British Iournul of Obstetrics atid Gjnuccologv October 1990. Vol 97, pp 930-933
Serum CA 125 levels during the menstrual cycle P. LEHTOVIRTA, D. APTER, U.-H. STENMAN Summary. Serum concentrations of CA 125 were measured in different phases of the menstrual cycle in 16 women with ovulatory and 12women with anovulatory cycles. CA 125 levels were significantly elevated during menstruation 111both groups. In women with anovulatory cycles, but not in those with ovulatory cycles, CA 125 levels were already increased in the premenstrual phase. A negative correlation was found between serum CA 125 and progesterone concentrations in the premenstrual phase of the cycle. We suggest that premenstrual elevation of serum CA 125 in womcn with anovulatory cycles ic related to premature endometrial vascular changec which are the result of the l o w serum progesterone concentration leading to insufficient endometrial control. Thus t h e cffcct of progesterone seem5 to be indirect rather than a direct effect 011 CA 125 syntheeic. When the CA 125 acsay is uced for diagnosic of cancer, sampling should not be done immediately before or during menstruation because the physiological elcvation of the CA 125 levels may give false positive results.
Serum C A 125 concentration is increased in over 80% of patients with ovarian cancer (Bast ct al. 1983; Halila rt nl. 1988). The specificity of the C A 125 test has given promise for this assay as a potential component of a strategy aimed at the early detection of ovarian cancer (Zurawski et al. 1987;Jacobs eral. 1988a). Howcvcr, previous reports have shown that some benign diseases like endometriosis (Barhieri et al. 1986; Giudice et al. 1986; Patton et nl. 1986; Masahashi et 01. 1988) and w e n normal physiological events likc pregnancy (Halila rr al. 1986) and menstrual bleeding (Mastropaolo et al. 1986; Pittaway & Fayez 1987; Masahashi et al. 1988) may elevate serum C A 125 levels. Therefore. to avoid misDepartment of Ob\tetrics and Gynecolog?, Helsinki [Jnivewity Central Hospital, Helsinki, Finland. P LEHTOVIRTA D APTER U - H STENMAN Correymndcnce Pentti Lehtovirta. M D , Department of Obstctrics and Gynecology, Helsinki Univer\it) Central Hospital. Sk-00290 Hcisinkl, Flnland
930
interpretation of elevated CA 125 levels during menstruation, the exact timing of blood sampling is important. The physiological changes in serum C A 125 concentrations inay indicate that it is under hormonal control. A progesterone-induced clcvation of serum CA 125 levels has been reported in patients with endometriosis ( O ~ a s ael cil. 1987). O n the othcr hand. CA 125 production was not affcctcd bv oestrogen, progestin or tamoxifen in immunodeficient mice inoculated with ovarian carcinoma (Holt et RI. 1987). The aim of our study was to mcasure serum C A 125 levels in different phases of the menstrual cycle and to examine a possible association with ovarian sex steroids. Subjects and methods Twenty-eight apparently healthy young women (mean age 20, rangc 15-32 ycars) were selected lor the study; 20 were < I 8 years of age Of the 28 women, 16 had normal menstrual cycles n7ith luteal phases of at leas1 10 days and a serum pro-
CA 12.5 in nienstrunl cycle
gestcrone concentration > l o nmolil. The length of the luteal phase was estimated on the basis of LH and progesterone concentrations. In 12 women aged 15-18 years; serum progesterone concentration remained below 10 nmolil throughout the cycle, and these cycles were classified as anovulatory. The cycles were divided into four phases: (I) cyclc days 1-7; (2) cyclc days 8-18; (3) last 7 day$ of cycle: (4) cycle days 1-7 of the next cycle. Thus phase 4 corresponds to phase 1. Blood samples were collected every 3-4 days during phases 1,3 and 4 and every 1-2 days during the estimated periovulatory period in phase 2. The specimens werc grouped retrospectively into appropriate phases. Serum samples were stored at -20°C until assayed for CA 125, progesterone, oestradiol and LH. An immunoradiometric CA 125 assay was used according to the manufacturer's instructions (Abbott IAoratoriers, Wiesbaden, FRG). The scnsitivity of the assay was 6.4 L[!ml. Levels >3S [Jim1 were considered elevated (Bast ef d.1983). To compare CA 125 levels during the menstrual cycle. the values were expressed as a percentage of thc mean value of all observations for each individual. Serum progesterone, oestradiol and LH concentrations were ineasurcd by routine radioimmunoassays. The data were analyzed by BMDP programs (BMDP Statistical Software of 1987, University of California, Los Angles. CA). Statistical assessment used analysis of variance for
931
repeated measurements and the paired Student's t-test within the phases of the cycle and Mann-Whitney U-lest between the ovulatory and anovulatory cycles. Results
CA 125 levels were significantly higher during the first week (phases 1 and 4) of the cycle than during the middle part (phase 2) of the cycle both in women with ovulatory and in those with anovulatory cycles (Tablc 1). Thc highest concentrations of CA 125 in ovulatory and anovulatory women during menstruation were 51 U/mI and 125 U/ml. respectively. In women with anovulatory cycles, hut not in those with ovulatory cyclcs. CA 125 levels were already significantly increased before the outset of menstruation (phase 3). CA 125 levels were slightly higher in the anovulatory than in the ovulatory group, hut the diffcrcncc was statistically significant only in phase 3 (Tablc 1 and Fig. 1). There was a negative correlation ( I = -0.48, P
Serum CA 125 levels during the menstrual cycle P. LEHTOVIRTA, D. APTER, U.-H. STENMAN Summary. Serum concentrations of CA 125 were measured in different phases of the menstrual cycle in 16 women with ovulatory and 12women with anovulatory cycles. CA 125 levels were significantly elevated during menstruation 111both groups. In women with anovulatory cycles, but not in those with ovulatory cycles, CA 125 levels were already increased in the premenstrual phase. A negative correlation was found between serum CA 125 and progesterone concentrations in the premenstrual phase of the cycle. We suggest that premenstrual elevation of serum CA 125 in womcn with anovulatory cycles ic related to premature endometrial vascular changec which are the result of the l o w serum progesterone concentration leading to insufficient endometrial control. Thus t h e cffcct of progesterone seem5 to be indirect rather than a direct effect 011 CA 125 syntheeic. When the CA 125 acsay is uced for diagnosic of cancer, sampling should not be done immediately before or during menstruation because the physiological elcvation of the CA 125 levels may give false positive results.
