Sex hormone profile and endometrial cancer risk in primary biliary cirrhosis: a case-control study

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Abstract

Objective: To investigate the sex hormone profile and endometrial histology in primary biliary cirrhosis (PBC). Study design: A prospective case-control study. Twenty-two females with PBC and 22 sex- and age-matched healthy controls underwent complete gynaecological examination including endometrial biopsy and a sex hormone serological profile including: oestrone, 17-β oestradiol, testosterone, progesterone, dehydroepiandrosterone sulphate (DHEA-S) and sex hormone binding protein (SHBG). The sex hormone profile was evaluated with respect to the body mass index (BMI), anthropometric measurements and endometrial histological/cytological patterns in each case. Statistical analysis was done with the chi-squared method, Student’s t-test for unpaired data, linear regression analysis, Spearman’s rank correlation test and stepwise multiple regression analysis. Results: The BMI was comparable in the two groups, while PBC cases had significantly smaller subscapular, waist, bicipital, tricipital and calf fold measurements than controls. Testosterone serum levels were significantly lower in PBC cases than in controls (0.9±0.6 versus 1.4±0.7 mmol/l, P<0.03), whereas SHBG was significantly higher than in controls (88.6±72.1 versus 63.6±27.6, P<0.005). No significant differences between the two groups were found for oestrone, 17-β oestradiol, DHEA-S, and progesterone levels. No difference patterns were observed in endometrial histological/cytological patterns. Multiple regression analysis identified SHBG as an independent variable associated with PBC. Conclusions: Changes in sex hormone profile are secondary to hepatic dysfunction in PBC. Females with PBC do not appear to carry a higher risk of endometrial cancer.

Introduction

Endocrinological dysfunctions are common in males with cirrhosis. Such conditions are characterised by low serum levels of testosterone and high levels of oestrone and oestradiol [1], [2]. This endocrinological pattern accounts for the clinical signs of “feminisation”, especially in alcoholic cirrhosis. Females with chronic alcoholic hepatitis show evidence of early menopause [3].

Primary biliary cirrhosis (PBC) is a chronic cholestatic liver disease that typically occurs in females, with a female/male ratio of 10:1 [4]. Its clinical presentation is around middle age, commonly in the peri-menopausal period [5]. Although the contribution of hormone factors may be relevant in the clinical expression of the disease, few reports in the literature deal with the role of endocrinological alterations in PBC. Becker et al. [6] found significantly higher levels of androstanedione and lower concentrations of oestrone and dehydroepiandrosterone sulphate (DHEA-S) in PBC patients than in controls. We previously found significantly higher levels of DHEA-S in PBC patients than in a group of females with cryptogenic chronic liver disease [7]. However, another indirect demonstration of endocrinological dysfunction in PBC comes from the paper by Stellon et al. [8], who found a high incidence of hysterectomies, curettages and menstrual cycle abnormalities in the history of PBC patients. Moreover, recent studies have shown an increased incidence of extrahepatic malignancies in PBC patients, including endometrial cancer [9], [10].

The aim of the present study was therefore to investigate the sex hormone profile and the endometrial histological pattern in PBC.

Section snippets

Study design

A prospective case-control study was performed.

Statistical analysis

Data were analysed using the chi-squared test, Student’s t-test for unpaired data, linear regression analysis and Spearman’s rank correlation test, as appropriate. Stepwise multiple regression analysis was carried out for each endocrine parameter to determine which characteristics were independently associated with PBC.

Analyses were performed with the EPI-Info 6.04 computer program supplied by the Centers for Disease Control of Atlanta (Georgia, USA) and the Statistical Package for the Social

Results

The body mass index (BMI) was comparable in the two groups, (26.6±2.6 versus 25.0±5.2, P non-significant, while subscapular (P<0.0001), tricipital (P<0.0004), hip (P<0.05), and trunk (P<0.05) folds were found significantly smaller in PBC cases than in controls (Table 2). No statistical correlation was found between the anthropometric measurements and each endocrine parameter, however.

Five of the 16 post-menopausal PBC patients had SHBG above normal, while this was only true of 1 control (P

Discussion

The results of this case-control study indicate that PBC patients present minimal differences in sex hormone profile compared to sex- and age-matched controls, consisting essentially in higher serum SHBG levels and lower serum testosterone levels. Stepwise multiple linear regression analysis identified SHBG as the only variable associated with PBC, suggesting that this is the most relevant change observed. The higher SHBG levels in PBC patients is more compatible with their hepatic dysfunction

Acknowledgements

This work was partially supported by a Ministerial grant (MURST 60%) and was presented as an oral communication at the 7th United European Gastroenterology Week, Rome, Italy 13–17 November 1999 (prize winner).

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