j. Soc. Cosmet. Chem., 42, 317-325 (September/October 1991) Quantitative assessment of spironolactone treatment in women with diffuse androgen-dependent alopecia D. HUGH RUSHTON, WALTER FUTTERWEIT, DAVID H. KINGSLEY, PHILIP KINGSLEY, and MICHAEL J. NORRIS, Philip Kingsley Trichological Clinic, London Wi, UK (D. H. R. ), Division of Endocrinology, Mount Sinai Medical Center, New York, NY (W.F.), Philip Kingsley Trichological Center, New York, NY (D.H.K., P.K.), and School of Pharmacy & Biomedical Sciences, Portsmouth Polytechnic, Portsmouth, UK (M.J.N.). Received December 16, 1990. Presented at the 16th IFSCC Congress, New York, October 8-11, 1990. Synopsis From a group of 12 Caucasian females with diffuse androgen-dependent alopecia, six were treated for 12 months with spironolactone (75 or 100 mg per day) and six remained untreated. In the untreated (control) group, mean values for total hair density (P 0.05) and meaningful hair density (P 0.01) were significantly lower 12 months later. In contrast to these findings, no significant change in total hair density or meaningful hair density could be found in treated subjects. In two women the initial dose of spirono- lactone was doubled, and treatment continued for a further 12 months in both cases increases in total hair density and meaningful hair density were observed. The androgenic hormonal variables all decreased on treatment. However, dihydrotestosterone and 3ot-androstanediol-glucuronide levels were almost 50% higher. Low-dose spironolactone, 75 to 100 mg per day, appears capable of stabilizing the course of diffuse androgen-dependent alopecia in women. Initially, dosages 150 mg per day may be necessary to improve hair quality and increase hair density. However, further long-term studies are required to confirm these findings. INTRODUCTION In women, thinning hair is predominantly a genetic condition (known as diffuse an- drogen-dependent alopecia, androgenic alopecia, androgenetic alopecia, common bald- ness, diffuse alopecia, diffuse hair loss, or female pattern baldness) that requires andro- gen-mediation for its phenotypic expression. The prevalence in women is frequently quoted to be around 30%, although precise epidemiological data are not available (1). The hair loss is typically diffuse, affecting the frontal and vertex areas with similar severity (2). Often a 1-2-cm band of denser hair is retained along the frontal hair line. A male-type pattern of hair loss, marked temporal or vertex recession, is less frequent (3). The major aesthetic change is the appearance of wider partings and a greater visibility of scalp through the hair. Changes in hair density may become apparent after 317

318 JOURNAL OF THE SOCIETY OF COSMETIC CHEMISTS an episode of increased hair shedding, but for some an insidious and gradual change occurs over many years. Diffuse alopecia in women has been associated with endocrine abnormalities, but a relationship cannot be established in all cases. Thirty per cent or more have no demon- strable endocrine abnormality (2,4-7). In Europe, the anti-androgen cyproterone acetate (CPA) has been available for many years and, in combination with ethinyl estradiol (EE2), has been successfully employed to treat acne, androgen-dependent alopecia, and hirsutism. Cyproterone acetate has never been available within the USA, and therefore an alternative anti-androgen was sought. In the late sixties, the aldosterone antagonist spironolactone was reported to have anti-androgen activity (8-10). Subsequent studies demonstrated its usefulness in the treatment of hirsutism (11-15) and acne (16,17), but only anecdotal evidence exists for androgen-dependent alopecia (17,18). Three fundamental hair variables--hair density, hair diameter, and hair length--can quantitatively characterize most scalp hair disorders. The unit area trichogram (19) is a technique capable of providing such information (20). This method has been employed to detail scalp hair changes during systemic anti-androgen therapy in women (21,22) and topical 2% minoxidil treatment in men with male pattern baldness (23). In view of the anti-androgen activity associated with spironolactone, we used the unit area tricho- gram to evaluate scalp hair in women with diffuse androgen-dependent alopecia treated for up to 24 months. METHODS AND MATERIALS SELECTION OF SUBJECTS WITH DIFFUSE ALOPECIA Twelve premenopausal Caucasian females, mean age 37 years (range 30-45 years), with diffuse androgen-dependent alopecia, participated in this study. Each had noticed cos- metically thinner hair for at least 36 months prior to entering the study. All gave their informed consent. No subject had suffered any illness lasting longer than seven days, nor had they taken prescribed medications (including oral contraceptives) or applied prod- ucts known to influence hair growth for six months prior to entering the study. None had been pregnant within the previous two years, and subsequent thyroid evaluations were all normal. None had been referred to an endocrine unit for obvious androgen excess or sought medical help for acne or hirsutism. Subjects with alopecia areata, cicatricial alopecia, or a history of thyroid dysfunction were excluded, as were those who exhibited alopecia of the male-type pattern. ALLOCATION OF CONTROLS AND SUBJECTS TREATED WITH SPIRONOLACTONE The treated group was comprised of six subjects, mean age 35 years (range 30-41 years), with total hair densities between 162 and 336 hairs per cm 2, who elected to undergo spironolactone therapy (75 or 100 mg per day) for 12 months. The control group was comprised of six subjects, mean age 38 years (range 30-45 years), matched for total hair density, who elected to remain untreated for 12 months. The duration of alopecia ranged from 3 to 16 years and was similar between and within the two groups. There was no significant difference between the mean age of control or treated subjects (unpaired