Endometrial Carcinoma Risks among Menopausal Estrogen plus Progestin and Unopposed Estrogen Users in a Cohort of Postmenopausal Women

Lacey, J.; Brinton, Louise A.; Lubin, Jay H.; Sherman, Mark E.; Schatzkin, Arthur; Schairer, Catherine

doi:10.1158/1055-9965.epi-05-0111

Cited by 87 publications

(84 citation statements)

References 70 publications

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“…11 Of the 6 studies that were included in the summary estimate, the only study 10 that reported a significantly increased risk allowed for previous unopposed estrogen use, which is a strong endometrial cancer risk factor. Our recent cohort study also reported significantly increased risks associated with sequential regimens, 14 which were defined as progestin taken for <15 days per month but could have included progestin used for <10 days per month. Adding the NIH-AARP findings to the summary estimate reported in the MWS may decrease the magnitude of the association between endometrial cancer and ever-use of sequential regimens that contain !10 days of progestin per cycle.…”

Section: Discussionmentioning

confidence: 92%

“…Other cohort 14 and case-control 7,9,10,12,13,15,21-23 studies have employed variable exposure definitions for estrogen plus progestin. The studies collectively captured different snapshots of the hormone therapy usage patterns that have changed substantially since the middle 1970s.…”

Section: Discussionmentioning

confidence: 99%

“…Alternatively, if vaginal bleeding prompts clinical examinations that detect endometrial lesions before invasion or leads to successful hormone treatment, then former use may be associated inversely with endometrial cancer. These dynamics 14 open doors for detection bias or confounding by indication to influence the observed associations. Future studies that systematically collect data on reasons for initiation and cessation of hormone therapy (plus subsequent gynecologic conditions) could address these issues.…”

Section: Discussionmentioning

confidence: 99%

“…Detection, treatment, and censoring of candidate endometrial cancer precursor lesions in randomized clinical trials of menopausal hormone therapy make direct comparisons between observational studies and clinical trials difficult for menopausal hormone therapy and endometrial cancer. 14 It seems unlikely that future randomized clinical trials will be designed specifically to evaluate endometrial cancer risks associated with long-duration use of today's most common estrogen-based and progestinbased menopausal hormone therapies. Therefore, continued follow-up of observational studies will provide useful data for risk assessment.…”

Section: Discussionmentioning

confidence: 99%

“…8 Compared with no use of hormone therapy, the use of continuous regimens has been associated with no increase 6,9 or a decreased [10][11][12] risk of endometrial cancer. Three recent epidemiologic studies reported statistically significant increased endometrial cancer risks [13][14][15] in women who used continuous estrogen plus progestin. Slightly different exposure definitions, low statistical power for specific regimens, or chance may explain the discrepancies across studies.…”

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confidence: 99%

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Endometrial cancer and menopausal hormone therapy in the National Institutes of Health‐AARP Diet and Health Study cohort

Lacey

Leitzmann

Chang

et al. 2007

Cancer

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BACKGROUND.Menopausal hormone therapy formulations for women without hysterectomy have included estrogen plus progestin for years, but endometrial cancer risks associated with the use of sequential and continuous estrogen‐plus‐progestin regimens remain unclear.METHODS.The National Institutes of Health‐AARP Diet and Health Study included 73,211 women who were ages 50 years to 71 years at baseline and who completed 2 questionnaires (1995–1996 and 1996–1997). Linkage to state cancer registries and mortality indices identified 433 incident endometrial cancers through 2000. Using proportional hazards regression, the authors estimated relative risks (RRs) and 95% confidence intervals (95% CIs) relative to never‐use of hormone therapy.RESULTS.In 51,312 women who never used hormones or only used estrogen‐plus‐progestin regimens at doses consistent with current practice, neither sequential estrogen plus progestin (daily estrogen plus progestin for 10–14 days per cycle: RR, 0.74; 95% CI, 0.39–1.40) nor continuous estrogen plus progestin (daily estrogen plus progestin for ≥20 days per cycle: RR, 0.80; 95% CI, 0.55–1.15) had any statistically significant association with endometrial cancer. Long durations (≥5 years) of sequential regimen use (RR, 0.79; 95% CI, 0.38–1.66) and of continuous regimen use (RR, 0.85; 95% CI, 0.53–1.36) were not associated with endometrial cancer.CONCLUSIONS.Confirmation that these estrogen‐plus‐progestin regimens neither increase nor decrease the risk of endometrial cancer could influence menopausal symptom management for women who are considering estrogen‐plus‐progestin therapy. Cancer 2007. Published 2007 by The American Cancer Society.

