Serum inhibin levels in polycystic ovary syndrome: effect of insulin resistance and insulin secretion

Insulin resistance is common in women with the polycystic ovary syndrome. We investigated the relationship between insulin resistance and the serum inhibin concentration in a group of 19 women with polycystic ovary syndrome and eight control subjects at different phases of the menstrual cycle. Insulin resistance was measured by the frequently sampled intravenous glucose tolerance test, and inhibin was measured by a specific radioimmunoassay. Insulin sensitivity (mean +/- SE) was significantly reduced in the polycystic ovary syndrome group compared with controls: reduced insulin sensitivity 46.7 +/- 5.0 min-1/(nmol/mL), normally insulin-sensitive 106.6 +/- 11.7 min-1/(nmol/mL) (P less than .01). The women with polycystic ovary syndrome had inhibin levels (126 +/- 15.2 microLEq/mL) comparable to those found during the early follicular phase of the control group (117 +/- 22.1 microLEq/mL), but significantly lower than late follicular phase (259 +/- 25.6 microLEq/mL) or luteal phase (448 +/- 91.8 microLEq/mL) levels in the control group. No association was found between the degree of insulin resistance and the inhibin concentration, which remained unaltered over a 3-hour period despite maximal stimulation of endogenous insulin secretion. The inhibin concentrations in polycystic ovary syndrome may reflect impaired follicular maturation. Inhibin secretion is not acutely affected by insulin secretion in normal or in hyperandrogenic women.     

Elevated soluble Fas ligand levels may suggest a role for apoptosis in women with endometriosis

OBJECTIVE: To evaluate soluble Fas ligand concentrations in serum and peritoneal fluid from women with endometriosis and from fertile controls without endometriosis, and to study levels of soluble Fas ligand in conditioned media of cultured endometrial stromal cells. DESIGN: Prospective, experimental trial. SETTING: Two academic IVF centers. PATIENT(S): Twenty-nine fertile women without endometriosis and 57 infertile women with endometriosis (32 with stage I or II disease and 25 with stage III or IV disease). MAIN OUTCOME MEASURE(S): Enzyme-linked immunosorbent assay was used to measure soluble Fas ligand concentrations in paired samples of serum and peritoneal fluid from women with and without endometriosis. Concentrations were also measured in conditioned media of cultured endometrial stromal cells at basal conditions and after stimulation with interleukin-8 (0.001-10 ng/mL) and tumor necrosis factor-alpha (1-10 ng/mL). RESULT(S): Compared with fertile controls and women with early-stage of endometriosis, women with moderate to severe endometriosis had elevated serum (87.2 +/- 6.4, 88.2 +/- 6.9, and 162.3 +/- 7.8 pg/mL, respectively) and peritoneal fluid (81.0 +/- 6.0, 80.5 +/- 6.8, and 166.2 +/- 10.3 pg/mL, respectively) concentrations of soluble Fas ligand. Serum levels of soluble Fas ligand positively correlated with levels in peritoneal fluid. Comparison of patients in the same menstrual cycle in each group revealed that increased levels of soluble Fas ligand in patients with advanced endometriosis were not attributable to the difference in cycle phases. Soluble Fas ligand was not detected in conditioned media of endometrial stromal cells under baseline conditions or after stimulation. CONCLUSION(S): Serum and peritoneal fluid of women with moderate to severe endometriosis contain elevated concentrations of soluble Fas ligand compared to women with minimal or mild endometriosis and women without endometriosis. These findings suggest a role for apoptotic dysregulation in the pathophysiology of endometriosis.     

Altered expression of interleukin-18 in the peritoneal fluid of women with endometriosis

