FEmale Metabolic Risk and Androgens: an Irish Longitudinal (FEMAIL) Study

NCT04912648 | Recruiting

• 1 other identifier: 20/49
• Study Type: observational
• Target: 500
• Locations: 1 country
• Sites: 1

Brief Summary

Androgen excess is the cardinal biochemical feature of polycystic ovary syndrome (PCOS), a lifelong metabolic disorder affecting 10% of women. Serum testosterone correlates with insulin resistance in women, however, there is an urgent need to improve our understanding of the association between androgens and the risk of type 2 diabetes. Recently, a new subclass of androgenic steroids known as 11-oxygenated androgens has been identified. Utilising highly sensitive liquid chromatography-tandem mass spectrometry (LC-MS/MS) techniques, our group has recently demonstrated that 11-oxygenated steroids are the predominant androgens in both health controls and women with PCOS, and that these correlate closely with markers of insulin resistance. The bioactive 11-oxygenated androgen 11-ketotestosterone (11KT) binds and activates the androgen receptor with equal affinity to testosterone, yet nothing is known about its impact on metabolism or glucose homeostasis. Intriguingly, unlike testosterone, 11-oxygenated androgens do not decline with age in women, and, therefore, may mediate an increased risk of T2DM in women across their life course. Therefore, this previously ignored androgen class is likely of major importance in female metabolic health, and may represent a novel metabolic risk factor and biomarker. However, 11-oxygenated androgens are not currently measured in routine clinical practice. To date, no population-based or human in vivo physiology studies have examined the association between 11-oxygenated androgens, glucose metabolism and diabetes risk in women, despite the high prevalence of PCOS in the female population. There is emerging evidence, even in women without a confirmed history of PCOS, that the levels of androgens over time correlate with their likelihood of developing metabolic and cardiovascular disease. This has not been studied to date in a prospective manner in healthy women in the background population using long term follow up data.

Conditions

Hyperandrogenism; Metabolic Disease; Sex Hormones Adverse Reaction

Outcome Measures

Primary Outcomes (1)

• Correlation of sex hormone profiles and the metabolome of women across the lifespan with risk of metabolic dysfunction, cardiovascular disease and quality of life.

  3 years

Secondary Outcomes (2)

• Development of risk prediction models for development of diabetes in women

  5 years

• Establishment of the longitudinal FEMAIL study database

  5 years

Study Arms (1)

Women age 18 years and older

* baseline anthropometry * bloods for metabolic phenotype; targeted and nontargeted Metabolomics * saliva and urine for steroid Metabolomics * bioimpedance * muscle biopsy for transcriptomics

Other: Longitudinal follow up

Interventions

Longitudinal follow up OTHER

Repeat follow up at 3,5 and 10 years

Women age 18 years and older

Eligibility Criteria

• Age: 18 Years+
• Gender Eligibility Details: Female 46XX
• Healthy Volunteers: Yes
• Age Groups: Adult (18-64), Older Adult (65+)
• Sampling Method: Probability Sample

Study Population

Women meeting the above inclusion criteria without exclusion criteria

You may qualify if:

• Age 18 years or above
• Ability to provide informed consent

You may not qualify if:

• Pregnancy or breastfeeding at the time of planned recruitment
• History of significant renal (eGFR\<30) or hepatic impairment (AST or ALT \>two-fold above ULN; pre-existing bilirubinaemia \>1.2 ULN)
• The investigators will retain the right not to recruit potential participants with severe health disorders which may impact on their ability to participate in the study; these may include, but are not limited to, metastatic cancer, severe cardio-respiratory disease or other life-limiting health disorders
• 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 or metabolic function or intake of such drugs during the six months preceding the planned recruitment
• Use of combined oral hormonal contraception in the three months preceding the planned recruitment

Sponsors & Collaborators

• Royal College of Surgeons, Ireland: lead

Study Sites (1)

Royal College of Surgeons in Ireland

Dublin, D9, Ireland

RECRUITING

Biospecimen

Retention: SAMPLES WITHOUT DNA

Serum; urine; saliva; muscle biopsy

MeSH Terms

Conditions

Hyperandrogenism; Metabolic Diseases

Condition Hierarchy (Ancestors)

46, XX Disorders of Sex Development; Disorders of Sex Development; Urogenital Abnormalities; Female Urogenital Diseases; Female Urogenital Diseases and Pregnancy Complications; Urogenital Diseases; Adrenogenital Syndrome; Male Urogenital Diseases; Congenital Abnormalities; Congenital, Hereditary, and Neonatal Diseases and Abnormalities; Gonadal Disorders; Endocrine System Diseases; Nutritional and Metabolic Diseases

Study Design

• Study Type: observational
• Observational Model: COHORT
• Time Perspective: PROSPECTIVE
• Sponsor Type: OTHER
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: May 28, 2021
• First Posted: June 3, 2021
• Study Start: April 1, 2021
• Primary Completion: September 1, 2025
• Study Completion (Estimated): August 31, 2031
• Last Updated: May 2, 2024

Record last verified: 2024-05

Locations

IE (1)