Public health research is an endeavour that often involves multiple relationships, far-reaching collaborations, divergent expectations and various outcomes. Using the Tall Girls Study as a case study, this paper will present and discuss a number of methodological, ethical and legal challenges that have implications for other public health research.
The Tall Girls Study was the first study to examine the long-term health and psychosocial effects of oestrogen treatment for tall stature.
Looking back in time: conducting a cohort study of the long-term effects of treatment of adolescent tall girls with synthetic hormones, BMC Public Health, BioMed Central, DOI: 10.1186/1471-2458-11-S5-S7, 25 November 2011.
In undertaking this study the research team overcame many hurdles: in maintaining collaboration with treating clinicians and with the women they had treated as girls – groups with opposing points of view and different expectations; using private practice medical records to trace women who had been patients up to forty years earlier; and exploring potential legal issues arising from the collection of data related to treatment.
While faced with complex challenges, the Tall Girls Study demonstrated that forward planning, ongoing dialogue between all stakeholders, transparency of processes, and the strict adherence to group-developed protocols were keys to maintaining rigour while undertaking pragmatic research.
Public health research often occurs within political and social contexts that need to be considered in the planning and conduct of studies. The quality and acceptability of research findings is enhanced when stakeholders are engaged in all aspects of the research process.
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 , clinicians in the United States (US) extended the treatment to tall girls with concerns about their height but who had no associated pathology. The first report of treatment of tall girls was published in 1956. There have been no randomised controlled trials of treatment effectiveness, and cohort studies have demonstrated that treatment is only moderately effective. Despite this, the treatment became an accepted clinical practice in many countries including Australia.
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 population. Determination of predicted adult height involved estimating bone age after an x-ray of the hand and wrist and assessing the remaining growth potential. The various methods for calculating predicted adult height are prone to error.
The earliest predicted height criterion for oestrogen treatment in the US was 173cm in 1956 and this gradually increased over time but continued to fluctuate between countries. During the 1970s, Australian girls with a predicted adult height of ?177cm were eligible for treatment; in the US, girls whose predicted adult height was above 173cm or 182.9cm were also treated; and in Germany and the Netherlands the treatment criterion was a predicted height of ?180cm. Age at initiation and duration of treatment also varied considerably and was strongly associated 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 diminished. Some clinicians waited until girls grew to an arbitrary height before initiating treatment: 167cm in Australia ; 169.5cm in the US ; and 170cm in Europe ; while others waited until girls reached puberty when they were more likely to be psychologically ready for the effects of treatment on their development but when treatment may be less effective. Duration of treatment varied but was generally two to four years. Treatment regimes varied considerably and initially were a combination of oestrogen and testosterone. Various preparations of oral synthetic or conjugated oestrogens were given continuously or cyclically; oestrogen pellets were inserted under the skin at six monthly intervals for some; and intramuscular injections of oestrogen were given to others.
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 cultural stereotypes. However, there was very little reporting of any evidence for these assumptions and there are very few published studies reporting psychosocial outcomes following treatment. Three relevant studies were limited by small sample sizes, the participants being still relatively young, and the fact that the investigators were treating clinicians which may have affected responses. While treatment is relatively uncommon now in Australia, it was still being used in the US in 2002 ; is currently recommended for the management of familial tall stature ; and more controversially has been proposed as a form of clinical management of disabled children to reduce their height and increase manageability.
The use of synthetic oestrogens as a medical treatment 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 Parliament on the use of human biological products and post-war medical experimentation. Subsequent to the media coverage of this issue, the need for a comprehensive 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 treatment.
Clinicians and Tall Girls Inc. alike had concerns about the possibility of long-term effects of oestrogen treatment, particularly exposure to diethylstilboestrol (DES), which is associated with serious adverse outcomes when given to pregnant women.
In early 1998, the paediatric endocrinology group at the Royal Children’s Hospital was under increasing pressure 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 Trobe University who were interested in the research and had significant experience in conducting long-term follow-up studies in women’s health met with treating clinicians. Following an agreement for the need for a study and for formal collaboration, a period of intense discussion and consultation was undertaken with all parties to formulate the study design and research questions. Given their investment in the project and the sense of disenfranchisement that many treated tall girls felt from the original decision-making, Tall Girls Inc. and particularly the president, Janet Cregan-Wood, were involved from inception in the study design process. In 2000, the National Health and Medical Research Council (NHMRC) provided funding for the study (known as the Tall Girls Study).
… click to download the full paper.
More DES DiEthylStilbestrol Resources