Dr Alba Moreno-Asso, Senior Researcher at the Institute for Health and Sport (iHeS), Victoria University, Australia
Women with polycystic ovary syndrome (PCOS) have an impaired response to exercise and don’t experience the same health benefits as women without PCOS. Our new research, published in The Journal of Physiology, found that the circulating factor, called transforming growth factor-beta-1 (TGFB1), has a negative effect on muscle cells, supressing genes related to muscle contractile function. This would cause the muscle cells to behave differently in women with PCOS compared to women without PCOS, impeding the body’s response to exercise.
What is polycystic ovary syndrome?
Polycystic ovary syndrome is characterised by a hormonal imbalance affecting the reproductive and metabolic health of 8-13% of women worldwide. Women living with PCOS can experience a number of health problems including difficulty getting pregnant, weight gain, insulin resistance and an increased risk of developing type 2 diabetes, cardiovascular disease and endometrial cancer (cancer of the uterus).
Therefore, exercise is often recommended as a first-line therapy to reduce these risk factors, e.g. improve insulin sensitivity and lower cholesterol levels. However, women with PCOS don’t seem to experience the same metabolic changes with exercise as women without PCOS.
What factors limit the response to exercise?
In this study, we analysed pathways in muscle cells in culture to explain this abnormal response. We used TGFB1 and Anti-Müllerian hormone (AMH) because they are known to be elevated in women with PCOS and affect the ovaries, causing reproductive dysfunction and harmful tissue organisation. These factors have been previously proposed to also affect other tissues in these women.
Tissue samples were taken from women with and without PCOS (6 overweight (BMI > 25 kg/m2) and 6 lean (BMI < 25 kg/m2)) aged between 18-40 years old. Electrical pulses were used to mimic exercise activity and stimulate the muscle cells (in culture) to contract. The muscle cells were also exposed to TGFB1 and AMH, and RNA-sequencing was used to monitor the changes in the expression of genes.
A knock-on effect and its negative consequences
There is a significant difference in the number of genes expressed with exercise-like stimulus between women with and without PCOS, with higher number of genes that cause inflammation activated in women with PCOS. While AMH has no effect on muscle cells, TGFB1 specifically alters the expression of genes activated with exercise, supressing those responsible for muscle contraction and essential for cell structure and mechanical support.
This mechanism could be the key to explaining why PCOS impedes women’s response to exercise and prevents them experiencing the same metabolic health benefits as women without PCOS. Following further research, we may be able to understand how these altered pathways can be targeted to improve the response to exercise in women with PCOS and ultimately improve their health and well-being.
Improving the health advice for women with PCOS
We carried out our study in muscle cells in culture. Therefore, we should seek to understand how circulating factors and hormones affect the exercise response in patients. This would allow us to optimise exercise programs and lifestyle interventions for women with PCOS.
Follow-up studies should investigate the influence of different fitness levels and obesity and find ways to overcome PCOS adverse effects on women’s health.
Read the Research Article to find out more about the role TGFB1 plays in altering the exercise-related signature in the muscles of women with PCOS.