**1. Introduction**

Sex steroid hormones are essential for normal reproductive health in both sexes. Estrogens in women and androgens in men are crucial for development of sexual organs and regulation of gametogenesis. They also play vital roles in regulating physiological functions of other non-target tissues and organs. For instance, estrogens are involved in the maintenance of bone mass, regulation of lipoprotein synthesis, prevention of urogenital atrophy, regulation of insulin responsiveness, and maintenance of cognitive function.

Sex steroids hormones are also linked with development, progression, or treatment of several cancers that include breast, uterine, prostate, and testicular cancer [1].

Indeed, the correlation between endogenous sex steroid hormones and the risk of developing breast cancer is well described in the literature. Besides, the use of anti-estrogenic therapy is associated with better local control and survival outcome in patients with breast cancer [2].

Esophageal cancer (EC) is the eighth most common cancer and the sixth most common cause of cancer mortality worldwide [3]. Despite developments in treatment modalities, estimated overall five-year survival rate for patients with EC is still poor, one of the characteristic features of EC, especially esophageal adenocarcinoma (EAC) is a persistence gender bias over several decades, in all races and across the world [3–5]. Although EC is not a hormone-dependant tumour, several epidemiological studies suggested that female sex hormones may have a protective role against

the development of this aggressive malignancy [6, 7]. There is mounting evidence that the male predominance associated with oesophageal cancer is age dependent. The gender ratio is at its highest at a younger age, whereas the incidence difference between older men and women is smaller afterwards [8, 9]. This gender ratio seems to have been consistent during the last decades, despite the increasing incidence in EAC.

Several epidemiological studies investigated the possible association between the endogenous and exogenous sex hormonal exposure and EC. Lindblad et al. suggested that the use of HRT was not associated with a reduced risk of EC of any histological type [10]. Similarly, two recent studies examined the association between the use of HRT and the risk of EAC and squamous cell carcinoma (ESCC) in postmenopausal women [11, 12]. Freedman et al. found that the use of HRT was significantly associated with lower risk of ESCC and with a non-significant lower risk of EAC. Moreover, older age at menopause was inversely associated with ESCC. This risk reduction was more evident in women with intact uteri and who received estrogen and progestin containing HRT. Therefore, it was suggested that higher estrogen and progesterone levels may be related inversely to EC and in this way help explain the lower incidence rates in women compared to men [11]. In contrast, another study of 161,086 postmenopausal women involved in the Women's Health Initiative (WHI), showed that the risk of ESCC was only lower among HRT users with a decreased risk mainly among current users of estrogen and progestin containing HRT. No association was observed between the use of HRT and the risk of EAC. Also, no other reproductive or hormonal factors were significantly associated with the risk of either ESCC or EAC [12].

A nested case–control study within a prospective UK cohort and meta-analysis found that women prescribed HRT had a reduced risk of OC (adjusted RR for HRT versus no HRT prescriptions, 0.68, 95% CI 0.53–0.88; p < 0.004) [13]. There were no significant differences in cancer risk by HRT type, estimated duration of HRT use or between past and current users [13]. Recently, the Million Women Study (MWS) by Green et al examined risk of esophageal and gastric cancers in relation to reproductive factors in a large UK cohort [14]. They have shown that risks of both esophageal and gastric cancers were higher in postmenopausal than in pre- or peri-menopausal women, and, among postmenopausal women, risks were higher the younger the women were at menopause [14]. In contrast to some studies where no association of childbearing on the risk of AEC was identified [15], the MWS demonstrated that the association between parity and risk of EC was more significant for ESCC than for EAC and age at menarche was significantly associated with EAC but not ESCC [14]. Green et al therefore suggested that the reduced risks associated with menopausal status and with hormone therapy use are consistent with a hypothesis that exposure to estrogens reduces the risk of EC [14].

On the other hand, in a large population-based cohort of 87, 323 postmenopausal women with breast cancer, the potential effects of tamoxifen (Selective ER modulator mostly acts as an anti-estrogen) used for breast cancer treatment was evaluated. In this study, there was no increase in the risk of developing EC in breast cancer patients who received adjuvant tamoxifen treatment in comparison to the control group [16, 17]. However, a different large population-based study of 138,885 women (by Chandanos et al.) suggested a 60% risk increase of EAC among the exposed group but did not achieve statistical significance. In contrast, there was an increased risk of ESCC and lung cancer observed only in the unexposed cohort, indicating that the confounding factor of smoking might explain the increased incidence during the unexposed period [18].

Interestingly, a dose-dependent risk reduction in EC by breastfeeding was suggested [19]. In a recent study, based on pooled data from several large case–control studies, endogenous reproductive factors and exogenous factors were evaluated in women. Breastfeeding was associated dose-dependently with a reduced risk of

#### *Serum Sex Hormone Profiles in Potentially Resectable Esophageal Cancer DOI: http://dx.doi.org/10.5772/intechopen.95030*

EAC, while parity, menstruation, history of pregnancy, use of oral contraceptives or of HRT were not associated with the risk of developing this tumour [20, 21].

In a cohort of patients with prostate cancer, a reduced risk of EAC but not of ESCC was noted. Hence, it was suggested that a diagnosis of prostate cancer may be linked with aetiological factors that are negatively associated with EAC, or antiandrogen therapy may influence the development of EAC [22]. In contrast, estrogen exposure in a national cohort of men with prostate cancer did not show any reduced risk of a second AEC [23]. Despite these efforts to explain the relation between female reproductive factors and risk of development of EC, the results are rather unclear and contradict each other. This could be partially explained by the fact that the number of women with EC included in those studies was relatively small, which could have the affected potential significance of the results [24].

Recently, it has suggested that the ER system is involved in EC progression and thus may provide a novel target for the treatment of EC [25]. However, there is little known about sex hormones levels in relation to the risk of EC development. In this study we aimed to:

