Metformin treatment is effective in obese teenage girls with PCOS

Department of Pediatrics, Obstetrics and Reproductive Medicine, Institute of Obstetrics and Gynecology, University of Siena, Siena, Italy.
Human Reproduction (Impact Factor: 4.57). 09/2006; 21(9):2252-6. DOI: 10.1093/humrep/del185
Source: PubMed


Polycystic ovary syndrome (PCOS) is the most frequent cause of menstrual disorders in teenage girls. Little information is available about the effects of metformin in adolescent girls with PCOS and its dose and its efficacy in regulating menstrual cyclicity and hyperandrogenic symptoms. We evaluated the effects of metformin treatment on ovulatory function, hirsutism, acne, hormonal patterns and body weight in adolescent girls with PCOS.
Eighteen girls, ranging in age from 15 to 18 years, were enrolled in the study. Clinical diagnosis of PCOS was based on the consensus criteria for PCOS accepted in May 2003 at Rotterdam. All subjects received 1700 mg/day metformin as tablets continuously for 6 months. They were then followed up for 6 months.
Two patients complained of side effects for >2 weeks and interrupted treatment; they were not evaluated. All the others showed an improvement in menstrual cyclicity. Menstrual periods were ovulatory, with progesterone levels up to 6 ng/ml in luteal phase and a significant reduction in testosterone, androstenedione and free testosterone. BMI was restored within normal limits in all girls between 21 and 24 kg/m(2). Six months after the end of metformin treatment, menstrual cycles continued to be regular and ovulatory with normal BMI. Side effects were slight.
The present results confirm the positive effects of metformin on menstrual periods and show that the drug can be administered to young women to improve ovulation and hyperandrogenic symptoms such as hirsutism, acne and weight gain.

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    • "In this context, initiation of insulin sensitizer therapy at such an early age appears to be an appropriate preventive measure [26]. However, the added advantage of correcting serum androgens, suggested by some trials, may be debatable [27] [28] [29]. This goal may be achieved by the adjunctive use of an antiandrogen which, although effective, needs to be justified in the long-term, as the existence of a correlation between hyperandrogenaemia per se and late cardiovascular complications in PCOS women is, so far, contradictory [6] [30]. "
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    ABSTRACT: Objective: To compare metformin and combined oral contraceptive pill (COC) effects over 24 months in adolescent PCOS. Design: Randomized controlled study. Setting: Alexandria ICSI centre. Patients: 117 adolescent girls with PCOS, were randomized to: group A (n = 40): metformin, group B (n = 40): COC, and group C (n = 39): control. Interventions: Group A: received metformin, group B: received combined oral contraceptives. Main outcome measures: Improvement in cycle rhythm and hirsutism. Results: In group B a significant decline in serum testosterone reached the lowest value by the end of the second year (0.7 ± 0.2 versus 1.3 ± 0.5 μg/ml). By the end of the study, group A showed a significant decline in fasting (18.6 ± 3.0–10.0 ± 3.0 μIU/ml) and after-load insulin levels (126 ± 43–64 ± 15 μIU/ml) with a significant rise in glucose/insulin ratio (GIR) from 4.1 ± 0.3 to 4.6 ± 0.5. Group B showed a significant rise in fasting and after-load insulin (from 15.0 ± 3.0 μIU/ml and 103.0 ± 91.0 μIU/ml to 19.0 ± 4.0 and 187.0 ± 22.0 μIU/ml, respectively) and GIR dropped significantly from 4.4 ± 0.2 to 3.1 ± 0.3. Metformin was associated with a significant loss of weight from 87.0 ± 6.0 to 72.0 ± 0.5 kg while COC was associated with a non-significant gain in weight (from 84.0 ± 6.0 to 91.0 ± 9.0 kg). Conclusions: Metformin and COC have comparable therapeutic effectiveness on cycle regularity and hirsutism. Metformin was associated with a significant improvement in metabolic syndrome, while COC was associated with a deterioration of metabolic syndrome.
    Middle East Fertility Society Journal 11/2014; 20(3). DOI:10.1016/j.mefs.2014.10.003
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    • "represent an extreme endpoint of a more prevalent asymptomatic endocrine imbalance underlying ovulatory infertility [16] [17] [18]. Few studies, however, have compared the independent risks of PA and calorie intake versus BMI on ART outcomes. "
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    ABSTRACT: To measure the effect of body mass index (BMI) versus calorie intake and physical activity (PA) on the outcomes of assisted reproductive technologies (ART). A prospective study was performed on 236 infertile women who underwent in vitro fertilization. BMI, level of PA and calorie intake were assessed at study entry, and associations between these variables and ART outcomes were analyzed. Participants were divided into four groups based on BMI and PA: normal BMI/inactive, normal BMI/active, overweight/inactive and overweight/active. BMI, adjusted for age, level of PA, calorie intake and aetiology of infertility, was not associated with the number of oocytes retrieved, fertilization rate, cleavage rate, number of embryos, number of high-quality embryos or pregnancy rate. For women aged <36 years, the number of oocytes retrieved and the number of embryos decreased with increasing BMI, independent of calorie intake and PA. The fertilization rate, cleavage rate, number of high-quality embryos and pregnancy rate were not associated with BMI. The number of oocytes retrieved was significantly higher in women of normal weight compared with overweight women, regardless of the level of PA. Age has a strong negative effect on ART parameters. Increased BMI, independent of calorie intake and PA, has an adverse effect on the number of oocytes retrieved in women aged <36 years, but does not affect the number of high-quality embryos or the success of the treatment cycle.
    European journal of obstetrics, gynecology, and reproductive biology 05/2012; 163(1):52-6. DOI:10.1016/j.ejogrb.2012.03.035 · 1.70 Impact Factor
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    • "A third uncontrolled study in 18 adolescent girls 15-18 years old similarly reported a reduction in levels of androgens and resumption of menstrual cyclicity and ovulatory cycles in all 16 girls who tolerated 1700 mg of metformin daily. Girls in this study also had a reduction in BMI that was maintained (along with regular and ovulatory menstrual cycles) six months after the end of metformin treatment [216]. The absence of a control group and significant weight loss in subjects in these studies make these data difficult to interpret in terms of metformin's efficacy independent of weight loss. "
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    ABSTRACT: ABSTRACT: PCOS, a heterogeneous disorder characterized by cystic ovarian morphology, androgen excess, and/or irregular periods, emerges during or shortly after puberty. Peri- and post-pubertal obesity, insulin resistance and consequent hyperinsulinemia are highly prevalent co-morbidities of PCOS and promote an ongoing state of excess androgen. Given the relationship of insulin to androgen excess, reduction of insulin secretion and/or improvement of its action at target tissues offer the possibility of improving the physical stigmata of androgen excess by correction of the reproductive dysfunction and preventing metabolic derangements from becoming entrenched. While lifestyle changes that concentrate on behavioral, dietary and exercise regimens should be considered as first line therapy for weight reduction and normalization of insulin levels in adolescents with PCOS, several therapeutic options are available and in wide use, including oral contraceptives, metformin, thiazolidenediones and spironolactone. Overwhelmingly, the data on the safety and efficacy of these medications derive from the adult PCOS literature. Despite the paucity of randomized control trials to adequately evaluate these modalities in adolescents, their use, particularly that of metformin, has gained popularity in the pediatric endocrine community. In this article, we present an overview of the use of insulin sensitizing medications in PCOS and review both the adult and (where available) adolescent literature, focusing specifically on the use of metformin in both mono- and combination therapy.
    International Journal of Pediatric Endocrinology 08/2011; 2011(1):9. DOI:10.1186/1687-9856-2011-9
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