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• W1993117675 abstract "In this issue, Ranke et al. [1] report a retrospective analysis of their institution’s decades long experience with growth hormone (GH) treatment of girls with Turner syndrome (TS), confirming previous observations by them and others that height outcome is determined by stature at the start of therapy (a reflection of the influence of familial stature, demonstrated by Lemli and Smith [2] a half century ago), GH dose, and initial (1st year) response. Serum IGF-1 and IGFBP3 levels were not a factor. Notable in this and other studies is the wide range of individual responses to GH treatment that make it important that patients and parents understand the uncertainty of outcome.In the 2007 Cochrane analysis, only 4 randomized controlled trials of GH treatment of TS were identified, including a total of 365 girls who had an average increase in growth velocity of 3 cm in the first year of treatment and 2 cm in the second year; only one trial reported adult height, in 61 women, to be 148 cm versus 141 cm in 43 untreated women [3]. The authors noted the absence of information about the effect of treatment on quality of life (QOL). Since the Cochrane report, the long-term placebo-controlled trial from the US National Institutes of Health (NIH) with 91 subjects followed to adult height has been published [4]. Ross et al. found that the introduction of very-low-dose oral ethinyl estradiol from age 12, to correspond with physiologic pubertal timing, had a moderately synergistic effect in promoting growth when used in combination with GH therapy.It has been suggested by Mah et al. [5] that the use of transdermal estrogen is associated with higher IGF-1 levels, lower waist-hip ratios, and greater GH sensitivity than with oral estrogen. For these reasons, very low doses of transdermal estradiol are now recommended for pubertal induction in girls with TS. In the study by Ranke et al. [1], the majority of subjects received oral conjugated estrogens as had been common practice for pubertal induction in this population. It is possible that greater gains in adult height would have been seen if these patients had been receiving less aggressive replacement with transdermal estradiol.In addition to the enhancement of GH effect with judicious estrogen replacement, the addition of small doses of oxandrolone needs to be considered. A recent study documented that the typical doses used (0.06 mg/kg/day) had an insignificant beneficial effect on growth response to GH, but that half this dose resulted in a mean height gain of 9.5 cm compared to 7.2 cm for GH plus placebo [6].Commenting on the NIH study, Cuttler and Rosenfield [7] editorialized that the decision to treat ‘take into account subjective factors such as perceptions, beliefs, and attitudes, as well as physiological data and scientific evidence’. Similarly, the Cochrane report notes: ‘A full consideration of the costs and benefits of hGH treatment in TS should include not only effects on height, but other outcomes such as psychological or cognitive effects, which in the past have received little attention in the evaluation of hGH in TS’ [3]. This is reasonable advice. Indeed, affected individuals are more distressed by infertility than stature [8]. A French study of over 500 women with TS found no association between QOL and height or estimated height gain from GH treatment. Furthermore, higher expectations from treatment were associated with lower QOL [9]. A recent Swedish study comparing 111 women with TS to a control population confirmed these observations [10].Current guidelines do not question the decision to treat girls with TS with GH [11], despite the absence of scientific evidence of health or QOL benefit for this costly intervention. Individuals who reach a height that is more normal are thought to have higher self-esteem, fewer physical obstacles, and more successful social lives and careers, but such observations have not been controlled nor can the effects of estrogen replacement be separated from those of growth promotion [12]. Possible benefits from height promotion must be weighed against the possibility that pharmacological doses of GH might adversely affect metabolism and mitogenesis over the long term. Initiation of GH therapy should be an individualized decision for each patient and her family." @default.
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• W1993117675 title "Growth Promotion in Turner Syndrome" @default.
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