Impact of 11-oxygenated Androgens on Metabolic Dysfunction of Women With Polycystic Ovary Syndrome

• Status: Recruiting
• Trial end date: 2025-05-30
• Target enrollment: 0
• Participant gender: Female

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.

• Phase: N/A
• Accepts Healthy Volunteers?: Accepts Healthy Volunteers

Details

• Lead Sponsor: University of Birmingham
• Treatments: Androgens; Dehydroepiandrosterone

Criteria

Part A

Inclusion Criteria:

• BMI between 30-40 kg/m2

• Age range 18-40 years

• Ability to provide informed consent

For women participating in the PCOS group, the diagnosis of PCOS will be established during their recruitment to DAISy-PCOS study on the basis of the Rotterdam Consensus Criteria for the Diagnosis of PCOS, as recommended by the current international PCOS guidelines (at least 2 out of 3 criteria):

• Androgen excess (clinical and/or biochemical evidence)

• Chronic oligo-/anovulation (clinical and/or biochemical evidence)

• Polycystic appearance of the ovaries on ultrasound (according to the most recent guidelines (10), taking into account the higher resolution capacity of modern ultrasound, the presence of ovarian PCOS morphology is defined as follows: 20 or more follicles of 2-9mm in diameter and/or an increased ovarian volume >10 millilitre [without a cyst or dominant follicle] in either ovary) In addition, we will perform clinical and/or biochemical exclusion, as appropriate, of other conditions that could explain the above manifestation (e.g. congenital adrenal hyperplasia, Cushing's syndrome, Prolactinoma, adrenal and gonadal tumours)

Exclusion Criteria:

• Pregnancy or breastfeeding at the time of planned recruitment

• History of significant renal (eGFR<30) or hepatic impairment (aspartate aminotransferase or alanine transaminase >two-fold above ULN; pre-existing bilirubinaemia >1.2 ULN)

• Any other significant disease or disorder that, in the opinion of the Investigator, may either put the participant at risk because of participation in the study, or may influence the result of the study, or the participant's ability to participate in the study.

• Participants who have participated in another research study involving an investigational medicinal product in the 12 weeks preceding the planned recruitment

• Glucocorticoid use via any route within the last six months

• Current intake of drugs known to impact upon steroid synthesis or metabolism or on metabolic function or intake of such drugs during the six months preceding the planned recruitment

• Use of oral or transdermal hormonal contraception in the three months preceding the planned recruitment

• Use of contraceptive implants in the twelve months preceding the planned recruitment

• Allergy or intolerance to any of the ingredients in the high fat meal, or any of the ingredients in the dehydroepiandrosterone and 11-ketoandrostenedione preparations.

• Diabetes or impaired glucose metabolism

Part B Inclusion criteria

• Women undergoing elective, abdominal, non-cancer surgery

• Age range 18-70 years

• Ability to provide informed consent

Exclusion criteria

• Pregnancy or breastfeeding at the time of planned recruitment

• Glucocorticoid use via any route within the last six months

• Current intake of drugs known to impact upon steroid synthesis or metabolism or on metabolic function or intake of such drugs during the six months preceding the planned recruitment

• Type 1 diabetes

• Medical treatment of type 2 diabetes