Polycystic ovary syndrome and its association with reproductive cancers in women.

OBJECTIVE

To determine whether individuals with polycystic ovary syndrome (PCOS) are at an increased risk of female reproductive cancers.

DESIGN

A retrospective cohort study was performed using Optum's deidentified Clinformatics Data Mart Database (2000-2022).

SUBJECTS: Females aged 18-50 with no prior reproductive cancer history.

EXPOSURE: Individuals with PCOS, identified through ICD9/10 codes for PCOS and codes for both hirsutism and irregular menses, were matched 1:5 by age and diagnosis month with women without PCOS.

MAIN OUTCOME MEASURES: The outcomes were incident female reproductive cancers, specifically: breast, uterine, ovarian/fallopian tube, and cervical. Stabilized inverse probability of treatment weights (IPTW) were used to control for confounding by race/ethnicity, education, and history of obesity, smoking, infertility, hypertension, hyperlipidemia, diabetes, and hormonal contraception use. The adjusted hazard (HR) of each outcome was calculated using doubly robust IPT-weighted Cox proportional hazards models adjusted for the variables in the IPTW models plus hereditary cancer syndrome. Censoring was performed at the time of diagnosis, date of surgery for the affected organ (e.g., date of hysterectomy for uterine cancer outcome), or end of time in Optum Clinformatics, as appropriate. Sensitivity analyses additionally controlled for medications used to treat medical comorbidities, including metformin, antihypertensives, and statins.

RESULTS

A total of 422,613 patients with PCOS were age-matched to 2,113,065 patients without PCOS, with a mean age of approximately 31 ± 7 years in both groups. At baseline, those with PCOS had a higher prevalence of all medical comorbidities assessed, yet equivalent prevalence of hereditary cancer syndrome (0.2%). Over an average of 3.6 ± 4.1 years of follow-up, those with PCOS had significantly higher hazard of breast cancer (adjusted hazard ratio [aHR] 2.66, 95% confidence interval [CI]: 2.50-2.83), uterine cancer (aHR 5.76, 95% CI: 5.13-6.48), ovarian/fallopian tube cancer (aHR 4.38, 95% CI: 3.90-4.92), and cervical cancer (aHR 2.22, 95% CI: 2.06-2.37). Sensitivity analyses showed similar results for all outcomes.

CONCLUSION

This large nationwide population-based study showed an increased risk of multiple reproductive cancers in reproductive-age women with PCOS compared with those without PCOS. Findings should be considered when determining future screening recommendations.