Ovulation induction in young girls with menometrorragia: a safe and effective treatment.

UNLABELLED: The prevalence of menometrorrhagia in fertile women is 11.4-13.2% and increases with aging. The presence of metrorrhagia is a relatively common cause of concern among adolescents and their parents, as well as a frequent cause of visits to emergency departments, gynaecologists, and pediatricians. Clomiphene is a selective estrogen receptor modulator (SERM) that increases the production of gonadotropins by inhibiting negative feedback on the hypothalamus. Clomiphene is primarily used in the treatment of female infertility for ovulation induction to reverse oligoovulation or anovulation, as occurs in polycystic ovary syndrome. OBJECTIVE: The aim of our study was to evaluate the use of clomiphene citrate in ovulation induction, and therefore, in the cessation of bleeding in adolescents with menometrorrhagia in the absence of uterine, ovarian, or systemic pathologies. DESIGN: Cohort study. MATERIALS AND METHODS: The study group was comprised of 50 subjects (age range, 13-16 years) with menometrorrhagia (bleeding >7 days in length with an average blood loss >80 ml). The treatment with clomiphene citrate at a dose of 50 mg/day for 5 days during the attack cycle, and from days 3 to 7 of three subsequent cycles, was offered to the patients. RESULTS: After three cycles of therapy, all patients had resolution of the menometrorrhagia and resumption of ovulatory cycles. No patient reported unwanted side effects. CONCLUSION: We propose that low-dose clomiphene should be the first step in the treatment of adolescent dysfunctional bleeding (DUB).

IL-6 serum levels and production is related to an altered immune response in polycystic ovary syndrome girls with insulin resistance.

Polycystic ovarian syndrome (PCOS) is frequently characterized by obesity and metabolic diseases including hypertension, insulin resistance, and diabetes in adulthood, all leading to an increased risk of atherosclerosis. The present study aimed to evaluate serum and production of inflammatory markers in adolescent Sardinian PCOS. On the basis of HOMA findings, patients were divided into noninsulin resistant (NIR) and insulin resistant (IR), and were weight- and age-matched with healthy girls. Inflammatory cytokines (TNF-α, IL-6, Il-10, TGF-ß) and lipokines (leptin, adiponectin), the reactant hs-CRP, and in vitro inflammatory lympho-monocyte response to microbial stimulus were evaluated. In healthy and PCOS subjects, leptin and hs-CRP were correlated with BMI, whereas adiponectin was significantly reduced in all PCOS groups. Although cytokines were similar in all groups, Interleukin-6 (IL-6) was significantly higher in IR PCOS. Moreover, in the latter group lipopolysaccharide-activated monocytes secreted significantly higher levels of IL-6 compared to NIR and control subjects. To conclude, IR PCOS displayed increased IL-6 serum levels and higher secretion in LPS-activated monocytes, whilst revealing no differences for other inflammatory cytokines. These results suggest that in PCOS patients an altered immune response to inflammatory stimuli is present in IR, likely contributing towards determining onset of a low grade inflammation.

The quantitative insulin sensitivity check index is not able to detect early metabolic alterations in young patients with polycystic ovarian syndrome.

OBJECTIVE: To verify whether QUICKY is a suitable method for the identification of metabolic deterioration in normal weight patients affected by polycystic ovarian syndrome (PCOS). DESIGN: Prospective clinical study. PATIENT(S): Seventy-nine PCOS normal weight adolescent subjects, 50 eumenorrheic, normal weight, non-hirsute controls matched for age and BMI. METHOD(S): Quantitative insulin sensitivity check index (QUICKY) and integrated secretory area under the curve of insulin values (I-AUC) during oral glucose tolerance test were calculated. RESULT(S): Seventy-nine PCOS and 50 controls were studied. Normal insulin sensitivity was defined as upper control 95th percentile by QUICKY values <0.31, I-AUC at 180 min < 16,645. When applying the calculated I-AUC cut-off, 41 PCOS were classified as normoinsulinemic and 38 as hyperinsulinemic, whereas using the calculated QUICKY cut-off, only 19 PCOS could be classified as insulin resistant (IR). Fifteen out of the 60 non-IR PCOS presented hyperinsulinemia; fasting glucose and insulin levels and QUICKY were not sufficient to identify these subjects. Thus, QUICKY displayed a low sensitivity (44%) and specificity (91%) in the diagnosis of the metabolic disorder disclosed by I-AUC. CONCLUSIONS.: In young normal weight patients with PCOS the prevalence of early alterations of insulin metabolism are not detectable by QUICKY studies.

Obesity-related lipid profile and altered insulin incretion in adolescents with polycystic ovary syndrome.

PURPOSE: The objective of this study was evaluate influence of body mass index (BMI), hyperinsulinemia and/or insulin resistance (IR), and androgens on the lipid profile of adolescent polycystic ovary syndrome (PCOS). METHODS: A total of 71 PCOS and 94 healthy adolescent girls from a Southern Italian region were included in the study. At day 5-8 of menstrual cycle, patients underwent a 75-g oral glucose tolerance test to evaluate insulin levels; lipid and homocysteine levels were also assessed, baseline hormonal assays and ultrasound examination performed, and anthropometric characteristics measured. RESULT: No differences were observed in the incidence of overweight or obesity and total cholesterol, high-density lipoprotein (HDL) cholesterol level, low-density lipoprotein cholesterol level; triglycerides and homocysteine levels did not differ between PCOS and control groups. All fasting metabolic indexes were similar, whereas insulin secretion after glucose load (I-AUC) was significantly higher in PCOS subjects. Total cholesterol levels were significantly related to waist-hip ratio (WHR). Low-density lipoprotein level was positively correlated with BMI, waist, WHR, and homeostasis model assessment (HOMA) but not I-AUC. Findings obtained for HDL correlated negatively to the same parameters, being also negatively correlated to both fasting insulin and HOMA, but not I-AUC. Moreover, HDL was positively correlated to circulating androstenedione (A) and negatively to circulating testosterone (T) levels. Triglycerides seemed to correlate positively with body BMI, waist, and WHR, and negatively with A levels. Homocysteine levels correlated positively with plasma triglyceride content. CONCLUSION: In the adolescent population studied, no differences were revealed in lipid profile between PCOS and controls. The PCOS is not a discriminant factor. The anthropometric characteristics resulted in the primary factor influencing the lipid derangement, confirming the importance of treating obesity at an early age to reduce morbidity rates. Hyperinsulinemia and IR, peculiarities of PCOS capable of influencing long-term evolution into cardiovascular diseases and diabetes mellitus, are not associated with worse lipid profile. Young patients should be encouraged and motivated to change their lifestyle, with the aim of losing weight and thus reducing risk of onset of overt dyslipidemia.