British Journal of Dermatology (1991) 124, 361-364. ADONIS 000709639100084G Isotretinoin treatment alters steroid metabolism in women with acne M.RADKMAKER. M.WALLACE.* W.CUNLIFFEt AND N.B.SIMPSON Departments of Dermatologii and "Biochemistrii. Glasgow Roijal Inftrmarij. Glasgow • ^Department of Dermatology, Leeds General Infirmarij. l^eds. U.K. Accepted for publication 1 October 1990 Summary The effect of isotretinoin (Roaccutane) on serum steroids and urinary steroid metabolites was investigated in seven female patients receiving the drug for treatment of severe acne over a 16-week period. Serum concentrations of deiiydroepiandrostcrone suiphate (DHAS). androstenedione (A2). and free androgen index (FAl) were not significantly altered. There was a significant fall in testosterone during treatment and a signiticant reduction in the 24 h urinary excretion of androsterone. tetrahydrocortisone (THE) and tetrahydrocortisol (THF) from week 8 onwards and for aetiocholanolone and allo-THF from week 12 (P<() 05). Although pretreatment levels of urinary steroid metabolites were not abnormal, the ratios of the 5a/5// metabolites (androsterone:aetiocho- lanolone and allo-THF:THF) were at the upper limit of the reference range and were lowered after treatment, suggesting that 5a-reductase activity is sensitive to isotretinoin. Tsotretinoin suppresses sebaceous gland activity by blocking the differentia lion of basal cells into sebocytes.' The exact mechanism is not known but because these glands are androgen-responsive the effects of isotreti- noin on androgens have been investigated. A number of studies suggest that sebaceous gland inhibition is not hormonally related but may cause secondary changes in the activity of the skin steroid 5a-reductase.^ To obtain more information on the response of steroid Sa-reduc- tion to treatment with isotretinoin we measured urinary steroid metabolites by capillary column gas liquid chromatography and serum androgen levels (testo- sterone, androstenedione (A2). and dehydroepiandro- sterone sulphate (DHAS)) by radioimmunoassay during the course of 16 weeks of therapy with isotretinoin (Roaccutane). Methods Subjects Seven women, median age 26-7 years (range 18-44 years) with persistent acne that was non-responsive to antibiotics were studied. All were using barrier methods of contraception and had a normal menstrual pattern with regular cycles of between 21 and 35 days. There was no evidence of hirsutism, hair loss or virilism. Correspondence: Dr M.Rademaker. Department of Dennatology. Glasgow Royal Infirmary. (liasgow CA OSF. U.K. Pretreatment liver function and fasting serum lipids were normal and remained so during treatment. All seven women were given a 16-week course of isotreti- noin (Roaccutane. Roche Products Ltd) at a dose of i mg/kg/body weight per day. The mean total acne grade' before starting was 3 5 (95% confidence interval, 0 3- 6 6) with a mean facial gradeof 1 4 (01-2-7). Twenty- four-hour urine samples were collected Immediately before starting the drug and at 4-weekly intervals thereafter. Facial and total acne were also scored at monthly intervals.' Hormone analysis Sex hormone binding globulin (SHBG) was measured by time-resolved fluoroimmunoassay ('Delfia' SHBG kits. Pharmacia). Testosterone. DHAS and A2 were mea- sured by conventional 'in house" radioimmunoassays. Derived free testosterone levels were calculated from the total testosterone and SHBG according to the method of Nanjee and Wheeler.'* Urinary steroid profiles analysis was performed by capillary column chromatography by a method similar to that of Bevan ct al.'' Separation of steroid methyloxime-trimethylsilyl ether derivatives was carried out on a model 438 gas chromatograph (Packer- Becker BV. Delft. The Netherlands) fitted with a 'Flexsil' 2 5 mxO-52 mm capillary column coated with OV-1 (Phase-Sep. Queensferry. Clwyd). Measurements were made of the most abundant androgen metabolites 361