Marty E. Sawaya

Alopecia: unapproved treatments or indications

There are various forms of alopecia, the most common being “androgenetic alopecia” (AGA), which affects millions of men and women. For both men and women, AGA may begin as early as the teen years but can even start in later decades of life. The severity of hair loss in women is usually much less than in men.1 In men with AGA, one of the earliest findings is an increase in the percentage of hairs in a telogen phase of the hair cycle, so that initial hair loss may appear indistinguishable from a telogen effluvium. As in men, AGA in women can be psychologically devastating to accept, giving an overall less body-image satisfaction and making it difficult to cope and retain integrity of personality functioning.2 Androgenetic alopecia has been reported to be a polygenic autosomal trait that is thought to involve several genes3 for both men and women.

Steroid chemistry and hormone controls during the hair follicle cycle.

Human hair follicles contain several steroid enzymes capable of transforming weak androgens, such as dehydroepiandrosterone, into more potent target tissue androgens, such as testosterone and dihydrotestosterone. Kinetic constants have been evaluated for the 3-alpha, 3-beta, and 17-beta hydroxysteroid dehydrogenase enzymes, 5a-reductase, and the aromatase enzyme in isolated human HF from scalp of men and women with androgenetic alopecia. The apparent Km values did not differ for each enzyme whether present in bald, receded HF or thick, anagen HF of men or women. However, levels of specific activity varied greatly in the frontal versus occipital HF analyzed. The androgen receptor content and activation factors also differ between men and women. The steroid mechanisms influencing AGA in men and women may be similar, but differences in the specific activity/amounts of enzymes, receptors, and activation factors differ between men and women. These findings may explain the varied clinical presentations of men and women with AGA, and may shape treatment options for the future.

Androgenetic alopecia. New approved and unapproved treatments.

Although there are new FDA-approved drug therapies to treat hair loss, there are many unapproved agents with claims of effectively treating hair loss. A variety of new over-the-counter agents are available for consumers to use; however, it is difficult to assess how these agents work, costs of these agents, and efficacy. This article covers the new approved and the large multitude of unapproved treatments that are used to treat hair loss.

Caspase-1 level is higher in the scalp in androgenetic alopecia.

Background and objectives Inflammasomes that activate caspase‐1 govern the innate immune inflammatory response. Whether hair loss associated with androgenetic alopecia (AGA) involves caspase‐1 activation is not known. Methods Immunohistochemical staining for caspase‐1 was performed on scalp tissue sections, and protein lysates were analyzed from individuals with AGA (no treatment), and individuals with AGA taking finasteride with apparent hair growth, individuals with AGA taking finasteride without noted hair growth, and normal controls. In vitro studies of human keratinocytes were conducted to establish effects of finasteride, dihydrotestosterone (DHT), and testosterone on caspase‐1 levels using immunoblot analysis. Results Caspase‐1 is expressed in normal human adult epidermal keratinocytes. Caspase‐1 expression is greater in men with AGA. In contrast, in men taking finasteride, caspase‐1 levels were lower and were similar to those in normal controls. In vitro studies showed that keratinocytes treated with finasteride in combination with testosterone or DHT resulted in a significant decrease in caspase‐1 expression. Conclusion In vivo and in vitro finasteride treatment resulted in lower caspase‐1 expression, supporting the idea that androgens influence innate immunity involved in the hair cycle in AGA. These findings may provide a basis for development of novel treatments for inflammatory skin and hair diseases.

CLINICAL UPDATES IN HAIR

It is now known that there are major differences in the systemic and cellular mechanisms that mediate hair loss in women versus men. The severity or degree of hair loss in women with androgenetic alopecia is usually much less than in men. It is usually assumed that the hormonal basis for androgenetic alopecia in women is the same as in men; that is, the same target tissue-active androgens, testosterone and dihydrotestosterone, are being produced systemically to aggravate scalp hair follicles, resulting in hair loss. This article reviews some of the latest findings in androgenetic alopecia for both men and women, along with new and old treatments and drugs, doses, and effectiveness. Research findings indicate that levels of androgen-metabolizing enzymes and receptors differ in the scalps of women versus men, which may be important in formulating more effective hair growth treatments in the future.

