Metformin for the treatment of hyperandrogenism in adolescents with type 1 diabetes mellitus.

BACKGROUND: A high prevalence of hyperandrogenism has been reported in women with type 1 diabetes (T1D). Metformin has been used as a therapeutic agent in patients with polycystic ovarian syndrome and in T1D patients without hyperandrogenism. This study sought to determine the effect of metformin on hyperandrogenism and ovarian function in adolescents with T1D. METHODS: We recruited 24 girls with T1D. The participants had hyperandrogenism and displayed suboptimal metabolic control. The patients were enrolled in a randomized, double-blind, placebo-controlled trial. One group received metformin (850 mg bid) and the other group received a placebo. Treatment was administered for 9 months. Ovulation, steroids and gonadotropin levels were evaluated. RESULTS: Metformin treatment was associated with decreases in testosterone, free androgen index, androstenedione, 17-OH progesterone and estradiol levels. The girls who were treated with placebo showed stable steroid, gonadotropin and sex hormone-binding globulin levels during the analysis. No differences were observed in the Ferriman-Gallwey scores, ovulation rates, HbA1c levels or daily insulin doses of the girls treated with metformin compared with the placebo group. CONCLUSION: Treating hyperandrogenic T1D adolescents with metformin significantly decreased the serum androgens compared to the placebo, but metformin therapy did not significantly affect clinical parameters, such as hirsutism, ovulation and metabolic control.

Ovulation rate in adolescents with type 1 diabetes mellitus.

OBJECTIVE: To study ovulation in adolescents with type 1 diabetes (T1D) and the effect of hemoglobin A1c (HbA1c) levels on their ovulatory function. DESIGN: Prospective investigation. SETTING: Academic research institute. PATIENT(S): Adolescents with T1D (n=31) and healthy girls (n=52). INTERVENTION(S): Ovulation assessed through the measurement of salivary progesterone (days 13, 18, 23, and 28 of each cycle). MAIN OUTCOME MEASURE(S): Proportion of ovulatory cycles. RESULT(S): A total of 168 and 281 menstrual cycles were studied in the T1D and control girls, respectively. Metabolic control was defined as optimal if HbA1c was <7.5%. The proportion of ovulatory cycles was similar in the TID and control groups (34.5% and 36.3%, respectively). Regression analyses showed that the presence of T1D did not have a statistically significant effect on the ovulatory rate. However, more ovulatory cycles were observed in girls with T1D who had optimal metabolic control compared with those who had insufficient control (51.3% vs. 29.4%). CONCLUSION(S): In adolescent girls, T1D did not affect the rate of ovulation. A higher ovulatory rate was observed in those with optimal control compared with those with insufficient metabolic control, but a substantial proportion of ovulatory cycles were still observed in patients with higher HbA1c levels.

Polycystic ovarian morphology in postmenarchal adolescents.

OBJECTIVE: To evaluate the association of polycystic ovary morphology (PCOM) with ovarian function in adolescents and to determine its time course during two years of follow-up. DESIGN: Prospective study. SETTING: Academic center. PATIENT(S): Twenty healthy adolescents were followed from 2-4 years after menarche. INTERVENTION(S): We performed annual ultrasonographic and hormonal studies. Ovulation was assessed during 6 consecutive months by measuring salivary progesterone levels. MAIN OUTCOME MEASURE(S): Persistence of PCOM during the years following menarche; ovulation in girls with PCOM. RESULT(S): PCOM was observed in 40%, 35%, and 33.3% of the ultrasonographic studies performed at 2, 3, and 4 years after menarche, respectively. The concordance between ultrasonographic diagnosis at 2 and 4 years postmenarche (50%) was nonsignificant (kappa = 0.08). PCOM was not associated with abnormalities in ovulatory rate, menstrual cycle duration, lipid levels, or homeostatic model assessment of insulin resistance. However, lower FSH (4.8 ± 1.3 vs. 6.1 ± 1.9 mUI/ml) were observed in girls with PCOM compared with those without PCOM. Similar T and stimulated 17-hydroxyprogesterone on the leuprolide test were observed in girls with and without PCOM. CONCLUSION(S): PCOM is an inconstant finding in healthy adolescents and does not appear to be associated with decreased ovulatory rate or metabolic abnormalities in healthy adolescents. This finding suggests that PCOM may correspond to a physiologic condition during early adolescence.

Menstrual cycle irregularities and their relationship with HbA1c and insulin dose in adolescents with type 1 diabetes mellitus.

OBJECTIVE: To evaluate the prevalence and risk factors of menstrual cycle irregularities in adolescents with type 1 diabetes mellitus. DESIGN: Prospective diary of menstrual cycle. SETTING: Pediatric diabetes clinics and nearby schools. PATIENT(S): Adolescents with type 1 diabetes mellitus treated with multiple daily insulin doses (n = 56) and 56 healthy adolescents. MAIN OUTCOME MEASURE(S): Duration and variability of menstrual cycle. RESULT(S): Duration of the menstrual cycle was 48 ± 39 and 32 ± 7 days in girls with type 1 diabetes mellitus and controls, respectively. Oligomenorrhea (58.9% vs. 19.6%) and amenorrhea (10.7% vs. 1.8%) were more prevalent in girls with type 1 diabetes mellitus than in controls. Oligomenorrhea was observed in 53.3% of the girls with type 1 diabetes mellitus with optimal metabolic control. Girls with an HbA1c level of 7.6% to 8.9% exhibited increased cycle duration, menstrual cycle variability, and prevalence of oligomenorrhea compared with controls. Regression analysis showed that, for each point of increase in HbA1c, the menstrual cycle duration increased by 5.1 days. Cycle variability was associated with a higher daily insulin dose. CONCLUSION(S): Despite optimal metabolic control, a higher prevalence of oligomenorrhea was observed in girls with type 1 diabetes mellitus compared with controls. This is the first report to describe the high variability of the menstrual cycle in type 1 diabetes mellitus. HbA1c and insulin dose are important factors related to menstrual irregularities in type 1 diabetes mellitus.