OBJECTIVE: Peritoneal fluid (PF) inflammatory factors may participate in the pathogenesis of endometriosis. The aim of this study was to investigate PF interleukin (IL)-18 levels in women with and without endometriosis. DESIGN: Controlled clinical study. SETTING: Women undergoing laparoscopy at a university hospital. PATIENT(S): Fifty women with previously untreated endometriosis, 8 women on GnRH agonists for endometriosis, and 18 control women with normal pelvic anatomy who were undergoing tubal ligation. INTERVENTION(S): Peritoneal fluid IL-18 levels as measured by ELISA. MAIN OUTCOME MEASURE(S): Peritoneal fluid IL-18 levels. RESULT(S): Peritoneal fluid IL-18 levels were significantly higher in women with previously untreated endometriosis (mean +/- SEM, 91.1 +/- 6.5 pg/mL) than in control women (59.4 +/- 2.0 pg/mL). Interestingly, women with superficial (100.0 +/- 10.2 pg/mL) and deep peritoneal implants (94.0 +/- 10.8 pg/mL) had significantly higher PF IL-18 levels than did women with endometriomas (57.8 +/- 1.8 pg/mL). Similarly, women with stage I-II endometriosis (97.3 +/- 8.0 pg/mL), but not women with stage III-IV endometriosis (74.9 +/- 9.9 pg/mL), had significantly higher PF IL-18 levels than did control women. Peritoneal fluid IL-18 levels were significantly higher in the luteal phase than in the follicular phase but did not discriminate between women with pelvic pain or infertility. CONCLUSION(S): Peritoneal fluid IL-18 is elevated in women with peritoneal, minimal- to mild-stage endometriosis.     

Demonstration of a gradient in inhibin activity, estrogen, progesterone, and delta 4-androstenedione in follicular fluid, ovarian vein blood, and peripheral blood of normal women

Ovarian vein serum from 3 subjects during the late follicular phase of the menstrual cycle had detectable inhibin activity, whereas ovarian vein serum of 12 other subjects during the early follicular phase and luteal phase had no detectable inhibin activity in a rat anterior pituitary cell culture assay. Subjects having detectable inhibin activity (102 +/- 47 U/100 microliters) had 1257 +/- 582 U/100 microliters inhibin activity in FF, whereas subjects having no detectable inhibin activity had FF levels of 711 +/- 203 U/100 microliters of inhibin activity. Estrogen levels of FF and ovarian vein serum of the group having detectable inhibin activity in ovarian vein serum were 282 +/- 239 ng/ml and 4.8 +/- 1.77 ng/ml, respectively. The estrogen content of FF and ovarian vein blood of the group having nondetectable inhibin activity in ovarian vein blood was 127 +/0 45 ng/ml and 3.03 +/- 0.6 ng/ml, respectively.     

Peritoneal fluid and serum levels of hepatocyte growth factor may predict the activity of endometriosis

BACKGROUND: The suitable parameter in PF as well as in serum that may predict the activity of endometriosis is not well described. Therefore, we tried to examine the peritoneal fluid (PF) and serum concentrations of hepatocyte growth factor (HGF) in different revised American Society of Reproductive Medicine (r-ASRM) staging and morphologic appearances of endometriosis in an attempt to determine whether HGF can be clinically useful to predict the activity of pelvic endometriosis. METHODS: Peritoneal fluid was collected from 137 women with endometriosis and 57 women without endometriosis during laparoscopy and blood sampling was collected from 37 women with endometriosis and 21 women without endometriosis before laparoscopy. The concentration of HGF in PF and serum was measured by enzyme-linked immunosorbent assay. The ability of isolated macrophages and stroma to secrete HGF in response to lipopolysaccharide (LPS) was evaluated. RESULTS: A significantly increased concentration of HGF in PF was found in women with endometriosis (1451.75 +/- 90.7 pg/mL) than that in non-endometriosis (1120.5 +/- 77.3 pg/mL, p < 0.01) without any remarkable difference in HGF levels between women with stage I-/II endometriosis and stage III-/IV endometriosis. When we distributed serum and PF levels of HGF according to different color appearances of endometriosis, we found a significantly higher serum and PF levels of HGF in women containing dominant red peritoneal lesions in pelvic cavity (740 +/- 109.3 pg/mL for serum; 1685 +/- 183.4 pg/mL for PF) than those having other pigmented lesions (649 +/- 79.5 pg/mL, p < 0.05 for serum; 1224 +/- 67.8 pg/mL, p < 0.05 for PF) or chocolate cysts (485 +/- 43.1 pg/mL, p < 0.05 for serum; 1118 +/- 83.1 pg/mL, p < 0.01 for PF). Exogenous stimulation with LPS significantly increased the production of HGF in the culture media by macrophages and stroma derived from women with endometriosis than that in women without endometriosis. CONCLUSIONS: These results suggest that women with early or advanced endometriosis as measured by r-ASRM scoring system are not associated with an increase in either serum or PF concentrations of HGF. Rather HGF levels in serum and PF were significantly increased in women harboring blood-filled red peritoneal lesions and may be clinically useful to predict the activity of pelvic endometriosis.     