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Section: Discussionmentioning

confidence: 92%

Section: Discussionmentioning

confidence: 99%

Section: Discussionmentioning

confidence: 99%

Section: Discussionmentioning

confidence: 99%

mentioning

confidence: 99%

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Endometrial cancer and menopausal hormone therapy in the National Institutes of Health‐AARP Diet and Health Study cohort

Lacey

Leitzmann

Chang

et al. 2007

Cancer

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Genetic susceptibility to rheumatoid arthritis: An emerging picture

Barton¹,

Worthington²

2009

Arthritis & Rheumatism

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Endometrial cancer is a disease primarily driven by cumulative exposure to estrogen unopposed by progesterone. Reproductive factors associated with changes in endogenous hormone levels and use of exogenous hormones such as postmenopausal hormones influence the risk of disease. The authors used the Nurses' Health Study, comprised of 121,700 nurses, to assess the above associations. Over 28 years of follow‐up, 778 adenocarcinoma cases were diagnosed and 1,850,078 person‐years were accumulated. Cox proportional hazards models were used to estimate relative risks (RR) and 95% confidence intervals (CI). A late age at menarche decreased the risk independent of body mass index (BMI) (P‐trend = 0.02). A late age at menopause increased cancer risk (P‐trend = 0.0003). An advanced age at last birth reduced the risk (P‐trend < 0.0001), however, an inverse association with age at first birth and parity diminished after adjustment for age at last birth. Compared with never users, an increased risk was observed among long‐term (≥5 years) users of both estrogen (E) (RR = 7.67, 95% CI: 5.57, 10.57) and combined estrogen plus progesterone (E+P) (RR = 1.52, 95% CI: 1.03, 2.23). Normal‐weight (BMI < 25) women had the highest risk following E or E+P use (P‐interaction‐E = 0.0008, P‐interaction‐E+P = 0.02). The findings from this study underscore the importance of hormonal mechanisms in endometrial carcinogenesis.

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Disease and host characteristics as predictors of time to first bone metastasis and death in men with progressive castration‐resistant nonmetastatic prostate cancer

Smith

Cook

Lee

et al. 2010

Cancer

164

115

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Background The natural history of castration-resistant nonmetastatic prostate cancer is poorly defined. Methods We used data from 331 subjects in the placebo group of a randomized controlled trial to evaluate the relationships between disease and host characteristics with time to first bone metastases in men with prostate cancer, rising PSA despite androgen deprivation therapy, and no radiographic evidence of metastases. Relationships between baseline covariates and clinical outcomes were assessed by Cox proportional hazard analyses. Covariates in the model were age, body mass index, prior prostatectomy, prior orchiectomy, Gleason score, performance status, PSA, urinary N-telopeptide, bone alkaline phosphatase, albumin, lactate dehydrogenase, and hemoglobin. Results At 2 years, 46% of subjects had developed bone metastases and 20% had died. Median bone metastasis-free survival was 25 months. In multivariate analyses, baseline PSA ≥ 13.1 ng/mL was associated with shorter overall survival (relative risk 2.34; 95% CI 1.71, 3.21; p<0.0001), time to first bone metastasis (relative risk 1.98; 95% CI 1.43, 2.74; p<0.0001), and bone metastasis-free survival (relative risk 1.98; 95% CI 1.45, 2.70; p<0.0001). PSA velocity was significantly associated with overall and bone metastasis-free survival. Other covariates were not consistently associated with clinical outcomes. Conclusions In men with progressive castration-resistant prostate cancer and no detectable metastases, baseline PSA was significantly associated with time to first bone metastasis, bone metastasis-free survival, and overall survival. Other disease and host characteristics, including body mass index and bone turnover markers, were not consistently associated with clinical outcomes.

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Endometrial Carcinoma Risks among Menopausal Estrogen plus Progestin and Unopposed Estrogen Users in a Cohort of Postmenopausal Women

Cited by 87 publications

References 70 publications

Endometrial cancer and menopausal hormone therapy in the National Institutes of Health‐AARP Diet and Health Study cohort

Endometrial cancer and menopausal hormone therapy in the National Institutes of Health‐AARP Diet and Health Study cohort

Genetic susceptibility to rheumatoid arthritis: An emerging picture

Disease and host characteristics as predictors of time to first bone metastasis and death in men with progressive castration‐resistant nonmetastatic prostate cancer

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