[Precocious pubarche: experience in 173 cases ]. / Pubarquia precoz: experiencia en 173 casos.

BACKGROUND: Precocious pubarche (PP), defined as the development of sexual pubic hair before 8 years of age in females and before 9 years in males, is usually a benign condition but it can also be the first sign of an underlying disease. AIM: To analyze the etiology and perform a short term follow up in a cohort of patients with PP. MATERIAL AND METHODS: A group of 173 patients (158 females) consulted for PP with a mean age of 7.4+/-0.1 years. These patients were followed between 15 to 60 months. Anthropometric measurements, bone age, serum levels of total testosterone, 17 OH progesterone (17 OHP) and dehydroepiandrosterone sulphate (DHEAS) were evaluated. RESULTS: Mean birth weight and length was 3024.1+/-50.5 g and 48.5+/-0.3 cm, respectively. Ten percent of children were small for gestational age at birth. Bone age was accelerated by 1.1+/-0.01 years. One hundred and twelve patients were classified as having idiopathic PP (64.7%; 105 females), 29 as central precocious puberty (16.8%; only females), 16 as exaggerated adrenarche (EA 9.2%; 13 females) and 16 as non classical adrenal hyperplasia (9.2%; 11 females). CONCLUSIONS: PP represents a common and usually benign sign. However, 26% of cases had a pathologic underlying condition. Therefore, all children with PP should be evaluated by a pediatric endocrinologist. Low birth weight was not frequent in this cohort and these patients did not show EA .

Pubarquia precoz: Experiencia en 173 casos / Precocious pubarche: Experience in 173 cases

Background: Precocious pubarche (PP), defined as the development of sexual pubic hair before 8 years of age in females and before 9 years in males, is usually a benign condition but it can also be the first sign of an underlying disease. Aim: To analyze the etiology andperform a short term follow up in a cohort of patients with PP. Material and methods: A group of 173 patients (158 females) consulted for PP with a mean age of 7.4±0.1 years. These patients were followed between 15 to 60 months. Anthropometric measurements, bone age, serum levels of total testosterone, 17 OH progesterone (17 OHP) and dehydroepiandrosterone sulphate (DHEAS) were evaluated. Results: Mean birth weight and length was 3024.1±50.5 g and 48.5±0.3 cm,respectively. Ten percent of children were small for gestational age at birth. Bone age was accelerated by 1.1±0.01 years. One hundred and twelve patients were classified as having idiopathicPP (64.7%; 105 females), 29 as central precocious puberty (16.8%; only females), 16 as exaggerated adrenarche (EA 9.2%; 13 females) and 16 as non classical adrenal hyperplasia (9.2%; 11 females). Conclusions: PP represents a common and usually benign sign. However, 26% of cases had apathologic underlying condition. Therefore, all children with PP should be evaluated by a pediatric endocrinologist. Low birth weight was not frequent in this cohort and these patients did not show EA

Diagnostic criteria for polycystic ovary syndrome and ovarian morphology in women with type 1 diabetes mellitus.

CONTEXT: The criteria for diagnosis of polycystic ovary syndrome (PCOS) have been modified and now include polycystic ovary morphology (PCOM). OBJECTIVE: The purpose of this study was to determine the frequency of PCOS and PCOM in women with type 1 diabetes mellitus (DM1). DESIGN: We evaluated the clinical, hormonal, and ultrasonographic characteristics in women with DM1 and compared them with a carefully matched group of normal women in a cross-sectional study. SETTING: The study was conducted at an academic research institute located within a general hospital. PATIENTS: All the women with DM1 attending our hospital who had experienced menarche at least 2.5 yr earlier were invited to participate and were compared with healthy women with regular menses and without a history of hyperandrogenism [controls (C)]. RESULTS: Hirsutism was present in 28.6 and 0.0% of DM1 and C, respectively (P < 0.001). Biochemical hyperandrogenism was present in 23.8 and 7.9% of DM1 and C, respectively. DM1 women had higher levels of testosterone and androstenedione and larger ovarian volume and follicle number by ovary than C. PCOM was present in 54.8% of DM1 and 13.2% of C (P < 0.001). Oligomenorrhea was present in 19% of women with DM1. The frequency of PCOS was 40.5 and 2.6% in DM1 and C, respectively (relative risk, 15.4; 95% confidence interval, 2.2-110.2; P < 0.0001). The proportion of women using intensive insulin treatment was higher in those with PCOM/PCOS (P < 0.05). Intensive treatment was a significant factor over having PCOM/PCOS (P < 0.05). CONCLUSIONS: A high frequency of hyperandrogenism, PCOM, and PCOS is observed in DM1, which appears to be associated with intensive insulin treatment.