Protein, progesterone, and protease inhibitors in uterine and peritoneal fluids of women with endometriosis

This study was undertaken to determine whether women with endometriosis have altered protein, progesterone (P), and protease inhibitor concentrations in their uterine fluid and peritoneal fluid (PF) compared with controls at different phases of the menstrual cycle. Uterine flushings (UFs), PF, and blood were obtained during the follicular and luteal phases of the cycle from 29 normal women and 16 women who were diagnosed as having endometriosis. Protein content in UF did not change significantly throughout the cycle in either group. However, PF protein in patients with endometriosis was significantly (P less than 0.05) higher than in controls during the luteal phase. Total UF P was significantly (P less than 0.05) reduced in women with endometriosis during the late luteal phase. During the early luteal phase, trypsin inhibitory activity in UF from normal women was significantly (P less than 0.05) higher than at any other phase of the cycle, whereas inhibitory activity in UF from patients with endometriosis remained relatively constant. Patients with endometriosis had significantly (P less than 0.05) higher total activity in PF during the early luteal phase than did controls. These results indicate that women suffering from endometriosis have significantly lower levels of P and less protease inhibitor within their uterine cavity during the luteal phase of the cycle, and significantly higher concentrations of protein and protease inhibitor in PF during the luteal phase.     

CA-125 levels in human uterine fluid.

OBJECTIVE: To measure uterine fluid CA-125 concentration and to determine if any menstrual cycle phase dependent changes exist in its level. Serum levels are measured for comparison. DESIGN: CA-125 levels in uterine fluid were measured during the follicular and luteal phases of the menstrual cycle. In a sequential study, paired uterine fluid and serum samples were obtained once in both midfollicular and midluteal phases of the same menstrual cycle. RESULTS: CA-125 in uterine fluid during the follicular phase (n = 14) ranged from 16.4 x 10(3) to 616.5 x 10(3) U/mL, and from 6.2 x 10(3) to 567.3 x 10(3) U/mL in the luteal phase (n = 11). In the paired sequential uterine fluid and serum samples, (1) the means (+/- SEM) CA-125 in uterine fluid were 81.5 x 10(3) +/- 37.9 x 10(3) U/mL and 91.4 x 10(3) +/- 56.8 x 10(3) U/mL in the midfollicular and midluteal phases, respectively (P = 0.75); (2) the CA-125 levels in serum increased in the midluteal phase (P less than 0.05); and (3) compared with serum, uterine fluid levels were greater with a wider range. CONCLUSIONS: When compared with serum CA-125, uterine fluid contains high concentrations varying over a wide range without fluctuation between the follicular and luteal phases of the menstrual cycle.     

