The effect of physical activity and weight-related factors on endogenous sex hormones in postmenopausal women: understanding independent and joint roles

  • Topic: Breast Cancer
  • Institution: DKFZ (German Cancer Research Centre)
  • Country: Germany
  • Status: Completed

Scientific abstract

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Background

Some evidence exists that in postmenopausal women, physical activity and weight-related factors are associated with endogenous sex hormone concentrations, which are determinants of breast cancer risk. We investigated independent and joint effects of physical activity and weight-related factors on sex hormone levels and hypothesised that physical activity affects hormone levels not solely via body composition changes.

Methods

The study subjects were participants in a population-based case-control study of postmenopausal breast cancer conducted in Germany (MARIE- Study, acronym for Mammary Carcinoma Risk factor Investigation). The concentrations of estrone, total and free estradiol and testosterone, androstenedione, and sex hormone-binding globulin (SHBG) were measured and their associations with different types of physical activity and weight- related factors were determined in 1,260 subjects.

Results

All weight-related factors (body mass index, waist and hip circumference, and waist-to-hip ratio) showed significant negative associations with SHBG and significant positive associations with all hormones except androstenedione. Regarding physical activity, higher levels of sports activity (yet not of total leisure-time physical activity, day-to-day walking or bicycling) were significantly associated with lower levels of estrone and total and free testosterone. After accounting for weight-related factors, associations with estrone and free testosterone were still significant but attenuated; the association with total testosterone remained unchanged. No physical activity variable was significantly related to total and free estradiol, androstenedione, or SHBG. We did not observe effect modification by any weight-related factor.

Conclusions

Results of our project suggest that sports activities lead to lower levels of estrone and total and free testosterone in postmenopausal women. With regard to estrone and free testosterone, there seems to be a strong joint effect with weight-related factors. On the contrary, effects on total testosterone appear to be mainly independent of associated effects on body weight and body composition. Our observed BMI-independent associations between sports activity and estrone and testosterone (especially total testosterone) could at least partly explain why physical activity has been frequently reported to be preventive for postmenopausal breast cancer, even after accounting for BMI.

Plain language abstract

Hypothesis

We hypothesised that physical activity and body composition (reflected by different weight related factors) affect endogenous hormone and sex hormone-binding globulin (SHBG) concentrations in postmenopausal women. Furthermore, we hypothesised that physical activity affects hormone concentrations not solely via body composition changes.

Background

There is strong evidence that women with low physical activity and/or a high body mass index (BMI) are at a higher risk of postmenopausal breast cancer than physically active women (1) or women with a lower BMI (2). The biological mechanisms responsible for these relationships are yet not fully understood. However, for BMI as well as for physical activity, it has been assumed that effects may be related to circulating levels of sex hormones and SHBG, which are well recognised to play important roles in the development of postmenopausal breast cancer (3, 4). To confirm this assumption, it is crucial to know whether those biomarkers are associated with a woman’s physical activity level as well as with factors related to her body weight or body composition. In addition, it is important to know whether physical activity affects hormone levels exclusively via changes in weight-related factors or also via different pathways.

Methods

In 1,260 postmenopausal women, blood concentrations of estrone, total and free estradiol and testosterone, androstenedione, and sex hormone-binding globulin (SHBG) were measured. We investigated associations between these hormones and different types of physical activity and weight-related factors using generalised linear models. The key objective was to explore independent and joint effects of physical activity and weight- related factors on hormone levels. Therefore, when we assessed associations with physical activity, we distinguished between statistical models adjusting and not adjusting for BMI, waist and hip circumference, and WHR (one variable at a time). Additionally, we assessed effect modification by weight-related factors.

Key findings

All investigated weight-related factors (BMI, waist and hip circumference, and waist-to-hip ratio) showed negative associations with SHBG and positive associations with all hormones except androstenedione. Regarding physical activity, higher levels of sports activity (yet not of total leisure-time physical activity, day-to-day walking or bicycling) were significantly associated with lower levels of estrone and total and free testosterone. After additional adjustment for weight-related factors, associations between sports activity and estrone and free testosterone were still significant but attenuated, which suggests that the effect of sports activity on these two hormones is largely mediated by changes in body composition. Associations between sports activity and total testosterone remained unchanged after accounting for any weight-related factor, indicating a mainly independent effect of sports activity on this hormone. No physical activity variable was significantly related to total and free estradiol, androstenedione, or SHBG. Results of our project did not support the hypothesis that the effect of physical activity on hormone levels may differ across levels of weight-related factors (e.g. high versus low BMI).

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