Primary ovarian failure

Abstract

The average age of menopause, denoted by the last menstrual period, occurs at an average age of 50.7 years in the western world (1) and this age has been found to be constant across generations, although one group have reported a secular trend to advancing menopausal age (2). The age of menopause in an individual is determined by both genetic and environmental factors (1, 3). Menopause before the age of 40 is most commonly taken to be the definition of ‘premature ovarian failure’ and this coincides approximately with youngest one percent of the frequency distribution of the age of menopause (Fig. 8.1.5.1). For every decade before 40 the prevalence of POF is estimated to decrease by a factor of 10. Thus, in presence of normal karyotype, 1:1000 of women at 30 has POF, 1:10 000 at 20 and 1:100 000 of women will present with gonadal failure and primary amenorrhoea. In terms of the mode of presentation, premature ovarian failure (POF) is the aetiology of 20% of cases with primary amenorrhoea and 10% of those with secondary amenorrhoea. Premature ovarian failure (POF) refers to the cessation of ovarian function at an earlier than expected age due to ovarian pathology. Primary ovarian failure is used in two contexts—to describe very early onset ovarian failure presenting with primary amenorrhoea and also to differentiate ovarian pathology from secondary ovarian failure, which refers to lack of ovarian activity as a result of gonadotropin deficiency. Primary ovarian insufficiency is recently favoured as an all-encompassing term that accounts for the variable course and occasional remission (4). The term hypergonadotropic hypogonadism is also used to emphasize ovarian origin. Resistant ovary syndrome (ROS) is an obsolete term, used to describe the coexistence of hypergonadotropic hypogonadism with normal ovarian follicles on histology of the ovary. It was soon realized that women with ROS progressed to complete ovarian failure and that ovarian follicles on histology were commonly found in established ovarian failure, negating the usefulness of this diagnostic label. Very early onset ovarian failure with a known genetic cause is often labelled inaccurately as ‘gonadal dysgenesis’ as in most situations it is thought that early ovarian development is normal.