Serum C A 125 concentration is increased in over 80% of patients with ovarian cancer (Bast ct al. 1983; Halila rt nl. 1988). The specificity of the C A 125 test has given promise for this assay as a potential component of a strategy aimed at the early detection of ovarian cancer (Zurawski et al. 1987;Jacobs eral. 1988a). Howcvcr, previous reports have shown that some benign diseases like endometriosis (Barhieri et al. 1986; Giudice et al. 1986; Patton et nl. 1986; Masahashi et 01. 1988) and w e n normal physiological events likc pregnancy (Halila rr al. 1986) and menstrual bleeding (Mastropaolo et al. 1986; Pittaway & Fayez 1987; Masahashi et al. 1988) may elevate serum C A 125 levels. Therefore. to avoid misDepartment of Ob\tetrics and Gynecolog?, Helsinki [Jnivewity Central Hospital, Helsinki, Finland. P LEHTOVIRTA D APTER U - H STENMAN Correymndcnce Pentti Lehtovirta. M D , Department of Obstctrics and Gynecology, Helsinki Univer\it) Central Hospital. Sk-00290 Hcisinkl, Flnland
930
interpretation of elevated CA 125 levels during menstruation, the exact timing of blood sampling is important. The physiological changes in serum C A 125 concentrations inay indicate that it is under hormonal control. A progesterone-induced clcvation of serum CA 125 levels has been reported in patients with endometriosis ( O ~ a s ael cil. 1987). O n the othcr hand. CA 125 production was not affcctcd bv oestrogen, progestin or tamoxifen in immunodeficient mice inoculated with ovarian carcinoma (Holt et RI. 1987). The aim of our study was to mcasure serum C A 125 levels in different phases of the menstrual cycle and to examine a possible association with ovarian sex steroids. Subjects and methods Twenty-eight apparently healthy young women (mean age 20, rangc 15-32 ycars) were selected lor the study; 20 were < I 8 years of age Of the 28 women, 16 had normal menstrual cycles n7ith luteal phases of at leas1 10 days and a serum pro-
CA 12.5 in nienstrunl cycle
gestcrone concentration > l o nmolil. The length of the luteal phase was estimated on the basis of LH and progesterone concentrations. In 12 women aged 15-18 years; serum progesterone concentration remained below 10 nmolil throughout the cycle, and these cycles were classified as anovulatory. The cycles were divided into four phases: (I) cyclc days 1-7; (2) cyclc days 8-18; (3) last 7 day$ of cycle: (4) cycle days 1-7 of the next cycle. Thus phase 4 corresponds to phase 1. Blood samples were collected every 3-4 days during phases 1,3 and 4 and every 1-2 days during the estimated periovulatory period in phase 2. The specimens werc grouped retrospectively into appropriate phases. Serum samples were stored at -20°C until assayed for CA 125, progesterone, oestradiol and LH. An immunoradiometric CA 125 assay was used according to the manufacturer's instructions (Abbott IAoratoriers, Wiesbaden, FRG). The scnsitivity of the assay was 6.4 L[!ml. Levels >3S [Jim1 were considered elevated (Bast ef d.1983). To compare CA 125 levels during the menstrual cycle. the values were expressed as a percentage of thc mean value of all observations for each individual. Serum progesterone, oestradiol and LH concentrations were ineasurcd by routine radioimmunoassays. The data were analyzed by BMDP programs (BMDP Statistical Software of 1987, University of California, Los Angles. CA). Statistical assessment used analysis of variance for
931
repeated measurements and the paired Student's t-test within the phases of the cycle and Mann-Whitney U-lest between the ovulatory and anovulatory cycles. Results
CA 125 levels were significantly higher during the first week (phases 1 and 4) of the cycle than during the middle part (phase 2) of the cycle both in women with ovulatory and in those with anovulatory cycles (Tablc 1). Thc highest concentrations of CA 125 in ovulatory and anovulatory women during menstruation were 51 U/mI and 125 U/ml. respectively. In women with anovulatory cycles, hut not in those with ovulatory cyclcs. CA 125 levels were already significantly increased before the outset of menstruation (phase 3). CA 125 levels were slightly higher in the anovulatory than in the ovulatory group, hut the diffcrcncc was statistically significant only in phase 3 (Tablc 1 and Fig. 1). There was a negative correlation ( I = -0.48, P
