A quantitative study of the pregnancy zone protein in sera of women taking oral contraceptives M.-G.
DAMBER
B.
VON
F.
SOLHEIM
T.
STIGBRAND
Urn&,
SCHOULTZ
Sweden
By means of a single radial immunodifjf usion the concentration of “the pregnancy zone protein” (PZ) was measured in sera from women taking oral contraceptizle drugs. Women taking only 0.3 mg. of norethisterone were found not to induce measurable amounts of PZ, whereas women taking combined contraceptive drugs showed a signi$cant rise in concentration of PZ. After six months’ treatment, 1 mg. of norethisterone and 0.1 mg. of meastranol daily were found to give an average concentration of PZ amounting to 59 mg. per 100 ml., that is, approximately half of the concentration of PZ in sera from women during the last trimester of pregnancy. Different combined contraceptive pills gave rise to diJferent concentrations of PZ. .
THE PREGNANCY ZONE protein (PZ), recently purified with a molecular weight of 359,000’. 2 is known to be found in sera of women during pregnancy.3-8 In nonpregnant women or men PZ is generally not detectable by immunodiffusion test (less than 4 mg. per 100 ml.). This cu,-globulin, first described by Smithies9 has been found to have immunosuppressive properties.iO-l2 During pregnancy PZ can be detected in increasing amounts from the end of the first trimester, and during the last trimester the average level is about 100 mg. per 100 ml. After delivery the concentration decreases rapidly. Estrogen seems to be necessary for the induction of PZ.z* * PZ is found not only in pregnant women but also in women taking oral contraceptive drugsi3-I5 and in men treated with estrogen for prostatic cancer.i6, i’ Previous investigations ~3 i5, l7 indicate that the occurrence of PZ is related to the composition of the drugs. From the Departments of Obstetrics Physiological Chemistry, University
and Gynecology of UmeB.
The purpose of the present investigation was to measure quantitatively the variations of PZ in women treated with oral contraceptive drugs and to study the level of PZ in relation to the composition of the oral contraceptive drugs.
Material and methods A total of 322 blood samples were drawn from 103 women prior to and during treatment with oral contraceptives. The blood samples were collected without anticoagulant. After coagulation the serum was decanted and stored at - 20” C. until use. All sera were coded and tested blindly. Of the 103 women, 80 were specially selected according to certain criteria. They were all healthy and were not taking other drugs. They had not been pregnant and they had never been treated with oral contraceptives before the investigation. These 80 women were divided into two groups: twenty-two were treated with a combination of 1 mg. of norethisterone and 0.1 mg. of mestranol (Norinyl 1 + 100) and 58 women were treated with 0.5 mg. of norgestrel and 0.05 mg. of ethinyl estradiol (Ovral). Blood samples were obtained before treatment and then after one month, three months, and, in some women, also after six months of treatment. In addition to these 80 women, a third group of 23 women were examined during treatment with low-dose progestin contraceptives. They had previously tried
and
Suppotied by grants to Drs. von Schoultz and Stigbrand from the Swedish Medical Research Council (Project B75-13X-4217-02). Received for publication Rezked
January
Accepted February
July 30, 1974..
20, 1975. 6, 1975.
Reprint requests: Dr. M.-G. Damber, Obst&cs and Gynecology, University Ume& Sweden.
Department of of Umeii, S 901-87
289
Table
I. Concentration
of pregnancy
zone protein
during
treatment
with oral contraceptive
Level of PZ mg. per 100 ml., (mean Composition
of drug
Norethisterone. 0.3 mg. (Nor-Q.D.) Norgestrel, 0.5 mg., ethinyl estradiol, 0.05 mg. (Ovral) Norethisterone. 1 mg., mestranol, 0.1 mg. (Norinyl 1 + 100)
Before
After
1 month
k S.D.)
After 3 months
After
6 months
drugs Per cent oj t(wnen ulith increased amounts of PZ (> 10 mg. prr 100 ml.) during treatment
DAMBER
B.
