Gastroenterology

Gastroenterology

Volume 135, Issue 1, July 2008, Pages 72-81
Gastroenterology

Clinical–Alimentary Tract
Effects of Estrogen With and Without Progestin and Obesity on Symptomatic Gastroesophageal Reflux

https://doi.org/10.1053/j.gastro.2008.03.039Get rights and content

Background & Aims: An association between female hormones and symptomatic gastroesophageal reflux disease (GERD) and may be modified by obesity is suggested but not proven. Factors affecting GERD progression, however, are largely unknown. Methods: At 40 US clinical centers, postmenopausal women with hysterectomy (n = 10,739) were randomly assigned to receive 0.625 mg/d of conjugated equine estrogens or placebo. Women without hysterectomy (n = 16,608) were randomly assigned to receive estrogen plus progestin, given as 0.625 mg conjugated equine estrogens/d plus 2.5 mg medroxyprogesterone acetate/d, or placebo. We performed secondary analyses using data from these trials. Results: After 1 year, there was a trend toward a higher incidence of symptomatic GER among women randomly assigned to the estrogen treatment (4.2%) than with placebo (3.1%). The estrogen plus progestin treatment did not affect this risk. Neither treatment affected the progression of existing GER symptom. There was a dose-response association between baseline obesity, particularly as measured by waist circumference, with more than double the risk of incident symptomatic GER at 1 year among women with the largest waist circumference (≥114 cm) compared with a normal waist circumference (70–80 cm). Weight gain at 1 year was associated with elevated risk of incident symptomatic GER. Weight loss at 1 year alleviated existing GER symptoms. No interaction between hormone therapy and obesity on symptomatic GER was observed. Conclusions: Estrogen treatment alone, but not with progestin, may cause GER symptoms in postmenopausal women. Increasing weight and girth increases the risk of developing GER symptoms, whereas weight loss alleviates existing GER symptoms. This trial was registered at www.clinicaltrials.gov as NCT00000611.

Section snippets

Study Population and Randomization

Detailed eligibility, recruitment methods, study population characteristics, hormone regimens, randomization, blinding, follow-up, and the main outcomes of the WHI hormones trials were published previously.22, 23, 24 Briefly, 27,347 postmenopausal women were recruited from 1993 to 1998 at 40 US clinical centers, primarily by mass mailings and other media announcements. Participants were aged 50–79 years at the initial screening, and were likely to reside in the study area for at least 3 years.

Baseline Characteristics

Among 27,347 randomly assigned women, ≈90% responded to the questions on heartburn symptoms both at baseline and at 1 year and were nearly equal in the active and placebo assignments in both trials (Figure 1). For the estrogen trial, 5549 (58.0%), 2776 (29.0%), 967 (10.1%), and 284 (3.0%) women reported no, mild, moderate, and severe heartburn at baseline, respectively. For the estrogen plus progestin trial, the corresponding figures were 9840 (65.1%), 3951 (26.1%), 1065 (7.0%), and 271 (1.8%).

Discussion

WHI is the first large randomized controlled trial to examine the effect of menopausal hormone therapy on the incidence and progression of symptomatic GER and also the first large prospective study on various measures of obesity to determine the most important physiologic factor for GER. Our data show that estrogen may modestly increase the incidence of symptomatic GER but does not affect its progression, and estrogen plus progestin affects neither the incidence nor the progression of

References (32)

  • J.E. Pandolfino et al.

    Obesity: a challenge to esophagogastric junction integrity

    Gastroenterology

    (2006)
  • D.A. Corley et al.

    Abdominal obesity and body mass index as risk factors for Barrett's esophagus

    Gastroenterology

    (2007)
  • P. Moayyedi et al.

    Gastro-oesophageal reflux disease

    Lancet

    (2006)
  • H. Nordenstedt et al.

    Postmenopausal hormone therapy as a risk factor for gastroesophageal reflux symptoms among female twins

    Gastroenterology

    (2008)
  • G.R. Locke et al.

    A new questionnaire for gastroesophageal reflux disease

    Mayo Clin Proc

    (1994)
  • M. Nilsson et al.

    Prevalence of gastro-oesophageal reflux symptoms and the influence of age and sex

    Scand J Gastroenterol

    (2004)
  • Cited by (24)

    • Environmental - Lifestyle related factors

      2010, Best Practice and Research: Clinical Gastroenterology
      Citation Excerpt :

      The effects of BMI on GORD occurrence seem to be independent of total caloric intake, dietary intake of fibre, fruits and vegetables, or other macro or micronutrients. [33] Weight gain also facilitates GORD occurrence [42] and GORD symptoms may improve after weight loss [45] and bariatric surgery. [46,47] Controversies exist concerning the association between hiatus hernia (HH), GORD and obesity.

    • The Diagnosis of Gastroesophageal Reflux Disease

      2010, American Journal of Medicine
    • Drug-induced esophagitis

      2020, Russian Journal of Evidence-Based Gastroenterology
    • Diabetic neuropathy and clinical practice

      2020, Diabetic Neuropathy and Clinical Practice
    View all citing articles on Scopus

    Supported by Wyeth and by the National Heart, Lung, and Blood Institute, National Institutes of Health, U.S. Department of Health and Human Services through contracts N01WH22110, 24152, 32100-2, 32105-6, 32108-9, 32111-13, 32115, 32118-32119, 32122, 42107-26, 42129-32, and 44221.

    The National Institutes of Health governed the overall design and conduct of the WHI study and approved the manuscript. Wyeth supplied study drugs but did not participate in any aspect of the aforementioned.

    All authors declare that they have no conflict of interest to disclose.

    View full text