Efficacy of leuprorelin acetate depot in symptomatic fibromatous uteri: the Italian Multicentre Trial.

A total of 110 nonmenopausal women (mean age 42.1 years) presenting with symptomatic uterine leiomyomata and/or fibromatous uteri have been enrolled in this trial to evaluate the efficacy of the depot formulation of leuprorelin acetate in decreasing uterine volume and minimizing menorrhagia, dysmenorrhoea and pressure over the bladder. All patients were treated with an intramuscular injection of leuprorelin acetate depot 3.75 mg every 4 weeks for 16 weeks. Clinical examinations and hormonal and ultrasound determinations were performed before, during and at the end of treatment. Appropriate follow-up is still ongoing for most patients. At the end of the treatment period, of 88 women with enlarged fibromatous uteri, 33 (37.5%) showed a decrease in uterine volume of greater than or equal to 50% of the original size, while nine (10.2%) remained with unchanged uterine volume. Of 80 fibromas measurable separately, 47 (52.8%) decreased by greater than 50% of the initial volume and 16 (18%) remained unchanged or even increased. During treatment, clinically advantageous effects were observed in the associated symptomatology, mainly in the production of amenorrhoea and restoration of normal haemoglobin levels. Most of the patients were affected by irregular menstrual blood loss with consequent anaemia that in 29 patients was expressed by low levels of haemoglobin (mean 9.2 g/dl; SD 1.5; range 4.5-11.8 g/dl). By the end of the treatment, only one patient still had moderate vaginal blood loss. Haemoglobin levels rose to a mean value of 11.8 g/dl (SD 1.3; range 8.5-14.1 g/dl). Three patients (2.7%) failed to complete the 16-week treatment protocol, because of headache (one patient) and increased blood pressure (two patients). As a result of the treatment, of the 107 patients who were candidates for surgery and who were included in this study, only nine (8.4%) required surgery during leuprorelin acetate treatment. Of these, four operations were vaginal excision of the submucous myomata protruding into the cervix during treatment, and in five hysterectomy performed because of persistence of symptoms. In most patients the achievement of amenorrhoea minimized the fear of surgical emergency, facilitating an increased awareness of their clinical condition. With the exception of the three patients who dropped out, side effects were mild in all patients, consisting mainly of hot flushes, which were easily tolerated. In the following 8-12 months, the regrowth of uterine volume to original size has been usual in most of the 82 patients now in follow-up.(ABSTRACT TRUNCATED AT 400 WORDS)

Usefulness of a hysteroscopic follow-up on patients with breast cancer in pre- and post-menopausal age.

Over the last years, the high incidence of multiple primary neoplasms has been of great interest. The association between carcinoma of the breast and endometrium has been particularly emphasized; it is based on similar epidemiological factors and common hormondependence in the two tumours. Following these assumptions, the Authors present the preliminary results of hysteroscopic and histological studies including 45 patients, 24 in pre-menopausal and 21 in post-menopausal age, who have undergone a mastectomy or quadrantectomy for breast cancer in the past 5 years. They were compared with respective control groups. In pre-menopausal women, there was a higher incidence of activated and irregular endometrium, precancerous lesions (such as glandular-cystic hyperplasia) and one case of adenocarcinoma of the endometrium in a completely asymptomatic woman. On the contrary, endometrial atrophy turned out to be the most frequent hysteroscopic and histological report in post-menopausal women. This supports the hypothesis of two different types of breast cancer that occur in pre- and post-menopausal age and it suggests the utility of a hysteroscopic follow-up, only in pre-menopausal women.

Relationship between maternal parity, basal prolactin levels and neonatal breast milk intake.

Basal serum levels of prolactin (PRL) in 21 nursing mothers were measured by radioimmunoassay on the 2nd, 3rd and 4th days of the puerperium. The quantity of breast milk suckled during the 4th day of life was also evaluated by calculating the difference in the baby's weight before and after each feeding. During the first postpartum days, mean basal levels of PRL did not change. However these levels were noted to be significantly lower in the multiparas (p less than 0.05) than in the primiparas. In addition, the milk intake in neonates of multiparous mothers was significantly greater (p less than 0.05) than that in neonates of primiparous mothers. The author's hypothesis, based on the results of animal experimentation described in the literature, is that initiation of breast-feeding is facilitated in multiparas by the increased number of occupied PRL receptors in the mammary glands reflected by the lowered serum levels of the hormone.

