Long-term outcome of ovarian function in women with intermittent premature ovarian insufficiency.

CONTEXT: Spontaneous resumption of ovarian function is not a rare phenomenon in patients with premature ovarian insufficiency (POI). The outcome of this resumption is not known. OBJECTIVE: To describe the outcome following the resumption of ovarian function in POI patients. DESIGN: Cross-sectional study. SETTING: University medical centre. PATIENTS AND MAIN OUTCOME MEASURES: Cumulative incidence of ovarian function resumption and risk factors arresting this resumption during follow-up were determined in a large cohort of POI women. RESULTS: Five hundred and seven patients were included in the study, with a follow-up of 3·44 ± 4·05 years (0-29). Of these, 117 (23%) had features of ovarian function resumption. The cumulative incidence of pregnancy was 3·5% among the whole cohort and 15·3% among patients with resumption of ovarian function. Fifty-five patients (47%) experienced an arrest of their resumption during the follow-up period. In univariate analysis, high FSH and DHEA levels at initial evaluation were risk factors for the arrest of the resumption of ovarian function. In multivariate analysis, high FSH levels at the initial evaluation [1·89 (1·10-3·23), P = 0·03] and older age at diagnosis [1·53 (1·01-2·33), P = 0·04] were risk factors for the arrest of this resumption. CONCLUSION: Resumption of ovarian function is not a rare or brief phenomenon in POI women. The identification of predictive factors of this resumption, as well as its duration, increases our knowledge of the natural history of POI, and will improve the medical management, especially infertility counselling of these patients.

Poor Compliance to Hormone Therapy and Decreased Bone Mineral Density in Women with Premature Ovarian Insufficiency.

Premature ovarian insufficiency leads to through infertility and estrogen deficiency. Optimal management encompasses estrogen replacement therapy. Long-term outcome of women with POI is not known. We design a study to evaluate the medical care, hormone replacement therapy compliance and bone mineral density (BMD) in POI women with at least a five-year follow-up after the first evaluation. One hundred and sixty-two patients (37.3±8.0 years) were evaluated (follow-up 7.9±2.8 years). Sixty-nine patients (42.6%) had stopped their hormone replacement therapy (HRT) for at least one year during the follow up period. BMD determination at initial evaluation and at follow-up visit was completed in 92 patients. At first evaluation, 28 patients (30%) had osteopenia and 7 (8%) had osteoporosis. At follow up, 31 women (34%) had BMD impairment with osteopenia in 61% and osteoporosis in 5%. In univariate analysis and multivariate analysis, there was a significant loss of femoral BMD in women who had stopped their HRT for over a year. In conclusion, this first study concerning long-term follow-up of POI patients shows the poor compliance to their HRT, despite its importance in the prevention of bone demineralization. This study reinforces the need for follow up and specific care for POI women.

Hypercortisolism due to a Pituitary Adenoma Associated with Beckwith-Wiedemann Syndrome.

BACKGROUND: Beckwith-Wiedemann syndrome (BWS) is an overgrowth syndrome with an increased risk of cancer. Most BWS patients show a molecular defect in the 11p15 region that contains imprinted genes. BWS has been associated with malignant neoplasms during infancy. Descriptions of benign tumors, especially in adult patients, are rarer. METHODS/RESULTS: We report the case of a BWS patient with pituitary adenoma caused by loss of methylation (LOM) at ICR2 (locus CDKN1C/KCNQ1OT1). The patient was referred to an endocrinology unit for suspicion of Cushing's disease due to a history of macroglossia and hemihyperplasia. Biological tests led to the diagnosis of ACTH-dependent hypercortisolism. MRI showed a microadenoma of the pituitary gland, confirming the diagnosis of Cushing's disease. DNA methylation analysis revealed LOM at ICR2 that was in a mosaic state in the patient's leukocytes, but was present in nearly all cells of the pituitary adenoma. The epigenetic defect was associated with a somatic USP8 mutation in the adenoma. CONCLUSION: Pituitary adenoma rarely occurs in patients with BWS. However, BWS should be considered in cases of pituitary adenoma with minor and/or major signs of BWS. The association between ICR2 LOM and USP8 mutation in the adenoma is questionable. © 2016 S. Karger AG, Basel.