Serum levels of inhibin in maternal and umbilical blood during pregnancy

Inhibin levels were measured by a double antibody heterologous radioimmunoassay in the peripheral serum of 75 pregnant women throughout gestation and in serum from the umbilical vein and artery, which was obtained at the time of delivery. For reference, samples were obtained from 20 nonpregnant women in the early (days 0 to 3), mid (days 4 to 8), and late (days 9 to 14) luteal or follicular phase. Maternal serum levels of inhibin (mean +/- SEM) in early (6 to 12 weeks) gestation (36.4 +/- 2.6 U/ml, n = 36) were significantly (p less than 0.01) higher than those in serum from nonpregnant women in the mid (23.9 +/- 2.5 U/ml, n = 19) or late (11.3 +/- 0.6 U/ml, n = 19) luteal phase. Inhibin levels in maternal serum fell to 15.9 +/- 1.4 U/ml (n = 24) in mid (14 to 20 weeks) gestation and then gradually increased during late (21 to 40 weeks) gestation to peak levels of 49.4 +/- 5.1 U/ml (n = 9) at 36 to 37 weeks. Inhibin levels declined in parallel with human chorionic gonadotropin concentrations during the first trimester (r = 0.587 at p less than 0.01). Significant positive correlations (p less than 0.001) were observed between serum levels of inhibin and 17 beta-estradiol (r = 0.560), progesterone (r = 0.648), and human placental lactogen (r = 0.715) during mid and late (20 to 40 weeks) gestation. Inhibin levels in umbilical vein serum (38.5 +/- 1.3 U/ml, n = 5) were not different from those in umbilical artery serum (39.4 +/- 3.6 U/ml) but were significantly (p less than 0.01) lower than those in maternal serum (50.9 +/- 5.3 U/ml), which was obtained at the time of delivery. By day 5 of puerperium, serum levels of inhibin in the maternal vein were extremely low (2.3 +/- 0.1 U/ml, n = 7); these levels were nearly one fifth lower than follicular phase levels of 10.9 +/- 3.4 U/ml (n = 38). We propose that maternal inhibin in early gestation is secreted from the corpus luteum of pregnancy but that increasing inhibin levels during mid and late gestation result from inhibin that is produced by the placenta. The lack of an umbilical arterial-venous gradient for inhibin and the higher levels of inhibin in maternal serum argue against a fetal source of inhibin in the maternal circulation. The physiologic function of inhibin that is produced by the corpus luteum and by the placenta remains to be determined.     

CA-125 and placental protein 14 concentrations in plasma and peritoneal fluid of women with deeply infiltrating pelvic endometriosis.

OBJECTIVE: To investigate the plasma and peritoneal fluid (PF) concentrations of CA-125 and placental protein (PP14) in women with deeply infiltrating endometriosis. DESIGN: Plasma and PF were collected during 384 consecutive laparoscopies for pelvic pain or infertility. MAIN OUTCOME MEASURE: The presence and extent of endometriosis were carefully assessed, including the area, depth of infiltration, and volume of subtle lesions, typical lesions, and endometriomas. The day of the menstrual cycle was ascertained by endometrial biopsy and/or basal body temperature charts. RESULTS: Peritoneal fluid concentrations were some 100 and 10 times higher than plasma concentrations for CA-125 and PP14, respectively. Cyclic variations of CA-125 concentrations were only found in women with endometriosis showing increased plasma concentrations at the end of the cycle and increased PF concentrations in the early follicular phase. Cyclic variations of PP14 concentrations were found in women with and without endometriosis both in plasma and PF showing increased concentrations in the late luteal and early follicular phases. In women with endometriosis the increased plasma concentrations of PP14 and CA-125 correlated with the presence and volume of endometriomas and of deeply infiltrating endometriosis. The increased concentrations in PF correlated only with the pelvic area of subtle endometriotic lesions. The diagnostic sensitivity and specificity of CA-125 for endometriosis were 25% and 87%, respectively, and for endometriomas and/or deeply infiltrating endometriosis 36% and 87%, respectively, for a cutoff concentration of 25 U/mL. CONCLUSION: Superficial pelvic endometriosis secretes PP14 and CA-125 mainly toward the PF, whereas endometriomas and deeply infiltrating endometriosis secrete mainly toward the plasma. The increased plasma concentrations of CA-125 are most pronounced during the late luteal phase, and endometriomas and/or deeply infiltrating endometriosis can be detected with a sensitivity of 36% and a specificity of 87%.     

Serum immunoreactive beta-endorphin in the human ovulatory cycle

Daily serum immunoreactive beta-endorphin (IR-beta-EP) levels, in conjunction with luteinizing hormone, follicle-stimulating hormone, 17 beta-oestradiol, progesterone, and prolactin, were measured during the ovulatory cycle in five healthy Chinese women. Standardization of raw data by conversion to the statistical "Z scores" and composite plot of the five cycles showed that serum IR-beta-EP levels fluctuated during the follicular, late luteal, and menstrual phases. A preovulatory rise occurred two to three days prior to the luteinizing hormone surge, followed by a postovulatory dip for two to three days. The concentrations of IR-beta-EP were (mean +/- S.E.M.): 85.5 +/- 10.5 pg/mL (n = 36) in the follicular phase; 92.4 +/- 36.5 pg/mL (n = 5) in the ovulatory phase; 72.3 +/- 16.6 pg/mL (n = 7) in the early luteal phase; 100.0 +/- 10.7 pg/mL (n = 38) in the late luteal phase. The values in the luteal phase were the highest of any in the ovulatory cycle. The findings suggest that the fluctuation of endogenous beta-EP is under the influence of, among other factors, ovarian sex steroids. The significance of beta-EP in the regulation of gonadotropin release during normal menstrual cycles is discussed.     

