F. J. Ebling

Control of hidradenitis suppurativa in women using combined antiandrogen (cyproterone acetate) and oestrogen therapy

The effects of combined treatment with the antiandrogen, cyproterone acetate, and ethinyl oestradiol on four women with long‐standing hidradenitis suppurativa have been investigated. The condition was controlled successfully in all patients with 100 mg/day cyproterone acetate using the reversed sequential regimen; lowering the antiandrogen to 50 mg/day caused deterioration. Before treatment, plasma testosterone levels were within the normal range, but plasma androstenedione values were raised and sex hormone binding globulin levels were low. On treatment, the androstenedione concentration fell and sex hormone‐binding globulin values were raised. However, since these levels were unaltered by reducing the antiandrogen dosage, the main action of the therapy is probably that of the antiandrogen within the target cells.

The hair cycle on the human thigh and upper arm

Hair follicle density, and definitive length, root status and rate of growth of hairs were determined for defined areas of the thigh and upper arm in 11 females and nine males aged 20–30 years. Hair follicle density did not differ between males and females. However, on the thigh the definitive length of hair was on average three times greater in males. This was attributable mainly to a longer duration of anagen (×2.46), but also to a greater rate of growth (×1.22). On the upper arm the hair was only 1.42 times longer and the duration of anagen only 1.27 times greater in males than in females. On the thigh the estimated average duration of anagen was 54 days in males and 22 days in females, with corresponding figures of 151 days and 84 days for the complete cycles. On the upper arms the duration of anagen was 28 days in males and 22 days in females, with corresponding figures of 108 and 106 days for the complete cycle. In females, oral contraceptives had no significant effects on any measurement.

THE PATHOGENESIS OF ALOPECIA AREATA

SUMMARY.— The pathogenesis of alopecia areata was studied by plucking hairs from each of a series of concentric zones, using felt patterns placed over lesions. It was possible to group lesions according to the zone with the greatest proportion of club hairs. The results are logically interpreted to mean that a wave of hair follicle damage or arrest moves centrifugally from a focal point beyond the area of alopecia.

HAIR LOSS IN WOMEN

HAIR loss in women usually causes disproportionate anxiety, often because of groundless fears of total baldness. Dermatologists in the United States of America, Italy and France (Sannino and Montemiuri, 1957; Sidi and BougeoisSpinasse, 1958; Sulzberger, Witten and Kopf, 1960) have seen increasing numbers of women with this complaint, but whether the condition is becoming TTiore common, or whether complaints are due to an increasing awareness of the appearance of hair in affluent societies, it is impossible to say. Post-partum and post-febrile hair loss is caused by a sudden shedding of club hairs, known as telogen effluvium and is usually temporary (Guy and Edmundsen, 1960; Kligman, 1961). Relatively little is known about the dynamics of other types. When hair loss is sufficiently severe to cause obvious thinning, two main patterns are evident. Either there is frontal recession with some central thirming similar to that seen in hereditary baldness of the male, or there is diffuse thimiing over the vertex with retention of the normal hair line. Cases in which such diffuse thinning is limited to an orbicular zone around the crown have been differentiated into a third group— skullcap alopecia by Ludwig (1904). In women, mild patterned baldness of the male type, involving temporal recession but not loss from the crown, was found by Hamilton (1951) to increase in incidence from the age of 20 to a maximum of 25% at 45, but not thereafter, as it does in males. No types of advanced baldness were seen in his group of 214 Caucasian women between the ages of 20 and 89. Patterned baldness appears, as in the male, to have an hereditary component. Wlien families of women with this condition were compared with those of patients with alopecia areata and of normal controls, Smith and Wells (1964) found a higher incidence of male-type baldness among the females as well as among the males. They concluded that the genetic mechanism was probably that of a dominant with partial penetrance, the penetrance being greater in the male than in the female, though they did not rule out the possibility of multifactorial inheritance.

Failure of progesterone to enlarge sebaceous glands in the female rat.

