The use of the estrogen ethinylestradiol is associated with an increased cardiovascular risk. It is not known whether this might be caused by an influence of ethinylestradiol on endothelium-derived factors or on the cardiovascular risk factor homocysteine. Our aim was to evaluate whether a short-term treatment with ethinylestradiol results in changes of nitric oxide (NO), endothelin-1 and homocysteine. Participants were ten healthy women with regular menstrual cycles. NO, homocysteine, endothelin-1, estradiol and progesterone were measured during one cycle and before and after treatment with ethinylestradiol at 50 microg/day. Homocysteine and NO did not change significantly during the menstrual cycle or after treatment. However, endothelin-1 levels decreased during the cycle (from 3.89 ng/l to 2.93 ng/l p < 0.05) and after ethinylestradiol (from 2.94 ng/l to 2.26 ng/l p<0.03). Analysis of the pretreatment data showed a positive correlation between homocysteine and NO and between NO and endothelin-1. Treatment with ethinylestradiol caused a shift in the balance between NO and endothelin-1 in the direction of vasodilatation. This finding is one factor concerning the effects of ethinylestradiol on the vascular system but does not explain the cardiovascular risk of this substance.

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The excretion of FSH, LH and 17-ketosteroids was studied in healthy men before, during and after administration of antiandrogens, Le. cyproterone-acetate and cyproterone. The first compound mainly decreased the FSH-activity and t~ a lo~er extent also the LH-activity in cases with comparatively high pretreatment levels, but did not clearly afTect these hormones in other subjects. The excretion of 17-ketosteroids was not much altered In contrast the free a1cohol, cyporoterone, tended to increase the FSH-and LH-Ievels in same, the 17-ketosteroids in alI cases.The possible reasons for these effects, i.e. the dose dependency or different mode of action of the two compounds are discussed Horm. Metab. Res. 3: 273-276 (1971) K e y -Wo r d s: IntrocluctionInterest in antiandrogenic compounds has considerably increased during the past few years. The treatment of male hypersexuality, precocious puberty and female hirsutism and virilization are the most challenging problems, which are or may be solved by the availability of such drugs.Cyproterone (1,2 a-methylene-6-chloro-A4,6 -pregnadiene-17 a-01-3,20-dione) and cyproterone-acetate (1,2 a -methylene-6-chloro-A4'6 -pregnadine-3,20-dione-17 a-acetate) are antiandrogenic steroids interfering with the hypothalamo-gonadal and hypothalamo-adrenal axis. 80th compounds have been successfully used for the treatment of human hypersexuality (Ott and Hoffet 1968, Laschet, Laschet, Tetzner, Glaesel, Mall and Naab 1967). Cyproterone, the free alcohol, however, proved to be much less effective than the acetate, which has also a marked progestational activity.The endocrine effects of the two compounds have been previously investigated in rats (Neumann, Eiger, v.Berswordt-Wallrabe and Kramer 1966, Neri, Monahan, Meyer, Afonso anti Tabachnik 1967) by me ans of parabiosis experiments. In man the urinary excretion of total gonadotropic activity and 17-ketosterReceived: 12 Sept. 1970 Acceptecl: 4 Feb. 1971 36 Horm. Metab. Res. 3, 71 oids as weIl as estrogens, testosterone and epitestosterone has been assessed (Voigt anti Klosterhalfen 1966, Voigt, Apostolakisand Klosterhalfen 1968, v.Berswordt-Wallrabe and Neumann 1969, Petry, Rausch-Stroomann, Mauss and Senge 1969). No specific determinations of follicle-stimulating and luteinizing hormone (FSH, LH), however, have been published so far, although these questions seem to be im· portant for a precise understanding. Hence attempts have been made in the present study to follow up the excretion of FSH, LH and 17-ketosteroids in males treated with the two antiandrogenic compounds. Materials and Methods SubjectsSeven healthy men, aged from 22 to 48 years, volunteered for this investigation. In a first part of the study cyproterone-acetate was given to six subjects. In a second experiment, which was conducted after a treatment-free interval of five months, two of them as weIl as a previously not included subject received cyproterone. 80th compounds were given orally in daily doses of 200 mg over 8-14 days.Consecutive 24-hour sampies of urine were...

The metabolie eharacteristies of HPL have been investigated by means of a radio-immunoassay. The highest eoneentration of this trophoblastie hormone was found in maternal blood and, to a lesser extent, amniotie fluid. The aetivity in umbilical cord blood was negligible, no HPL could be detected in fetal urine. The titres in maternal urine were about 150 times lower than in the serum, the mean renal clearance was 0.0057 ml/min. After surgical removal of the plaeenta HPL disappeared very quiekly from the maternal blood; after one hour the mean eoneentration was only 10-21%. The biological half-life was estimated to be approximately 21 minutes, the daily produetion rate more than 0.5 g. No eircadic rhythms were found. The significanee of these findings is diseussed.

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