Elevated peritoneal fluid luteinizing hormone and prolactin concentrations in infertile women with endometriosis

In this study, we compared (Mann-Whitney U-test) the peritoneal fluid FSH, LH and PRL levels, measured by RIA, at the follicular and luteal phases of the menstrual cycle in women with (n = 43; age 25-44 years) and with no evidence of endometriosis (n = 35; age 25-39 years) who were considered as controls. Both follicular and luteal phase FSH concentrations of women with endometriosis were not statistically different (n = 22 vs 18; 0.32-5.8 vs 0.50-8.2 IU/l, P = 0.247; n = 13 vs 14; 0.6-6.5 vs 0.66-6.7 IU/l, P = 0.604) compared to their respective controls. In contrast to FSH, the concentrations of LH at follicular (n = 19 vs 17; 3.1-34.2 vs 2.3-12.2 IU/l, P = 0.01) and luteal (n = 17 vs 15; 2.1-95.4 vs 1.3-17.9 IU/l, P = 0.02) phases of the test group was significantly elevated at both phases of the cycle. With respect to differences in PRL concentrations at follicular phase no significant change (n = 21 vs 16; 1030-5800 vs 1305-4650 mIU/l; P = 0.255) was observed. The greatest difference in luteal PRL concentrations (P = 0.007) was obtained between the women with endometriosis and controls (n = 17 vs 17; 1895-8600 vs 1041-5000 mIU/l). The results suggest that disordered synchronization of neuroendocrine mechanisms controlling LH and PRL may be the underlying abnormality causing infertility in our group of patients with endometriosis.     

子宫内膜异位症患者腹腔液白细胞介素17水平的变化及其意义

目的探讨白细胞介素17(IL17)与子宫内膜异位症(内异症)发病的关系。方法应用酶联免疫吸附(ELISA)法检测36例不同期别内异症患者(内异症组)和26例非内异症患者(对照组)腹腔液中的IL17水平。结果内异症组和对照组腹腔液IL17水平分别为(5.7±1.9)ng/L和(5.3±1.4)ng/L,两组比较,差异无统计学意义(P>0.05)。按1985年美国生育学会内异症分期标准(rAFS)进行分期,Ⅰ～Ⅱ期内异症患者(16例)腹腔液IL17水平为(6.4±1.7)ng/L,Ⅲ～Ⅳ期内异症患者(20例)为(5.1±1.8)ng/L,两者比较,差异有统计学意义(P<0.05)。卵泡期和黄体期腹腔液IL17水平在两组间比较,差异均无统计学意义(P>0.05)。内异症不孕患者腹腔液IL17水平为(6.4±1.8)ng/L,内异症未合并不孕患者为(5.1±1.8)ng/L,两者比较,差异有统计学意义(P<0.05)。结论IL17水平变化可能与早期内异症及内异症不孕的发病有关。     

Serum levels of inhibins are differentially altered in patients with polycystic ovary syndrome: effects of being overweight and relevance to hyperandrogenism

OBJECTIVE: To explore the abnormalities of serum inhibin isoform concentrations in a large group of patients with polycystic ovary syndrome (PCOS) and to evaluate the influence of body mass index (BMI), age, LH, and androgens on serum inhibin levels. DESIGN: Prospective study. SETTING: Reproductive endocrinology unit of an academic medical center. PATIENT(s): Forty-one women with PCOS were compared with 24 healthy women. INTERVENTION(s): Blood sampling was performed in the early follicular phase in patients and in control women. MAIN OUTCOME MEASURE(s): Serum levels of inhibin A, inhibin B, alpha-inhibin, pro-alphaC (alpha-inhibin precursor proteins), LH, FSH, E(2), T, and androstenedione (A) were assessed in all subjects. RESULT(s): Serum alpha-inhibin levels together with LH, T, and A levels were significantly increased in women with PCOS. Serum inhibin A levels were lower in patients with PCOS than controls (median +/- SD: 7.35 +/- 2.9 vs. 9.4 +/- 4.7 pg/mL), pro-alphaC levels were higher (264 +/- 136.7 vs. 127 +/- 81.5 pg/mL), and inhibin B levels did not differ between the groups (110.5 +/- 51.5 vs. 108 +/- 47.5 pg/mL). Simple regression analysis showed that inhibin A and B levels were negatively correlated with BMI in patients with PCOS (r = -0.43 and r27 kg/m(2)) displayed significantly lower inhibin A and inhibin B levels and a higher pro-alphaC-inhibin A ratio than nonobese patients with PCOS (BMI 相似文献   