THERE have been eonfiicting re])orts on the effects of progesterone on sebaceous glands. On the one hand, Haskin, Lasher and Rothman (1953) and Lasher, Lorincz and Rothman (1954) have stated that its stimulatorv action on the sebaceous glands of spayed adult rats is comparable Avith that of testosterone. Zeligman and Hubener (1957) ha^e claimed that it produces mild to moderate aene in Avonien, invohdng slight l)ut not statistically significant enlargement of the sebaceous glands. On the other hand, Ebling (1948) found no eAadenee that the sebaceous glands of intact immature rats were affected by progesterone (1 mg. daily for 20 days) e en though they Avere markedly enlarged by a similar dose of testosterone. These findings are in line with those of Jarrett (1959) Avho shoAved that Avhereas testosterone both increases sebum production and aggraA^ates the lesions of acne vulgaris in man, progesterone has neither of these effects. The contradiction betAveen the results of Haskin et al. (1953) and those of Ebling (1948) might have one of several explanations. First, Ebling used intact rats and Haskin et al. used spayed ones : it is possible that the efFeets of progesterone can be prevented or offset by the presenee of the ovaries, sinee it is Avell established that oestrogens reduce the size of the sebaceous glands (Fbling, 1948, 1954, 1955). Seeondly, the responses of immature rats as used by Ebling may not be the same as those of adult rats as used by Haskin et al. The sebaceous gland may resemble the mammary in that it only responds to progesterone after priming Avith oestrogen. The experiments reported here were designed to investigate these hypotheses.

The sebotrophic action of growth hormone (BGH) in the rat.

Sebum production of rats was assessed by measuring the levels of fat cxtractable by diethyl ether from samples of hair clipped immediately after shampooing with sodium lauryl sulphate and 2 days later. By the use of matched litter mates it was unequivocally demonstrated that the response of the sebaceous glands to testosterone is virtually abolished by hypophysectomy and that it can be completely restored by pure bovine growth hormone.

Is the metabolism of testosterone to 5α-dihydrotestosterone required for androgen action in the skin?

The assumption that the metabolism of testosterone to 5α‐dihydrotestosterone (5α‐DHT) is required for androgen action in the skin was investigated by studying the uptake and metabolism of testosterone by skin and other tissues of the rat in vivo. The skin resembled the classical androgen target organs in the uptake and retention of radioactivity, but the proportions of the steroids present were markedly different. In the ventral prostate most of the testosterone was metabolized, mainly to 5α‐DHT, after only 20 min. In the skin testosterone was always the predominant steroid identified and androstenedione, 5α‐DHT, 5α‐androstane‐3α, 17β‐diol, androsterone and 5α‐androstane‐3β, 17β‐diol were only present in much smaller quantities, even after 5 h.

Steroid inhibitors of androgen-potentiated actions on skin.

Antiandrogens, such as cyproterone acetate, and oestrogens both inhibit sebaceous secretion in rats and have a potentiality for the treatment of hirsutism and acne in the human female. However, they act at different points. In castrated rats treated with testosterone, 3 micrograms/day oestradiol produced a greater decrease in sebum secretion than a dose of cyproterone acetate over 1000 times larger; moreover the antiandrogen reduced the incidence of sebaceous mitoses whereas the oestradiol did not. In hirsute women, oral administration of 100 mg of cyproterone acetate daily caused a 40% reduction in sebum secretion within 10 days; a further 20% was subsequently produced by combined therapy with cyproterone acetate and ethinyloestradiol. Significant decreases in the diameter and rate of growth of thigh hairs were not established until around the fourth monthly cycle of treatment. The actions were believed to be mainly peripheral, though contributory factors could also have been the small but significant reductions in plasma androgens produced by the antiandrogen, and the marked rise in sex hormone binding globulin produced by the oestrogen. That it is theoretically possible for cyproterone acetate or oestradiol to act locally follows from an unequivocal demonstration that either compound produced a local depression of sebum secretion when applied topically to rats.