Search PubMed⌕ Search

Biomedical subjects

H Kuhl

Publications and source records attributed to H Kuhl.

At least 91 records · Page 5Linked to original sources
PubMed1991

[Contraception with cyclic administration of buserelin and gestagens: increase in testosterone and free testosterone serum concentration].

During contraception with the LH-RH analogue buserelin, some women developed mild androgenic symptoms. Therefore, we investigated in 10 women various hormonal serum parameters during one cycle of treatment with daily 300 micrograms buserelin intranasally (day 1-22) and 5 mg medroxyprogesterone acetate (MPA) orally (day 16-22), and, after a washout cycle, during another cycle of treatment with daily 300 micrograms buserelin intranasally (day 1-15) and 5 mg norethisterone acetate (NETA) orally (day 16-22). The serum parameters were investigated on day 1, 15 and 21 during the 4 hours after administration of the drugs. During the treatment, LH release was significantly reduced, whereby additional MPA had no effect whatsoever, while NETA profoundly suppressed LH. During treatment with buserelin and MPA, the average oestradiol levels remained unaltered, but were significantly suppressed by 65% during intake of NETA. Contrary to 17 alpha-hydroxyprogesterone, which did not change, serum testosterone was significantly increased by 30% when buserelin was given with or without MPA, while NETA had no effect. During both regimens, the serum concentrations of SHBG were reduced by 15 to 25%, and those of free testosterone were increased by 30 to 50%. These alterations in hormonal parameters may have contributed to the development of seborrhoeic symptoms and acne of the facial skin which were observed in 6 of the 10 women treated with intranasal buserelin for contraception.

Administration, Intranasal↗
PubMed1991

Oral contraceptives containing 20 or 30 micrograms ethinylestradiol and 150 micrograms desogestrel: pharmacokinetics and pharmacodynamic parameters.

The serum concentrations of ethinylestradiol (EE) and 3-keto-desogestrel (KDG) were compared during treatment with a combination of 20 micrograms EE + 150 micrograms DG (20EE/DG) or of 30 micrograms EE + 150 micrograms DG (30EE/DG). During intake of both preparations, the peak levels and the areas under the curve (AUC) of EE increased significantly by approximately 100% between days 1 and 10. In the steady state, the maximal EE levels were 75 +/- 34 pg/ml (20EE/DG) and 136 +/- 55 pg/ml (30EE/DG), and the AUC were 464 +/- 236 pg.h/ml and 840 +/- 492 pg.h/ml. The KDG levels, which were identical with both preparations, increased between days 1 and 21 by approximately 300% up to values of 4.5 +/- 1.6 ng/ml. There were large interindividual variations in the AUC of EE and KDG and no correlation between the levels of EE and KDG. On day 21 of intake of 30EE/DG, the serum concentrations of sex-hormone- and corticosteroid-binding globulin were higher by 16% and 12%, respectively than with 20EE/DG. Although the morning peak levels of cortisol did not differ, the decrease which occurred thereafter, according to the circadian rhythm, was slower with 30EE/DG. There was no relationship between the serum concentrations of EE and/or KDG and the occurrence of irregular bleedings, which was similar during treatment with both preparations. As most of the women who bled had bleedings both with 20EE/DG and 30EE/DG, an influence of predisposition can be assumed.(ABSTRACT TRUNCATED AT 250 WORDS)

Adult↗
PubMed1990

Pharmacokinetics and pharmacodynamics of oral contraceptive steroids: factors influencing steroid metabolism.

