Menstrual cyclicity of CA-125 in patients with endometriosis.

OBJECTIVE: To examine the serum levels of CA-125 in the menstrual, follicular, and luteal phases of the menstrual cycle in women with endometriosis and to determine if serum CA-125 levels drawn during menses improve the clinical utility of the test in diagnosing endometriosis. DESIGN: Serum CA-125 was measured in the menstrual, follicular, and luteal phases of the cycle preceding surgery. CA-125 levels for each phase were categorized by postoperative diagnosis and endometriosis stage. SETTING: The reproductive endocrine unit of a tertiary care university-affiliated hospital. PATIENTS: A total of 65 patients were recruited from the Fertility and Endocrine Unit and the Gynecology Service of Brigham and Women's Hospital. MAIN OUTCOME MEASURE: Serum CA-125 levels were measured by an immunoradiometric assay and were stratified by menstrual cycle phase, diagnosis, and stage of endometriosis. The menstrual cycle phase was confirmed by serum estradiol and progesterone measurements. RESULTS: Serum CA-125 levels in patients with stages II to IV endometriosis were significantly elevated in the menstrual phase compared with levels drawn in the nonmenstrual follicular and luteal phases. The sensitivity and specificity of CA-125 for the diagnosis of endometriosis were not significantly better in the menstrual than in the follicular or luteal phases. CONCLUSIONS: Despite menstrual cyclicity of CA-125, measurement of serum CA-125 during menses does not improve the clinical utility of the test in the diagnosis of endometriosis.     

Correlation between peripheral CA-125 levels and ovarian activity

Serum CA-125 concentrations were measured at three different times in normal cycles, pill-suppressed cycles, and cycles stimulated for intrauterine insemination (IUI) or oocyte retrieval, i.e., (1) during the first half of the cycle, (2) at midcycle or at the moment of oocyte retrieval, and (3) the second half of the cycle. Significant variations of serum CA-125 concentrations were not seen during the cycle in normally cycling women or in women taking oral contraceptives: mean +/- SD 28.9 +/- 13.3 U/mL and 26.9 +/- 11.3 U/mL, respectively. In patients stimulated for in vitro fertilization, luteal phase CA-125 levels (60.6 +/- 38 U/mL) were significantly higher than during stimulation (21.5 +/- 5.9 U/mL) or at oocyte retrieval (19.6 +/- 6.4 U/mL). In stimulated cycles for IUI, without laparoscopy or follicular puncture, a comparable rise of CA-125 was observed in the luteal phase (49.6 +/- 37.8 U/mL). However, in patients undergoing laparoscopic sterilization, serum CA-125 concentrations before and after laparoscopy were not significantly different (22.8 +/- 6.3 U/mL and 25 +/- 4.2 U/mL, respectively).     

Menstrual cyclicity has a profound effect on glucose homeostasis

Results from oral glucose tolerance tests have frequently demonstrated a deterioration in glucose metabolism during the luteal phase of the menstrual cycle. To examine this issue further, eight women underwent both midfollicular (days 3 to 10) and midluteal (days 20 to 25) phase hyperglycemic clamp studies (+125 mg glucose/dl) after an overnight fast. Glucose levels rose from 83 +/- 1 to 207 +/- 2 and 87 +/- 1 to 207 +/- 2 mg/dl, respectively, during the follicular and luteal phases. The basal (6 +/- 1 versus 7 +/- 1 microU/ml) and glucose-stimulated (42 +/- 5 versus 43 +/- 6 microU/ml) insulin responses were similar in the follicular and luteal studies. However, glucose uptake was significantly higher during the follicular versus the luteal phase (10.99 +/- 0.97 versus 6.93 +/- 0.37 mg/kg-min; P less than 0.01), as was the ratio of glucose uptake to insulin concentration (30.0 +/- 5.5 versus 19.7 +/- 3.7, P less than 0.01). The authors conclude that: (1) Glucose metabolism is impaired in the luteal phase of the menstrual cycle; (2) This defect cannot be explained by differences in the plasma insulin response; and (3) This impairment in the ability to promote glucose uptake under hyperglycemic conditions suggests a defect in the mass action effect of glucose per se.     

Prolactin response to secretin during the spontaneous menstrual cycle in women.

