Polycystic ovary syndrome – burden and adverse outcomes

Subramanian, Anuradhaa (2023). Polycystic ovary syndrome – burden and adverse outcomes. University of Birmingham. Ph.D.

Preview

Subramanian2023PhD.pdf
Text
Available under License All rights reserved.
Download (2MB) | Preview

Abstract

Background
Polycystic ovary syndrome (PCOS) is the most common, yet underdiagnosed, endocrine disorder in women of reproductive age, posing lifelong threats to their health with limited therapeutic options. Within UK primary care, there is a lack of evidence exploring the extent of missed PCOS diagnosis and possible ethnic variation in the incidence of PCOS. Furthermore, there is lack of (conclusive) evidence on the burden of PCOS including trends in the incidence of impaired glucose regulation outcomes, risk of adverse obstetric outcomes and susceptibility to COVID-19. Finally, the effectiveness of combined oral contraceptive pills (COCP), commonly prescribed for the management of PCOS symptoms, for longer term benefits such as prevention of impaired glucose regulation has not been explored. In this doctoral thesis, I undertook a series of retrospective studies using UK primary and secondary care data to address these research gaps.

Methods
A retrospective cohort of all eligible patients registered within the Clinical Practice Research Datalink (CPRD) Gold database between 1995 and 2019 was used to explore the incidence and prevalence trends of confirmed and possible PCOS diagnosis (based on relevant symptom codes) to estimate the extent of missed diagnosis, and the incidence estimates were stratified by ethnic subgroups. In subgroups of women with confirmed and possible PCOS diagnosis, incidence trends of type 2 diabetes, impaired glucose regulation (IGR) and gestational diabetes mellitus (GDM) were estimated. Using CPRD Gold Pregnancy Register and linked Hospital Episode Statistics data, pregnancies of women with PCOS between 1997 and 2020 were age matched to pregnancies of women without PCOS to observe the odds of four primary outcomes among the two groups of pregnancies: (1) preterm delivery, (2) mode of delivery, (3) high and low birthweight, and (4) stillbirth. Using contemporaneous data from The Health Improvement Network (THIN) provided by Cegedim (January-July 2020), the hazard of confirmed or suspected COVID-19 was estimated among women with PCOS compared to an age matched cohort of women without PCOS. Finally, using a nested case-control design of a base cohort of women with PCOS identified from THIN, women with and without incident development of impaired glucose regulation were matched, and the odds of COCP prescription within a predefined exposure window was estimated.

Results
The incidence and prevalence of PCOS rose sharply in the year 2004, followed by stabilisation of the incidence rate. In addition to confirmed diagnosis, inclusion of symptom codes representing Rotterdam criteria resulted in 299 (95% CI, 198–299) missed PCOS diagnoses per 100,000 person-years. The prevalence of PCOS was highest among South Asians followed by Afro-Caribbeans. The incidence of type 2 diabetes, IGR and GDM has been rising in women with PCOS. Pregnancies of women with PCOS were at an increased risk of preterm and operative (emergency caesarean, elective caesarean and instrumental vaginal) delivery [adjusted OR: 1.11 (95% CI, 1.06-1.17), 1.10 (1.05-1.15), 1.07 (1.03-1.12), 1.04 (1.00-1.09), respectively]. Women with PCOS had a 28% increased risk of COVID-19 [adjusted HR: 1.28 (95% CI, 1.05-1.561)]. Women with PCOS and COCP use had a reduced risk of impaired glucose regulation [adjusted OR: 0.72, (95% CI, 0.59–0.87)].

Conclusion
There is a high level of missed PCOS diagnosis in primary care and an increasing ethnic disparity in the incidence of PCOS. The increased risk of adverse obstetric outcomes and susceptibility to COVID-19 should be clearly conveyed to women with PCOS. Future investigations should explore barriers to care and management of women with PCOS, especially from ethnic minority communities, and should examine the efficacy of COCP in prevention of impaired glucose regulation in a randomized controlled trial setting.

Type of Work:

Thesis (Doctorates > Ph.D.)

Award Type:

Doctorates > Ph.D.

Supervisor(s):