Auxological outcome and time to menarche following long-acting goserelin therapy in girls with central precocious or early puberty

W F Paterson, E McNeill, D Young, M D C Donaldson
Clinical Endocrinology 2004, 61 (5): 626-34

OBJECTIVE: Following a successful clinical trial in 1996, the long-acting GnRH analogue goserelin (Zoladex LA 10.8 mg; Astra Zeneca) has been our preferred treatment for central early (CEP) or precocious puberty (CPP). However, some female patients have expressed concern about perceived weight gain during therapy and delay in the onset or resumption of menses on completion of therapy. The primary aim of this study was to investigate these concerns by determining the auxological parameters and timing of menarche or re-menarche in all girls with CEP/CPP who have completed a course of Zoladex LA treatment. The secondary aim was to assess auxological outcome in girls who have attained final height.

DESIGN AND PATIENTS: Case records of all girls with idiopathic CEP/CPP or CEP/CPP secondary to CNS pathology treated with Zoladex LA since 1996 were reviewed. A total of 46 girls who have completed therapy were identified, of whom 11 had reached final height. measurements Height, weight and bone age (RUS (TW2) method) were measured before treatment, when Zoladex LA was stopped and at final height. Body mass index (BMI) was calculated as a clinical measure of body fatness. Pubertal status was assessed pre- and post-treatment by Tanner staging and pelvic ultrasonography. Timing of menarche or re-menarche following cessation of treatment was recorded.

RESULTS: The mean (range) age of starting GnRH analogue therapy was 8.3 (1.8-10.5) years and the duration of treatment was 2.9 (0.7-8.9) years. Pre-treatment height was above average at 0.72 SD but had declined to 0.28 SD by the end of therapy. The 46 girls were heavier than average before treatment (Wt SDS 1.04) with no change in weight status on completion of therapy. Mean BMI SDS increased significantly from 0.93 to 1.2 during treatment, indicating that the girls became relatively fatter. Using recommended BMI cut-off values for defining overweight and obesity in children of the 85th and 95th centiles, 41% of the cohort were overweight and 28% were obese before treatment, rising to 59% and 39%, respectively, at the end of therapy. The average time interval to onset or resumption of menses after stopping treatment was 1.46 years (median 1.5, range 0.8-2.0 years). None of the following variables was found to be predictive of the time interval to menarche after completion of therapy: duration of treatment; chronological age; bone age; Tanner breast stage or uterine maturation at the end of treatment; the frequency of injections required to suppress puberty; or treatment with alternative GnRH analogue prior to Zoladex LA. Mean final height in 11 girls was 159.7 cm (-0.63 SD), close to the mean parental target height of 160.9 cm (-0.48 SD). Nine of the 11 girls (82%) attained final heights within or above their target range. In keeping with the whole cohort this subset of girls became fatter during treatment, although this difference was not statistically significant. However, they returned to their pretreatment size at final height (mean BMI SDS 1.18, 1.41 and 1.16 before, at the end of treatment and at final height, respectively).

CONCLUSIONS: Our cohort of 46 girls treated with long-acting goserelin was already considerably overweight at the start of therapy and became fatter during treatment. However, adiposity appeared to return to pretreatment levels in the 11 girls followed up to final height. Most of the girls who have attained final height are within or above their expected target range. The relatively long time interval to menarche of 1.5 years after stopping treatment is unexplained but may reflect a residual suppressive effect on the hypothalamo-pituitary axis of this long-acting GnRH analogue. Anticipation of the timing of menarche has proved to be of value in planning when to stop therapy in girls in whom treatment is mainly for practical and/or psychological reasons.

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