Chapter 7. Conclusions

1. The present results demonstrate that the prevalence of PCO is dependent on age among healthy women, the prevalence being significantly higher in the younger age group (≤ 35 years) than it was among older women (≥ 36 years). This may be due to a physiological decline of the follicular cohort, leading to a normalized ovarian ultrasonographic appearance with advanging age. The overall prevalence of PCO in Finnish women with no other overt symptoms of PCOS was 14.2%. This is slightly lower than that reported in previous studies (16-23%). The hormonal parameters and clinical findings in these women with an isolated finding of an ultrasonographic appearance of PCO mimic those associated with PCOS. Women with PCO have higher a LH/FSH ratio, serum T concentrations, incidence of minor cycle irregularities and problems in conceiving significantly more often than women with normal ovaries.

2. The carrier frequency of the v-LHβ allele in the entire study population was 18.5%. The v-LH carrier frequency was similar in obese and nonobese controls in each country studied, but was significantly lower in obese PCOS subjects in the Netherlands and Finland, where the proportions of v-LH carriers in obese PCOS subjects were only 2.0% and 4.5%, respectively. In contrast to these countries, no such difference was observed in the United Kingdom. Both the present results and those from previous studies on other pathological gonadal conditions indicate that the prevalence of v-LH varies among different ethnic groups. The high overall frequency of the v-LH allele in women in general and its low frequency in obese PCOS patients also suggests that v-LH may somehow protect obese individuals from developing PCOS. It must be kept in mind, however, that many widely used immunoassay reagents do not detect v-LH and thus, an elevated LH/FSH ratio may not be discovered among PCOS women.

3. Women with previous GDM displayed a high prevalence of PCO (39.4%), being two-fold higher than that reported in healthy premenopausal women. Women with PCO and previous GDM showed insulin sensitivity and blood glucose responses in the OGTT comparable with those of women with normal ovaries and previous GDM. They had a more marked hyperinsulinemia, however, which could not be explained by obesity. This may indicate that these women have a lowered metabolic clearance rate of insulin. They also had subtle clinical, endocrine and metabolic features characteristic of PCOS, although clinical symptoms typical of PCOS were scarce. These findings suggest that the ultrasonographic presence of PCO may be a predictive factor as regards abnormal glucose tolerance during and after pregnancy and these women should therefore be advised as to the possible consequences. As women with PCO have metabolic abnormalities resembling PCOS, they may be at risk for increased morbidity associated with PCOS, i.e. DM, hypertension, coronary artery disease etc. with ageing. Our data also demonstrate that women with previous GDM often have abnormal OGTT results in general, they are insulin resistant, mainly as a result of lowered glucose nonoxidation in the peripheral tissues, and, furthermore, they show inappropriately low insulin responses to glucose, due to impaired ß-cell function. They also demonstrate a higher adrenal androgen secretion than the control women. Health education and the follow-up of these women is of great importance.

4. Obese women with PCOS displayed a distinctly different steroidogenic response pattern to a single dose of hCG compared with the control women followed for 4 days. Peak peripheral serum A and T concentrations were achieved in the PCOS women at 48 hours after hCG injection, preceded by peak levels of 17-OHP and E₂ at 24 hours. In contrast, all steroids measured in the control women reached their maximum serum concentrations at 96 hours. It remained unclear, however, if this exaggerated 17-OHP and E₂ response to hCG in PCOS women is due to a dysregulation of certain enzyme(s), or to higher theca cell activity or mass in polycystic ovaries. The slight alleviation of hyperandrogenism brought about by metformin therapy may be explained by decreased ovarian steroidogenesis due to reduced serum insulin concentrations.

   In addition to hMG containing equal amounts of both FSH and LH, FSH alone also stimulated the production of ovarian androgens after suppression of the pituitary-ovarian axis with GnRHa. Under this experimental condition, women with PCOS did not display any distinctly exaggerated steroidogenic response to gonadotrophin stimulation compared to endocrinologically normal women.