IMPAIRED REPRODUCTIVE FUNCTION IN WOMEN TREATED FOR GROWTH-HORMONE DEFICIENCY DURING CHILDHOOD

OBJECTIVE There are limited data which suggest that disturbances of re productive function may occur in GH-deficient women. We have evaluated the consequences of growth hormone (GH) deficiency on reproductive fu nction in women treated for GH deficiency during childhood. DESIGN Que stionnaires were sent to 73 GH-deficient women who had been treated fo r GH deficiency during childhood. The response rate was 82%. These 60 women were then visited to obtain further information concerning their reproductive status. During these visits, blood samples were obtained from 39 women, to evaluate their hormonal status, and 29 of them had a standard insulin tolerance test (ITT), as part of an adult GH substi tution trial. Paediatric and gynaecological records were evaluated in aln 60 women. SUBJECTS Sixty GH-deficient women treated in childhood f or this deficiency were included in the study. The median age at follo w up was 27 years (range 20-43). GH treatment had been discontinued fo r 9 years (range 2-26). MEASUREMENTS In the questionnaire and during t he, visit, attention was paid to GH treatment, pubertal development, m enstrual cycle disturbances and fertility. In the 39 blood samples IGF -1, IGFBP-3, TSH, T4 and T3 were measured. GH responses were measured by a standard ITT. RESULTS Thirty-four women showed no spontaneous pub ertal development. Of the 26 women who did, menarche occurred in 39% a t the age of 16 years or older. At the time of the study, menstrual cy cles in these 26 women were as follows: 12 had regular menstrual cycle s, three had developed secondary amenorrhoea after discontinuation of GH treatment, five had irregular menstrual cycles and six had oligomen orrhoea. The 34 women with disturbed pubertal development and the thre e with secondary amenorrhoea were infertile because of hypogonadotroph ism. Only 13 out of 60 women desired pregnancy or had been pregnant. T hree with regular menstrual cycles had primary infertility. Ten had ov ulation induced or IVF. Six of these became pregnant after 1-7 cycles. Three were still under treatment, the duration of their treatment var ying from 3 to 7 years. One woman discontinued treatment. At the time of the study, nine women had actually conceived. Five out of ten compl eted pregnancies resulted in Caesarian sections because of cephalo-pel vic disproportion or arrest of labour. During the ITT three of 29 wome n showed GH responses exceeding 5 mu g/l (10 mU/I), ruling out complet e GH deficiency. Higher GH peaks (NS), IGF-1 (P<0.01) and IGFBP-3 (P<0 .01) levels were found in women with regular menstrual cycles, compare d to women using sex-steroid substitution and amenorrhoeic women. CONC LUSIONS From this study, it can be concluded that disturbances in repr oductive function can be expected in women treated for GH deficiency d uring childhood, so it is advisable to inform these women of this poss ibility and to maintain follow-up after discontinuation of GH treatmen t. Whether the somatotrophic axis exerts a direct effect on ovarian fu nction or whether more severe GH deficiency is more frequently accompa nied by disturbances in gonadotrophin secretion still has to be elucid ated.