Provider Tools

Testosterone Metabolism Partition Model

Visualize testosterone partitioning across SHBG binding, aromatization, and 5α-reduction. Model pharmaceutical and botanical interventions in real time.

Estrogen metabolism modifier, not an aromatase inhibitor

Providing measured lab values back-calculates your personal conversion rates, replacing population averages.

Testosterone Partitioning

Estrogen Metabolism Routing (DIM effect)

DIM shifts estrogen metabolism toward the 2-hydroxylation pathway without reducing serum E2 levels.

Testosterone Binding

Estradiol Metabolism

DHT Metabolism

How this works

This tool models testosterone's metabolic fate through three pathways: SHBG binding (which sequesters T from biological activity), aromatization to estradiol via the aromatase enzyme (CYP19A1), and 5α-reduction to dihydrotestosterone via 5α-reductase enzymes.

Free testosterone is calculated using the Vermeulen equation, validated against equilibrium dialysis (r = 0.918) and implemented with the ISSAM reference constants (KSHBG = 1.0 x 109 L/mol). This is the same constant used in the ISSAM reference calculator co-developed by Vermeulen himself. Many online calculators use the Sodergard 1982 constant (5.97 x 108), which overestimates free T by 12-37%, particularly at high SHBG values where the calculation matters most.

Estradiol estimation uses a 0.3% daily aromatization transfer constant (Longcope 1969) scaled by body fat percentage, reflecting the adipose tissue's role as the primary site of peripheral aromatization. The body fat scaling is a linear approximation; the actual relationship is likely nonlinear and depends on visceral fat distribution, insulin levels, and inflammatory cytokines. Lab anchoring (providing your measured E2) replaces this approximation with your personal aromatization rate.

DHT estimation uses Saez and Forest's 1972 isotope-dilution measurement of a 2.8% transfer constant for systemic T to DHT conversion. Pharmaceutical inhibitor dose-response curves are from published clinical trials: Drake 1999 for finasteride, Clark 2004 for dutasteride, Geisler 1996/Pfizer PI for anastrozole, and Mauras 2003 for exemestane.

Botanical interventions are modeled where clinical data supports quantitative estimates. Saw palmetto DHT suppression (25-35%) is from Marks 2000 biopsy-confirmed data. Stinging nettle root's SHBG displacement is modeled conservatively from Schottner 1997 and Safarinejad 2005. DIM is shown separately because it modifies estrogen metabolism routing (2-hydroxylation vs 16α-hydroxylation) without reducing serum E2.

References

  1. Vermeulen A, Verdonck L, Kaufman JM. A critical evaluation of simple methods for the estimation of free testosterone in serum. J Clin Endocrinol Metab. 1999;84(10):3666-3672. PMID: 10523012
  2. Longcope C, Kato T, Horton R. Conversion of blood androgens to estrogens in normal adult men and women. J Clin Invest. 1969;48(12):2191-2201. PMID: 5355335
  3. Saez JM, Forest MG, Morera AM, Bertrand J. Metabolic clearance rate and blood production rate of testosterone and dihydrotestosterone in normal subjects. J Clin Invest. 1972;51(6):1226-1234. PMID: 5024036
  4. Drake L, Hordinsky M, Fiedler V, et al. The effects of finasteride on scalp skin and serum androgen levels in men with androgenetic alopecia. J Am Acad Dermatol. 1999;41(4):550-554. PMID: 10495374
  5. Geisler J, King N, Anker G, et al. In vivo inhibition of aromatization by exemestane in postmenopausal breast cancer patients. Clin Cancer Res. 1998;4(9):2089-2093.
  6. Mauras N, Lima J, Patel D, et al. Pharmacokinetics and dose finding of a potent aromatase inhibitor, exemestane, in young males. J Clin Endocrinol Metab. 2003;88(12):5951-5956. PMID: 14671195
  7. Finkelstein JS, Lee H, Burnett-Bowie SM, et al. Gonadal steroids and body composition, strength, and sexual function in men. N Engl J Med. 2013;369(25):2457. PMID: 24024714
  8. Geisler J, Haynes B, Anker G, Dowsett M, Lonning PE. Influence of anastrozole on intratumour and plasma oestrogen levels in postmenopausal breast cancer. Br J Cancer. 1996;74(8):1286-1291. PMID: 8883419
  9. Clark RV, Hermann DJ, Cunningham GR, Wilson TH, et al. Marked suppression of dihydrotestosterone in men with benign prostatic hyperplasia by dutasteride. J Clin Endocrinol Metab. 2004;89(5):2179-2184.
This tool is for healthcare provider education and clinical decision support. It uses population-level pharmacology data and does not replace individualized clinical assessment. Inhibitor dosing should be guided by serial lab monitoring.