299 Horm. Metab. Res. 8 (1976) 299-302
© Georg Thieme Verlag Stuttgart
Effect of an Oral Contraceptive on the Lysine-8-Vasopressin Test in the Diagnostic Evaluation of Pituitary Function I.M. Penttilä, P. Pystynen and S. Nummi Department of Clinical Chemistry and the Clinic of Obstetrics and Gynecology, University Central Hospital of Kuopio, Finland
Summary A comparative study was performed on the plasma ll-hydroxycorticosteroids (ll-OHCS) responses to lysine-8-vasopressin (L VP) before and during ingestion of an oral contraceptive with oestrogenic activity. A total of 19 healthy women with a normal menstrual cycle and normal plasma ll-OHCS content in blood sampIes at 8 a.m. and 4 p.m. were included in the study.
the administration of LVP. After further investigation of the cases we found that these subjects had used oral contraceptives with oestrogenic activity before and even du ring the L VP test.
and during ingestion of the contraceptive, although the baseline value of 11-0HCS doubled as a result of the treatment. On the other hand, during contraceptive treatment the increase in plasma 11-0HCS concentration after the administration of LVP was somewhat slower, reaching its peak later than before treatment. The noticeable variation in individual responses of plasma II-OHCS to LVP increased during the treatment. Three subjects showed weak responses to LVP, although the adrenocortical responses to exogenous ACTH were quite normal. The individual responses to LVP before and during ingestion of an oral contraceptive with oestrogenic activity are discussed. Key-Words: ACTH - Oral Contraceptive - Plasma Copper Plasma jj·Hydroxycorticosteroids - Vasopressin
Introduction There are several studies on the application of the lysine-8-vasopressin (LVP) test for clinical purposes since its introduction by Gwinup (1965). Generally, a eie ar rise in the plasma Il-hydroxycortieosteroid (11-0HCS) level has been produeed by the administration of LVP. In some cases, however, an impaired response to L VP has been reported by Andersson, Amer, Hedner and Mulder (1972), by Nelson, Mackay, ,f', B uus and Sh en'dan and Weaver (1966) an d by '1' 1 0, t, Nielsen (1971), although other examinations have not revealed pituitary hypofunction. On the other hand, Toft, Buus and Nielsen (1971) have found a normal response to LVP also in verified cases of hypofunction Therefore it seems that the reliability of the LVP test is not as good as was originally expected. .
.
.
..
When usmg the LVP test as an mdlcator of pltUltary function in women, we noticed in some cases that both the relative and the absolute responses in the plasma11-0HCS content were impaired. In these cases the .
'
.
ll-OHCS mcrement was less than 5 J.Lg/l00 ml, WhlCh value according to Andersson et al. (1972) is generally usea as a limit for a normal response 60 minutes after Received: 3 Nov. 1975
Accepted: 5 Jan. 1976
Material and Methods These subjects selected for the study consisted of 21 apparentIy healthy young women (20-30 years of age) with anormal, regular menstrual cycle and normal plasma 11-0HCS values at 8 a.m. and 4 p.m. Determinations of the plasma l1-OHCS were performed on the 17th day after the beginning of menstruation. On the following morning at 8 o'dock the LVP test was performed by injecting 10 units of LVP (Postacton®, Ferring Ab, Sweden) intramuscularly and by determining the plasma l1-OHCS level in blood sam pies 30, 60, 90 and 120 minutes after injection of the drug. During the test, the subjects were recumbent. On the 5th day of the following menses, the subjects started taking an oral contraceptive piII daily (Lyndiot®, 2.5 mg Iynestrenol and 0.05 mg ethinyl oestradiol, Organon NV, Holland) according to instructions. On amid· cyde day of the second menstrual cycle, the plasma ll-OHCS content was determined from blood sam pIes drawn at 8 a.m. and 4 p.m., and the LVP test was performed on the following morning at 8 o'clock. The study was completed on 19 subjects; two subjects discontinued the experiment due to nausea. Determination of plasma cop per content was carried out to ascertain that the oral contraceptive treatment was continuous, since according to Adlercreutz, Eisalo, Heino, Luukkaine~, Penttilä and Saukkonen (196.8) even ~hort-term contracephve treatme~t causes a 2-3-fold mcrease m the plasma copper concentratlOn. To investigate adrenocortical function during contraceptive treatment, a tolerance test with adrenocorticotrophic hormone (ACTH) was later performed on the subjects on a midcycle day at 8 a.m. The subjects were given 10 units of synthetic human ACTH (I-21Homactid®, Ferring Ab, Sweden) intramuscularly. The plasma ll-OHCS content was determined 30 and 60 minutes after the injection. Determination of the plasma ll-OHCS concentration was performed fluorometrically with a modified method of DeMoor, Osinski, Deckx and Steeno (1962). To follow the accuracy and precision of the method w,e used Seronorm®control serum (batch No. 116) from whlch 2: analysc: s durmg the study gave a mean value of 429 nmol!1 wlth a varJance of 5.8 per cent. Our reference values for the plasma ll-OHCS content at 8 a.m. are 330-880 nmol/I (12-32 1Jg!100 ml). The plasma copper concentration was determined from sampIes diluted 1:1 by means of a Perkin-Elmer 290 B atomic absorption spectrophotometer according to Parker, Humaller and Mahler
Downloaded by: Boston University. Copyrighted material.
Since on the basis qf these findings, it seemed possible that the response to vasopressin could be different in normal subjects and in those on contracepThe results show that the mean response of plasma 11-OHCS tive treatment, we decided to investigate the matter to the administration of LVP was equal in magnitude before in greater detail.
300
I.M. Penttilä, P. Pystynen and S. Nummi
Table 1. The concentrations of 11-OHCS and copper in plasma of 19 healthy young women before and during contraceptive treatment (one tablet daily containing 2.5 mg of lynestrenol and 0.05 mg of ethinyl oestradiol). The results are expressed as mean values ± S.D. xxxp
© Georg Thieme Verlag Stuttgart
Effect of an Oral Contraceptive on the Lysine-8-Vasopressin Test in the Diagnostic Evaluation of Pituitary Function I.M. Penttilä, P. Pystynen and S. Nummi Department of Clinical Chemistry and the Clinic of Obstetrics and Gynecology, University Central Hospital of Kuopio, Finland
Summary A comparative study was performed on the plasma ll-hydroxycorticosteroids (ll-OHCS) responses to lysine-8-vasopressin (L VP) before and during ingestion of an oral contraceptive with oestrogenic activity. A total of 19 healthy women with a normal menstrual cycle and normal plasma ll-OHCS content in blood sampIes at 8 a.m. and 4 p.m. were included in the study.
the administration of LVP. After further investigation of the cases we found that these subjects had used oral contraceptives with oestrogenic activity before and even du ring the L VP test.
and during ingestion of the contraceptive, although the baseline value of 11-0HCS doubled as a result of the treatment. On the other hand, during contraceptive treatment the increase in plasma 11-0HCS concentration after the administration of LVP was somewhat slower, reaching its peak later than before treatment. The noticeable variation in individual responses of plasma II-OHCS to LVP increased during the treatment. Three subjects showed weak responses to LVP, although the adrenocortical responses to exogenous ACTH were quite normal. The individual responses to LVP before and during ingestion of an oral contraceptive with oestrogenic activity are discussed. Key-Words: ACTH - Oral Contraceptive - Plasma Copper Plasma jj·Hydroxycorticosteroids - Vasopressin
Introduction There are several studies on the application of the lysine-8-vasopressin (LVP) test for clinical purposes since its introduction by Gwinup (1965). Generally, a eie ar rise in the plasma Il-hydroxycortieosteroid (11-0HCS) level has been produeed by the administration of LVP. In some cases, however, an impaired response to L VP has been reported by Andersson, Amer, Hedner and Mulder (1972), by Nelson, Mackay, ,f', B uus and Sh en'dan and Weaver (1966) an d by '1' 1 0, t, Nielsen (1971), although other examinations have not revealed pituitary hypofunction. On the other hand, Toft, Buus and Nielsen (1971) have found a normal response to LVP also in verified cases of hypofunction Therefore it seems that the reliability of the LVP test is not as good as was originally expected. .
