SOME NEW CONSIDERATIONS ABOUT THE CHEMISTRY OF ACNE VULGARIS By THELMA GOLUB WARSHAW, M.D. Presented at the May loth, 1957, Meeting of the Society of Cosinetic Chemists, New York City. TaE FO•.•.OW•NG discussion about the pathologic mechanism causing acne vulgaris is offered in all humility, on the basis of. medical practice, clinical research and arm-chair philosophy. The theory to be presented is, to this observer, the most plausible key to the pathogenesis of acne vulgaris, and is the simplest explanation for all the known facts about the condition. The prevailing dermatological thought about acne vulgaris is that it is a sebaceous gland dysfunction of the adolescent years, predicated upon an androgen plus progesterone/estrogen imbalance. Androgen is male sex hormone, estrogen and progesterone are female sex hormones. It is considered that androgens tend to predominate, and that the adrenal cortices are ii• some way involved. Secondary infection of the basic acne lesionq the blackhead or comedone--produces the pustules of ache. At this point it is necessary to realise that repeatedly observed clinical and laboratory data about acne are factual but some serious illogic is involved in the current explanatory theory of androgen/estrogen imbalance. 1. It is a fallacy to assume that, because events coincide chronologically, they are causally related. For example, the epiphyses of the long bones fuse during puberty, but that does not mean that epiphyseal union is a cause of the acne of adolescence. In like fashion, it is very questionable that, because androgens and estrogens come into play during adolescence, they therefore must cause acne. 2. It is erroneous to assume that factors that have an influence upon a situation must necessarily cause that situation. For example, bacterial infection can cause pustular lesions in acne, but that does not mean that bacterial infection causes acne. In like fashion, the androgens, progesterones, and estrogens that come into play during the teen years persist throughout a great part of mature life, when acne vulgaris is not generally present. These hormones influence the course of ache, but do not produce acne. A study on the urinary excretion of 17 ketosteroids (a neutral hormone that represents androgen and adrenal cortical activity) showed no difference in values between acne and non-acne patients. In the same study, the 17 KS/estrogen ratios were the same in normal persons as in acne patients. • It has been observed that administration of the androgen, testosterone, can produce an acneform eruption however, even in boys 50 to 70 per cent of the body steroid output (that is measured by 17 KS excretion) comes 252

THE CHEMISTRY OF ACNE VULGARIS 253 from the adrenal cortical hormones. Adrenosterone, the adrenal cortical androgen, is only very weakly androgeric, and only an abnormal variant of adrenosterone is secreted in adrenal virilising turnouts, where acne results. • 17-Hydroxy progesterone, an intermediary product in the metabolism of adrenal cortical hormones, has marked androgenic effects. a These evidences thus argue against androgens alone being etiologic in acne vulgaris. 3. It is customary to speak of an acheform eruption that follows the use of ACTH, cortisone and its derivatives. This acne is referred to as steroid acne and is a simple case of poor semantics. Estrogen, which is known to inhibit ache, is asteroid also, 'and has that same phenanthrene nucleus common to all steroids. A more apt name here would be ache due to adreno- tropic and adrenal cortical hormones. 4. Another fallacy is the assumption that the androgen/estrogen ratio must be out of balance in acne vulgaris, because estrogen is antagonistic to androgen and because estrogen inhibits acne. It is necessary to look further to see what other hormones are antagonistic in effect to estrogen. A new field then appears, where estrogen is antagonistic to pituitary growth hormone, to gonadotropic hormones of the anterior pituitary, and where estrogen has other effects, such as the ability to stimulate adrenotropic hormone production. • 5. Negative evidence must be weighed with care. For example, to say that an object is not green, does not mean that the object is blue. It could be violet, yellow, or red also. The effect of testosterone in producing acne has been supported by the observation that prepubertal castrates and eunuchoid males do not develop the skin condition. Other factors enter here. These abnormal individuals also do not develop beards, have altered body growth and hormone output, and do not present the usual emotional adaptation problems of adolescence. , 6. Lest it still is a temptation to ascribe acne entirely to hormonal aberrations, it should be noted that other mammalsmthat have hormone systems--nevertheless do not have ache. 4 When the current misconceptions are laid aside, then slightly more rigorous thinking may be indulged. To begin the development of a more rational theory, some fairly definite facts about sebaceous glands, adolescence and acne vulgaris must be reviewed. The sebaceous glands, which are the site of acne, empty into tke hair follicle, the whole being referred to as the pilosebaceous apparatus. Like other organs and systems, the sebaceous glands enlarge markedly in size during adolescence and the secretion of sebum has been found 'to be propmtionate to the gland surface. * How,ever, the sebum output fails to a stationary level between ages 20 to 25, 0 while the gland surface area remains the same. So another additional reason for the highly' accelerated