Endometriosis is thought to be an ovarian-dependent benign disease that affects up to 12% of women during their reproductive life. For the past ten years the gonadotropin-releasing hormone (GnRH)-agonists have been proved effective and safe drugs in the treatment of endometriosis. Nevertheless, gestagens such as lynestrenol still remain the most often used hormonal drugs for the treatment of this disease. The primary objective of this study was to compare the efficacy of the GnRH-agonist leuprorelin acetate depot (LAD) (Enantone-Gyn) 3.75 mg subcutaneously per month with that of the gestagen lynestrenol (LYN) (Orgametril) 5 mg orally twice per day in women with severe endometriosis, in terms of postoperative revised American Fertility Society (r-AFS) scores I-IV at first-look laparoscopy (score after removal of endometriotic lesions or adhesions) to the r-AFS score after six months' treatment. Secondary objectives were the improvement of clinical symptoms and the side-effect profile. Forty-eight women with postoperative r-AFS scores I-IV were evaluated in an open prospective randomized study between 1996 and 1998. All the participants underwent a first-look laparoscopy with resection of endometriotic lesions and six months' therapy with one of the above mentioned drugs, and a further second-look laparoscopy. The six months' treatment with LAD or LYN led to a significant reduction of the r-AFS score points in both groups. The mean r-AFS score in points for the LAD group after the first-look laparoscopy was 21.8 and was 27.2 for the LYN group. After the medical treatment a mean value of 11.5 points was observed in the LAD group compared with a mean value of 25.5 in the LYN group. This difference was statistically significant (p = 0.000014, Wilcoxon test). The improvement in the symptoms of dysmenorrhea, chronic pelvic pain and dyspareunia was also more pronounced in the LAD-treated group. LAD was more effective than LYN in the suppression of circulating serum 17 beta-estradiol levels after 6 months of treatment (mean 27.7 +/- 9.3 pg/ml versus 42.6 +/- 59.3 pg/ml). All the observed side-effects were deemed tolerable by the women who participated in this study. As the reduction of the r-AFS score in points was much more pronounced in the LAD group than in the LYN group, GnRH-agonists should therefore be used as first-choice drugs in the treatment of endometriosis. Due to the limited treatment of 6 months' duration of GnRH-agonists, gestagens might be used as second-line drugs for long-term and continuous treatment in the management of endometriosis to maintain the primary beneficial effect of GnRH-agonist treatment in patients who have completed their families.
Integrins are cell adhesion molecules that undergo cell-specific dynamic changes during the normal menstrual cycle in the human endometrium. Here, using immunohistochemistry, we have investigated the expression pattern of the integrins alphav, alpha2beta1, alpha3beta1, alpha3, alpha6, beta1, beta2 and beta3 in the human ectopic endometrium of 30 patients and in nine cases in the corresponding eutopic endometrium. The biopsies were obtained during the early or late follicular phase (25 cases), during the corpus luteum phase (four cases) and in one case after 6 months' treatment with a gonadotrophin releasing hormone (GnRH) agonist. The integrin expression was independent of the ovarian steroid situation at the time of biopsy. The integrin alpha6 was expressed in all endometriotic and endometrium samples. The integrin alpha3 was absent in all endometrium tissues of patients with endometriosis. However, the corresponding endometriotic lesions re-expressed this adhesion molecule in 15 cases. No change in integrin beta3 expression pattern could be demonstrated in either endometriotic lesions or endometrium samples, regardless of the menstrual cycle phase. A correlation between serum oestradiol and progesterone concentrations and the expression of the investigated integrins was not observed, thus indicating that these two hormones play a minor role in the regulation of the cell adhesion molecules examined. Our investigation suggests that endometriosis is a dedifferentiated disease as it expressed different integrins in comparison with the eutopic endometrium, and independently of the hormonal situation. The ability of endometriotic tissues to express integrins may explain the high recurrence rates in patients with endometriosis, as these samples retain their adhesion potency after retrograde menstruation and are thus able to establish cell-cell and cell-matrix interactions with the surrounding peritoneum.