The effect of an intravenous infusion of secretin (2.0 CU/kg/h) on serum prolactin (PRL) and estradiol levels and plasma levels of vasoactive intestinal polypeptide and somatostatin (SRIH) was studied in 8 healthy and normally cycling women during the midfollicular phase (cycle day 7), at midcycle (day 14), and during the midluteal phase (day 21) of the menstrual cycle. When compared to basal preinfusion levels, a significant decrease in serum PRL levels was observed at steady state concentrations of plasma secretion (+30 to +60 min) both during the follicular (p less than 0.03) and the luteal (p less than 0.0001) phases. At midcycle a nonsignificant decrease was observed. A significant and negative correlation existed between serum PRL and plasma secretin levels in the follicular phase (r = -0.33; p less than 0.05) and in the luteal phase (r = 0.73; p less than 0.0001). The plasma concentrations of SRIH increased significantly at steady state conditions of secretin at midcycle (p less than 0.02) and in the luteal phase (p less than 0.04), while no effect was found during the follicular phase. A significant and positive correlation between plasma levels of SRIH and secretin was observed at midcycle (r = 0.63; p less than 0.002) and in the luteal phase (r = 0.46; p less than 0.02). No effect of secretin on plasma vasoactive intestinal polypeptide and serum estradiol concentrations was demonstrated. These results suggest that the suppression of PRL in the follicular phase of the spontaneous menstrual cycle can be ascribed to an effect of secretin alone.(ABSTRACT TRUNCATED AT 250 WORDS)     

High CA-125 concentrations in peritoneal fluid of normal cyclic women with various infertility-related factors as demonstrated with two-step immunoradiometric assay

OBJECTIVE: To determine CA-125 concentrations and total amounts in peritoneal fluid (PF) of women with various infertility-related factors throughout the menstrual cycle. DESIGN: Peritoneal fluid was obtained at laparoscopy. CA-125 was determined using the assessed two-step immunoradiometric assay (IRMA) which, in contrast to the one-step IRMA, gives valid results. SETTING: University Hospital Nijmegen, Nijmegen, The Netherlands. PATIENTS: One hundred six infertile women with a regular and ovulatory cycle were included. INTERVENTIONS: None. MAIN OUTCOME MEASURE(S): The mean PF CA-125 concentration and total amount were significantly lower during the luteal phase as compared with other phases of the menstrual cycle. No correlation was found with the presence or absence of endometriosis, adhesions, a male and/or cervical mucus infertility factor, and with patent or closed fallopian tubes. RESULTS: Peritoneal fluid CA-125 concentrations varied from 630 to 12,000 arbitrary units/mL (mean +/- SD = 3,437 +/- 2,286). Total PF CA-125 amounts (concentration x PF volume) varied from 1,760 to 13,300 arbitrary units (mean +/- SD = 30,219 +/- 26,841). CONCLUSIONS: CA-125 secretion into the abdominal cavity varies during the menstrual cycle. Retrograde menstruation is not the main source of CA-125 in PF.     

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%.     

Increased tumor necrosis factor-alpha in whole blood during the luteal phase of ovulatory cycles

OBJECTIVE: To evaluate whether the fact that blood from premenopausal, ovulatory women shows a significant fluctuation in tumor necrosis factor-alpha (TNF-alpha) levels when tested randomly over time is related to the hormonal cycle. STUDY DESIGN: In this pilot study, whole blood was collected from 8 women during the follicular, ovulatory and midluteal phases of the menstrual cycle. Ovulation was confirmed by luteinizing hormone surge and mid-luteal progesterone levels. For each subject at each phase of the menstrual cycle, TNF-alpha levels were measured at baseline and after stimulation of whole blood with 10 microg/mL of lipopolysaccharide (LPS). Supernatant was collected and assayed by enzyme-linked immunosorbent assay. TNF-alpha levels were compared with the Wilcoxon matched pairs signed rank sum test. RESULTS: Whole blood unstimulated by LPS showed increasing TNF-alpha levels over the hormonal cycle, with significantly increased median levels during the luteal phase (903 pg/mL; range, 0-3707) as compared with the follicular phase (162 pg/mL; range, 0-656) (P = .03). Blood stimulated with LPS showed increased TNF-alpha levels overall but no association with cycle timing. CONCLUSION: TNF-alpha levels in unstimulated whole blood appear to be associated with menstrual cycle timing, with highest levels during the luteal phase. However, the lack of variation in TNF-alpha production after LPS stimulation suggests that experiments do not need to be timed with the menstrual cycle.     

