P-642 Estrogen deprivation and related risks in primary ovarian insufficiency with various hormone therapy initiation time points - evaluating 122,785 Asian women
Authors: Lee H J , Yu E H , Kim I , Cho J R , Joo J K 
Published: June 2023

Abstract

Study question
Does the initiation time point and/or duration of hormone therapy affect the long-term health consequences in primary ovarian insufficiency (POI)?

Summary answer
POI women with immediate hormone therapy following their diagnosis showed significantly reduced risk of metabolic syndrome and dyslipidemia, and such effect magnified with aging.

What is known already
POI women are exposed to extended duration of estrogen deficiency and premature aging, consequently associated with higher risks of cardiovascular, metabolic, osteoporotic and neurodegenerative diseases. The first line of treatment is hormone therapy (HT), preferably until the age of natural menopause. “Timing hypothesis” in terms of hormone replacement therapy (HRT) in menopause has globally changed the treatment protocol, but its evidence in POI is scarce.

Study design, size, duration
This population-based retrospective cohort study included 122,785 women registered to the National Health Insurance in South Korea from 2009 to 2015. The study group with POI diagnosis contained 24,557 women, determined by the International Classification of Disease, tenth revision (ICD-10) code E283 in the database. Women aged more than 40 years with the E283 code were considered being previously-diagnosed POI. The 1:4 age-matching control group with the systematic random-sampling method included 98,228 women.

Participants/materials, setting, methods
The participants’ demographic data, diagnosis codes, use of inpatient and outpatient services, pharmacy dispensing claims and mortality data were retrieved and statistically analyzed. According to their use of HT, the study group was further divided into two groups: with (n = 13,240) or without HT (n = 11,317); their routine health check-up data collected in the database were then compared. In all analysis, a p-value &lt;0.05 was considered statistically significant.

Main results and the role of chance
Compared to the control group, POI women had significantly lower body mass index (BMI), blood pressure, serum total cholesterol and triglyceride (TG), but the incidence rate ratio (IRR) was significantly higher in POI regarding thyroid diseases, type 2 diabetes, dyslipidemia, hypertension, osteoporosis and cardiovascular diseases (IRR with 95% confidence interval (CI) of 1.731[1.691; 1.772], 1.300[1.260; 1.342], 1.499[1.470; 1.529], 1.100[1.071; 1.129], 2.449[2.388;2.513] and 1.468[1.392; 1.547], respectively). Among POI women overall, the HT users had significantly lower BMI, lower systolic blood pressure but similar diastolic blood pressure, and lower serum total cholesterol and TG, compared to the non-users. In terms of IRRs for chronic diseases, the HT users under the age of 40 years did not show any statistically significant difference in comparison to the non-users; however, the HT users aged more than 40 years had significantly lower IRRs for type 2 diabetes, dyslipidemia and hypertension compared to the non-users (0.876[0.822; 0.933], 0.873[0.840; 0.907], 0.849[0.805; 0.896], respectively). Such effect became more statistically vivid when the participants grew older (IRR[95% CI] of 0.849[0.749; 0.963] for thyroid diseases; 0.806[0.708; 0.917] for type 2 diabetes; 0.652[0.592; 0.718] for dyslipidemia; 0.739[0.662; 0.825] for hypertension; 0.835[0.752; 0.928] for osteoporosis; and 0.890[0.728; 1.089] for cardiovascular disease, respectively).

Limitations, reasons for caution
The current study relied on the health insurance claim data which did not include detailed patient medical record including menstruation pattern and obstetrical/gynecological histories. Also, critical biochemical assay results such as anti-mullerian hormone or pituitary hormones were not available because they were not covered by the national health insurance program.

Wider implications of the findings
Agreeing with the previous literature, the immediate use of HT is associated with the reduced incidence of chronic diseases in POI women, and its extended use exerts more significant results with aging. If acknowledged early and initiated with HT, previously-inevitable health risks with POI could be conceivably compensated.

Trial registration number
The current study was supported by Biomedical Research Institute Grant (#202201970001), Pusan National University Hospital.