Women's health implications of ovulatory dysfunction

The association between ovulatory dysfunction and the occurrence of future CVD events remains largely unsettled.The association between PCOS and cardiometabolic abnormalities (e.g. obesity, dyslipidemia, insulin resistance) has indeed been clearly established, and was reaffirmed in the current thesis. However, the degree to which surrogate markers of CVD risk correlate with the development of CVD events in PCOS remains unclear since previous reports have been inconclusive.Furthermore, the available studies concerning this topic either lack sufficient numbers of clearly phenotyped women with PCOS, or have limited time to follow up. Results from the current thesis support the recommendation of various experts panels that screening for CVD risk factors in women with PCOS is justified. This CVD screening should at least encompass the assessment of BMI, waist circumference, serum lipid/glucose levels, and blood pressure for all women with PCOS. Furthermore oral glucose tolerance testing should be considered in PCOS in those women with obesity, advanced age, personal history of gestational diabetes, or a family history of type 2 diabetes mellitus. This screening is of importance in women with PCOS who want to conceive as well, since cardiometabolic abnormalities further increase the chance of developing gestational diabetes and pregnancy complications such as pregnancy induced hypertension, preeclampsia, premature delivery. Lifestyle changes, especially focusing on weight reduction should be encouraged, and further cardiovascular risk factor reduction should be performed according to existing CVD prevention guidelines.

The association between POI and CVD risk appears to be less pronounced, despite the observed inverse correlation between age at menopause and CVD risk in the general population.Furthermore, two meta-analyses on CVD risk in women with POI reported a modest increased risk of death from ischemic heart disease. These results denominate POI as a modest independent predictor of CVD. This has led experts to recommend annual CVD risk screening in women with POI through the assessment of blood pressure, weight and smoking habits with lipids, fasting glucose and HbA1c being assessed upon indication. In addition, the promotion of an optimal postmenopausal health through lifestyle modifications appears justified. Despite a lack of longitudinal outcome data, hormone replacement therapy (HRT) with early initiation is recommended to limit future CVD risk in women with POI, at least until the average age of natural menopause. In women with an average age at menopause HRT is not indicated for primary or secondary prevention of CVD, and is associated with an increased risk of stroke and venous thromboembolic events. However, HRT is the most effective treatment for vasomotor and other climacteric symptoms and reduces osteoporotic fracture risk in postmenopausal women. Benefits of HRT may exceed risks for the majority of symptomatic postmenopausal women who are under the age of 60 years, or under 10 years since the onset of menopause. HRT use should therefore be individualized by health care professionals based on clinical factors and patient preference.