Ovarian 17\g=a\-hydroxyprogesteroneresponses to GnRH analog testing in oligomenorrheic insulin-dependent diabetic adolescents Raffaele Virdis, Maria Zampolli, Maria E Street, Maurizio Vanelli, Neus Potau, Cesare Terzi, Lucia Ghizzoni and Lourdes Ibanez 'Division of Pediatrics. Teaching Hospital of Piacenza. Piacenza, Italy, 2Department of Pediatrics. University of Parma, Parma, Italy and ^Adolescent and Endocrine Unit. Hospital Universitario Materno-lnfantil 'Vali d'Hebrón. Barcelona, Spain (Correspondence should be addressed to R Virdis, Istituto di Pediatria, Università di Parma. Via Gramsci, 14, 43100 Parma. Italy) Abstract Objective: To investigate the pituitary-ovarian function in adolescent girls with insulin-dependent diabetes mellitus (IDDM). Design: Clinical case-control study. Methods: The GnRH analog leuprolide acetate was administered subcutaneously to 16 adolescents with IDDM (seven eumenorrheic and nine oligomenorrheic) and 13 controls between 0800 and 0900 h. Blood samples were collected at baseline and 0\m=.\5, 3, 6 and 24 h after leuprolide to measure levels of gonadotropins, 17\g=a\-hydroxyprogesterone(17-OHP), androgens and estradiol. Results: Mean baseline serum LH levels were significantly higher in eumenorrheic compared with oligomenorrheic IDDM patients, while peak LH responses to GnRH analog testing were similar in all subjects. Oligomenorrheic IDDM girls showed, as a group, a distinct 17-OHP response to GnRH analog stimulation, which in five out of nine girls was in the range of functional ovarian hyperandrogenism (\m=ge\ 8\m=.\6 nmol/l). Androgen and estradiol levels were not significantly altered in any group. No correlation was found between steroid levels and HbA1c levels, although the latter were significantly higher in oligomenorrheic than in eumenorrheic patients. Conclusion: About 50% of the oligomenorrheic IDDM adolescents had an increased ovarian 17-OHP response to GnRH analog stimulation in the range of functional ovarian hyperandrogenism. Factors other than metabolic control, such as stress, may play an etiologic role in IDDM ovarian dysfunction. European Journal of Endocrinology 136 624\p=n-\629 Introduction Women with insulin-dependent diabetes mellitus (IDDM) have an increased incidence of menstrual abnormalities, particularly oligo- and amenorrhea and, less frequently, polymenorrhea (1-3); moreover women with IDDM have a shorter fertile life because of slightly delayed menarche and earlier menopause (1,2). The delayed menarche appears to be more frequent when IDDM starts before 10 years of chronological age, while a later development of the disease does not seem to affect menarcheal age (2). Studies on pituitary-gonadal function in adult women with IDDM with amenorrhea are controversial. Some authors have found low basal luteinizing hormone (LH) levels and decreased LH responses to gonadotropin- releasing hormone (GnRH) despite low estrogen levels (4, 5), while others have reported normal LH responses to GnRH challenge but fewer LH pulses/secretory episodes, suggesting a compromise of the GnRH pulse generator (6). Furthermore, ovarian steroid secretion seems to be altered in IDDM patients: while normally menstruating women with IDDM have normal estrogen and normal or, more often, elevated androgen levels, amenorrheic IDDM patients show normal or decreased estrogen and andro¬ gen concentrations (3, 7, 8). Despite the increased androgen levels, free hormone fractions remain in the normal range in eumenorrheic patients, thus explaining the maintenance of a normal menstrual pattern and the absence of hyperandrogenic manifestations (3). GnRH analogs induce gonadal androgen secretion by producing an acute and sustained release of both pituitary LH and follicle-stimulating hormone (FSH) (9, 10). In this setting, Rosenfield and colleagues have determined that a subset of hyperandrogenic women have exaggerated ovarian 17a-hydroxyprogesterone (17-OHP) responses to GnRH agonists, suggestive of disordered ovarian cytochrome P450cl7a activity (9- 11). This pattern of ovarian steroidogenic response appears to be particularly frequent in hyperandrogenic adolescents after challenge with the GnRH agonist Ieuprolide acetate (LA) (12, 13). Downloaded from Bioscientifica.com at 09/27/2018 05:17:10AM via free access