The expression of insulin-like growth factor-I (IGF-I) was measured at the mRNA and protein level in myometrium and fibroids from women with and without preoperative treatment with a gonadotrophin-releasing hormone (GnRH) agonist for 3 months, from post-menopausal women, from pregnant women and in myometrium from women without fibroid disease. Women with menstrual periods were classified according to the phase of the cycle. In tissues from non-treated premenopausal women, IGF-I mRNA expression was significantly higher in fibroids than in myometrium, with no differences related to phase of the menstrual cycle. In post-menopausal women and in GnRH agonist-treated women responding to treatment, similar mRNA expression was seen in myometrium and fibroids but the concentrations were lower than in untreated premenopausal women. The IGF-I mRNA value in fibroids from pregnant women was higher than in any other group and myometrium from pregnant women exhibited higher mRNA expression than myometrium from non-treated premenopausal women. The IGF-I protein was more abundant in fibroids than in myometrium of non-treated premenopausal and of pregnant women and in both tissues the concentration was significantly higher in the group of pregnant women. The IGF-I protein concentrations in fibroids and myometrium from GnRH agonist-treated and post-menopausal women were similar to those from premenopausal non-treated women. High sex steroid concentrations in pregnant and non-pregnant women of fertile age seem to be associated with a higher expression of IGF-I in fibroids than in myometrium, suggesting that IGF-I contributes to the selective growth advantage of these tumours.

Uterine leiomyomas (uterine fibroids) are sex-steroid dependent benign tumors. Limited knowledge is available regarding the role of estrogen and their receptors in the regulation of fibroids in premenopausal women, and in their shrinkage after treatment with a gonadotropin-releasing hormone analogue (GnRHa). The expression of the two subtypes of the estrogen receptor (ER), ER alpha and ER beta, was studied in leiomyoma and homologous myometrium from women in the proliferative phase of the menstrual cycle and from women treated with GnRHa. The mRNA levels of ER alpha and ER beta were monitored by solution hybridization and in situ hybridization, and receptor proteins were detected and localized by immunohistochemistry. Both ER alpha and ER beta were present in the leiomyomas and homologous myometrium. The ER alpha mRNA level in the leiomyomas was higher than in the surrounding myometrium. The ER beta mRNA level was lower than that of ER alpha in both groups. ER beta immunoreactivity was lower in leiomyomas when compared with the myometrium after GnRHa treatment, while ER alpha was higher in the leiomyomas. The present results imply that the increased ratio of ER alpha/ER beta observed in the fibroids after GnRHa treatment could reflect or be the cause of the shrinkage of the leiomyoma, which is the clinical outcome of this treatment.

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Eighty-four patients with bacterial vaginosis were examined in an open randomized trial, the aim of which was to define clinical results and the microbiological panorama after topical treatment for 1 week with either an acetic acid jelly (A), an estrogen cream (B), a fermented milk product (C) or metronidazole (D). After exclusion because of chlamydia infection (15 cases) or for other reasons, 61 cases remained for complete evaluation 4 weeks after the start of treatment. Clinical cure was obtained in 3 cases out of 17 on regimen A, in 1 out of 16 on regimen B, in 1 of 14 on regimen C, and in 13 out of 14 on regimen D. The patients were conclusively either symptomless or symptomatic when examined on 113 occasions. Statistically significant reduction after treatment resulting in relief of symptoms was observed in the numbers of corynebacteria and anaerobic cocci, whereas lactobacilli increased in numbers. The instillation of high numbers of Lactobacillus acidophilus (C) into the vagina cured only 1 patient and did not influence the predominance of lactobacilli in the vagina at the follow-up examination. The difference in microbiological profile of women in symptomatic and asymptomatic conditions becomes still more apparent when the results of the present and previously published studies on the subject by the present group of investigators are combined. The symptomatic woman is significantly more often harboring corynebacteria, Gardnerella vaginalis, peptostreptococci, peptococci, eubacteria and Bacteroides species. Lactobacilli are significantly reduced in numbers. However, only 51 % of our previously symptomatic, but now symptomless women show predominant growth of lactobacilli, which is less than expected for healthy women. Therefore, lactobacilli may not be the specific factor that protects against bacterial vaginosis.

The content of estrogen and progesterone receptors (ER, PR) is higher in fibroid tissue than in homologous myometrium, and both receptors seem to be regulated by the levels of circulating sex steroids. Myometrial and fibroid tissues were recovered from women undergoing gynecological operations during different phases of the menstrual cycle and during treatment with an analogue of GnRH (GnRHa). Contents of ER and PR in the tissue cytosol were determined by enzyme immunoassay. The ER levels were significantly higher in fibroid tissue than in homologous myometrium in all the endocrine conditions. During the secretory phase, when luteal progesterone production is prominent, the ER levels in the myometrium and fibroids were lower than during the proliferative phase. During GnRHa treatment, the ER levels in both tissues were similar to those in the proliferative phase but significantly higher than in the secretory phase. The PR levels were also significantly higher in fibroids than in myometrium in all the different endocrine conditions. In both tissues, the PR levels were lower in the secretory phase and during GnRHa treatment, compared with the proliferative phase. Our data suggest that, in these categories of women, both ER and PR are overexpressed in fibroid tissue. Apparently, high progesterone levels down-regulate the ER in both fibroids and myometrium, whereas estrogen mediates the up-regulation of the PR during the proliferative phase. Increased knowledge about the mechanisms by which sex steroids regulate their own receptors in uterine tissues might provide a basis for development of new treatment strategies for women with fibroid disease.

The content of RNA and DNA in human myometrium and fibroids obtained at different endocrine conditions varied, with the highest RNA/DNA ratio in tissues from pregnant patients, intermediate ratios in women during the menstrual cycle and the lowest in tissues from postmenopausal and GnRHa-treated patients. mRNA expression of two house-keeping genes, γ-actin and GAPDH, was highest in myometrium from pregnant women, intermediate in untreated women of fertile age and lowest in tissues from GnRHa-treated and postmenopausal women. To control for degradation of nucleic acids when measuring mRNA expression, we suggest additional analysis of gene(s), where the expression pattern is known, and that expression, whenever possible, is related to DNA, which is a more stable parameter than RNA and total nucleic acids, when there are differences in proliferation between tissues and/or groups of patients.

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