Bone loss and the aromatase inhibitors

The increasing use of systemic adjuvant therapies has considerably improved the prognosis from early breast cancer. However, some of these therapies affect bone metabolism, resulting in osteoporosis. Aromatase inhibitors lower circulating oestrogen levels to almost unrecordable levels in postmenopausal women, predisposing them to bone loss with an increase in fracture risk. Ongoing clinical trials are favouring the use of the aromatase inhibitors over tamoxifen and this may advocate greater use of these drugs in the future. Strategies for the identification and management of treatment-induced bone loss are currently being defined

CLINICAL HISTORY AND OUTCOME OF 59 PATIENTS WITH IDIOPATHIC HYPERPROLACTINEMIA

Objective: To investigate the clinical course of hyperprolactinemia without demonstrable cause. Design: Prospective study of all patients with idiopathic hyperprolactinemia first seen between 1974 and 1985. Setting: Outpatient Department of University Hospital. Patients: Fifty-nine patients followed for 6 to 190 months (median 78 months). Medical treatment given only in case of anovulatory infertility or hypogonadism. Outcome Measures: Development of pituitary (micro)prolactinoma, prolactin (PRL) levels, and clinical signs of menstrual dysfunction. Results: With exception of one woman in whom it probably had been missed by hypocycloidal tomography, no demonstrable prolactinoma developed. Prolactin levels rose in two patients, one using oral contraceptives and the other with prolactinoma. At the end of follow-up, 15 of 16 patients using a dopaminergic drug had a normal cycle; 13 had normal final PRL levels. From the 43 patients off medication, 28 (66%) had normal PRL levels and 23 (54%) had a normal cycle. There were no significant differences between women who had and had not been pregnant. Dopaminergic medication had no appreciable influence on the course of the disease. Conclusion: In idiopathic hyperprolactinemia, progression to pituitary prolactinoma seldom, if ever, occurs. There is a high tendency to spontaneous cure, and pregnancy or medication have no apparent effect. Frequent pituitary imaging was found to be not necessary in our patient population. It may best be reserved for situations in which the PRL level in symptomatic hyperprolactinemia is inconsistent with pituitary imaging results

The postmenopausal ovary as an androgen-producing gland; hypothesis on the etiology of endometrial cancer

Postmenopausal estrogens originate from the peripheral conversion of androgens, which are produced by the adrenal glands and the ovaries. Estrogens are considered to contribute to the neoplastic development of endometrium. Hyperplasia of ovarian stroma is associated with an increased androgen production by the ovaries and with the development of endometrial pathology. We hypothesize that, in cases of endometrial pathology, an increased production of aromatizable androgens by postmenopausal ovaries will lead to elevated prehormone availability for estrogen formation in utero. Following the conversion of ovarian androgens, a reaction catalyzed by the cytochrome P450 aromatase, estrogens may function as a local mitogenic factor eventually leading to the development of endometrial cancer. We consider the local availability of androgens and the local activity of aromatase relevant for this process. If this hypothesis proves to be right it may give rise to the introduction of aromatase inhibitors in treatment strategies of hormone dependent endometrial malignancies. (C) 2002 Published by Elsevier Science Ireland Ltd