The time-dependent alterations in the serum concentrations of ethinyl estradiol, gestodene, and 3-keto-desogestrel during treatment with 30 micrograms of ethinyl estradiol + 75 micrograms of gestodene or 30 micrograms of ethinyl estradiol + 150 micrograms of desogestrel were investigated during 12 months. The levels of gestodene and 3-keto-desogestrel increased between days 1 and 21 of each cycle, reaching maximal levels during the third and sixth cycles. The serum concentrations of gestodene were fourfold to fivefold higher than those of 3-keto-desogestrel. The ethinyl estradiol levels increased significantly between days 1 and 10 during each cycle and were significantly higher by 70% during intake of ethinyl estradiol/gestodene compared with ethinyl estradiol/desogestrel, although the dose was identical. Intake of gestodene, in addition to 35 micrograms of ethinyl estradiol + 2 mg of cyproterone acetate, caused a rise in ethinyl estradiol levels. During treatment with ethinyl estradiol/gestodene and an additional 150 micrograms of levonorgestrel, there was a continuous increase in gestodene levels, although sex hormone-binding globulin level did not change. During treatment with 30 or 35 micrograms of ethinyl estradiol and 75 micrograms of gestodene, 150 micrograms of desogestrel, or 2 mg of cyproterone acetate, there were large intraindividual and interindividual variations in the steroid levels and ratios of estrogen: progestogen levels. There was no correlation with the occurrence of intermenstrual bleedings. It is concluded that ethinyl estradiol and nortestosterone derivatives may inhibit steroid-metabolizing enzymes in the liver, which results in a rise in the serum levels of contraceptive steroids. The cause of the large intraindividual variations is as yet unknown, but it is probably from changes in steroid metabolism.

Adolescent↗
PubMed1990

Time-dependent alterations in lipid metabolism during treatment with low-dose oral contraceptives.

The effect of sex steroids on lipid metabolism depends on the type and dose of the compounds, the route of administration, and the duration of treatment. Therefore the composition of an oral contraceptive determines the resultant effect on lipids and lipoproteins. During 12 months of treatment, the effects of two oral contraceptives containing 30 micrograms of ethinyl estradiol and 150 micrograms of desogestrel (EE/DG) or 75 micrograms of gestodene (EE/GSD) on 19 serum parameters of lipid metabolism were followed in 11 women each. There was no change in total cholesterol and phospholipids. Total triglyceride levels were significantly elevated only by EE/GSD. After 3 and 6 months of intake of both preparations, a transitory increase in the triglyceride content of very low-density lipoprotein and low-density lipoprotein and a decrease in low-density lipoprotein-phospholipids was observed. After 12 months, very low-density lipoprotein cholesterol, very low-density lipoprotein phospholipids, and apolipoprotein B were significantly elevated, whereas very low-density lipoprotein triglycerides and all components of low-density lipoprotein were unchanged. Most of the components of high-density lipoprotein (HDL) were increased as a result of a rise in HDL3 and apolipoprotein A2, whereas HDL2 and apolipoprotein A1 were not altered. There was no significant difference between the effects of the two preparations, although those of EE/GSD were mostly more pronounced. The increase in high-density lipoprotein, very low-density lipoprotein, and total triglycerides reflects a slight preponderance of the effect of the estrogen component. Because low-density lipoprotein cholesterol and total cholesterol were not changed, treatment with both formulations is in all probability not associated with an elevated risk of atherosclerosis.

Adolescent↗
PubMed1990

Intra- and interindividual variations in contraceptive steroid levels during 12 treatment cycles: no relation to irregular bleedings.

During one year of treatment with oral contraceptives containing 30 micrograms ethinylestradiol and 150 micrograms desogestrel (EE/DG) or 30 micrograms EE and 75 micrograms gestodene (EE/GSD), the serum concentrations of EE, 3-keto-desogestrel (KDG) and GSD were determined on day 1, 10 and 21 of the 1st, 3rd, 6th and 12th cycle. The areas under the time-versus-concentration curves were calculated from the levels before and 0.5, 1, 1.5, 2, 3, 4 and 24 hours after intake of a tablet. There were large intra- and interindividual variations both revealing coefficients of variation (C.V.) between 25% and 80% (EE),, 30% and 50% (KDG) and 30% and 65% (GSD). During each cycle, the EE levels increased significantly between day 1 and 10 by 70% on average reaching a steady-state, while the progestogen concentrations rose by 100% (KDG) and 150% (GSD) up to a steady-state between day 10 and 21. After reaching the steady-state, the C.V. were generally lower. The ratios between the levels of EE and the progestogens showed still higher variations indicating different influences on the estrogen and progestogen component. There was no correlation between the steroid levels and weight, height or age. In spite of the large intraindividual variations, most of the women showed a distinct pattern of the levels of EE and the progestogens throughout the year of treatment indicating a genetic or acquired predisposition. The difference in the average AUC of EE, KDG and GSD between the women was 300% at most. During the first cycle of treatment with EE/DG and EE/GSD, about half of the women recorded intermenstrual bleedings which decreased thereafter. There was no relation between the occurrence of irregular bleedings and the average serum levels of EE and the progestogens of the individual women, neither during the first cycle nor during the whole treatment period of 12 cycles. It is concluded that spottings or breakthrough bleedings during treatment with oral contraceptives are not dependent on a distinct pattern of the serum levels of EE and the progestogen.

