Abstract
The aim of study was to evaluate endocrine changes in PCOS women during metformin treatment. One hundred women with PCOS, aged 20-40 years were included. A complete hormonal and metabolic pattern was recorded for each subject every 6 months. Metformin treatment after 6 and 12 months significantly reduced weight, BMI, waist circumference, insulin and HOMA-IR (p=0.000) with high differences of variances within repeated measurements. There was significant reduction of PRL, testosterone and estradiol (p=0.000) with small differences within repeated measurements. Metformin did not have effect on TSH. However, results showed important reduction of CRP, LH, LH/FSH, androstendione, DHEA-S and progesterone (p=0.000) with moderate differences within measures. Metformin restored menstrual cyclicity in most participants. At baseline in study group was 69% women with oligomenorrhoea, amenorrhoea or polymenorrhoea. After 12 months of treatment, only 20% PCOS women had irregular menstrual cycle (p=0.000). Hirsutism was also reduced. Intriguingly, during first 6 months of treatment in PCOS women 9 pregnancies occurred (p=0.000), while during last 6 months treatment were 2 pregnancies (p=0.317), in total 11(13%). Multiple regression model revealed that the presence of anovulation in PCOS women was strongly associated with BMI, waist, FSH and age. Insulin resistance was significantly predicted by BMI, cholesterol, progesterone and presence of hirsutism. The metformin therapy significantly improved insulin resistance, imbalance of endocrine hormones, hirsutism and menstrual cyclicity in women with PCOS. The most important predictors for duration of metformin treatment in PCOS women were testosterone, progesterone, FSH, CRP and presence of anovulation.
Highlights
The aetiology of the neuroendocrine irregularities in women with polycystic ovary syndrome (PCOS) remains uncertain; though, latest studies have shown decreased sensitivity of the gonadotropin-releasing hormone (GnRH) pulse generator to inhibition by ovarian steroids, mostly progesterone [ ]
Continuous variables were analysed with the one-way analysis of variance for repeated measures with Bonferroni test for the post-hoc analysis
In a prospective, controlled and randomized trial Billa et al [ ] determined that the metformin administration lowered luteinizing hormone (LH) activity in all PCOS women and in ovulatory responders and compromised PRL stimulated secretion in the latter cases. These findings have indicated an effect of metformin on pituitary activity
Summary
The aetiology of the neuroendocrine irregularities in women with PCOS remains uncertain; though, latest studies have shown decreased sensitivity of the gonadotropin-releasing hormone (GnRH) pulse generator to inhibition by ovarian steroids, mostly progesterone [ ]. Women with polycystic ovary syndrome (PCOS) need higher levels of progesterone to slow the frequency of GnRH pulse secretion, resulting in insufficient plasma follicle-stimulating hormone (FSH) synthesis and persistent plasma luteinizing hormone (LH) stimulation of ovarian androgens. In hyperandrogenemic girls certain to develop PCOS, increase in ovarian steroids may not be adequate to suppress the GnRH pulse generator, leading to a persistently rapid LH pulse frequency, reduced. PCOS is often accompanying to irregular gonadotropin levels, lower levels of insulin growth factor-binding protein- (IGF-BP ), increased insulin resistance and increased ovarian -hydroxiprogesterone ( -OHP) and androgen answers to GnRH-agonists [ ]. Therapy for PCOS becomes necessary in adults in order to induce ovulatory cycles and fer-
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