Luteinizing hormone receptors in human ovarian follicles and corpora lutea during the menstrual cycle

The binding of 125I-labeled human luteinizing hormone (hLH) to the 2000-g fraction of human ovarian follicles and corpora lutea during the entire menstrual cycle was examined. Specific high affinity, low capacity receptors for hLH were demonstrated in the 2000-g fraction of both follicles and corpora lutea. Specific binding of 125I-labeled hLH to follicular tissue increased from the early follicular phase to the ovulatory phase. Specific binding of 125I-labeled hLH to luteal tissue increased from the early luteal phase to the midluteal phase and decreased towards the late luteal phase. The results of the present study indicate that the increase and decrease in receptors for hLH during the menstrual cycle might play an important role in the regulation of the ovarian cycle.     

Side of ovulation and its effects on uterine and ovarian stromal blood flow and reproductive hormones

OBJECTIVE: Effect of the side of ovulation on uterine, ovarian, and follicular blood flow parameters and various hormone levels. DESIGN: Prospective, observational study. SETTING: Fertility Clinic, St. George's Hospital. PATIENT(S): Nineteen women with regular menstrual cycles. Pulsed Doppler measurements and serum hormonal concentrations during midfollicular, periovulatory, and midluteal phase for three successive cycles. MAIN OUTCOME MEASURE(S): Doppler blood flow and serum hormones. RESULT(S): Doppler blood flow of the ovarian stroma and follicular and uterine arteries showed no differences in the three phases between the right and left sides. Left-side uterine peak systolic velocity (PSV) (right-side PSV, 31.51cm/s; left-side PSV, 37.38 cm/s) during the periovulatory phase tended to be higher in the nondominant ovary; however, this was not quite significant. The serum hormone concentration showed no significant differences. CONCLUSION(S): The side of ovulation did not influence the Doppler blood flow to the ovarian stroma or follicular and uterine arteries. The side of ovulation had no effect on serum FSH, LH, 17beta-estradiol, P, inhibin A, or inhibin B levels.     

Changes in endometrial wave-like movements in accordance with the phases of menstrual cycle

OBJECTIVE: To investigate whether endometrial wave-like movements change with phases of the menstrual cycle. METHODS: Endometrial wave-like movements were observed by transvaginal sonographic tomography during 50 menstrual cycles of 20 regularly menstruating women. RESULTS: Endometrial wave-like movements were not observed during the early follicular phase. These movements proceeded perpendicularly to the longitudinal uterine axis and appeared at the midfollicular phase. In the periovulatory phase, waves reached a peak and moved from cervix to fundus. In the postovulatory phase, endometrial wave-like movements became parallel to the longitudinal uterine axis. In the midluteal phase, most of these waves disappeared. Immediately before menstruation, the waves reappeared moving from fundus to cervix. These movements continued until day 1 of the subsequent menstrual phase. CONCLUSION: Endometrial wave-like movements change with the passage of menstrual cycle. They appear to play an important role in the transport of sperm and cervical mucus and the excretion of menstrual flow.     

Pulsatile secretion of gonadotropins and prolactin during the follicular and luteal phases of the menstrual cycle: analysis of instantaneous secretion rate and secretory concomitance.

OBJECTIVE: To characterize the pulsatile secretions of luteinizing hormone (LH), follicle-stimulating hormone (FSH), and prolactin (PRL) during the menstrual cycle and to statistically evaluate their secretory concomitance. DESIGN: Pulsatility study performed during the midfollicular and midluteal phases of a same menstrual cycle, blood samples being collected every 10 minutes for 6 hours. SETTING: Participants investigated in the Division of Endocrinology, University Hospital. PARTICIPANTS: Nine healthy women (22 to 38 years) with regular menstrual cycles. MAIN OUTCOME MEASURES: Plasma LH, FSH, and PRL values were analyzed as raw and deconvoluted data, and the specific (nonrandom) secretory concomitance was evaluated statistically. RESULTS: The pulsatile secretion of LH was confirmed, and that of FSH and PRL was clearly established during both phases of the cycle by characterization of peak frequency, period, and amplitude. A specific secretory concomitance was assessed between LH and FSH in the follicular but not the luteal phase, and a tight concomitance between LH and PRL was demonstrated during both phases. CONCLUSIONS: These results are supportive of significant pulsatile secretions of the three hormones during the menstrual cycle, and they are demonstrative of a definite copulsatility of these hormones, suggestive of common regulatory factors in the complex temporal patterns of gonadotropin and PRL secretions along the cycle.     

