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Ovarian Function during Puberty in Girls with Type 1 Diabetes Mellitus: Response to Leuprolide

Institute of Maternal and Child Research (E.C., D.M.-K., R.A.B., N.U., H.S., G.I., F.C.), School of Medicine, University of Chile, 836-0160 Santiago, Chile; Hospital Exequiel G. Cortés (F.U.), 891-0108 Santiago, Chile; and Hospital San Borja Arriarán (A.A.), 836-0160 Santiago, Chile

Address all correspondence and requests for reprints to: Ethel Codner, M.D., Institute of Maternal and Child Research, School of Medicine, University of Chile, Casilla 226-3, Santiago, Chile. E-mail: ecodner{at}med.uchile.cl.

Context: An increased prevalence of polycystic ovary syndrome (PCOS) has been reported in adult women with type 1 diabetes mellitus (DM1). We investigated whether these hormonal abnormalities begin during puberty by evaluating the ovarian steroidogenic response to leuprolide acetate.

Methods: We studied 56 adolescent girls with DM1 (aged 12.3 ± 0.2 yr) and 64 healthy girls (C) (aged 11.9 ± 0.2 yr) up to 2 yr post menarche, matched by age, body mass index, and pubertal development. We evaluated anthropometrical data and Ferriman-Gallway score and performed a leuprolide test (500 µg sc) to study ovarian function. Ovarian volume was determined by transabdominal ultrasonography.

Results: We found five DM1 but no C girls with abnormally located terminal hair (Fisher’s exact, P < 0.05). Free androgen index increased throughout puberty in girls with DM1 (ANOVA, P < 0.0001), which was associated with a decrease in SHBG levels in girls with DM1 (ANOVA, P < 0.0001). Stimulated 17OH progesterone (17OHProg) increased throughout puberty only in girls with DM1 (ANOVA, P < 0.01). Girls with DM1 at Tanner stage 5 had higher stimulated LH to FSH ratio, testosterone, and 17OHProg levels than girls at Tanner stage 4. In contrast, in C girls the stimulated testosterone, 17OHProg, and LH to FSH ratio were similar at Tanner stages 4 and 5. Ovarian volumes and uterine length were larger in girls with DM1 (analysis of covariance, P < 0.05).

Conclusions: These data suggest that patients with DM1 have differences in ovarian steroidogenic response to leuprolide, compared with C girls during puberty. Future studies in young women should clarify whether these findings are related to the pathogenesis of hyperandrogenism later in life

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