Physiopathological aspects of corpus luteum defect in infertile patients with mild/minimal endometriosis

Purpose: We describe a physiopathological model to the luteal insufficiency of infertile patients with mild/minimal endometriosis with normal hormone measurements in the early follicular phase. Methods: We designed a case-control study with 24 patients, 14 fertile with in-phase endometrium (control group) and 10 infertile with mild/minimal endometriosis and luteal insufficiency (study group). The histologic dating of endometrium was performed during cycle days 23–25 and serum TSH, FSH, LH, prolactin, and estradiol levels were measured during the early follicular phase (cycle day 3). Progesterone serum levels were measured in three different occasions during the luteal phase. Results: Patients with out-of-phase endometrium have lower estradiol levels (P = 0.031) and decreased progesterone secretion (P = 0.012) during the late luteal phase. Serum prolactin, TSH, FSH, and LH levels were similar between the groups (P > 0.05). Conclusions: The physiopathology of luteal phase defect in infertile patients with mild/minimal endometriosis is associated with a small and large luteal cells dysfunction, characterized by abnormal follicular phase (lower estradiol serum levels) and lower progesterone LH-dependent secretion.     

Elevated angiogenin levels in the peritoneal fluid of women with endometriosis correlate with the extent of the disorder

OBJECTIVE: To assess the release of angiogenin into peritoneal fluid in women with and without endometriosis by measuring its concentration with reference to disease stage, presence of red lesions, and phase of the menstrual cycle. DESIGN: Retrospective study. SETTING: Nagoya City University Hospital. PATIENT(S): Sixty-four women with endometriosis (n = 38) and cystadenomas (n = 26) for whom surgery was scheduled in the proliferative or secretory phase of the menstrual cycle. INTERVENTION(S): Peritoneal fluid samples were obtained at laparotomy or laparoscopy. MAIN OUTCOME MEASURE(S): Angiogenin concentrations in the peritoneal fluid, as measured by ELISA. RESULT(S): Angiogenin concentration in the peritoneal fluid was markedly elevated in the endometriosis patients (median 515 ng/mL, interquartile range 151-1763 ng/mL) compared with the cystadenoma (control) patients (195 ng/mL, 98-324 ng/mL), with values correlating with the extent of the disease. No significant differences between the proliferative phase and the secretory phase were observed in either the controls or the endometriosis patients. CONCLUSION(S): The inflammation associated with endometriosis, through increasing levels of peritoneal fluid angiogenin, might promote angiogenesis for progression of the disease and correlate with the extent of the disorder.     

Decreased levels of interleukin-18 in peritoneal fluid but not in serum of patients with endometriosis

OBJECTIVE: To determine the concentrations of interleukin-18 (IL-18) in peritoneal fluid and serum in patients with endometriosis in comparison with the control group. DESIGN: A prospective analytical study. SETTING: The obstetrics and gynecology department of an academic training hospital. PATIENT(S): Forty-four patients who underwent laparoscopic surgery for benign gynecologic diseases. INTERVENTION(S): Specimens of peripheral blood and peritoneal fluid were obtained before and during laparoscopic procedures, and the levels of IL-18 were analyzed. MAIN OUTCOME MEASURE(S): The concentrations of IL-18 in peritoneal fluid and serum were correlated with the presence of endometriosis, disease stage, and the phase of the menstrual cycle. RESULT(S): Interleukin-18 was detectable in 98% of the peritoneal specimens and 84% of the serum specimens of the patients tested. Peritoneal fluid IL-18 concentrations were statistically significantly lower in patients with endometriosis than in patients without endometriosis; the difference in serum IL-18 levels showed no statistically significant difference between the patients with and without endometriosis. The concentrations of IL-18 in peritoneal fluid and serum were not correlated with the stage of endometriosis or the phase of the menstrual cycle. CONCLUSION(S): Our results suggest that the decreased levels of IL-18 in peritoneal fluid in patients with endometriosis as compared with the control group may play an important role in the pathogenesis of this disease.     

