E0202 - Hormone Replacement Therapy Is Associated With Reduced Risk of Squamous Cell Carcinoma of the Esophagus in Post-Menopausal Women: A Systematic Review and Meta-Analysis

Tuesday, October 25, 2022

3:00 PM – 5:00 PM ET

Location: Crown Ballroom

Presenting Author(s)

Nabil El Hage Chehade, MD

Case Western Reserve University MetroHealth Medical Center
Beachwood, OH

Nabil El Hage Chehade, MD¹, Sara Ghoneim, MD², Serge Baroud, MD³, Sherif Saleh, MS, MD³, Gengqing Song, MD, FACG⁴, Ronnie Fass, MD⁵
¹Case Western Reserve University MetroHealth Medical Center, Beachwood, OH; ²University of Nebraska Medical Center, Omaha, NE; ³MetroHealth Medical Center, Cleveland, OH; ⁴Case Western Reserve University MetroHealth Medical Center, Cleveland, OH; ⁵The Esophageal and Swallowing Center, MetroHealth Medical System, Case Western Reserve University, Cleveland, OH

Introduction: It has been hypothesized that female sex hormones, mainly estrogen, are protective against esophageal cancer. The aim of our systematic review was to determine the association between HRT and either esophageal adenocarcinoma (AC) or squamous cell carcinoma (SCC).

Methods: We performed a review of the literature across major databases including PubMed/MEDLINE, Embase, and Google Scholar in May 2022. Retrospective cohort and case-controlled studies including post-menopausal women who either received or did not receive HRT were eligible for inclusion. The primary endpoint was the association between HRT and esophageal AC or SCC. Subgroup analyses were performed based on the type of HRT used. Results were pooled together using Reviewer Manager 5.4 software.

Results: 6 studies involving 2,403,608 post-menopausal women who either received or did not receive HRT were included in the pooled analysis. Our findings suggest that there was no statistically significant association between HRT use and esophageal AC (OR=0.63, 95% CI [0.36,1.11], P=0.11). Subgroup analysis showed that the rate of esophageal AC was similar between the estrogen only versus estrogen and progesterone group. The test for subgroup differences was not statistically significant (P=0.83, I²=0%). On the other hand, the use of HRT was associated with a statistically significant decrease in the rate of esophageal SCC compared to controls (OR=0.54, 95% CI [0.33, 0.90], P=0.02). The use of combined estrogen and progesterone therapy was associated with a greater decreased risk of esophageal SCC compared to estrogen only therapy (P=0.03, I²=78.9%). Stratified analysis showed that the rate of esophageal cancer in patients receiving HRT was similar between past and current users (OR=1.18, P=0.66). Shorter duration of HRT use were not associated with decreased rate of esophageal cancer as well (OR=0.65, P=0.19). The age at menarche (OR=1.46, P=0.18), menopause (OR=0.99, P=0.99), and first birth (OR=1.08, P=0.84) were not associated with any increased risk of esophageal cancer in women who received HRT.

Discussion: HRT use in post-menopausal women was associated with a reduced risk of esophageal squamous cell carcinoma but not adenocarcinoma. Combined estrogen and progesterone therapy was associated with a greater reduction in the risk of esophageal SCC compared to estrogen only therapy. The duration of HRT use and years of estrogen exposure were not associated with any increased risk of esophageal cancer.

Figure: Forest plots of the association between hormone replacement therapy use and the incidence of esophageal adenocarcinoma (A) or squamous cell carcinoma (B).

Outcome	Subgroup	OR [95% CI]	P-value	Test for Subgroup Differences P (I²%)
AC	Estrogen only	0.59 [0.29, 1.21]	0.15	0.83 (00.0)
AC	Estrogen + Progesterone	0.54 [0.32, 0.90]	0.02	0.83 (00.0)
SCC	Estrogen only	0.52 [0.31, 0.89]	0.02	0.03 (78.9)
SCC	Estrogen + Progesterone	0.27 [0.20, 0.36]	< 0.00001	0.03 (78.9)

Variables		Rate of Esophageal Cancer (/1000)	OR [95% CI]	P-value
Duration of HRT Use	< 10 years	0.142	0.65 [0.35, 1.23]	0.19
	≥ 10 years	0.270
Status of HRT Use	Past Users	0.212	1.18 [0.57, 2.44]	0.66
	Current Users	0.193
Menarche Onset	Early (< 12 years)	0.529	1.46 [0.84, 2.53]	0.18
	Late (≥ 15 years)	0.235
Menopause Onset	Early (< 45 years)	0.243	0.99 [0.23, 4.17]	0.99
	Late (≥ 55 years)	0.319
Age at First Birth	Early (< 20 years)	0.511	1.08 [0.52, 2.23]	0.84
	Late (≥ 30 years)	0.273

Table: (A) Subgroup analysis investigating the association between hormone replacement therapy use and the rates of esophageal adenocarcinoma or squamous cell carcinoma based on the type of HRT used (B) Evaluation of influencing factors affecting the rate of esophageal cancer in post-menopausal women who received hormone replacement therapy.

Abbreviations: HRT, hormone replacement therapy; AC, adenocarcinoma; SCC, squamous cell carcinoma; OR, odds ratio; CI, confidence interval.

Disclosures:

Nabil El Hage Chehade indicated no relevant financial relationships.

Sara Ghoneim indicated no relevant financial relationships.

Serge Baroud indicated no relevant financial relationships.

Sherif Saleh indicated no relevant financial relationships.

Gengqing Song indicated no relevant financial relationships.

Ronnie Fass: Adcock-Ingram – Speaker. AstraZeneca – Speaker. Celexio – Advisor or Review Panel Member. Dexcel – Advisor or Review Panel Member. Eisai – Speaker. GERDcare – Advisor or Review Panel Member. GI Supply – Speaker. Ginger Health – Stock Options. Johnson & Johnson – Speaker. Medicamenta – Speaker. Medtronic – Advisor or Review Panel Member. Phathom Pharmaceuticals – Advisory Committee/Board Member, Consultant. Salix – Grant/Research Support. Takeda Pharmaceuticals – Advisory Committee/Board Member, Speakers Bureau.

Nabil El Hage Chehade, MD¹, Sara Ghoneim, MD², Serge Baroud, MD³, Sherif Saleh, MS, MD³, Gengqing Song, MD, FACG⁴, Ronnie Fass, MD⁵. E0202 - Hormone Replacement Therapy Is Associated With Reduced Risk of Squamous Cell Carcinoma of the Esophagus in Post-Menopausal Women: A Systematic Review and Meta-Analysis, ACG 2022 Annual Scientific Meeting Abstracts. Charlotte, NC: American College of Gastroenterology.