Poster Presentation ESA-SRB-ANZBMS 2024 in conjunction with ENSA

What contributes to hyperandrogenism in women? (#533)

Madeleine Haygarth 1 , Meg Henze 1 , Ee Mun Lim 1 2 , Bronwyn Stuckey 1 3 4
  1. Department of Endocrinology and Diabetes, Sir Charles Gairdner Hospital , Perth, WA
  2. PathWest QE2 Medical Centre, Perth, WA
  3. Keogh Institute for Medical Research, Perth, WA
  4. Medical School, University of Western Australia, Perth

Introduction 

Polycystic ovary syndrome (PCOS) is a prevalent disorder, affecting 5-20% of premenopausal women. Metabolic and reproductive subtypes of PCOS based on clinical and biochemical phenotype have been described (1).  

Elevated androgens are the biochemical hallmark of PCOS, with hyperandrogenism noted in >70%, either elevated total testosterone or free androgen index (FAI)(2). Testosterone levels vary according to age and weight, menstrual phase, or as measured by LCMS or immunoassay (IA).  

Methods 

Androgen assays results performed at PathWest QE2 Medical Centre between January 2020-2022 from females between 18-40 years were extracted. Testosterone assays were performed primarily by Abbott Architect IA. Results above reference intervals - testosterone ≥ 2 nmol/L or FAI ≥6 - were included. Transgender results were excluded. 

Results

There were 4730 IA testosterone results, 98 also with LCMS measurement – LCMS/AI correlation (R2=0.76). 737 females had increased FAI ≥6 and 460 testosterone ≥2 nmol/L.  Of those with testosterone ≥2 nmol/L, 217 were identified as PCOS/?PCOS on the request form. High FAI was contributed to by high total testosterone (284/737), or low SHBG (632/737), or both (187/737). Of 165 women with PCOS/?PCOS in follicular phase, 59 had an LH/FSH ≥2, of whom 44 had increased FAI and 27 a low SHBG (see Table 1). 

Conclusion

The correlation between IA and LCMS testosterone  supports IA to assess hyperandrogenism in women. The majority of females with PCOS/?PCOS had a mildly elevated testosterone (2-3 nmol/L). Among them, 19% had an elevated LH/FSH ratio ≥2 with normal or higher SHBG (reproductive subtype), while 35% had a normal LH/FSH ratio with reduced SHBG (metabolic subtype).  Even so, significant biochemical heterogeneity highlights the need for improved PCOS phenotype characterisation. 

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  1. Dapas M, Lin FTJ, Nadkarni GN, Sisk R, Legro RS, Urbanek M, Hayes MG, Dunaif A. Distinct subtypes of polycystic ovary syndrome with novel genetic associations: An unsupervised, phenotypic clustering analysis. PLoS Med. 2020 Jun 23;17(6):e1003132. doi: 10.1371/journal.pmed.1003132. PMID: 32574161; PMCID: PMC7310679.
  2. Kanbour, S.A. and Dobs, A.S. (2022) ‘Hyperandrogenism in women with polycystic ovarian syndrome: Pathophysiology and controversies’, Androgens: Clinical Research and Therapeutics, 3(1), pp. 22–30. doi:10.1089/andro.2021.0020.