Primary Ovarian Insufficiency

Primary ovarian insufficiency (POI) is a disease spectrum that not only affects female fertility but also contributes to morbidity and mortality associated with the long-term withdrawal of estrogen. This disease spectrum has previously been referred to as premature ovarian failure. However, this terminology has fallen out of favor as the degree of ovarian impairment may fluctuate over time. The typical onset of POI is in women less than 40 years of age and is diagnosed in the setting of amenorrhea lasting 4-6 months in combination with elevated follicle-stimulating hormone (FSH) and decreased estradiol levels obtained 1 month apart. POI differs from menopause due to the remaining variability of ovarian function and primordial follicles, whereas menopause occurs when primordial follicles are exhausted, resulting in the cessation of menstruation altogether. Other causes of secondary amenorrhea include, but are not limited to, pregnancy, hypothyroidism, and genetic abnormalities. These conditions must be excluded before diagnosing POI. All women have the highest number of oocytes (approximately 6-7 million) present while still in utero at 20 weeks of gestation. The dramatic decline in oocytes, irrespective of ovulation, continues down to approximately 300,000-400,000 oocytes at reproductive age. Once menstruation begins, ovulation and ongoing oocyte attrition continue to reduce ovarian reserve until menopause. Throughout a woman’s reproductive lifetime, only 400-500 oocytes are released with ovulation. Normal menstruation and regular ovulation have significant impacts on overall female health. For example, in the absence of normal ovarian function due to decreased estradiol, sex steroid production is reduced, leading to inadequate bone density and the development of osteoporosis or osteopenia. This greatly increases a woman’s risk of bone fracture. As a result, it is of great importance for POI to be recognized early within its disease process in order to prevent and reduce the morbidity and mortality associated with hypoestrogenemia and to increase the quality of life of the women affected.