Premature Ovarian Failure

Abstract

. Twenty‐six patients with premature ovarian failure (last menstrual period before the age of 30 years) were evaluated clinically and endocrinologically and, in addition, ovarian biopsies were obtained in 15 out of the 26 patients. Only 1 of the patients revealed a family history of early menopause. The typical menstrual pattern indicated a normal age at menarche with regular periods for various length of time followed either by amenorrhoea abruptly or by a period of oligomenorrhoea before the onset of amenorrhoea. All patients showed normal or slightly underdeveloped secondary sexual characteristics, and it should be noted that 2 patients had been pregnant previously. It was characteristic of all patients that the excretion of total gonadotropins was constantly increased and that the excretion of total oestrogens was low, whereas both the adrenal and thyroid function were normal. All patients were X‐chromatin positive. In 13 out of the 15 patients, in whom ovarian biopsies were obtained, the histological examination revealed a normal stroma without or with very few primordial and atretic follicles, a picture very similar to that characteristic of the postmenopausal ovary. In the last 2 patients, however, the histological examination showed a quite different picture, viz. a normal stroma with numerous primordial and primary follicles and even a few growing follicles. In spite of these morphologically normal follicles, it was not possible to stimulate the follicular development and to induce ovulation even with very high doses of human gonadotrophins. It is, therefore, concluded that the presence of a few growing follicles in the ovaries does not seem to exclude the diagnosis of premature ovarian failure. Only 14 out of the 26 patients had the typical symptoms of the climacteric, and even in these cases the nuisance was only of a mild to moderate degree. It is generally agreed that all patients with symptoms should receive substitution therapy, but the essential risk of ischaemic heart disease and osteoporosis, together with the unquestionable psychological effect of having regular menstrual bleeding, have led us to the conclusion that this therapy is indicated in all cases of premature ovarian failure. Cyclical treatment either with a sequential preparation or with oestrogens alone is the treatment of choice.

Germ Cell Deficient (gcd) Mouse as a Model of Premature Ovarian Failure1

“…This is in contrast to the situation in many inbred strains of mice not bearing known mutations affecting germ cells, which will ovulate normally until at least 1 yr of age [8]. Patients who suffer from POF often experience oligomenorrhea before per- manent amenorrhoea develops [1,2]; this pattern is similar to that discussed above for gcd/gcd mice. In some POF patients, laparoscopy reveals a lack of developing follicles and ovarian biopsy shows a network of connective tissue interspersed with fibroblasts [27].…”

“…The basis for a diagnosis of POF includes menarche at a normal age, complete development of the secondary sexual characteristics, and secondary amenorrhoea commencing before age 35 [1]. These phenotypic features are also observed in gcd/gcd female mice.…”

“…The normal response to this regime is an elevated level of serum progesterone as a result of the increased recruitment of developing follicles followed by the production of eggs. Most patients with POF do not respond to superovulation, including those who have previously borne children [1,2,4]. The overall rate of viable pregnancy for POF patients following superovulation is only 2.2% [32].…”

“…Ovarian function in POF patients has been assayed by superovulation with high levels of gonadotropins [1,4]. The normal response to this regime is an elevated level of serum progesterone as a result of the increased recruitment of developing follicles followed by the production of eggs.…”

“…Premature ovarian failure (POF) is a syndrome characterized by menopause commencing before age 35 [1]. This syndrome affects 0.3% of all women and is recognized as one of the most intractable causes of female infertility [2].…”