Reproductive factors and the risk of incident peripheral arterial disease hospitalization or death: a cohort study of UK Biobank participants.

Early and late menarche were both associated with increased peripheral arterial disease risk.

• Age at menarche <12 years was associated with an adjusted hazard ratio of 1.43 (95% CI: 1.32, 1.55; P<.001).
• Age at menarche >14 years was associated with an adjusted hazard ratio of 1.36 (95% CI: 1.23, 1.49; P<.001).
• The reference category was presumably menarche at age 12–14 years.
• Analysis was conducted in 272,557 women over a median follow-up of 13.2 years.

Older age at first birth was associated with a cumulative reduction in peripheral arterial disease risk.

• Each additional year of age at first birth was associated with an adjusted hazard ratio of 0.95 (95% CI: 0.94, 0.96; P<.001).
• This represents a 5% reduction in peripheral arterial disease risk per year of older age at first birth.
• Analysis was performed using Cox proportional hazard regression with confounder adjustment.

Each miscarriage, stillbirth, and abortion was associated with a cumulative increased risk of peripheral arterial disease.

• Per miscarriage: adjusted hazard ratio 1.06 (95% CI: 1.01, 1.11; P=.027).
• Per stillbirth: adjusted hazard ratio 1.18 (95% CI: 1.03, 1.36; P=.014).
• Per abortion: adjusted hazard ratio 1.09 (95% CI: 1.01, 1.18; P=.028).
• These associations were cumulative, meaning risk increased with each additional pregnancy loss or termination.

Oral contraceptive pill use was associated with reduced peripheral arterial disease risk.

• Adjusted hazard ratio for oral contraceptive use was 0.85 (95% CI: 0.78, 0.93; P<.001).
• This represents a 15% reduction in peripheral arterial disease risk associated with oral contraceptive use.
• A longer duration of reproductive years and later natural menopause were also associated with reduced peripheral arterial disease risk.

Hysterectomy and oophorectomy were each associated with increased peripheral arterial disease risk.

• Hysterectomy was associated with an adjusted hazard ratio of 1.24 (95% CI: 1.13, 1.35; P<.001).
• Oophorectomy was associated with an adjusted hazard ratio of 1.24 (95% CI: 1.10, 1.39; P<.001).
• Both procedures showed a 24% increase in peripheral arterial disease risk compared to women without these procedures.

The association between number of children and peripheral arterial disease was U-shaped and similar for both women and men.

• Having 4 or more children was associated with an adjusted hazard ratio of 1.13 (95% CI: 1.00, 1.25; P=.041) for women.
• Having 4 or more children was associated with an adjusted hazard ratio of 1.25 (95% CI: 1.16, 1.34; P<.001) for men.
• The U-shaped association and similar effect in men suggest a shared behavioral or socioeconomic mechanism rather than a purely biological reproductive one.
• The association between number of children and peripheral arterial disease was examined in both sexes and compared between them.

Over a median follow-up of 13.2 years, peripheral arterial disease incidence was lower in women than in men.

• 2,942 of 272,557 women developed peripheral arterial disease.
• 5,432 of 227,403 men developed peripheral arterial disease.
• Poisson regression was used to estimate sex-specific incidence rates per 10,000 person years.
• Participants with a prior diagnosis of peripheral arterial disease were excluded from the cohort.

Hormone replacement therapy use was included as an exposure but specific hazard ratio results for HRT were not reported in the abstract.

• Exogenous hormone use examined included both oral contraceptive pill and hormone replacement therapy use.
• The abstract reports results for oral contraceptive pill use (aHR 0.85) but does not provide a specific hazard ratio for hormone replacement therapy.
• Reproductive factors examined included age at menarche, parity-related factors, menopause-related factors, and exogenous hormone use.