From Primary Hypergonadotropic Amenorrhea to “POI”: Aetiology and Therapy

Abstract

Premature ovarian damage with onset before menarche is expressed clinically with primary hypergonadotropic amenorrhea. The term premature ovarian insufficiency (POI) currently used in the literature worldwide substitutes the previously used POF (premature ovarian failure). The very concept of POI refers to the many, varied clinical expressions of ovarian insufficiency, including the possible albeit usually transitory recuperation of ovarian function. The primary characteristic of POI is amenorrhea, lasting at least 4 months in a row, with increased levels of FSH (to more than 30-40 IU/liter ) and decreased E2 (to less than 50 pg /ml) based on a minimum of 3 measurements done at 1 month intervals. The causes can be genetic, metabolic, autoimmune, and/or iatrogenic. Known risk factors include some infections as well as certain pre-existing pathological conditions and environmental factors. The clinical expressions in the pre- to post-menarcheal period have a common denominator:hypoestrogenism due to follicular damage. In cases of early onset the patient’s genital tract remains immature and peak bone mass is not achieved; there is hypotrophy of the vulvovaginal mucosae, osteopenia and osteoporosis, related to the estrogenization period before the amenorrhea, as well as increased risk of cardiovascular conditions, reduced libido, and psychological repercussions including low self-esteem mostly in relation to the reproductive function damage. The causes are individuated by genetic studies to find numeric and structural defects on chromosome X and immunological investigations with screening for polyendocrine conditions. Therapy of hypergonadotropic primary amenorrhea is targeted to induce and/or stimulate complete development of secondary sexual characteristics, with maturation of the genital tract and achievement of peak bone mass. Treatment begins with low (very low) doses of estrogen; the doses are increased over time. The most physiological drug is transdermal 17β E2 which has both minor impact on the liver and minor pro-coagulative impact compared to other drugs and methods of administration. Associated administration of progesterone or progestin (preferably non-androgenic, for metabolic reasons) is advised after two years of estrogen treatment, or when bleeding occurs.