Low grade chronic inflammation as reflected by increased C-reactive protein (CRP) concentrations independently predicts those at risk for coronary heart disease (CHD) and type 2 diabetes. Women with polycystic ovarian syndrome (PCOS) are insulin resistant and have increased risk for CHD and type 2 diabetes, but currently there are no data on markers of inflammation in women with PCOS. Seventeen women with PCOS (defined on the basis of elevated testosterone and oligomenorrhea) and 15 healthy women matched as a group for body mass index were recruited. Measurement of CRP concentrations was made using a highly sensitive assay. Insulin resistance was assessed using the hyperinsulinemic euglycemic clamp technique. The women with PCOS had significantly elevated CRP concentrations relative to controls (geometric means, 2.12 and 0.67 mg/L, respectively; P = 0.016). Log CRP correlated with body mass index in both PCOS and controls (r = 0.58; P < 0.05 and r = 0.78; P < 0.01, respectively) and inversely with insulin sensitivity (r = -0.57; P < 0.05 and r = -0.69; P < 0.01). Total testosterone did not correlate with log CRP in either group. On adjustment for body mass index and age, there remained a significant difference in log CRP between PCOS and controls (t = 2.13; P < 0.05). On further adjustment for insulin sensitivity, log CRP was no longer significantly different between groups (t = 1.51; P = 0.14). We conclude that women with PCOS have significantly increased CRP concentrations relative to women with normal menstrual rhythm and normal androgen levels. We propose low grade chronic inflammation as a novel mechanism contributing to increased risk of CHD and type 2 diabetes in these women.
The use of circulating AMH to individualize treatment strategies for COS may result in reduced clinical risk, optimized treatment burden and maintained pregnancy rates, and is worthy of prospective randomized examination.
Objective To compare the effectiveness of clomifene citrate and unstimulated intrauterine insemination with expectant management for the treatment of unexplained infertility. Design Three arm parallel group, pragmatic randomised controlled trial. Setting Four teaching hospitals and a district general hospital in Scotland. Participants Couples with infertility for over two years, confirmed ovulation, patent fallopian tubes, and motile sperm. Intervention Expectant management, oral clomifene citrate, and unstimulated intrauterine insemination. Main outcome measures The primary outcome was live birth. Secondary outcome measures included clinical pregnancy, multiple pregnancy, miscarriage, and acceptability. Results 580 women were randomised to expectant management (n=193), oral clomifene citrate (n=194), or unstimulated intrauterine insemination (n=193) for six months. The three randomised groups were comparable in terms of age, body mass index, duration of infertility, sperm concentration, and motility. Live birth rates were 32/193 (17%), 26/192 (14%), and 43/191 (23%), respectively. Compared with expectant management, the odds ratio for a live birth was 0.79 (95% confidence interval 0.45 to 1.38) after clomifene citrate and 1.46 (0.88 to 2.43) after unstimulated intrauterine insemination. More women randomised to clomifene citrate (159/170, 94%) and unstimulated intrauterine insemination (155/162,
Hirsutism is a common and distressing symptom frequently encountered in women with polycystic ovary syndrome (PCOS), who also show relative insulin resistance. The aim of this trial, in which hirsutism was the primary end point, was to compare the efficacy of the oral antihyperglycemic medication metformin with that of an established treatment, combined ethinyl estradiol and cyproterone acetate. Patients (n = 52) were randomized to receive either metformin (500 mg, three times daily) or Dianette (ethinyl estradiol, 35 micro g; cyproterone acetate, 2 mg) treatment for 12 months, with assessments before treatment, at 6 months, and at 12 months. Both objective and subjective methods of evaluating hirsutism were used, and in addition, patient perceptions were examined. The results show that metformin is potentially an effective treatment for moderate to severe hirsutism in women with PCOS. They also suggest that in some respects (Ferriman-Gallwey score and patient self-assessment), it is more efficacious than the standard treatment (Dianette). The objective evaluation of hair diameter reduction showed that both treatments were moderately effective at multiple anatomical sites. Dianette treatment was responsible for profound suppression of androgen activity, in contrast to metformin, which induced negligible change. However, metformin did reduce markers of insulin resistance. The data suggest that hirsutism may be effectively treated by reducing hyperinsulinemia.
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