The genes governing how your body produces and converts sex hormones determine your baseline hormonal environment.
Aromatase activity, DHT conversion rate, steroid biosynthesis capacity, and vitamin D receptor efficiency. Four variants with direct implications for hormone optimization.
On Varia's active watchlist. We monitor the peer-reviewed literature on these variants and add them to the catalog the moment replicated evidence meets our standard.
The Biology
Sex hormones are not produced at fixed rates. Their synthesis and interconversion is regulated by enzymatic pathways encoded by genes that vary between individuals. The same testosterone molecule will be converted to estradiol at different rates in two people with different CYP19A1 aromatase activity. The same testosterone will be converted to DHT at different rates depending on SRD5A2 5-alpha reductase activity. These differences carry implications for hormone optimization, fertility, hormone-sensitive conditions, and pharmacological interventions.
The variants we are watching
Four variants govern the primary sex-hormone synthesis and conversion enzymes, and Varia is tracking each. CYP19A1 (aromatase, rs4646) controls the rate of testosterone-to-estrogen conversion. SRD5A2 (rs523349) governs DHT production from testosterone via 5-alpha reductase type 2, the same enzyme finasteride targets. CYP17A1 (rs743572) regulates a rate-limiting step in both androgen and estrogen biosynthesis. VDR Fok1 (rs2228570) sets vitamin D receptor transcriptional efficiency; vitamin D acts as a steroid hormone with effects on sex-hormone production, calcium metabolism, and immune modulation. These are candidates under review, not findings Varia reports today.
Why they are of interest
These enzymes sit directly on the pathways people care about most in hormone optimization. CYP19A1 and SRD5A2 shape how much of a given testosterone level is aromatized to estrogen or converted to DHT. VDR Fok1 provides context for how efficiently the receptor responds to a given vitamin D level, which is relevant to most of the population in northern latitudes. The biology is well characterized and the questions are common, which is why these stay on our watchlist.
Where this stands
Varia does not report these variants yet. The enzymatic biology is well established, but the replicated, peer-reviewed evidence tying these specific genotypes to outcomes that would change what you do has not met Varia's bar for an individual finding. We monitor the literature on all four, and when the evidence is strong and replicated enough, they enter the catalog and your scan.
Key sources
- Haiman CA, et al. Genetic variation at the CYP19A1 locus predicts circulating estrogen levels. Cancer Res. 2007.
- Makridakis NM, et al. Association of mis-sense substitution in SRD5A2 gene with prostate cancer. Lancet. 1999.
- Arai H, et al. A vitamin D receptor gene polymorphism in the translation initiation codon: effect on protein activity. J Bone Miner Res. 1997.