Oestrogen and progesterone receptors in lentigo maligna

We have measured oestrogen and progesterone binding in specimens of histopathologically confirmed lentigo maligna (LM) lesions excised from five elderly white men, using a dextrancoated charcoal method. Oestrogen binding was observed in four of the five specimens, and progesterone binding in all five. Marginal normal skin showed only non‐specific binding for oestrogen and progesterone. The presence of steroid hormone receptors in LM suggests the possibility that hormone responsiveness may be relevant in the transformation of a lentigo maligna into malignant melanoma.

Hair Loss and Hirsutism in the Elderly

This article contains a brief review of hair follicle biology, followed by a presentation of the workup of elderly patients who present with hair loss or hirsutism. Common hair disorders, such as graying, telogen effluvium, androgenic alopecia, senescent alopecia, alopecia arcuata, hirsutism, and hypertrichosis, are discussed.

Interleukin 1 protects hair follicles from cytarabine (ARA-C)-induced toxicity in vivo and in vitro.

ImuVert, a biologic response modifier, and interleukin 1 (IL 1) have been shown to protect the young rat from alopecia induced by cytarabine (ARA‐C). In the present study the inhibition by ARA‐C of DNA synthesis in hair follicles (HFs) and the protective effect of ImuVert and IL 1 were investigated in vivo and in vitro. Both ImuVert and IL 1 were equally effective in protecting rats from ARA‐C‐induced alopecia. DNA synthesis in HFs isolated from ARA‐C‐treated animals was 10–20% of untreated controls. Follicles isolated from animals given either ImuVert or IL 1 before ARA‐C exhibited normal DNA synthesis. In vitro, the incubation of normal rat HF with ARA‐C resulted in 80% inhibition of [3H]‐thymidine uptake. Preincubation of the follicles for 1 hr with IL 1 before the addition of ARA‐C completely blocked the inhibition. Preincubation with imuVert, however, was less effective in blocking the inhibition from ARA‐C.—Jimenez, J. J.; Sawaya, M. E.; Yunis, A. A. Interleukin 1 protects hair follicles from ARA‐C‐induced toxicity in vivo and in vitro. FASEB J. 6: 911‐913; 1992.

Transformation of dehydroepiandrosterone into dihydrotestosterone by isolated cells from rat preputial gland.

After the rat preputial gland was treated with collagenase and trypsin, five bands of cells were isolated by centrifugation in Ficoll gradients. Homogenates of the heavier cells (Bands IV and V) which contained less lipids, were more active than the homogenates of the lighter cells (Bands I, II and III) in transforming [1,2-3H]-dehydroepiandrosterone ([1,2-3H]-DHA) into [3H]-androstenedione and [3H]-testosterone and the latter into [3H]-dihydrotestosterone (DHT). In the presence of NAD, NADH and NADPH-generating system, [1,2-3H]-DHA was transformed into [3H]-DHT in 50-60% yield by homogenates of cells in Bands IV and V. DHT levels in the preputial gland were measured by radioimmunoassay. The levels in female rats reduced by 77% from 3.14 +/- 0.27 to 0.72 +/- 0.10 pg/mg tissue after adrenalectomy, and by 45% to 1.71 +/- 0.10 pg/mg tissue after ovariectomy. In male rats, the level reduced by 15% from 4.58 +/- 0.55 to 3.88 +/- 0.62 pg/mg tissue after adrenalectomy and by 40% to 2.74 +/- 0.21 pg/mg tissue after orchidectomy. These results demonstrated the transformation of DHA into DHT in the preputial gland of the rat, and that the adrenal is an important source of precursor steroid (DHA) for DHT formation in the preputial gland.