Adolescent↗
PubMed1990

Changes in lipid metabolism during 12 months of treatment with two oral contraceptives containing 30 micrograms ethinylestradiol and 75 micrograms gestodene or 150 micrograms desogestrel.

The effect of two oral contraceptives containing 30 micrograms ethinylestradiol + 75 micrograms gestodene (EE/GSD) or 30 micrograms ethinylestradiol + 150 micrograms desogestrel (EE/DG) upon serum lipids and lipoproteins were measured in 11 women each on days 1, 10, and 21 of the first, third, sixth, and twelfth treatment cycle and compared to the levels on days 1, 10, and 21 of the preceding control cycle. There was no change in total cholesterol (CH) and phospholipids (PL), while total triglycerides (TG) were significantly elevated only during treatment with EE/GSD. After 3 and 6 months of intake of both oral contraceptives, a transitory increase in the TG content of very low-density lipoprotein (VLDL) and low-density lipoprotein (LDL), and a decrease in LDL-PL was observed. After 12 months, VLDL-CH, VLDL-PL, and apolipoprotein B were significantly elevated, while VLDL-TG and all components of LDL were unchanged. Most of the components of high-density lipoprotein (HDL) were increased due to a rise in HDL3 and apolipoprotein A-II, while HDL2 and apolipoprotein A-I were not altered. There was no significant difference between the effects of the two preparations, although those of EE/GSD were mostly more pronounced. The time-dependent change in the effects of the oral contraceptives on various parameters of lipid metabolism demonstrates that the relevance of results of short-time studies may be questionable. There was also a significant alteration in some parameters between day 1 and 10 of the treatment cycles and a tendency to return to the pretreatment levels during the pill-free week, e.g., in total TG and in the PL component of VLDL, LDL and HDL. The increase in HDL, VLDL, and total TG reflects a slight preponderance of the effect of ethinylestradiol on lipid metabolism. The unchanged total CH and LDL-CH and the elevated HDL levels indicate that the risk of the development of atherosclerosis is in all probability not increased during treatment with both preparations.

Adolescent↗
PubMed1990

Pharmacokinetics of oestrogens and progestogens.

There are large inter- and intra-individual variations in the serum concentrations of natural and synthetic sex steroids irrespective of the route of administration. Oral ingestion of steroids has a stronger effect on hepatic metabolism than parenteral administration, as the local concentration in liver sinusoids are 4-5 times higher during the first liver passage. Oestradiol and oestrone are interconvertible, dependent on the local concentrations in liver and target organs, and oestrone sulphate serves as a large reservoir. The oestrone/oestradiol ratio has no physiological significance, as oestrone is only a weak oestrogen. Oestrone is both a precursor and a metabolite of oestradiol. Oestriol is extensively conjugated after oral administration. Therefore, the oestriol serum levels are similar after oral intake of 10 mg and after vaginal application of 0.5 mg oestriol resulting in similar systemic effectiveness. Conjugated oestrogens can easily enter the hepatocytes but are hormonally active only after hydrolyzation into the parent steroids. Ethinylestradiol which exerts strong effects on hepatic metabolism and inhibits metabolizing enzymes, should not be used for hormone replacement therapy. Among the progestogens, the progesterone derivatives have less effects on liver metabolism than the norethisterone derivatives (13-methyl-gonanes and 13-ethyl-gonanes). The highly potent 13-ethyl-gonanes are effective at very low doses, because of a slow inactivation and elimination rate due to the ethinyl group.