.
.
..
When usmg the LVP test as an mdlcator of pltUltary function in women, we noticed in some cases that both the relative and the absolute responses in the plasma11-0HCS content were impaired. In these cases the .
'
.
ll-OHCS mcrement was less than 5 J.Lg/l00 ml, WhlCh value according to Andersson et al. (1972) is generally usea as a limit for a normal response 60 minutes after Received: 3 Nov. 1975
Accepted: 5 Jan. 1976
Material and Methods These subjects selected for the study consisted of 21 apparentIy healthy young women (20-30 years of age) with anormal, regular menstrual cycle and normal plasma 11-0HCS values at 8 a.m. and 4 p.m. Determinations of the plasma l1-OHCS were performed on the 17th day after the beginning of menstruation. On the following morning at 8 o'dock the LVP test was performed by injecting 10 units of LVP (Postacton®, Ferring Ab, Sweden) intramuscularly and by determining the plasma l1-OHCS level in blood sam pies 30, 60, 90 and 120 minutes after injection of the drug. During the test, the subjects were recumbent. On the 5th day of the following menses, the subjects started taking an oral contraceptive piII daily (Lyndiot®, 2.5 mg Iynestrenol and 0.05 mg ethinyl oestradiol, Organon NV, Holland) according to instructions. On amid· cyde day of the second menstrual cycle, the plasma ll-OHCS content was determined from blood sam pIes drawn at 8 a.m. and 4 p.m., and the LVP test was performed on the following morning at 8 o'clock. The study was completed on 19 subjects; two subjects discontinued the experiment due to nausea. Determination of plasma cop per content was carried out to ascertain that the oral contraceptive treatment was continuous, since according to Adlercreutz, Eisalo, Heino, Luukkaine~, Penttilä and Saukkonen (196.8) even ~hort-term contracephve treatme~t causes a 2-3-fold mcrease m the plasma copper concentratlOn. To investigate adrenocortical function during contraceptive treatment, a tolerance test with adrenocorticotrophic hormone (ACTH) was later performed on the subjects on a midcycle day at 8 a.m. The subjects were given 10 units of synthetic human ACTH (I-21Homactid®, Ferring Ab, Sweden) intramuscularly. The plasma ll-OHCS content was determined 30 and 60 minutes after the injection. Determination of the plasma ll-OHCS concentration was performed fluorometrically with a modified method of DeMoor, Osinski, Deckx and Steeno (1962). To follow the accuracy and precision of the method w,e used Seronorm®control serum (batch No. 116) from whlch 2: analysc: s durmg the study gave a mean value of 429 nmol!1 wlth a varJance of 5.8 per cent. Our reference values for the plasma ll-OHCS content at 8 a.m. are 330-880 nmol/I (12-32 1Jg!100 ml). The plasma copper concentration was determined from sampIes diluted 1:1 by means of a Perkin-Elmer 290 B atomic absorption spectrophotometer according to Parker, Humaller and Mahler
Downloaded by: Boston University. Copyrighted material.
Since on the basis qf these findings, it seemed possible that the response to vasopressin could be different in normal subjects and in those on contracepThe results show that the mean response of plasma 11-OHCS tive treatment, we decided to investigate the matter to the administration of LVP was equal in magnitude before in greater detail.
300
I.M. Penttilä, P. Pystynen and S. Nummi
Table 1. The concentrations of 11-OHCS and copper in plasma of 19 healthy young women before and during contraceptive treatment (one tablet daily containing 2.5 mg of lynestrenol and 0.05 mg of ethinyl oestradiol). The results are expressed as mean values ± S.D. xxxp
