The natural history of the metabolic syndrome in young women with the polycystic ovary syndrome and the effect of long-term oestrogen-progestagen treatment

OBJECTIVE Little is known about the natural history of polycystic ovary syn drome (PCOS), although preliminary data indicate that affected women are mo re susceptible than the general population to diabetes and cardiovascular d iseases at post-menopausal ages. The aim of this study was to follow-up all main features of the metabolic syndrome in a group of young women with PCO S and to investigate the long-term effects on metabolism and body compositi on of oestrogen-progestagen (OP) compounds, which are frequently used in th ese women to treat hyperandrogenism and related clinical features. DESIGN Long-term follow-up study. SUBJECTS AND METHODS Thirty-seven women with PCOS were re-evaluated 10.3 +/ - 0.8 years (range 6-18 years) after their first assessments (age: before 1 9.8 +/- 4.9 years; after 29.9 +/- 4.4 years). When first examined, women we re instructed to follow a hypocaloric diet if they were obese plus OF, if t hey agreed to such treatment. Main anthropometric parameters, basal sex hor mones and lipids, fasting and glucose-stimulated glucose and insulin levels and several clinical data were recorded before and after follow-up. RESULT S In the whole group of women with PCOS we found no changes in body weight and fat mass, whereas both the waist-to-hip ratio and the waist-to-thigh ra tio were significantly reduced. No significant changes occurred in mean fas ting and glucose-stimulated glucose and insulin concentrations, whereas a s ignificant increase in high-density lipoprotein-cholesterol was found. No s ignificant changes occurred in testosterone levels. During the follow-up pe riod 16 women took OF for an average of 97 +/- 18 months (range 12-180 mont hs) (OP-users) whereas 21 women never took OP (non-OP-users). All OF-users were still taking OP when re-evaluated at the follow-up examination. With r espect to baseline values, body mass index was higher in non-OF-users than in their counterparts. Waist circumference (P<0.025), the waist-to-hip (P<0 .05) and the waist-to-thigh (P<0.01) ratios decreased significantly only in the OF-users. In addition, percentage changes in waist circumference (P<0. 05) and waist-to-hip ratio (P<0.05) during the follow-up period were signif icantly different between the groups. Glucose tolerance las area under the curve (AUC)) improved (P<0.05) in OF-users but not in non-OF-users. Moreove r, compared to baseline values, basal insulin levels were significantly (P< 0.01) reduced in OF-users but not in non-OF-users. On the contrary, no sign ificant change was found in insulin(AUC) in the former, whereas it signific antly increased (P<0.05) in the latter. Accordingly, fasting C-peptide decr eased (P<0.05) in OF-users, whereas both fasting (P<0.01) and stimulated (P <0.01) C-peptide significantly increased in non-OF-users. Changes in fastin g or stimulated insulin and C-peptide in non-OF-users were not associated w ith parallel changes in testosterone levels. Total cholesterol and triglyce rides did not change in either group, but HDL-cholesterol increased (P<0.05 ) only in OP-users. Sex hormone-binding globulin concentrations increased s ignificantly (P<0.01) in OP-users, without any significant change in non-OP -users. Testosterone concentrations did not change significantly in either group, but the testosterone :SHBG ratio significantly decreased in OP-users (P<0.05) but not in the non-F-users. Among the clinical features, acanthosi s nigricans significantly (P<0.01) worsened in non-OF-users but not in the OF-users, without any significant change in the hirsutism and acne scores. Pregnancy rates during the follow-up were similar in both groups. CONCLUSIONS These data indicate that hyperinsulinaemia and insulin resistan ce tended to worsen spontaneously in women with PCOS, without any :worsenin g of the hyperandrogenism. Long-term oestrogen-progestagen treatment counte red this tendency, probably because it improved the pattern of body:fat dis tribution, by reducing abdominal fat depots.