Inhibition of the primate ovarian cycle by a porcine follicular fluid protein(s)

Monkeys received twice daily intramuscular injections of 3 mg of purified porcine follicular fluid protein(s) for the first 14.5 days of the menstrual cycle. Two of five treated monkeys had anovulatory menstrual cycles. Three monkeys had cycles characterized by long follicular phases, low follicular and luteal phase serum estradiol concentrations, and subnormal luteal progesterone production. Serum gonadotropin concentrations were not affected by the follicular fluid protein(s). The data demonstrate in the nonhuman primate that porcine follicular fluid contains a protein(s) that acts at the ovarian level to inhibit gonadotropin action.     

Peritoneal fluid inhibin during the menstrual cycle.

Serum and peritoneal fluid inhibin levels were measured by radioimmunoassay throughout the menstrual cycle in 14 women with endometriosis and in 16 controls. In controls, serum values (+/- standard error of the mean) increased from the early follicular phase (49.8 +/- 6.5 microLEq/mL) to the late follicular phase (178 +/- 37.8 microLEq/mL) and the luteal phase (346 +/- 98.3 microLEq/mL). Peritoneal fluid inhibin levels were several-fold higher than those in serum and reached a maximum value during the late follicular phase (early follicular: 2404 +/- 85 microLEq/mL, late follicular: 22,922 +/- 7145 microLEq/mL, luteal: 5195 +/- 1959 microLEq/mL). There was no difference in peritoneal fluid or serum inhibin concentrations between patients with and without endometriosis. These findings suggest that human gametes in the fallopian tube may be exposed to a very high concentration of inhibin. The lack of difference in inhibin concentrations between patients with and without endometriosis suggests that this hormone does not play a role in endometriosis-related infertility.     

Suppression of luteal phase, but not midcycle, prolactin levels by chronic follicular phase opiate antagonism

Objective: To investigate whether establishment and maintenance of chronic opioid blockade throughout the follicular phase of the menstrual cycle influences midcycle and luteal phase prolactin levels.Design: Randomized, double-blind, crossover study.Setting: Academic research environment.Patient(s): Volunteers, aged 21–35 years, with regular menstrual cycles.Intervention(s): Naltrexone (50 mg) or placebo were administered on cycle days 2–14. Blood samples were obtained in the early follicular phase and in the periovulatory and midluteal phases of the menstrual cycle.Main Outcome Measure(s): Serum prolactin levels.Result(s): In the early follicular phase, serum prolactin levels were equivalent in naltrexone (12.0 ± 2.7 μg/L; mean ± SE) and placebo (12.1 ± 2.9 ug/L) cycles. A statistically significant increase in serum prolactin was observed on the day of the LH surge (naltrexone: 22.6 ± 3.7 μg/L; placebo: 21.7 ± 2.7 μg/L; P < 0.05 versus early follicular phase), but no difference between treatments was observed. However, midluteal prolactin levels were statistically significantly lower in naltrexone cycles compared with placebo cycles (12.6 ± 3.3 versus 15.4 ± 3.0 )ug/L; P < 0.05).Conclusion(s): Chronic blockade of opioid activities during the follicular phase does not affect midcycle prolactin increments, but withdrawal of opioid blockade may enhance opioid effects on prolactin levels in the luteal phase.     

Serum leptin level across different phases of menstrual cycle in normal weight and overweight/obese females

We compared serum leptin levels during various phases of menstrual cycle and its correlation with serum estradiol between normal weight and overweight/obese young females. Fifty-six young females with normal menstrual cycle were grouped into 26 normal weight and 30 overweight/obese subjects. Serum leptin and estradiol levels were measured during early follicular, pre-ovulatory and luteal phases of menstrual cycle in both groups using ELISA technique. Serum leptin levels were significantly different across different phases of menstrual cycle with a steady increment from follicular phase (9.97?±?5.48?ng/dl) through pre-ovulatory phase (11.58?±?6.49?ng/dl) with their peaks in luteal phase (12.52?±?6.39?ng/dl, p?相似文献   

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.     

