What is the clinical utility of measuring Total Estrogen?
In urine testing, total estrogen is the sum of measured estrogens and/or their metabolites (E1, E2, E3 ± hydroxylated and methoxylated forms), normalized to creatinine. It reflects overall estrogen burden being excreted, not circulating bioactive estrogen or tissue exposure.
Measuring total estrogen as the sum of all estrogens and metabolites normalized to creatinine provides a robust assessment of overall estrogen exposure, which is strongly and positively associated with breast cancer risk in postmenopausal women (Sampson et al., 2017).
This aggregate measure captures total estrogen production and can be useful for evaluating overall hormonal burden, and can be used for longitudinal tracking for intraindividual variability, in conjunction with metabolite quantification to enable identification of specific deficiencies or imbalances in estrogen metabolism pathways.
Why total estrogen can be misleading
- Can be elevated due to one problematic metabolite (e.g., 4-OH estrone) while others are low
- Can appear “normal” despite unfavorable pathway distribution
- Encourages over-simplified estrogen dominance narratives
Rather, clinically salient findings relate to the parent estrogens E1 or E2 or metabolites, not the sum itself.
Best-practice interpretation
Total estrogen should be viewed as:
- ✅ Contextual
- ❌ Not actionable alone
- ❌ Not a therapeutic target
Primary clinical utility lies in:
- Individual estrogens (E1, E2, E3)
- Phase I hydroxylation balance
- Phase II methylation adequacy
- Ratios and patterning over time
Reference
Sampson JN, Falk RT, Schairer C, et al. Association of Estrogen Metabolism with Breast Cancer Risk in Different Cohorts of Postmenopausal Women. Cancer Res. 2017;77(4):918-925. doi:10.1158/0008-5472.CAN-16-1717 PMID: 28011624