Comorbidities in women with polycystic ovary syndrome: a sibling study.

BACKGROUND: Polycystic ovary syndrome (PCOS) has previously been associated with several comorbidities that may have shared genetic, epigenetic, developmental or environmental origins. PCOS may be influenced by prenatal androgen excess, poor intrauterine or childhood environmental factors, childhood obesity and learned health risk behaviors. We analyzed the association between PCOS and several relevant comorbidities while adjusting for early-life biological and socioeconomic conditions, also investigating the extent to which the association is affected by familial risk factors. METHODS: This total-population register-based cohort study included 333,999 full sisters, born between 1962 and 1980. PCOS and comorbidity diagnoses were measured at age 17-45 years through national hospital register data from 1997 to 2011, and complemented with information on the study subjects´ early-life and social characteristics. In the main analysis, sister fixed effects (FE) models were used to control for all time-invariant factors that are shared among sisters, thereby testing whether the association between PCOS and examined comorbidities is influenced by unobserved familial environmental, social or genetic factors. RESULTS: Three thousand five hundred seventy women in the Sister sample were diagnosed with PCOS, of whom 14% had obesity, 8% had depression, 7% had anxiety and 4% experienced sleeping, sexual and eating disorders (SSE). Having PCOS increased the odds of obesity nearly 6-fold (adjusted OR (aOR): 5.9 [95% CI:5.4-6.5]). This association was attenuated in models accounting for unobserved characteristics shared between full sisters, but remained considerable in size (Sister FE: aOR: 4.5 [95% CI: 3.6-5.6]). For depression (Sister FE: aOR: 1.4 [95% CI: 1.2-1.8]) and anxiety (Sister FE: aOR: 1.5 [95% CI: 1.2-1.8), there was a small decrease in the aORs when controlling for factors shared between sisters. Being diagnosed with SSE disorders yielded a 2.4 aOR (95% CI:2.0-2.6) when controlling for a comprehensive set of individual-level confounders, which only decreased slightly when controlling for factors at the family level such as shared genes or parenting style. Accounting for differences between sisters in observed early-life circumstances influenced the estimated associations marginally. CONCLUSION: Having been diagnosed with PCOS is associated with a markedly increased risk of obesity and sleeping, sexual and eating disorders, also after accounting for factors shared between sisters and early-life conditions.

Early Life Factors and Polycystic Ovary Syndrome in a Swedish Birth Cohort.

Polycystic ovary syndrome (PCOS) is a medical condition with important consequences for women's well-being and reproductive outcomes. Although the etiology of PCOS is not fully understood, there is increasing evidence of both genetic and environmental determinants, including development in early life. We studied a population of 977,637 singleton women born in in Sweden between 1973 and 1995, followed sometime between the age 15 and 40. The incidence of PCOS was measured using hospital register data during 2001-2012, complemented with information about the women's, parents' and sisters' health and social characteristics from population and health care registers. Cox regression was used to study how PCOS is associated with intergenerational factors, and a range of early life characteristics. 11,594 women in the study sample were diagnosed with PCOS during the follow-up period. The hazard rate for PCOS was increased 3-fold (HR 2.98, 95% CI 2.43-3.64) if the index woman's mother had been diagnosed with PCOS, and with 1.5-fold (HR 1.51, 95% CI 1.39-1.63) if their mother had diabetes mellitus. We found associations of PCOS with lower (<7) one-minute Apgar score (HR 1.19, 95% CI 1.09-1.29) and with post-term birth (HR 1.19, 95% CI 1.13-1.26). Furthermore, heavy (10+ cigarettes/day) maternal smoking (HR 1.30, 95% CI 1.18-1.44) and maternal obesity (HR 1.90, 95% CI 1.62-2.36) were strongly associated with PCOS. This study finds support for the heritability and fetal origins of PCOS. Risk of PCOS could be reduced by further emphasizing the importance of maternal and early life health.

Early life exposure to cigarette smoking and adult and old-age male mortality: Evidence from linked US full-count census and mortality data.

BACKGROUND: Smoking is a leading cause of premature death across contemporary developed nations, but few longitudinal individual-level studies have examined the long-term health consequences of exposure to smoking. OBJECTIVE: We examine the effect of fetal and infant exposure to exogenous variation in smoking, brought about by state-level cigarette taxation, on adulthood and old-age mortality (ages 55-73) among cohorts of boys born in the United States during the 1920s and 1930s. METHODS: We use state-of-the-art methods of record linkage to match 1930 and 1940 US full-count census records to death records, identifying early life exposure to the implementation of state-level cigarette taxes through contemporary sources. We examine a population of 2.4 million boys, estimating age at death by means of OLS regression, with post-stratification weights to account for linking selectivity. RESULTS: Fetal or infant exposure to the implementation of state cigarette taxation delayed mortality by about two months. Analyses further indicate heterogenous effects that are consistent with theoretical expectations; the largest benefits are enjoyed by individuals with parents who would have been affected most by the tax implementation. CONCLUSIONS: Despite living in an era of continuously increasing cigarette consumption, cohorts exposed to a reduction in cigarette smoking during early life enjoyed a later age at death. While it is not possible to comprehensively assess the treatment effect on the treated, the magnitude of the effect should not be underestimated, as it is larger than the difference between having parents belonging to the highest and lowest socioeconomic groups. CONTRIBUTION: The study provides the first estimates of long-run health effects from early life exposure to cigarette smoking.

The Long-Lasting Influenza: The Impact of Fetal Stress During the 1918 Influenza Pandemic on Socioeconomic Attainment and Health in Sweden, 1968-2012.

The 1918 influenza pandemic had not only a massive instant death toll but also lasting effects on its survivors. Several studies have shown that children born in 1919, and thus exposed to the H1N1 virus in utero, experienced worse health and socioeconomic outcomes in older ages than surrounding birth cohorts. This study combines several sources of contemporary statistics with full-population individual-level data for Sweden during 1968-2012 to examine the influence of fetal exposure to the Spanish flu on health, adulthood income, and occupational attainment. For both men and women, fetal exposure resulted in higher morbidity in ages 54-87, as measured by hospitalization. For males, exposure during the second trimester also affected mortality in cancer and heart disease. Overall, the effects on all-cause mortality were modest, with about three months shorter remaining life expectancy for the cohorts exposed during the second trimester. For socioeconomic outcomes, results fail to provide consistent evidence supporting any long-term consequences of fetal exposure. We conclude that although the immediate health effects of exposure to the 1918 pandemic were huge, the long-term effects were modest in size.