Epristeride

The evidence is strongest at the enzyme and weakest in people.

The enzymology is excellent: multiple independent laboratories measured sub-nanomolar potency at the type 2 isoform, and the uncompetitive mechanism was established with proper kinetic analysis ^[1][3]. The human pharmacokinetics are complete and well done ^[5].

⚠️ No placebo-controlled efficacy trial of epristeride has ever been published, and no human study reports how much it lowers dihydrotestosterone. A 141-patient Chinese study was open-label and uncontrolled, reporting an 81 percent figure that is a composite of four different measures rather than an interpretable efficacy rate ^[7]. A 906-patient randomised comparison of seven marketed drugs included epristeride as one arm and found no difference between arms in symptom improvement, but did not break out epristeride's own numbers ^[8].

The best comparative data is in ten beagles: epristeride reduced serum dihydrotestosterone by 14 percent against finasteride's 43 percent, while both reduced prostate dihydrotestosterone by around half ^[6]. That is the basis of its prostate-selective positioning, and it rests on ten dogs. A rat comparison at matched doses found epristeride the least effective of three inhibitors tested ^[11].

⚠️ For hair loss there is nothing. No clinical study exists, and searches of the trial registry return no epristeride trial of any kind.

⚠️ The signal that should lead any safety discussion is a rat carcinogenesis study. In chemically induced prostate carcinogenesis, carcinoma incidence was 9.5 percent in controls against 31.6 percent at 10 mg/kg and 45.0 percent at 50 mg/kg of epristeride, a statistically significant increase at the lower dose ^[9]. The authors noted the result contradicted their own earlier work. All lesions were in-situ and none metastasised, and a single rodent study is not a human risk estimate, but a five-alpha-reductase inhibitor increasing prostate carcinoma incidence is not a finding to omit.

A six-month dog study at high doses found toxicity to testicular interstitial cells and to DNA content in prostate epithelium that did NOT reverse over 60 days of recovery, while every other measured change did ^[10].

Rat work reports reduced testis weight and impaired sperm count at high doses, and direct sperm toxicity has been shown in vitro including for human sperm, though at concentrations well above those a 5 mg dose produces in blood.

Genotoxicity testing was negative across bacterial mutation, chromosome aberration, micronucleus and sperm-abnormality assays.

As with any drug of this class it will suppress prostate-specific antigen and confound prostate cancer screening. Human safety data is limited to two uncontrolled or non-disaggregated studies, in which erectile dysfunction was reported in about 2 percent ^[7].

SmithKline Beecham developed epristeride in the late 1980s from a programme on steroidal A-ring carboxylic acids, taking a deliberately different chemical route to finasteride's azasteroids. The molecule was designed as a transition-state mimic, and the resulting uncompetitive kinetics were presented as an advantage: potency that rises rather than falls as substrate accumulates. It reached phase 3 for prostate enlargement in the United Kingdom, United States and Japan, was licensed to Ono Pharmaceutical for Asian markets, and was also pursued for acne. Neither the prostate nor the acne programme produced a published phase 3 result, and the compound was never approved in the West. It has remained available in China, and has acquired a second life as a research-chemical hair-loss product, which is why Chinese regulators now screen cosmetics for it as an illegal additive ^[12].