TY - JOUR

T1 - The influence of hormone therapies on type I and II endometrial cancer

T2 - A nationwide cohort study

AU - Mørch, Lina S.

AU - Kjær, Susanne K.

AU - Keiding, Niels

AU - Løkkegaard, Ellen

AU - Lidegaard, Øjvind

PY - 2016/3/15

Y1 - 2016/3/15

N2 - The influence of hormone therapy (HT) on risk for endometrial cancer is still casting which type of HT the clinicians recommend. It is unrevealed if HT has a differential influence on Type I versus Type II endometrial tumors, and little is known about the influence of, e.g., different routes of administration and about the influence of tibolone. We followed all Danish women aged 50–79 years without previous cancer or hysterectomy (n = 914,595) during 1995–2009. From the National Prescription Register, we computed HT exposures as time-dependent covariates. Incident endometrial cancers (n = 6,202) were identified from the National Cancer Registry: 4,972 Type I tumors and 500 Type II tumors. Incidence rate ratios (RRs) and 95% confidence intervals (Cls) were estimated by Poisson regression. Compared with women never on HT, the RR of endometrial cancer was increased with conjugated estrogen: 4.27 (1.92–9.52), nonconjugated estrogen: 2.00 (1.87–2.13), long cycle combined therapy: 2.89 (2.27–3.67), cyclic combined therapy: 2.06 (1.88–2.27), tibolone 3.56 (2.94–4.32), transdermal estrogen: 2.77 (2.12–3.62) and vaginal estrogen: 1.96 (1.77–2.17), but not with continuous combined therapy: 1.02 (0.87–1.20). In contrast, the risk of Type II tumors appeared decreased with continuous combined therapy: 0.45 (0.20–1.01), and estrogen therapy implied a nonsignificantly altered risk of 1.43 (0.85–2.41). Our findings support that continuous combined therapy is risk free for Type I tumors, while all other hormone therapies increase risk. In contrast, Type II endometrial cancer was less convincingly associated with hormone use, and continuous combined therapy appeared to decrease the risk.

AB - The influence of hormone therapy (HT) on risk for endometrial cancer is still casting which type of HT the clinicians recommend. It is unrevealed if HT has a differential influence on Type I versus Type II endometrial tumors, and little is known about the influence of, e.g., different routes of administration and about the influence of tibolone. We followed all Danish women aged 50–79 years without previous cancer or hysterectomy (n = 914,595) during 1995–2009. From the National Prescription Register, we computed HT exposures as time-dependent covariates. Incident endometrial cancers (n = 6,202) were identified from the National Cancer Registry: 4,972 Type I tumors and 500 Type II tumors. Incidence rate ratios (RRs) and 95% confidence intervals (Cls) were estimated by Poisson regression. Compared with women never on HT, the RR of endometrial cancer was increased with conjugated estrogen: 4.27 (1.92–9.52), nonconjugated estrogen: 2.00 (1.87–2.13), long cycle combined therapy: 2.89 (2.27–3.67), cyclic combined therapy: 2.06 (1.88–2.27), tibolone 3.56 (2.94–4.32), transdermal estrogen: 2.77 (2.12–3.62) and vaginal estrogen: 1.96 (1.77–2.17), but not with continuous combined therapy: 1.02 (0.87–1.20). In contrast, the risk of Type II tumors appeared decreased with continuous combined therapy: 0.45 (0.20–1.01), and estrogen therapy implied a nonsignificantly altered risk of 1.43 (0.85–2.41). Our findings support that continuous combined therapy is risk free for Type I tumors, while all other hormone therapies increase risk. In contrast, Type II endometrial cancer was less convincingly associated with hormone use, and continuous combined therapy appeared to decrease the risk.

KW - endometrial cancer

KW - types of endometrial cancer

KW - hormone therapy

KW - types of hormone replacement therapy

U2 - 10.1002/ijc.29878

DO - 10.1002/ijc.29878

M3 - Journal article

C2 - 26421912

VL - 138

SP - 1506

EP - 1515

JO - International Journal of Cancer

JF - International Journal of Cancer

SN - 0020-7136

IS - 6

ER -