子宫内膜异位症患者腹腔液及血清中前列腺素E2与bcl-2蛋白的含量变化及意义

目的探讨子宫内膜异位症(内异症)患者腹腔液及血清中,前列腺素E2(PGE2)和bcl-2蛋白的含量变化及其与内异症发病的关系。方法采用酶联免疫吸附法(ELISA)检测36例内异症患者(内异症组,其中Ⅰ、Ⅱ期患者16例,Ⅲ、Ⅳ期患者20例)和30例因卵巢囊肿或浆膜下子宫肌瘤手术患者(对照组)腹腔液及血清PGE2与bcl-2含量。结果内异症组患者腹腔液中PGE2、bcl-2蛋白的含量分别为(1987±532)ng/L、(177±53)U/L,对照组为(386±215)ng/L、(86±21)U/L,两组比较,差异均有统计学意义(P<0.01)。Ⅲ、Ⅳ期内异症患者腹腔液中PGE2的含量[(2221±1352)ng/L]较Ⅰ、Ⅱ期患者[(1694±381)ng/L]明显升高,差异也有统计学意义(P<0.01);Ⅲ、Ⅳ期内异症患者腹腔液中bcl-2的含量[(190±63)U/L]较Ⅰ、Ⅱ期患者[(162±49)U/L]升高,差异有统计学意义(P<0.05)。内异症组血清中的PGE2与bcl-2含量[(3787±514)ng/L、(96±44)U/L]均高于对照组[(129±97)ng/L、(53±40)U/L],差异均有统计学意义(P<0.01)。Ⅲ、Ⅳ期内异症患者血清中的PGE2含量[(964±290)ng/L]也高于Ⅰ、Ⅱ期患者[(590±362)ng/L],差异也有统计学意义(P<0.01);内异症患者腹腔液中PGE2及bcl-2的含量均高于血清。结论内异症患者腹腔中高含量的PGE2与bcl-2,可能对内异症发病有影响;内异症患者腹腔液与血清中PGE2和bcl-2含量与病变的范围有一定关系。     

Elevated interleukin-6 levels in peritoneal fluid of patients with pelvic pathology.

OBJECTIVE: To determine if interleukin 6 (IL-6) is a normal constituent of peritoneal fluid (PF), and if various types of pelvic pathology influence its presence within the PF microenvironment. STUDY DESIGN: Peritoneal fluid from 73 women obtained at the time of laparoscopy was examined for the presence of IL-6 using an IL-6 specific sandwich enzyme-linked immunosorbent assay. Thirty-nine patients had pelvic endometriosis, 17 had nonendometriotic pelvic adhesive disease, and 17 subjects undergoing tubal sterilization without evidence of pelvic pathology served as controls. RESULTS: Immunoreactive IL-6 was observed in the PF of all 73 subjects (range 0.26 to 11.16 ng/mL). The mean concentration of IL-6 was higher in women with nonendometriotic pelvic adhesions as compared with control subjects (1.28 +/- 0.16 versus 0.80 +/- 0.06 ng/mL, P less than 0.03). There was no difference in the mean peritoneal concentrations of IL-6 between women with endometriosis (1.16 +/- 0.28 ng/mL) and controls, P = 0.38. Twenty-seven of 73 patients (37%) demonstrated elevated levels (greater than 1.0 ng/mL) of IL-6. Patients with pelvic adhesions were significantly more likely to have elevated concentrations of IL-6 than controls (10/17 [59%] versus 3/17 [18%], P less than 0.02). Alternatively, the percentage of patients with elevated IL-6 concentrations did not differ between patients with endometriosis or controls (14/39 [36%] versus 3/17 [18%], P greater than 0.10). CONCLUSIONS: These findings demonstrate that IL-6 is a normal constituent of PF and that elevated levels are found in many patients with pelvic adhesions.     

