Bruinsma et al. BMC Public Health 2011, 11(Suppl 5):S7 http://www.biomedcentral.com/1471-2458/11/S5/S7 Background Very little information is available on the evolution of the use of high dose oestrogens as a treatment for tall stature in healthy adolescents. After the successful use of this treatment in children with pituitary gigantism in the 1940s [10], clinicians in the United States (US) extended the treatment to tall girls with concerns about their height but who had no associated pathology [3]. The first report of treatment of tall girls was published in 1956 [11]. There have been no randomised controlled trials of treatment effectiveness, and cohort studies have demonstrated that treatment is only moderately effective [9]. Despite this, the treatment became an accepted clin- ical practice in many countries including Australia [12,13]. Treatment was based on the knowledge that normally in puberty oestrogen inhibits further increases in height by fusing the epiphyses (growth-plates) of the long bones. Most treating clinicians considered treatment acceptable if a girl’s adult height was predicted to be above the 97th percentile or two standard deviations above the mean female adult height in the given popula- tion [2,4]. Determination of predicted adult height involved estimating bone age after an x-ray of the hand and wrist and assessing the remaining growth potential [14-16]. The various methods for calculating predicted adult height are prone to error [17]. The earliest predicted height criterion for oestrogen treatment in the US was 173cm in 1956 [11,18,19] and this gradually increased over time but continued to fluc- tuate between countries. During the 1970s, Australian girls with a predicted adult height of ≥177cm were eligi- ble for treatment [2]; in the US, girls whose predicted adult height was above 173cm [20] or 182.9cm [21] were also treated; and in Germany and the Netherlands the treatment criterion was a predicted height of ≥180cm [22,23]. Age at initiation and duration of treat- ment also varied considerably and was strongly asso- ciated with overall treatment effectiveness. The clinical challenge was that the accuracy of predicting adult height increased after the age of ten years (or closer to puberty) however the potential height reduction dimin- ished [24]. Some clinicians waited until girls grew to an arbitrary height before initiating treatment: 167cm in Australia [2]; 169.5cm in the US [24]; and 170cm in Europe [25]; while others waited until girls reached pub- erty when they were more likely to be psychologically ready for the effects of treatment on their development but when treatment may be less effective [26]. Duration of treatment varied but was generally two to four years [2,23,27]. Treatment regimes varied considerably and initially were a combination of oestrogen and testoster- one [11]. Various preparations of oral synthetic [2,23,28] or conjugated oestrogens [25] were given continuously Page 2 of 8 or cyclically; oestrogen pellets were inserted under the skin at six monthly intervals [29] for some; and intra- muscular injections of oestrogen were given to others [24,26,30,31]. The rationale for treatment was to reduce perceived psychosocial ‘risks’ tall girls may face in adulthood. These included physical deformity, through tall girls’ adoption of slouching in an effort to reduce their height; and psychological distress and social withdrawal as a consequence of tall girls’ difficulty conforming to cul- tural stereotypes [2,3,18,24,32,33]. However, there was very little reporting of any evidence for these assump- tions [13] and there are very few published studies reporting psychosocial outcomes following treatment. Three relevant studies [33-35] were limited by small sample sizes, the participants being still relatively young, and the fact that the investigators were treating clini- cians which may have affected responses. While treat- ment is relatively uncommon now in Australia, it was still being used in the US in 2002 [36]; is currently recommended for the management of familial tall sta- ture [37]; and more controversially has been proposed as a form of clinical management of disabled children to reduce their height and increase manageability [38]. The use of synthetic oestrogens as a medical treat- ment to reduce the height of tall girls was relatively unknown among the general public during the decades it was at its peak in Australia and elsewhere. Even within some families a girl’s height assessment and treatment was kept a secret from other family members. Public awareness of the treatment of tall girls came about in Australia in 1997, when the treatment became part of a wider debate in the Australian Federal Parlia- ment on the use of human biological products and post- war medical experimentation [39]. Subsequent to the media coverage of this issue, the need for a comprehen- sive follow-up study was raised independently both by Australian endocrinologists and by women who had been assessed and treated for tall stature as adolescents. These women formed a lobby group, Tall Girls Inc., to petition the government for a follow-up study citing a range of health concerns and that their families had been unaware of the experimental nature of this treat- ment [40]. Clinicians and Tall Girls Inc. alike had concerns about the possibility of long-term effects of oestrogen treat- ment, particularly exposure to diethylstilboestrol (DES), which is associated with serious adverse outcomes when given to pregnant women [41,42]. In early 1998, the paediatric endocrinology group at the Royal Children’s Hospital was under increasing pres- sure to conduct a follow-up study to examine long-term outcomes of treatment and was looking for a group of researchers with whom to collaborate. Researchers at La