yoav Hayut1
  • Noa Lavi-Shoseyov2,3
  • Michal Neeman2
  • Noa Hovav4
  • Yoel Toledano5
  • Uri Alon6
6 affiliations
  1. 1Dept. Molecular Cell Biology, Weizmann Institute of Science, Rehovot, Israel.
  2. 2Dept. Immunology and Regenerative Biology, Weizmann Institute of Science, Rehovot, Israel.
  3. 3IVF Unit, Department of Obstetrics and Gynecology, Kaplan Medical Center, Rehovot, Israel.
  4. 4Menopause Community Center, Clalit Health Care, Ness-Ziona, Israel.
  5. 5Division of Maternal Fetal Medicine, Helen Schneider Women's Hospital, Rabin Medical Center, Petah Tikva, Israel.
  6. 6Dept. Molecular Cell Biology, Weizmann Institute of Science, Rehovot, Israel. [email protected].
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Abstract

Menopause reshapes female physiology, yet current understanding is limited by small longitudinal cohorts that characterize it as a gradual transition. Large-scale biomedical datasets remain underutilized because the final menstrual period (FMP) age is rarely recorded. Here we present a computational framework, inspired by astronomy, that reconstructs FMP-anchored trajectories from cross-sectional data by removing the blurring caused by variation in FMP age across individuals. Applying this to two independent cohorts totaling 300 million laboratory tests revealed a step-like physiological cliff at the FMP including endocrine, skeletal, hepatic, renal and lipid systems. These discontinuities are absent in male individuals, are concordant across populations and appear markedly attenuated by menopausal hormone therapy. Dysregulation began more than a decade before FMP. These findings support a systemic, quantifiable view of menopause and provide a generalizable strategy for recovering hidden biological trajectories applicable to other transitions such as puberty or disease progression.

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Cite

BibTeXRIS
BibTeX
@article{pridham2026populationscale,
  title = {{Population-scale reconstruction of menopause dynamics reveals a physiological cliff at the final menstrual period.}},
  author = {Glen Pridham and Yoav Hayut and Noa Lavi-Shoseyov and Michal Neeman and Noa Hovav and Yoel Toledano and Uri Alon},
  journal = {Nature medicine},
  year = {2026},
  month = oct,
  doi = {10.1038/s41591-026-04614-0},
  url = {https://europepmc.org/article/MED/42864411},
  note = {CC BY-NC-ND},
}
RIS
TY  - JOUR
TI  - Population-scale reconstruction of menopause dynamics reveals a physiological cliff at the final menstrual period.
AU  - Glen Pridham
AU  - Yoav Hayut
AU  - Noa Lavi-Shoseyov
AU  - Michal Neeman
AU  - Noa Hovav
AU  - Yoel Toledano
AU  - Uri Alon
PY  - 2026
DA  - 2026/10/12
JO  - Nature medicine
DO  - 10.1038/s41591-026-04614-0
UR  - https://europepmc.org/article/MED/42864411
AB  - Menopause reshapes female physiology, yet current understanding is limited by small longitudinal cohorts that characterize it as a gradual transition. Large-scale biomedical datasets remain underutilized because the final menstrual period (FMP) age is rarely recorded. Here we present a computational framework, inspired by astronomy, that reconstructs FMP-anchored trajectories from cross-sectional data by removing the blurring caused by variation in FMP age across individuals. Applying this to two independent cohorts totaling 300 million laboratory tests revealed a step-like physiological cliff at the FMP including endocrine, skeletal, hepatic, renal and lipid systems. These discontinuities are absent in male individuals, are concordant across populations and appear markedly attenuated by menopausal hormone therapy. Dysregulation began more than a decade before FMP. These findings support a systemic, quantifiable view of menopause and provide a generalizable strategy for recovering hidden biological trajectories applicable to other transitions such as puberty or disease progression.
SN  - 1078-8956
SN  - 1546-170X
ER  -