Low Testosterone in Men With Type 2 Diabetes: The Role of Estrogen Excess and Aromatase Activity
Authors' conclusion
In men with type 2 diabetes, low testosterone is associated with adiposity, glycaemic control, and increased adipose aromatase expression. Relative estrogen excess may contribute to hypothalamic-pituitary-testicular axis suppression and represents a novel target for diagnostic and therapeutic strategies.
Study context
- Population
- Men with T2D and healthy men (reference cohort); factors associated with low total testosterone and calculated free testosterone (CFT)
- Participants
- 180 vs 92
- Exposure
- Men with T2D vs healthy reference cohort
- T2Dn = 180
- Healthy controlsn = 92reference
- Outcome
- Factors associated with low testosterone in men with T2D
Main finding
As reported in the abstract
- Lower total testosterone (<10 nM) associated with HbA1c
- p < 0.001
- Lower total testosterone (<10 nM) associated with BMI
- p = 0.007
- Lower total testosterone (<10 nM) associated with leptin
- p = 0.009
- Lower total testosterone (<10 nM) associated with insulin resistance
- p = 0.026
- Lower CFT (<220pM) associated with age
- p = 0.049
- Lower CFT (<220pM) associated with BMI
- p < 0.001
- Lower CFT (<220pM) associated with interleukin-6
- p < 0.001
- Lower CFT (<220pM) associated with leptin
- p = 0.003
- Lower CFT (<220pM) associated with insulin
- p = 0.020
- Multivariable: BMI independently associated with CFT
- p < 0.001
- Multivariable: CYP19A1 expression independently associated with CFT
- p = 0.020
- Multivariable: HbA1c independently associated with CFT
- p = 0.006
Observational data: associations, not effects.
Further findings
| Outcome | Healthy controls | P value |
|---|---|---|
| Relative estrogen excess (Estradiol T score − Testosterone T score)T2D with low testosterone vs Healthy controls | 0.06 (interval −0.74–0.51) | P < 0.001 |
- Relative estrogen excess (Estradiol T score − Testosterone T score): T2D with low testosterone 1.63 (interval 0.94–2.76)
Common CYP19A1 variant
- Associated with increased adipose CYP19A1 expression
- P = 0.044
- Associated with low CFT
- P = 0.042
Original publication
Low Testosterone in Men With Type 2 Diabetes: The Role of Estrogen Excess and Aromatase Activity. Clin Endocrinol (Oxf). Published 21 January 2026. doi:10.
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