Puberty timing associated with diabetes, cardiovascular disease and also diverse health outcomes in men and women: the UK Biobank study

Abstract

Early puberty timing is associated with higher risks for type 2 diabetes (T2D) and cardiovascular disease in women and therefore represents a potential target for early preventive interventions. We characterised the range of diseases and other adverse health outcomes associated with early or late puberty timing in men and women in the very large UK Biobank study. Recalled puberty timing and past/current diseases were self-reported by questionnaire. We limited analyses to individuals of White ethnicity (250,037 women; 197,714 men) and to disease outcomes with at least 500 cases (~ 0.2% prevalence) and we applied stringent correction for multiple testing (corrected threshold P < 7.48 × 10(-5)). In models adjusted for socioeconomic position and adiposity/body composition variables, both in women and men separately, earlier puberty timing was associated with higher risks for angina, hypertension and T2D. Furthermore, compared to the median/average group, earlier or later puberty timing in women or men was associated with higher risks for 48 adverse outcomes, across a range of cancers, cardio-metabolic, gynaecological/obstetric, gastrointestinal, musculoskeletal, and neuro-cognitive categories. Notably, both early and late menarche were associated with higher risks for early natural menopause in women. Puberty timing in both men and women appears to have a profound impact on later health.

Figure 1. Distribution of effect sizes by quintile of menarche age for all of the 140 tested diseases and adverse health outcomes in women.

The odds ratio for each disease for each quintile is calculated relative to the middle quintile (Q3). The box in each plot represents the inter quartile range (IQR) of the effect estimates the whiskers represent the range of effects that are 1.5 × IQR beyond the IQR, odds ratios for disease more extreme than this are plotted as individual points.

Figure 2. Associations between early or late menarche timing and adverse health outcomes in women.

Displayed outcomes showed study-wise significant (P < 7.48 × 10^-5) associations in any model (linear, early or late menarche). Effect estimates (± 95% CI) are shown for early (the earliest quintile) or late (the latest quintile) menarche groups compared to the middle quintile (reference group). Purple centres (with purple error bars) indicate significant associations from baseline models (adjusted for birth year, age and age squared). Green centres (with green error bars) indicate significant associations from models adjusted for socio-economic and adiposity/body composition variables (except for Obesity). Grey error bars indicate associations that did not reach study-wise significance.

Figure 3. Distribution of effect sizes for early or late relative age at voice breaking for all 119 tested diseases and adverse health outcomes in men.

The odds ratio for each disease for those with early or late voice breaking is calculated relative to the group with a normal age at voice breaking. The box in each plot represents the inter quartile range (IQR) of the effect estimates, the whiskers represent the range of effects that are 1.5 × IQR beyond the IQR, outliers more extreme than this are plotted as individual points.

Figure 4. Associations between early or late voice breaking and adverse health outcomes in men.

Displayed outcomes showed study-wise significant (P < 7.48 × 10^-5) associations in any model (early or late). Effect estimates (± 95% CI) are shown for early or late voice breaking groups compared to the “about normal age” reference group). Purple centres (with purple error bars) indicate significant associations from baseline models (adjusted for birth year, age and age squared). Green centres (with green error bars) indicate significant associations from models adjusted for socio-economic and adiposity/body composition variables (except for Obesity). Grey error bars indicate associations that did not reach study-wise significance.