VON
F.
SOLHEIM
T.
STIGBRAND
Urn&,
SCHOULTZ
Sweden
By means of a single radial immunodifjf usion the concentration of “the pregnancy zone protein” (PZ) was measured in sera from women taking oral contraceptizle drugs. Women taking only 0.3 mg. of norethisterone were found not to induce measurable amounts of PZ, whereas women taking combined contraceptive drugs showed a signi$cant rise in concentration of PZ. After six months’ treatment, 1 mg. of norethisterone and 0.1 mg. of meastranol daily were found to give an average concentration of PZ amounting to 59 mg. per 100 ml., that is, approximately half of the concentration of PZ in sera from women during the last trimester of pregnancy. Different combined contraceptive pills gave rise to diJferent concentrations of PZ. .
THE PREGNANCY ZONE protein (PZ), recently purified with a molecular weight of 359,000’. 2 is known to be found in sera of women during pregnancy.3-8 In nonpregnant women or men PZ is generally not detectable by immunodiffusion test (less than 4 mg. per 100 ml.). This cu,-globulin, first described by Smithies9 has been found to have immunosuppressive properties.iO-l2 During pregnancy PZ can be detected in increasing amounts from the end of the first trimester, and during the last trimester the average level is about 100 mg. per 100 ml. After delivery the concentration decreases rapidly. Estrogen seems to be necessary for the induction of PZ.z* * PZ is found not only in pregnant women but also in women taking oral contraceptive drugsi3-I5 and in men treated with estrogen for prostatic cancer.i6, i’ Previous investigations ~3 i5, l7 indicate that the occurrence of PZ is related to the composition of the drugs. From the Departments of Obstetrics Physiological Chemistry, University
and Gynecology of UmeB.
The purpose of the present investigation was to measure quantitatively the variations of PZ in women treated with oral contraceptive drugs and to study the level of PZ in relation to the composition of the oral contraceptive drugs.
Material and methods A total of 322 blood samples were drawn from 103 women prior to and during treatment with oral contraceptives. The blood samples were collected without anticoagulant. After coagulation the serum was decanted and stored at - 20” C. until use. All sera were coded and tested blindly. Of the 103 women, 80 were specially selected according to certain criteria. They were all healthy and were not taking other drugs. They had not been pregnant and they had never been treated with oral contraceptives before the investigation. These 80 women were divided into two groups: twenty-two were treated with a combination of 1 mg. of norethisterone and 0.1 mg. of mestranol (Norinyl 1 + 100) and 58 women were treated with 0.5 mg. of norgestrel and 0.05 mg. of ethinyl estradiol (Ovral). Blood samples were obtained before treatment and then after one month, three months, and, in some women, also after six months of treatment. In addition to these 80 women, a third group of 23 women were examined during treatment with low-dose progestin contraceptives. They had previously tried
and
Suppotied by grants to Drs. von Schoultz and Stigbrand from the Swedish Medical Research Council (Project B75-13X-4217-02). Received for publication Rezked
January
Accepted February
July 30, 1974..
20, 1975. 6, 1975.
Reprint requests: Dr. M.-G. Damber, Obst&cs and Gynecology, University Ume& Sweden.
Department of of Umeii, S 901-87
289
Table
I. Concentration
of pregnancy
zone protein
during
treatment
with oral contraceptive
Level of PZ mg. per 100 ml., (mean Composition
of drug
Norethisterone. 0.3 mg. (Nor-Q.D.) Norgestrel, 0.5 mg., ethinyl estradiol, 0.05 mg. (Ovral) Norethisterone. 1 mg., mestranol, 0.1 mg. (Norinyl 1 + 100)
Before
After
1 month
k S.D.)
After 3 months
After
6 months
drugs Per cent oj t(wnen ulith increased amounts of PZ (> 10 mg. prr 100 ml.) during treatment