Presence of positive feedback between oestrogen and LH in patients with Klinefelter's syndrome, and Sertoli-cell-only syndrome.

In five adult patients with Klinefelter's syndrome and two with Sertoli-cell-only syndrome, exogenous administration of 17 beta-oestradiol, resulting in a sustained and prolonged elevation of circulating oestrogen levels, had a biphasic effect on LH release. After an initial decrease, a dramatic rise in peripheral levels of LH (positive feedback) was observed in all patients. The timing and magnitude of the induced LH surge was similar to that observed in postmenopausal women after administration of large doses of Ethinyloestradiol. A similar positive feedback effect on the secretion of FSH could not be demonstrated. In two patients with the Sertoli-cell-only syndrome, oestrogen treatment induced marked variations in serum testosterone levels, which appeared to be related to the LH changes. Similar changes were not present in patients with Klinefelter's syndrome, indicating a decrease in the sensitivity of the testicular Leydig cell. These experiments demonstrate that positive feedback between oestrogen and luteinizing hormone is present in the adult human male.

Effects of estrogen on the release of gonadotropins and prolactin in male pseudohermaphrodites.

Three adult patients with male pseudohermaphroditism were given 15 microgram/kg body weight of 17 beta-estradiol im daily (at 08:00 hours) for 12-15 days and circulating levels of gonadotropins, prolactin and estradiol were determined by radioimmunoassay before and during the steriod course. All patients had elevated gonadotropin levels prior to starting on estradiol. During estrogen treatment all patients demonstrated suppression of FSH and LH with a subsequent rise in LH (positive feedback) while estrogen levels remained elevated. A similar positive feedback effect on the secretion of FSH could not be demonstrated. In two patients, who had never received estrogen treatment prior to this study, estradiol induced a significant elevation of serum prolactin levels within 24 h and levels remained higher than basal values for the rest of the estrogen treatment period. In the third patient, who had been previously treated with estrogen, serum prolactin levels did not change significantly during estrogen treatment. This study was afforded evidence for the presence in humans of an estrogen mediated LH release concomitant with an augmented prolactin secretion.

Enchancement of deficient pituitary response to luteinizing hormone releasing hormone in patients with primary amenorrhea.

Although the absence of pituitary response to the luteinizing hormone releasing hormone (LHRH) test has been considered proof of a lesion primarily localized at the pituitary level, the possibility exists that an absent pituitary response may represent only the effect of a chronic deficiency of hypothalamic secretion. To verify this hypothesis, 4 patients with primary amenorrhea, hypogonadotropic hypogonadism, and deficient or absent responses to a 25 mug LHRH rapid IV test were treated with 400 mug LHRH infused in 7 hours during each of 3 successive days. The finding that patients with deficient LH responses to a rapid LHRH test became normally responsive to a second equivalent test after a slow and prolonged treatment with the decapeptide suggests that, in these patients, besides a lesion at the pituitary level, a primary defect at the hypothalamic or higher centers may also be suspected.

[Gonadotropins]. / Gonadotropine

The clinical usefulness of plasma LH and FSH radioimmunoassays, both in basal and dynamic conditions, is briefly discussed. While occasional LH and FSH determinations may indicate only a serious gonad failure, at least when high values are found, dynamic studies before and after LH-RH i.v. injection may suggest a hypothalamic or pituitary lesion. In this regard the LH-RH test is presented as the most evident demonstration of the utility of gonadotropin radioimmunoassay. Different patterns of response are presented and their correlation with menstrual disorders is discussed in view of different distribution (Tab.1). Moreover, the AA. suggest a primary hypothalamic deficiency in LH-RH in the cases of "deficient" response that, being a constant finding in different days, became a "normal" response after 3 days therapy with LH-RH infusion and returned to basal levels 2 months later. Equally, an "exaggerated" response consistenly found in some patients with secondary amenorrhea, is suspected to be of hypothalamic origin since "normalization" may be obtained after a similar LH-RH treatment.