Abstract P5-11-10: Gonadotropins Plasma Levels Are Significantly Influenced by Body Mass Index in Postmenopausal Breast Cancer Patients Undergoing Endocrine Therapy with Aromatase Inhibitors: Is This a Surrogate Marker for Serum Estrogen Bioactivity?
Authors: Hubalek M , Oberguggenberger A , Beer B , Meraner V , Oberacher H , Sperner-Unterweger B , Kemmler G , Holzner B , Marth C. 
Published: April 2011

Background: Estrogens play a crucial role in breast carcinogenesis and progression. The third-generation aromatase inhibitors (AIs) have therefore become the first choice endocrine drugs for post-menopausal women with breast cancer, since they present greater efficacy when compared with tamoxifen. However, mode of action, side effects and tolerability are distinct compared to tamoxifen. In this study, we evaluated clinical side-effects, levels of gonadotropin, prolactin, progesterone and estradiol in postmenopausal women undergoing endocrine treatment with aromatase inhibitors.

Materials and Methods: 128 postmenopausal patients undergoing endocrine therapy with aromatase inhibitors were included in the study. They completed the assessment at their regular 3-month check up. For the assessment of side-effects and symptom burden we used the FACT-B/+ES and the HADS. Blood samples were collected within the routine blood collection and measurement of follicle stimulation hormone (FSH), luteinizing hormone (LH), progesterone, estradiol and prolactin plasma levels were performed by Immunoassay. Data were analyzed using Spearman rank correlation.

Results: We found a significant negative correlation of LH and FSH with body mass index (BMI) of postmenopausal breast cancer patients (LH r=- 0.281, p=0.014; FSH r=-0.250, p=0.029) receiving aromatase inhibitors. Analyses revealed a significant positive correlation for LH and FSH levels with subjectively experienced weight gain (LH r=0.499, p=0.008; FSH r=0.550, p=0.003), dyspareunia and vaginal dryness. Moreover, patients with a BMI ≥25 had significantly more gynaecological symptoms (dyspareunia p=0.008 and vaginal dryness p=0.026) than patients witha lower BMI. Progesterone was significantly associated with subjective weight gain (r=0.248, p=0.014). Prolactin significantly correlated with loss of sex drive (r=0.256, p=0.050), mood swings (r=0.239, p=0.050) and irritability (r=0.244, p=0.046).

Conclusion: Our results reveal distinct endocrine changes among postmenopausal breast cancer patients undergoing endocrine treatment with AIs. These results confirm the central role of estrogens in the evolution of adverse events to aromatase inhibitors. The main observation in this study, however, was the correlation of BMI and levels of hormone influenced by estrogenic activity. LH and FSH which are under control of various estrogen metabolites, were significantly associated with the BMI and might therefore serve as surrogate marker of estrogenic activity in serum of breast cancer patients. Direct measurement of estradiol (E2) showed no correlation with BMI indicating the influence of various other estrogen metabolites on the secretion of gonadotropins. Analysis of serum estrogen receptor bioactivity in these patients is currently underway.

Citation Information: Cancer Res 2010;70(24 Suppl):Abstract nr P5-11-10.