Impact of 11-oxygenated Androgens on Metabolic Dysfunction of Women With Polycystic Ovary Syndrome
Status:
Recruiting
Trial end date:
2025-05-30
Target enrollment:
Participant gender:
Summary
Polycystic ovary syndrome (PCOS) affects 10% of all women and usually presents with irregular
menstrual periods and difficulties conceiving. It is also a lifelong metabolic disorder and
affected women have an increased risk of type 2 diabetes, high blood pressure, and heart
disease. Increased blood levels of male hormones, also termed androgens, are found in most
PCOS patients. Androgen excess appears to impair the ability of the body to respond to the
sugar-regulating hormone insulin (also termed 'insulin resistance'). Androgens circulating in
the blood in women with PCOS are comprised of classic androgens (for example testosterone),
and the less-characterised 11-oxygenated androgen subclass that arises from the adrenal
glands. The investigators have recently demonstrated that 11-oxygenated androgens make up the
majority of circulating androgens in women with PCOS.
In preliminary studies using minimally invasive adipose tissue sampling, the investigators
have found that the fat tissue of women with PCOS overproduces classic androgens. This can
lead directly to disturbances in the ability of fat cells to store fat effectively
(lipotoxicity), resulting in insulin resistance and the consequent risk of liver damage.
However, there are no published studies on in vivo androgen concentrations in the adipose
tissue of women with PCOS. Furthermore, the scientific community do not have any information
on whether adipose concentrations of 11-oxygenated androgens are also increased in women with
PCOS.
Research Questions The investigators aim to examine the metabolism of classic and
11-oxygenated androgens in detail in both circulations and in the adipose tissue of women
with PCOS. The investigators will examine how precursor variants of both 11-oxygenated and
classic androgens, which are converted by the body into active hormones, are broken down
(metabolised) within the adipose tissue of women with PCOS. The investigators will also
investigate if the 11-oxygenated androgens have a differential impact on metabolic function
as compared to classic androgens. This will give important insights into the adipose tissue
metabolome in women with PCOS, and how locally generated androgens impact on adipose tissue
function and metabolic risk.