Reduced atrial natriuretic peptide concentrations in premenstrual syndrome

Atrial natriuretic peptide (ANP) concentrations were determined by radioimmunoassay technique in 23 women, 11 women with premenstrual syndrome (PMS) and 12 comparable asymptomatic women. The asymptomatic women showed no change in ANP concentration during the menstrual cycle. In the PMS group ANP levels showed a significant fall in the midluteal phase compared to levels in the follicular phase. Throughout the cycle ANP concentrations were lower in the PMS group than in the comparison group. This difference was statistically significant in the early, mid and late luteal phases of the cycle. The lower ANP concentration in the PMS group in the luteal phases may indicate either a lower plasma volume or a decrease in the total body sodium content or both. These findings are contrary to those expected.     

Reduced atrial natriuretic peptide concentrations in premenstrual syndrome

Summary. Atrial natriuretic peptide (ANP) concentrations were determined by radioimmunoassay technique in 23 women, 11 women with premenstrual syndrome (PMS) and 12 comparable asymptomatic women. The asymptomatic women showed no change in ANP concentration during the menstrual cycle. In the PMS group ANP levels showed a significant fall in the midluteal phase compared to levels in the follicular phase. Throughout the cycle ANP concentrations were lower in the PMS group than in the comparison group. This difference was statistically significant in the early, mid and late luteal phases of the cycle. The lower ANP concentration in the PMS group in the luteal phases may indicate either a lower plasma volume or a decrease in the total body sodium content or both. These findings are contrary to those expected.     

The corpus luteum: determinants of progesterone secretion in the normal menstrual cycle

Fourteen normal volunteers were studied during one menstrual cycle. Follicular development, the luteinizing hormone (LH) surge, and the relationship between LH and progesterone secretion in the luteal phase were studied to determine the factors that control corpus luteum function. Follicular development was assessed by measuring follicle size and daily estradiol (E2) levels; the LH surge was quantified by determining the area under the curve. Although there was a significant positive correlation between mean follicle diameter and E2, these same parameters did not correlate with postovulatory progesterone secretion; nor did the LH surge correlate with progesterone secretion. A decrease in LH pulse frequency occurred in moving from the follicular to the luteal phase. There was a trend toward an increase in the late luteal LH pulse frequency compared with the midluteal phase, but this was not significant. Progesterone was secreted in an intermittent (pulsatile) fashion in the midluteal and late luteal phases. The general decrease in progesterone in the latter days of the menstrual cycle appears to be due to a decrease in the progesterone pulse amplitude. A significant correlation between LH and progesterone was present when the data were "smoothed"; however, there was not a significant synchrony for LH and progesterone pulses for most of the subjects when the initial data were analyzed by objective criteria. Progesterone secretion in the luteal phase is quite complex and leads to highly variable serum levels of progesterone when samples are obtained at random from normal women.     

Analysis of the levels of CA125, CEA and CA19-9 in the cervical mucus samples obtained at various phases of the menstrual cycle and with inflammatory diseases of the uterine cervix

Recently, normal cervical glandular cells have been reported to synthesize and secrete CA125 as a common constituent of normal cervical mucus. However, the levels of CA125 in the cervical mucus samples during the menstrual cycle and with cervical inflammatory diseases have not been determined. Therefore, we measured CA125 in cervical mucus samples in various phases of the menstrual cycle and in patients with cervical polyp or vaginitis. In addition to CA125, CEA and CA19-9 were also examined in the same samples. CA125 levels in the mucus samples of women (45 cases) without any gynecologic disorders (control) were 102,200 +/- 8,600 (M +/- S.E.) U/ml. Significantly higher levels were noted in the samples obtained in the follicular phase than in the luteal phase. CA125 levels in the mucus with atrophic vaginitis (12 cases) were significantly lower than those of controls. CEA and CA19-9 levels in the control samples were 3,400 +/- 550 ng/ml and 3,470 +/- 500 U/ml, respectively, and both of these showed no significant difference between the follicular and luteal phases. However, both CEA and CA19-9 levels in the cervical mucus with cervical polyps (15 cases) or vaginitis were much higher than in the controls. Accordingly, the present study revealed that CA125 in the cervical mucus fluctuates during the menstrual cycle, probably under the influence of ovarian sex steroids. In addition, CEA and CA19-9 in the cervical mucus samples obtained from women without any gynecologic disorders showed low levels, but those with inflammatory diseases were high, and this suggested that inflammatory diseases in the cervix and/or vagina may affect the constituent of the tumor-associated carbohydrate antigens in the cervical mucus.