The forties are a time of irregular and sometimes heavy menstrual loss due to fluctuating levels of sex hormones. Some months are characterized by low estrogen secretion and anovulation and others by extremely high levels of estradiol (E2). In a 20-year-old woman, E2 usually peaks at 500–1000 pmol/L. In contrast, some perimenopausal women may have cycles where E2 levels peak at around 5000 pmol/L. These high levels of estrogen are often not followed by ovulation and so progesterone is either not secreted at all, or levels are too low to counter these high-estrogen months. As we will see shortly, many gynecologic pathologies are driven by these unbalanced sex hormone levels.