Hormone Replacement Therapy in Endometrial Cancer Survivors: A Meta-Analysis

Abstract

The purpose of this study is to investigate the effect of hormone therapy (HT) on the oncological outcomes of endometrial cancer (EC) survivors. A systematic literature review was conducted in July 2021 to identify studies detailing the effect size for the relationship between HT use in EC and oncological outcomes (survival and disease recurrence). This included studies that evaluated the different recurrence rates among women treated for EC who subsequently underwent HT and those who did not. The collected studies were evaluated for quality, heterogeneity, and publication bias, and a pooled odds ratio (OR) or hazard ratio (HR) was calculated with a confidence interval of 95% (95% CI). In total, 5291 studies were collated, and after the review process, one randomized trial and seven observational studies were included, comprising 1801 EC survivors treated with HT and 6015 controls. The time-dependent analysis could be conducted for four studies, and considering the disease-free survival, the pooled HR of 0.90 (95% CI 0.28 to 2.87) showed no significant differences. However, among Black American women treated with continuous estrogen HT, the HR was 7.58 (95% CI 1.96 to 29.31), showing a significantly increased risk of recurrence for women in this ethnic group. Considering the pooled OR of all included studies 0.63 (95% CI 0.48 to 0.83), a significantly reduced risk of recurrence was found among EC survivors treated with HT. Considering the type of HT, the most risk-reducing was combined estrogen and progestin therapy and the cyclic regimen. Although supporting evidence is based mainly upon observational studies, evidence of no increased risk or even decreased risk was generally found, apart from in Black American women where a significantly increased recurrence risk was evident. The data are rather reassuring for the short-term administration of HT to symptomatic EC survivors. Future studies with a longer follow-up are necessary to better clarify the long-term effects of HT.

GCIG-Consensus guideline for Long-term survivorship in gynecologic Cancer: A position paper from the gynecologic cancer Intergroup (GCIG) symptom benefit committee

“…A meta-analysis that investigated associations of hormone replacement therapy on oncologic outcomes of endometrial cancer survivors showed a significantly increased recurrence risk in black American women. However, these findings should be interpreted with caution due to several limitations of the meta-analysis including the quality of included studies that were mostly observational, lack of data regarding molecular subtypes of endometrioid carcinoma, and the inclusion of patients with only early stage disease [64]. A short-term administration in symptomatic survivors can be discussed individually.…”

Quantification of Women Who Could Benefit from Hormone Therapy after Endometrial Cancer Treatment: An Analysis of SEER Data

“…The main reasons for avoiding HT after surgical removal of stage I low-grade EC are essentially unproven. There is no evidence in vivo that, after surgery, estrogens stimulate the growth of residual microscopic cancer cells [ 5 , 20 ], or that adjuvant therapy targeted to the estrogen pathways, as in breast cancer, has any clinical benefit [ 21 ]. Metastatic EC cells has reduced estrogen receptor expression [ 22 ].…”

“…The typical surgical management of EC comprises total hysterectomy and bilateral salpingo-oophorectomy, leading to hesitation in surgical menopause in pre-menopausal patients. The hazards associated with hormone therapy (HT) use in stage I or II EC survivors were the object of a recent meta-analysis [ 5 ]. The probability of EC recurrence was not increased by HT per survival analysis (HR 0.90, CI.95 0.28 to 2.87) [ 5 ].…”

“…The hazards associated with hormone therapy (HT) use in stage I or II EC survivors were the object of a recent meta-analysis [ 5 ]. The probability of EC recurrence was not increased by HT per survival analysis (HR 0.90, CI.95 0.28 to 2.87) [ 5 ]. The analyses, when stratified by tumor stage, hormone therapy type, timing and duration, revealed the same pattern of effects.…”

“…The analyses, when stratified by tumor stage, hormone therapy type, timing and duration, revealed the same pattern of effects. The recurrence incidence related to HT was considerably higher in black American women (HR 7.58, CI.95 1.96 to 29.31) [ 5 ].…”