Age at menopause and hormone replacement therapy as risk factors for head and neck and oesophageal cancer

Abstract

There were ~986,000 cases of head and neck cancer (HNC) and oesophageal cancer diagnosed worldwide in 2012. The incidence of these types of cancer is much higher in males than females, although this disparity decreases in the elderly population, suggesting a role for hormones as a risk factor. This systematic review investigates the potential role of female hormones [age at menopause and use of hormone replacement therapy (HRT)] as risk factors for HNC/oesophageal squamous cell carcinoma (SCC). The electronic databases MEDLINE, Web of Science, EMBASE and Cochrane were searched. Only studies with at least 50 cases of HNC/oesophageal SCC, with data on age at menopause, smoking, alcohol, age and socioeconomic status or educational attainment, were included. The Newcastle Ottawa Scale was used for assessing risk of bias. Eight studies met the inclusion criteria (5 oesophageal SCC, 2 HNC and 1 combined oesophageal SCC and HNC). HRT was shown to reduce the risk of HNC (HR, 0.78; 95% CI, 0.61-0.99) in one study. Our results showed that earlier age at menopause is a risk factor for oesophageal SCC, with women entering menopause at <45 years having double the risk of those entering menopause at age >50 years. Similar, but less striking, results were observed for HNC. HRT was found to reduce the risk of HNC/oesophageal SCC, but the evidence is inconclusive. We, therefore, recommend that consideration should be given to collecting data on reproductive factors and exposure to HRT, as routine practice, in future epidemiological and clinical studies of these cancers. The concept of oestrogen deficiency as a risk for HNC/oesophageal SCC deserves further exploration in future laboratory and clinical studies.

Interaction of Estradiol and Endoplasmic Reticulum Stress in the Development of Esophageal Carcinoma

“…There are sex differences in the development of esophageal cancer, and women who underwent resection has a higher overall survival rate than men ( 9 ). The known causes (such as smoking, obesity, etc.)…”

“…Previous report showed that the increased risk of esophageal cancer is related to the decrease in estrogens level ( 6 ). Early menopause increases the risk factors for esophageal squamous cell carcinoma ( 9 ). It has been shown that premenopausal female patients have a prolonged survival than postmenopausal patients and that female ESCC patients with higher serum estradiol level have a favorable survival rate ( 10 ).…”

“…The identified risk factors for esophageal cancer also cannot fully explain this gender difference and may be related to sex chromosome mechanism. However, the epidemiological studies (8)(9)(10) and some preclinical studies indicate that sex hormones might play an important role in esophageal cancer. Sex steroids such as estrogens contribute to the physiological maturation and cell proliferation of estrogendependent tissues, such as breast, ovary, and endometrium (11,12).…”

Anthropometry, body fat composition and reproductive factors and risk of oesophageal and gastric cancer by subtype and subsite in the UK Biobank cohort

“…It has been suggested that sex hormones, particularly oestrogens, may protect against the development of oesophageal and gastric cancer [16,17]. Several epidemiological studies have investigated the role of hormonal and reproductive factors in the development of oesophageal and gastric cancer risk [18][19][20][21][22]; however, few prospective studies have examined the association between reproductive factors and risk of oesophageal and gastric cancer by subtype and subsite and the published findings are inconsistent [23][24][25][26][27].…”

Focus on patients with early esophageal cancer—a prognostic nomogram

“…In general, the impact of marital status on patients is achieved through changes of sex hormones (24)(25)(26), which has often been shown in endocrine diseases, such as thyroid cancer (27), breast cancer, and melanoma (28). A review mentioned that estrogen level was a contributing factor in the pathogenesis of esophageal SCC, and hormone replacement therapy might help reduce the risk of esophageal SCC (29). A prospective cohort study (30) showed that moderate expression of estrogen receptor β (ERβ) was associated with increased survival in patients with gastroesophageal junction cancer.…”