Effect of PPARγ2 Polymorphism and NSAIDs on Acute Alcohol-induced Changes in Serum Estrogens Among Post-menopausal Women

Alcohol-related Breast Cancer in Postmenopausal Women - Effect of PPARG2pro12ala Polymorphism on Female Sex-hormone Levels and Interaction With Alcohol Consumption and NSAID Usage

Postmenopausal women, stratified by a peroxisome proliferator-activated receptor gamma-2 (PPARG) polymorphism, were given the following treatments in a random order with a 5w wash-out period: a 400mg ibuprofen tablet or a placebo tablet; both treatments were followed after 30min by a single acute dose of 0.4g alcohol per kg bw. Serum estrogen levels were measured before and at three timepoints after alcohol intake. It is hypothesized that the acute decrease in estrogen sulphate and other markers of estrogens after alcohol intake is modulated by ibuprofen and by PPARG genotype.

In a pilot human intervention trial we aimed to determine the effect of the PPARG Pro12Ala polymorphism and the PPARγ stimulator, Ibuprofen, on sex-hormone levels following alcohol intake in postmenopausal women. Seven women with PPARG Pro12Ala and 18 PPARG wildtype women were included.The study was performed as a randomised, double-blinded, placebo controlled 2x24 h crossover study. The volunteers were randomised to 1 of 2 groups who got the two treatments in different orders. Treatment 1 was a placebo tablet with water followed after 30min by an alcoholic drink providing 0,4g alcohol per kilogram bw and treatment 2 was an Ibuprofen tablet (400mg) with water followed by the same alcoholic drink. The two treatments were separated by a 5-7 weeks washout period. Alcohol was supplied as 7.7% ethanol in a lime-flavoured drink and was consumed over 15 min. EDTA-plasma was collected 40min before and 30, 60 and 90 min after ethanol intake as well as after 24 hours. Ibuprofen (400mg) was provided together with 100mL water 30min before the ethanol. Urine was collected throughout the 24 hour interval. Serum estrone, estrone sulphate, serum estrogen-binding globulin (SHBG), and ethanol were determined. It is hypothesized that the acute decrease in estrogen sulphate and other markers of estrogens after alcohol intake is modulated by ibuprofen and by PPARG genotype.

Inclusion Criteria:

1. postmenopausal (last menses at least 1 year earlier);
2. having a weekly alcohol use of less than 14 drinks
3. having a BMI of 18-35;

Exclusion Criteria:

1. a history of alcohol abuse
2. alcohol abstaining
3. history of hysterectomy before last menses with preservation of both ovaries (unless a medical confirmation for the postmenopausal status exists or the participant is 60 years or older);
4. major health problems, such as ulcers, heart diseases, diabetes or cancer
5. previous or current use of HRT
6. taking prescription medications that could interfere with the study (i.e. daily use of NSAIDs and/or medication that interact with PPARγ e.g. cholesterol lowering medicine);
7. being allergic to alcohol and/or Ibuprofen
8. smoking