# Age at Menarche and Risk of Hypertensive Disorders of Pregnancy: A Retrospective Cohort Study

**Authors:** Erick Ordoñez-Villordo, Monica Alethia Cureño-Díaz, Erika Gómez-Zamora, Miguel Trujillo-Martínez, Ricardo Castrejón-Salgado, Fani Villa-Rivas, Rocío Castillo-Díaz, Nadia Velázquez-Hernández, Juan Carlos Fernando Sánchez-Velázquez, Ximena Solis-Gómez, José Ángel Hernández-Mariano

PMC · DOI: 10.3390/clinpract16020032 · 2026-01-29

## TL;DR

This study found that both early and late age at menarche are linked to a higher risk of hypertensive disorders during pregnancy in Mexican women.

## Contribution

The study reveals a U-shaped relationship between age at menarche and hypertensive disorders of pregnancy, independent of BMI and gestational diabetes.

## Key findings

- Early (<12 years) and late (>14 years) menarche were associated with increased HDP risk compared to 12–14 years.
- The U-shaped association was confirmed using restricted cubic spline models.
- Prepregnancy BMI and gestational diabetes explained little of the observed associations.

## Abstract

Background/Objectives: Hypertensive disorders of pregnancy (HDP) remain a major contributor to maternal morbidity and mortality worldwide, yet early-life reproductive factors such as age at menarche have been insufficiently explored in relation to HDP. Therefore, we aimed to evaluate the association between age at menarche and the risk of HDP in a cohort of Mexican pregnant women. Methods: We conducted a retrospective cohort study among 1344 women with singleton pregnancies receiving care at a tertiary hospital in Mexico City in 2024. Age at menarche was categorized as <12, 12–14, and >14 years. HDP diagnoses were extracted from clinical records. Poisson regression with robust variance was used to estimate adjusted risk ratios (RRs). Sensitivity analyses included alternative menarche categorizations and restricted cubic spline models. Counterfactual mediation analyses assessed indirect effects through reconstructed prepregnancy BMI and gestational diabetes. Results: Both early (<12 years) and late (>14 years) menarche were associated with higher HDP risk than the 12–14-year reference (adjusted RR = 1.81; 95% CI 1.42–2.30, and 1.74; 95% CI 1.27–2.38, respectively). Spline models confirmed a U-shaped association. Mediation analyses indicated that prepregnancy BMI did not meaningfully mediate the association for either early or late menarche (<5% mediated). Gestational diabetes explained a modest proportion of the association for early menarche (≈14%), but not for late menarche. Conclusions: Age at menarche showed a robust U-shaped association with HDP, mostly independent of adiposity and gestational diabetes, within the limits of the available measurements. Incorporating pubertal timing into routine reproductive history taking may enhance contextual risk assessment for HDP.

## Linked entities

- **Diseases:** gestational diabetes (MONDO:0005406)

## Full-text entities

- **Diseases:** systemic (MESH:D015619), puberty (MESH:D011628), adiposity (MESH:D018205), type 2 diabetes (MESH:D003924), chronic illness (MESH:D002908), endothelial (MESH:D005642), maternal or neonatal death (MESH:D066087), Hypertensive Disorders (MESH:D006973), undernutrition (MESH:D044342), insulin resistance (MESH:D007333), eclampsia (MESH:D004461), HELLP syndrome (MESH:D017359), ischemic heart disease (MESH:D017202), preterm birth (MESH:D047928), HDP (MESH:D046110), cardiovascular disease (MESH:D002318), overweight (MESH:D050177), stroke (MESH:D020521), organ dysfunction (MESH:D009102), Gestational diabetes (MESH:D016640), obesity (MESH:D009765), placental abruption (MESH:D000037), renal, hepatic, or hematologic involvement (MESH:D019337), proteinuria (MESH:D011507), vascular dysregulation (MESH:D021081), seizures (MESH:D012640), intrauterine growth restriction (MESH:D005317), metabolic syndrome (MESH:D024821), injury to (MESH:D014947), inflammation (MESH:D007249), chronic kidney disease (MESH:D051436), preeclampsia (MESH:D011225), diabetes (MESH:D003920), endothelial dysfunction (MESH:D014652)
- **Chemicals:** lipid (MESH:D008055), Alcohol (MESH:D000438), progesterone (MESH:D011374)
- **Species:** Homo sapiens (human, species) [taxon 9606], Nicotiana tabacum (American tobacco, species) [taxon 4097]

## Figures

3 figures with captions in the complete paper: https://tomesphere.com/paper/PMC12939861/full.md

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Source: https://tomesphere.com/paper/PMC12939861