Dr Elisabet Stener-Victorin

The Role of Sex-Steroids in the Development of Polycystic Ovary Syndrome – Efficacy of Acupuncture and Physical Exercise

Background: Polycystic ovary syndrome (PCOS) is the most common female endocrine disorder, affecting ~10% of women of reproductive age. The syndrome is associated with hyperandrogenism, ovulatory dysfunction, abdominal obesity, and a high risk of hyperinsulinemia, insulin resistance, and progression to type 2 diabetes, hypertension, and cardiovascular disease. Despite extensive research the etiology is largely unknown (see figure 1) and treatment symptom orientated. Stener-Victorin was the first researcher to demonstrate that acupuncture may exert long-lasting effects on endocrine function and has since then been at the forefront in the research area internationally. Translational research studies have been performed to explain the mechanism of results from clinical studies with the use of different rat models of PCOS. The research aims to understand how sex steroids and metabolic processes may contribute to PCOS. We use molecular approaches to understand female pathology caused by sex steroid alterations, particularly androgens and elucidate mechanisms of acupuncture and exercise on metabolic and endocrine function. These projects have the potential to uncover new knowledge, and the multidisciplinary strategy guarantees successful outcomes.

   

Figure 1. Several theories have been proposed to explain the pathogenesis of PCOS. 1) Neuroendocrine defects, leading to increased pulse frequency and amplitude of LH with relatively low FSH. 2) Intrinsic defects in ovarian androgen production. 3) Alteration in cortisol metabolism and impaired adrenal androgen production. 4) Insulin resistance with compensatory hyperinsulinemia which results in incrased ovarian androgen production directly and indirectly via inhibition of hepatic SHBG production. 5) Increased sympathetic nerve activity. 6) Genetic defects. (ACTH – adrenocorticotrophic hormone, CVD – cardiovascular disease, DHEA – dehydroepiandrosterone, DHEAS – dehydroepiandrosterone sulfate, FSH – follicle stimulating hormone, HPA – hypothalamic-pituitary-adrenal, LH – luteinizing hormone, SHBG – sex hormone binding globulin, T2DM – type 2 diabetes mellitus)

Stener-Victorin demonstrated that PCOS is associated with increased activity in the sympathetic nervous system and found evidence that ovarian nerve growth factor exerts pathogenic effects through its action on ovarian adrenoceptor expression, specifically on the ovarian responsiveness to sympathetic input. Exercise almost normalized ovarian morphology, and electro-acupuncture (EA) and physical exercise normalized expression of sympathetic markers, which suggests that these interventions have a therapeutic effect. In 2008, she also demonstrated that low-frequency EA and physical exercise reduces high sympathetic nerve activity in women with PCOS and upcoming papers will demonstrate that these interventions improve endocrine and clinical symptoms. She has also developed a new experimental PCOS model, in which metabolic abnormalities caused by androgen excess is explored. In this model, she demonstrate that low-frequency EA and exercise improve insulin sensitivity. This effect may involve regulation of adipose tissue metabolism and production, as EA and exercise each partly restored divergent adipose tissue gene expression as well as induce more regular cycles. These studies demonstrates that both exercise and EA may break the vicious circuite caused by androgens (See Figure 2). This is especially interesting but warrants further investigation.

Figure 2. The hallmarks of PCOS – hyperinsulinemia and hyperandrogenism – are part of a vicious circuite. 1) Androgens can directly influence insulin action in adipocytes and skeletal muscle. 2) Androgens can also influence insulin sensitivity indirectly via effects on lipid metabolism, adiposity/body fat distribution and adipokine secretion. Adipokines, in turn, may influence ovarian and adrenal function directly. 3) Hyperinsulinemia, compensatory to insulin resistance, enhances hyperandrogenism via direct actions on androgen production and indirectly via an inhibition of hepatic SHBG production.
 

The projects in this research plan aim to yield new key information on the pathophysiology of PCOS. A further aim is to elucidate if new treatment strategies such as low-frequency electro-acupuncture (EA) and physical exercise can improve PCOS related symptoms. The various projects involve translational research with rat models exposed to androgens, women with PCOS and a female population cohort born 1956.

Projects:
Polycystic ovary syndrome: Focus on adipose tissue and ovarian morphology and the therapeutic effects of physical exercise and electro-acupuncture (human and rat studies)

Polycystic Ovary Syndrome and the Metabolic Syndrome ─ Neuroendocrine function and molecular Processes in the Muscle and Adipose tissue – Effects of Acupuncture (human and rat studies)

Psychological variables in relation to sex steroids in women with polycystic ovary syndrome- effects of electro-acupuncture and physical exercise (human study)

Effect of electro-acupuncture on central nervous system in adult female rats with dihydrotestosterone induced polycystic ovary syndrome (rat studies)

Polycystic Ovary Syndrome ─ morphologic and dynamic evaluation by magnetic resonance imaging (human study)

Women with polycystic ovary syndrome experience of acupuncture treatment – A qualitative study (human study)

To estimate the prevalence of PCOS in obese premenopausal women and elucidate how they respond to a weight reduction treatment program (human study)