Obesity and serum luteinizing hormone level have an independent and opposite effect on the serum inhibin B level in patients with polycystic ovary syndrome

OBJECTIVE: To elucidate whether the negative effect of obesity on the serum inhibin B level that we previously reported is specific or not to polycystic ovary syndrome (PCOS) and whether it may explain the wide interindividual variability in serum inhibin B levels found in patients with PCOS. DESIGN: Prospective study.Setting: Reproductive endocrinology unit of an academic medical center. PATIENT(S): One hundred thirty-four consecutive patients with PCOS (mean age, 27.4 +/- 4.7 years; mean body mass index [BMI], 28.3 +/- 7.6 kg/m(2); BMI > 25, 53%) and in 78 control women (mean age, 30.1 +/- 4.1 years; mean BMI, 24.3 +/- 4.9; BMI > 25, 34%). INTERVENTION: Blood sampling was performed in the early follicular phase in patients and in control women. MAIN OUTCOME MEASURE(S): BMI and waist circumference (WC), serum levels of inhibin B, LH, FSH, E(2), androstenedione, T, fasting insulin, and leptin were assessed in all subjects. RESULT(S): No difference was observed in the mean inhibin B level between patients and controls. The BMI and WC correlated negatively with inhibin B in patients with PCOS and in controls, with similar regression slopes, thus indicating that the influence of obesity on inhibin B is not specific to PCOS. In addition, we found a positive relationship between serum LH and inhibin B levels in PCOS. There was no significant interaction between the effects of BMI and LH on the serum inhibin B levels by analysis of variance (ANOVA). The mean serum inhibin B level in patients with PCOS with high serum LH (i.e., >the 90th percentile of LH in controls) was significantly higher than in those patients with normal LH or in controls. The highest mean inhibin B level was noted in nonobese patients with PCOS with high LH levels (121.0 +/- 51.2 pg/mL), while nonobese patients with PCOS with normal LH levels and obese patients with normal LH or high LH levels had similar mean levels (94.5 +/- 40.0, 84.9 +/- 34 and 91.6 +/- 51.7 pg/mL, respectively). CONCLUSION(S): We confirm that obesity has a negative effect on inhibin B serum level, which is not specific to PCOS. Obesity and excess LH, acting oppositely and independently on inhibin B production, may explain the discrepancies between the previous reports studying serum inhibin B level in patients with PCOS. Further work is required to elucidate the mechanisms underlying the antagonistic effects of LH and obesity on inhibin B production in patients with PCOS.     

Serum pattern of circulating free leptin, bound leptin, and soluble leptin receptor in the physiological menstrual cycle

OBJECTIVE: To investigate the serum pattern of free leptin, bound leptin, and soluble leptin receptor throughout the physiological menstrual cycle. DESIGN: Prospective observational study. SETTING: Tertiary care center for gynecological endocrinology and reproductive medicine and a university research laboratory. PATIENT(S): Thirty regularly cycling volunteers (age, 29 +/- 4.2 years). INTERVENTION(S): Blood sampling was performed at different phases (early and mid follicular phase, preovulatory phase, and early and late luteal phase) of three consecutive menstrual cycles; each phase of the menstrual cycle was investigated twice. MAIN OUTCOME MEASURE(S): Free leptin, bound leptin, soluble leptin receptor, LH, E(2), P, vaginal ultrasound. RESULT(S): A peak of serum free leptin levels was found in the late luteal phase followed by a significant drop in the early follicular phase and again by a continuous increase up to the next luteal peak. There were no significant alterations in serum bound leptin and soluble leptin receptor levels. CONCLUSION(S): The present study shows that there are significant circacyclic fluctuations of free leptin levels with the highest concentrations in the late luteal phase and the lowest levels in the early follicular phase, which suggests that circulating free leptin is up-regulated by the C(21)-steroid (P). Circulating bound leptin and soluble leptin receptor are not altered by the cyclic hormone status. The significant rise of the leptin bioequivalent, free leptin, in the late luteal phase might be of importance for the luteal-follicular and the luteal-preimplantatory functional shift.