Maintenance therapy involving a tapering dose of danazol or mid/low doses of oral contraceptive after gonadotropin-releasing hormone agonist treatment for endometriosis-associated pelvic pain.

Pelvic pain associated with endometriosis was treated by the long-term administration of a tapering dose of danazol or mid/low doses of oral contraceptives after the end of therapy involving a GnRH agonist (GnRH-a). Results demonstrated that each of these three therapies is a practical and efficient treatment regimen to maintain the relief of pelvic pain achieved by GnRH-a therapy, at least for a period of 12 months.

Differential effects of progestogens, by type and regimen, on estrogen-metabolizing enzymes in human breast cancer cells.

OBJECTIVES: To investigate the in vitro effects of five progestogens commonly used in hormone replacement therapy (HRT) on estrogen-metabolizing enzymes in human breast cancer cells. METHODS: The human hormone-dependent breast cancer cell lines T47D, MCF-7, and MCF-7aro were cultured with estradiol (E(2)) and progestogens. The mRNA levels of estrogen-metabolizing enzymes were determined by RT-PCR or Northern blot, and enzyme activities by radiolabeled substrates. Cell proliferation was measured by bromodeoxyuridine incorporation. In vitro models for continuous combined regimen (CCR) and sequential combined regimen (SCR) were established to mimic the in vivo conditions of HRT. RESULTS: Medroxyprogesterone acetate (MPA) plus E(2) (10(-8)M) stimulated the mRNA levels and activities of estrogen-activating enzymes aromatase (at 10(-8)M MPA), 17beta-hydroxysteroid dehydrogenase type 1 (17betaHSD1) (at 10(-6)M), and sulfatase (at 10(-8) to 10(-6)M) compared to E(2) only. Progesterone also stimulated enzyme activity, but to a lower magnitude. Levonorgestrel, norethindrone, and dienogest showed no enzyme stimulation. The estrogen-inactivating enzymes 17beta-hydroxysteroid dehydrogenase type 2 and sulfotransferase were not affected by any of the progestogens tested. However, all the progestogens (at 10(-8) to 10(-6)M) inhibited E(2)-stimulated cell proliferation. While increased aromatase and 17betaHSD1 activities were observed in the CCR model, no significant enzyme stimulation was observed in the SCR model. CONCLUSIONS: The present study suggested that progestogens exert different actions on estrogen-metabolizing enzymes in breast cancer cells dependent on the specific progestogen and regimen used. Further studies are needed to elucidate whether MPA, a progestogen currently used in HRT, leads to a higher risk of breast cancer development than other progestogens.

Synergistic effect of interleukin-6 promoter (IL6 -634C/G) and intercellular adhesion molecule-1 (ICAM-1 469K/E) gene polymorphisms on the risk of endometriosis in Japanese women.

PROBLEM: Endometriosis is an immune-related, chronic inflammatory disease with a polygenic predisposition. The aim of this study was to investigate whether the interleukin-6 (IL-6) gene promoter region polymorphism (-634C/G) and the intercellular adhesion molecule-1 (ICAM-1) gene 469K/E polymorphism are responsible in part for the genetic susceptibility to endometriosis. METHODS OF STUDY: The IL-6 -634C/G and ICAM-1 469K/E genotypes were determined in 202 patients with endometriosis and 236 control women by polymerase chain reaction-restriction fragment length polymorphism. RESULTS: There were no differences in the IL-6 -634C/G or the ICAM-1 469K/E genotypes and allele frequencies between control women and endometriosis patients collectively, or between control women and each clinical subgroup of endometriosis patients. Interestingly, the frequency of ICAM-1 EE homozygotes who concomitantly carried the IL-6 -634G allele was significantly higher in patients with endometriosis (chi(2) = 6.458, P = 0.0396, d.f. = 2). CONCLUSION: Our results suggest that the IL-6 -634C/G and ICAM-1 469K/E polymorphisms synergistically affect the susceptibility for endometriosis in the Japanese population.

Association of two polymorphisms in the peroxisome proliferator-activated receptor-gamma gene with adenomyosis, endometriosis, and leiomyomata in Japanese women.

OBJECTIVE: The peroxisome proliferator-activated receptor-gamma (PPAR-gamma) is a nuclear hormone receptor that plays an important role in many diseases. This study investigated whether two polymorphisms (Pro12Ala in exon B and C161T in exon 6) of the PPAR-gamma2 gene are related to adenomyosis, endometriosis, or leiomyomata. METHODS: A total of 390 patients with adenomyosis, endometriosis, and/or leiomyomata were classified into four groups: 103 patients with adenomyosis (21 adenomyosis only and 82 adenomyosis with endometriosis and/or leiomyomata), 95 patients with endometriosis only, 100 patients with leiomyomata only, and 92 patients with endometriosis and leiomyomata. RESULTS: There was no association between distribution of genotype or allele frequencies for the PPAR-gamma Pro12Ala polymorphism and the presence of adenomyosis, endometriosis, and/or leiomyomata. However, compared with results for controls, the PPAR-gamma 161CC genotype and 161C allele frequencies were significantly increased in patients with adenomyosis (genotype: chi2 = 8.185, corrected P value [Pc] = .0169; allele: chi2 = 8.337, Pc = .0155) and in patients with endometriosis (genotype: chi2 = 6.748, Pc = .0375; allele: chi2 = 6.413, Pc = .0453). CONCLUSION: The results suggest that the PPAR-gamma 161CC genotype could be a genetic risk factor for adenomyosis and endometriosis, whereas the Pro12Ala polymorphism was not associated with these estrogen-dependent benign uterine diseases in a Japanese population.

Usefulness and limits of CA-125 in diagnosis of endometriosis without associated ovarian endometriomas.

BACKGROUND: The aim of this study was to evaluate the diagnostic significance of CA-125 for endometriosis without ovarian endometriomas. METHODS: Preoperative serum CA-125 levels were measured in 775 consecutive women diagnosed by laparoscopy or laparotomy with endometriosis, adenomyosis, leiomyomas, or normal pelvis. RESULTS: Receiver operating characteristic curve analysis revealed that the area under the curve for endometriosis without endometriomas was 0.788, significantly smaller than that for endometriosis with endometriomas (0.935, P < 0.05). In diagnosis of endometriosis without endometriomas, both the maximal accuracy of 78.8% and the maximal diagnostic value of 61.2% were obtained at the cutoff value of 20 U/mL. Negative predictive value was 78.0% at the cutoff value of 20 U/mL, whereas positive predictive value was 92.9% at the cutoff value of 30 U/mL. This range is clearly superior to the empirical single cutoff of 35 U/mL. CONCLUSIONS: In the diagnosis of endometriosis without endometriomas, combined use of two cutoff values for CA-125, 20 and 30 U/mL, provides improved diagnostic performance. However, the accuracy of using only CA-125 testing for diagnosis is still limited. Serum CA-125 testing can be done during initial screenings of women with possible endometriosis.