The Joint Annual Scientific Meetings of the Endocrine Society of Australia and the Society for Reproductive Biology 2018

Polymorphisms in the 5α-reductase gene (SRD5A2) modulate serum testosterone, dihydrotestosterone and sex hormone-binding globulin, and polymorphisms in the aromatase gene (CYP19A1) modulate serum estradiol and luteinising hormone in men (#65)

Bu B Yeap 1 2 , Matthew W Knuiman 3 , David J Handelsman 4 , Ken KY Ho 5 , Jennie Hui 6 , Mark L Divitini 3 , Gillian M Arscott 6 , Brendan McQuillan 1 7 , Joseph Hung 1 7 , John P Beilby 6
  1. The Medical School, University of Western Australia, Perth, WA, Australia
  2. Department of Endocrinology and Diabetes, Fiona Stanley Hospital, Perth, WA, Australia
  3. School of Population and Global Health, University of Western Australia, Perth, WA, Australia
  4. ANZAC Research Institute, University of Sydney, Sydney, NSW, Australia
  5. Garvan Institute of Medical Research, Sydney, NSW, Australia
  6. PathWest Laboratory Medicine, Sir Charles Gairdner Hospital, Perth, WA, Australia
  7. Department of Cardiology, Sir Charles Gairdner Hospital, Perth, WA, Australia


Secretion of luteinising hormone (LH) by the pituitary stimulates testicular production of testosterone (T) and is under negative feedback control. T is metabolised to dihydrotestosterone (DHT) by 5α-reductase and to estradiol (E2) by aromatase. How activity of population variants in these enzymes impact on the male gonadal axis is unclear.


We examined whether polymorphisms in 5α-reductase (SRD5A2) and aromatase (CYP19A1) genes predict circulating sex hormone concentrations.

Participants and methods

1,865 community-dwelling men aged 50.4±16.8 years. Early morning sera assayed for T, DHT and E2 using mass spectrometry, and sex hormone-binding globulin (SHBG) and LH using immunoassay. Two SRD5A2 and eleven CYP19A1 polymorphisms were analysed by PCR with genotyping successful in >98% of samples. Regression models were adjusted for age and cardiometabolic risk factors.


SRD5A2 polymorphism rs9282858 GA vs GG was associated with higher serum T (+1.5 nmol/L, P<0.001), lower DHT (-0.14 nmol/L, P=0.029) and higher SHBG (+3.3 nmol/L, P=0.001). Four CYP19A1 polymorphisms were associated with higher serum E2 and lower LH: rs2470152 CC/CT vs TT (E2 +3.4 pmol/L, P=0.048; LH -0.47 IU/L, P=0.003), rs17703883 TT/TC vs CC (E2 +7.1 pmol/L, P=0.014; LH -1.62 IU/L, P<0.001), rs2899470 GG/GT vs TT (E2 +3.8 pmol/L, P=0.039; LH -0.54 IU/L, P=0.006) and rs11575899 II/ID vs DD (E2 +7.2 pmol/L, P=0.001; LH -0.78 IU/L, P<0.001). CYP19A1 polymorphisms were associated with larger differences in circulating LH in men aged ≥65 years compared with <60 years. The two-copy haplotype rs10046=T, rs2899470=G, rs11575899=I, rs700518=G and rs17703883=T (prevalence 27.5%) was associated with higher E2 (+6.8 pmol/L, P=0.001) and lower LH (-0.61 IU/L, P=0.001).


A 5α-reductase polymorphism predicts circulating androgens and SHBG, while aromatase polymorphisms predict circulating E2 and LH. Further studies are needed to determine how these functional 5α-reductase and aromatase gene polymorphisms impact on male gonadal axis activity in reproductive and general health outcomes.