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Cyproterone acetate, applied as 1% solution in ethanol or isopropyl myristate, did not decrease the sebum excretion rate (SER) when applied to forehead skin of patients with acne, although SER is decreased when the drug is given systemically. The probable explanation is that cyproterone acetate owes its local action to a metabolite formed systemically. The present study shows this is unlikely to be the 17 beta-hydroxy cyproterone acetate.

17 alpha Propyltestosterone produced a mean inhibition of sebum excretion of 20% when it was applied topically for four weeks to the forehead skin of patients with acne.

Lipogenesis from [14C] glucose was measured in skin biopsies from the shoulder-blade region of forty-two male subjects. In the acne age range, dermal lipogenesis showed an upward trend with increasing severity of acne; a similar trend was found in forehead sebum excretion rate, but no correlation was obvious between dermal lipogenesis (back) and sebum secretion rate (forehead) in the same subject. In older subjects, dermal lipogenesis was significantly increased in those with a past history of severe acne. At high rates of dermal lipogenesis there was a small but significant increase in wax ester labelling relative to triglyceride and squalene. No increase was found in squalene labelling relative to other lipids, either with increasing lipogenic rate or in severe acne. Dermal and epidermal lipogenesis rates showed no correlation with age. In dermis, however, there was a decrease in wax ester labelling relative to triglyceride, and a marked decrease in squalene labelling relative to both triglyceride and wax esters, with increasing age.

It is argued that the close endocrine control of human sebaceous glands and the likely effects of acne on selection indicate that both gland and disease have persisted because they are biologically useful. Two possibilities are proposed: sebum may provide precursor substrates for metabolism and synthesis by the epidermis of compounds of both local and systemic importance; and the adjuvent properties of corynebacteria which colonise the active sebaceous glands of acne may facilitate certain general immunological membrane.

Thirteen patients with severe acne were treated for 16 weeks with 1.0 mg/kg/day isotretinoin. There were significant increases in serum cholesterol (P less than 0.02), triglycerides (P less than 0.02) and apolipoprotein B (P less than 0.02). No changes were found in serum apolipoprotein A-1, non-esterified fatty acids (NEFA), carnitine, lactate, pyruvate, glycerol, alanine, beta-hydroxybutyrate, glucose or insulin. We therefore found no evidence that the hyperlipidaemia of isotretinoin therapy is due to increased fluxes of NEFA from adipose tissue to the liver, although we cannot exclude the possibility that there are changes in the proportion of NEFA being esterified to triglyceride or undergoing beta-oxidation. We suggest that the hyperlipidaemia induced by isotretinoin may be due to an increase in circulating lipoprotein from increased production or impaired catabolism.

Serum lipid concentrations were measured in eighteen patients with severe acne before, during and after treatment with 0.8 mg/kg 13-cis-retinoic acid for 3 months. Cholesterol and triglyceride concentrations increased and HDL-cholesterol concentrations fell significantly during therapy. There were significant abnormalities of liver function and small decreases in indices of thyroid function. These changes had reverted to normal by 1 month after treatment. The data suggest that use of the drug in acne is likely to be limited by its toxicity.

Cimetidine, 1g orally per day, partially inhibited sebum excretion in patients with acne. Whether this was the result of H2-receptor blockade or an antiandrogen action is unknown.

Twenty-seven males with severe acne were treated for 12 weeks with 0.05 mg/kg/day isotretinoin (ten patients) or 5 mg daily cyproterone acetate (eight patients) or both drugs together in these doses (nine patients). With isotretinoin, the sebum excretion rate (SER) fell by 45% +/- 9% s.e.m. (P less than 0.0025), lesion count fell by 65% +/- 10% (P less than 0.0005) and median clinical 17% +/- 12% (NS) fall in SER, a 15% +/- 10% (NS) fall in lesion count and the median severity was unchanged. Patients unchanged. Patients treated with both drugs showed a 42% +/- 13% reduction in SER (P less than 0.005), a 68% +/- 11% decrease in lesion count (P less than 0.0005) and a decrease in median severity from 8 to 4 (P less than 0.01) which was no different from the response to isotretinoin alone. Isotretinoin increased serum cholesterol from 4.4 mmol/l +/- 0.3 s.e.m. to 4.7 mmol/l +/- 0.3 s.e.m. (P less than 0.01), serum triglyceride from 0.73 mmol/l +/- 0.07 s.e.m. to 0.96 mmol/l +/- 0.14 s.e.m. (P less than 0.05) and gamma-glutamyltransferase (GGT) from 15.9 i.u./l +/- 2.1 s.e.m. to 19.0 i.u./l +/- 2.4 s.e.m. (P less than 0.01). Comparison of the area under the concentration-time curve for triglyceride and high density lipoprotein (HDL)-cholesterol showed that the changes were smaller when isotretinoin was combined with cyproterone acetate. We conclude that the effect of isotretinoin in acne was not enhanced by the antiandrogen, but the increase in serum triglyceride and decrease in HDL-cholesterol produced by the retinoid were reduced by combination with the antiandrogen.

Lipid biosynthesis from glucose was increased in severe acne both in dermis and in epidermis which included the top portions of the pilosebaceous follicles. Both tissues retained their characteristic lipid labelling pattern. The magnitude of the increase in dermis and epidermis was similar, suggesting that epidermis may be subject to the same sebotrophic-lipogenic stimulus which affects sebaceous glands.