Polycystic ovary syndrome (PCOS) is among the most common endocrine disorder in women of reproductive age, and is associated with several burdensome comorbidities. Around half of women with PCOS are either unaware of their condition or only become diagnosed a considerable time after symptoms initially manifest. PCOS presents significant challenges for both healthcare professionals and the women affected by the condition. Due to its multifaceted nature, there is currently no straightforward treatment available, and this has been the status quo for decades. Further investigation is needed to understand the etiology of PCOS and how PCOS contributes to socioeconomic and health inequalities. 

This PhD thesis aims to generate new knowledge on intergenerational and early life drivers of PCOS, while contributing to a better understanding of the mechanisms that generate social inequalities in PCOS. The four individual studies are based on register data for large population samples of Swedish women born between 1962 and 1995. 

Study I investigated associations of intergenerational and early life factors with PCOS. Maternal PCOS diagnosis, maternal diabetes mellitus, maternal obesity and heavy maternal smoking (10+ cigarettes/day) were strongly associated with PCOS among offspring. Additionally, lower (<7) one-minute Apgar score and post-term birth were associated with diagnosis of PCOS.

Study II investigated associations between PCOS and several comorbidities, exploring the extent to which these associations are sensitive to familial confounding by exploiting variation between biological sisters. After controlling for some shared familial environmental, social, and genetic risk factors, the findings indicated that women with a PCOS diagnosis had a fourfold increase in the odds of being diagnosed with obesity, a 1.4-fold higher likelihood of experiencing depression or anxiety, and a twofold greater likelihood of developing sleep, sexual, or eating disorders compared to their sisters without PCOS.

Study III focused on labor market attachment trajectories of working age women diagnosed with PCOS. While the majority of women in the study sample entered the labor market with stable employment, those with PCOS were more likely to encounter negative labor market outcomes, such as exclusion from the labor market or prolonged sickness absence. 

Study IV aimed to quantify educational and income-related inequalities and their relation to PCOS diagnosis. Women with low socioeconomic position had highest risk for being diagnosed with PCOS even after controlling for confounding factors. A modifying effect of education on the association of income with PCOS was also observed. 

The findings of this thesis highlight the impact of intergenerational factors and early life conditions on the risk of developing PCOS later in life. In addition to its developmental origins, PCOS leads to disadvantaged labor market attachment trajectories later in life. The thesis also explores the link between a disadvantaged socioeconomic situation and PCOS.

The complexity of working with register data and diagnosed cases of PCOS lies in chronological delays and underdiagnosis. Women whose PCOS diagnosis is not captured by the registries or is only observed later than the onset of the disease may bias estimates obtained from register studies, which is a limitation. Screening for PCOS, particularly among women with risk factors such as obesity, or a family history of the condition, could help identify the disorder earlier. Early detection allows for timely interventions and could also reduce the risk of associated comorbidities such as obesity, type 2 diabetes, cardiovascular disease, and mental health disorders. Integrated care models are needed that address the full spectrum of PCOS-related health and social issues.

Objectives: Polycystic ovary syndrome (PCOS) is an endocrine disorder in women of fertile age which may also affect the labor market attachment. We investigated labor market attachment trajectories among working age women diagnosed with PCOS.

Methods: A cohort of 157,356 women born in 1975–1977 were followed annually between the ages of 30 and 39, using data from Swedish administrative registers. Multinomial logistic regression was employed to assess associations between being diagnosed with PCOS (after the age of 15) and belonging to the identified clusters of labor market attachment trajectories.

Results: Women with PCOS spent less time in employment and were more dependent on sickness benefits during the follow-up time than those without PCOS. Five labor market attachment clusters were identified: stable employment, education into employment, labor market exclusion, continuously unstable position, long-term sickness. Compared to being in the stable employment cluster, women diagnosed with PCOS were more likely to experience long-term sickness [RRR (relative risk ratio): 1.97 (CI: 1.90–2.05)], and education into employment [RRR: 1.11 (CI: 1.07–1.15)].

Conclusion: PCOS can lead to disadvantaged labor market outcomes. Better strategies are needed to prevent economic exclusion among women diagnosed with PCOS.

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.

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.