Impaired reproductive function in women treated for growth hormone deficiency during childhood.

Abstract

There are limited data which suggest that disturbance of reproductive function may occur in GH-deficient women. We have evaluated the consequences of growth hormone (GH) deficiency on reproductive function in women treated for GH deficiency during childhood. Questionnaires were sent to 73 GH-deficient women who had been treated for 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 substitution trial. Paediatric and gynaecological records were evaluated in all 60 women. Sixty GH-deficient women treated in childhood for this deficiency were included in the study. The median age at follow up was 27 years (range 20-43). GH treatment had been discontinued for 9 years (range 2-26). In the questionnaire and during the visit, attention was paid to GH treatment, pubertal development, menstrual 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. Thirty-four women showed no spontaneous pubertal development. Of the 26 women who did, menarche occurred in 39% at the age of 16 years or older. At the time of the study, menstrual cycles in these 26 women were as follows: 12 had regular menstrual cycles, three had developed secondary amenorrhoea after discontinuation of GH treatment, five had irregular menstrual cycles and six had oligomenorrhoea. The 34 women with disturbed pubertal development and the three with secondary amenorrhoea were infertile because of hypogonadotrophism. Only 13 out of 60 women desired pregnancy or had been pregnant. Three with regular menstrual cycles had primary infertility. Ten had ovulation induced or IVF. Six of these became pregnant after 1-7 cycles. Three were still under treatment, the duration of their treatment varying from 3 to 7 years. One woman discontinued treatment. At the time of the study, nine women had actually conceived. Five out of ten completed pregnancies resulted in Caesarian sections because of cephalo-pelvic disproportion or arrest of labour. During the ITT three of 29 women showed GH responses exceeding 5 micrograms/l (10 mU/l), ruling out complete 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, compared to women using sex-steroid substitution and amenorrhoeic women. From this study, it can be concluded that disturbances in reproductive function can be expected in women treated for GH deficiency during childhood, so it is advisable to inform these women of this possibility and to maintain follow-up after discontinuation of GH treatment. Whether the somatotrophic axis exerts a direct effect on ovarian function or whether more severe GH deficiency is more frequently accompanied by disturbances in gonadotrophin secretion still has to be elucidated.