{'fraction_non_alphanumeric': 0.019604037267080744, 'fraction_numerical': 0.010675465838509316, 'mean_word_length': 5.076650943396227, 'pattern_counts': {'":': 0, '<': 1, '<?xml version=': 0, '>': 0, 'https://': 0, 'lorem ipsum': 0, 'www.': 0, 'xml': 0}, 'pii_count': 0, 'substrings_counts': 0, 'word_list_counts': {'cursed_substrings.json': 0, 'profanity_word_list.json': 0, 'sexual_word_list.json': 0, 'zh_pornsignals.json': 0}}
How robust is the methodology for trials of therapy in hirsute women?

All endocrinologists have their own preferred therapy for the medical treatment of hirsute women. Their choice is likely to be based on a combination of cumulative uncontrolled personal experience, anecdotes and published data. However, despite the plethora of publications on the treatment of hirsute women, how many studies have been controlled and in how many has there been any systematic control over the methodology? These factors are of critical importance since the clinical evaluation of hirsute women is entirely subjective. Furthermore, the most widely employed hair scoring system for hirsute women was designed to evaluate hirsutism for epidemiological studies rather than for changes in the density of hair growth (Ferriman & Gallwey, 1961). During the past 10 years, there have been 41 papers in three major clinical endocrine journals concerning the treatment of hirsute women. The journals examined were: Clinical Endocrinology, Fertility and Sterilityand theJournal of Clinical Endocrinology and Metabolism. Hair growth was measured in the majority (34) of studies by the subjective assessment of Ferriman and Gallwey (1961) and a further 3 used the method of Lorenzo (1970). Objective assessments of hair growth were given in 21 studies. There are two major issues regarding the design of these studies. First, only 6/41 were performed double blind. Secondly, the scoring systems employed are subjective yet only 3 gave data on the reproducibility of the subjective assessment. There were slightly more data on reproducibility given by those investigators who used objective measurements of hair growth but even this was <50% (10/21 studies). In contrast, details of hormone assays were given in 34 studies and 26 (72%) gave their analytical precision (CV). It appears therefore that the rigorous clinical trial methodology of double blind randomized studies with assessment of methods is not used to evaluate the reduction in hair growth by anti-androgenic therapies in hirsute women. The reason for this difference would appear to be that some of the studies did not primarily address the effect on hair growth but were designed to study the pharmacological effects of the drugs on hormonal variables. Since there is considerable variation in subjective scoring for hair growth even when assessed by the same individual, it is questionable how valid are the reports of subjective changes in hair growth. Moreover, under these circumstances the statement in numerical format of changes in hair growth and their statistical evaluation is inappropriate. It is likely that the results of many of these studies will be used to justify the use of these agents for the treatment of hirsute women despite the lack of critical measurement. The use of high rather than low dose cyproterone acetate (CPA) may be cited as an example. The high dose formulation is based on the studies by Hammerstein (reviewed 1990) in which the beneficial effect of CPA is based on the higher rate of patient ‘improvement’; but no definition of improvement is given despite the studies having been performed in a number of different centres. This high dose regimen is still employed despite the lack of support for a dose effect in 3 dose-ranging studies. It is necessary for hair growth assessment methods to be standardized and controlled. First, individuals have fixed beliefs in the efficacy of various therapies. Secondly, with subjective scoring systems, there is considerable inter-observer variation; and thirdly, there is a degree of intra-observer variation. It is difficult to quantify the degree of this latter effect since so few investigators publish these data. However, my experience (Barthet al., 1989) of using the Ferriman and Gallwey scale shows a reproducibility index of 3 points (Bland & Altman, 1986). This should be interpreted in the light of most hirsute women having a total score of approximately 12–30. While this imprecision of method does not necessarily invalidate studies, it may explain the discrepancy between open investigations and the views of sceptical physicians. Since the standard subjective scoring system for hirsutism designed by Ferriman and Gallwey was designed for epidemiological studies, other systems have been designed to measure both density and distribution of hair. Although these would be more appropriate for therapeutic studies of hirsute women, they are quite complex and difficult to learn and have not gained popular support. The use of objective measurements of hair growth would seem to be an alternative; but has problems in standardization. There is considerable variation in hair shaft size within any given area which requires large numbers of hairs to be measured. Secondly, hair shafts are oval and twisted and the diameter will depend on the angle at which the hairs are viewed. Thirdly, sensitivity of hairs to androgenic stimulation varies over the body and therefore the response to treatment can be dependent on the site of hair sampling. Some of the papers that have used objective measurements of hair Commentary