In Ethiopia cervical carcinoma is the most frequent cancer in women. HPV infection is a prerequisite for this disease. However, to date there have been no data on human papilloma virus (HPV) prevalence in Ethiopia. Outpatients attending Attat hospital in rural Ethiopia were examined for the presence of HPV DNA using the Digene HPV test. 15.9% of patients were found to be HPV positive. The proportion of HPV high risk types was 13.2% [age-standardised rates: HPV: 14.4% (95% CI: 8.5-20.2); HPV high risk: 11.6% (95% CI: 6.3-16.9)]. Compared to other countries HPV prevalence is high, especially of high risk types. Until vaccination programmes take effect, screening programmes should not be based on HPV testing alone as this will lead to significant overtreatment of healthy women.
The expression of gap junction connexins (Cx) in the female reproductive tract of rodents and in the human endometrium is highly regulated by steroid hormones. Here we have investigated the distribution and regulation properties of Cx43, Cx26 and Cx32 in the human ectopic endometrium of 41 patients, using immunohistochemistry. The biopsies were obtained during the early or late follicular phase (26 cases), during the corpus luteum phase (five cases) and after a 6 month treatment with a gonadotrophin-releasing hormone (GnRH) agonist (three cases) or progestin (seven cases). Aberrant expression of Cx43 was found in the epithelium of nearly all endometriotic glands whereas Cx26, typical for human uterine epithelium cells, was only detected in 18 cases; in 17 it was co-expressed with Cx43. The stromal compartment of the tissues did not express any connexins investigated. Staining for Cx32 was absent in all endometriotic tissues. Strong expression of Cx43 was correlated with a high serum value of 17 beta-oestradiol, whereas a strong expression of Cx26 was found with high values of progesterone mainly in patients after progestin treatment. The epithelium of endometriotic implants collected after GnRH agonist treatment expressed Cx26 and Cx43 only moderately. The patterns described demonstrate an aberrant connexin expression and a different hormonal regulation pattern in endometriotic tissues compared to the normal cyclic uterine endometrium, thus indicating a high dedifferentiation from the normal situation. However, endometriosis still remains a hormonally-dependent benign disease, and hence, can be treated hormonally.
Endometriosis is thought to be an ovarian-dependent benign disease that affects up to 12% of women during their reproductive life. For the past ten years the gonadotropin-releasing hormone (GnRH)-agonists have been proved effective and safe drugs in the treatment of endometriosis. Nevertheless, gestagens such as lynestrenol still remain the most often used hormonal drugs for the treatment of this disease. The primary objective of this study was to compare the efficacy of the GnRH-agonist leuprorelin acetate depot (LAD) (Enantone-Gyn) 3.75 mg subcutaneously per month with that of the gestagen lynestrenol (LYN) (Orgametril) 5 mg orally twice per day in women with severe endometriosis, in terms of postoperative revised American Fertility Society (r-AFS) scores I-IV at first-look laparoscopy (score after removal of endometriotic lesions or adhesions) to the r-AFS score after six months' treatment. Secondary objectives were the improvement of clinical symptoms and the side-effect profile. Forty-eight women with postoperative r-AFS scores I-IV were evaluated in an open prospective randomized study between 1996 and 1998. All the participants underwent a first-look laparoscopy with resection of endometriotic lesions and six months' therapy with one of the above mentioned drugs, and a further second-look laparoscopy. The six months' treatment with LAD or LYN led to a significant reduction of the r-AFS score points in both groups. The mean r-AFS score in points for the LAD group after the first-look laparoscopy was 21.8 and was 27.2 for the LYN group. After the medical treatment a mean value of 11.5 points was observed in the LAD group compared with a mean value of 25.5 in the LYN group. This difference was statistically significant (p = 0.000014, Wilcoxon test). The improvement in the symptoms of dysmenorrhea, chronic pelvic pain and dyspareunia was also more pronounced in the LAD-treated group. LAD was more effective than LYN in the suppression of circulating serum 17 beta-estradiol levels after 6 months of treatment (mean 27.7 +/- 9.3 pg/ml versus 42.6 +/- 59.3 pg/ml). All the observed side-effects were deemed tolerable by the women who participated in this study. As the reduction of the r-AFS score in points was much more pronounced in the LAD group than in the LYN group, GnRH-agonists should therefore be used as first-choice drugs in the treatment of endometriosis. Due to the limited treatment of 6 months' duration of GnRH-agonists, gestagens might be used as second-line drugs for long-term and continuous treatment in the management of endometriosis to maintain the primary beneficial effect of GnRH-agonist treatment in patients who have completed their families.
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