Physiologic exhaustion of ovarian follicles in women occurs, as a rule, at an age between 40 and 55 years. When ovarian function ceases before the age of forty, this condition is described as premature ovarian failure (POF). It occurs in 4 -10% of women (7). Three different hypotheses can be proposed to explain the early depletion of ovarian follicles:
Premature ovarian failure is not always a permanent phenomenon. Recently, it has been reported that some women spontaneously resumed or initiated their menstruation and/or pregnancy (6). Various etiologic factors have been proposed for this syndrome and a classification of the possible causes of POF is presented in Table 1. The diagnosis is made in presence of the triad amenorrhea, elevated FSH, and diminished 17ß-estradiol levels, before the age of forty years. The syndrome is no doubt heterogeneous, and efforts must be directed toward elucidating its pathophysiologic bases. It is important to determine possible etiologies so that rational treatment may be established hopefully prior to the loss of all follicles. The presence of elevated gonadotropin concentrations can no longer be considered evidence of permanent ovarian failure.
For the evaluation of the different etiologies of POF, the diagnostic protocol presented in Table 4 is proposed.
In young women with hypergonadotropinemia, it is mandatory to differentiate between POF and gonadotropin pituitary adenoma. For this purpose, the following diagnostic approach is useful:
Cases of false hypergonadotropinemia due to interferences in RIA should also be ruled out (4).
The characteristics of 85 POF patients observed in our department during a ten year period are illustrated in Table 5. As regards treatment of these young patients, the main goals are prevention of hypoestrogenism signs, and attempt to achieve conception in those patients who wish a pregnancy. Replacement therapy with estrogens and progestins (transdermal estradiol and medroxyprogesterone acetate) is used to prevent hot flushes, urogenital atrophy, psychological disturbances and osteoporosis. Treatment for infertility can be accomplished by the suppression of pituitary gonadotropins with estrogen followed by ovarian stimulation with hMG. Induction of ovulation has also been reported after therapy with GnRH analogues, with and without hMG therapy. Very few pregnancies have been reported with hMG alone (1).
We were able to induce normal follicular development and ovulation in one patient of a group of 10 idiopathic POF patients, who had been treated with estrogens together with hMG to induce FSH receptor formation in granulosa cells (5).
Accurate determination of the cause of POF is important for at least two reasons: to verify a possible reversibility if the patient wishes a pregnancy; and for early detection of autoimmune polyendocrinopathies, when POF is associated with functional alterations of other endocrine glands. Furthermore, it is mandatory to rule out the possibility, although rare, of gonadotropin-secreting adenomas in these young patients.
Edited by Aldo Campana,