Estrogens↗
PubMed1990

[Ovulation inhibitors: the significance of estrogen dose].

The large prospective studies on adverse effects of oral contraceptives have unanimously revealed an increased risk of thromboembolic diseases, which seem to be associated with the dose of ethinylestradiol (EE). According to the recommendations of several medical committees, the dose of EE has, therefore, been more and more reduced; in some countries there are now ovulation inhibitors containing 20 micrograms EE. Since serious reactions, which have a relatively low incidence, are highly underreported (less than 10%), it is difficult to prove dose-dependent differences in the rates of cardiovascular diseases. There is, however, virtually no doubt that not only the incidence of thromboembolic diseases and stroke, but also that of benign liver tumours and gall bladder diseases is increased in relation to the EE-dose. A series of metabolic serum parameters, e.g. serum binding proteins, coagulation and fibrinolysis factors, angiotensinogen, is changed by EE in a dose-dependent manner which is, however, limited when the effects are receptor-mediated. Higher doses of EE have been shown to facilitate fibrin deposits on vascular subendothelium. The pharmacological effects of EE are to a large extent dependent on the dose, e.g. the irreversible reactions of EE and other ethinylated steroids with hepatic enzymes which are involved in the metabolism of steroids, drugs and toxic compounds. After long-term treatment with combinations containing 50 micrograms EE, in half of the women, abnormal liver function tests with pathological morphological alterations have been found. As combinations with low EE doses and a sufficiently effective progestogen component do not differ from higher dosed oral contraceptives in their contraceptive safety and cycle control, there are no indications for pills containing 50 micrograms EE, except the normophasic sequential preparations for women with sustained irregular bleedings when taking low dose combinations.

Contraceptives, Oral, Hormonal↗
PubMed1989

Interaction with the pharmacokinetics of ethinylestradiol and progestogens contained in oral contraceptives.

The serum concentrations of ethinylestradiol (EE) during the first 4 h and 24 h after intake of an oral contraceptive containing 30 micrograms EE and 75 micrograms gestodene (EE/GSD) were compared to those after intake of a preparation containing the same EE dose and 150 micrograms desogestrel (EE/DG) in each of 11 women on days 1, 10, and 21 of their 1st, 3rd, 6th, and 12th cycles. There were great interindividual variations, but during treatment with EE/GSD the EE levels were higher and the EE peaks occurred by 30 min later than during treatment with EE/DG. The areas under the EE serum concentration-versus-time curves (AUC) between 0 and 4 h were higher by 37% (p less than 0.03) and between 0 and 24 h higher by 70% (p less than 0.002) during treatment with EE/GSD. During each treatment cycle, the EE levels rose between day 1 and 10. The serum levels of corticosteroid-binding globulin (CBG), which is known to be influenced only by the estrogenic component of the combination pill, increased significantly (p less than 0.01) during each treatment cycle. CBG was elevated on day 21 of the 6th and 12th cycle by 150 to 155% and by 120 to 130% with EE/GSD and EE/DG, respectively. The difference between the two drugs was significant (p less than 0.02). During the pill-free intervals of 7 days between the treatment cycles, the CBG levels decreased but were still elevated by 85% with EE/GSD and 50% with EE/DG at the beginning of the following cycle as compared to the control cycle. The serum levels of cortisol were also significantly more elevated (p less than 0.05) during treatment with EE/GSD as compared to EE/DG. Despite the same EE dose during treatment, the higher EE levels with EE/GSD as compared to EE/DG seem to be due to a retardation of the inactivation and elimination of EE caused by the progestogen component. The rise in the EE levels during each cycle seems to be due to a reduction in the oxidative metabolism by EE itself.

Adolescent↗
PubMed1988

Effect of two oral contraceptives containing 30 micrograms ethinylestradiol and 75 micrograms gestodene or 150 micrograms desogestrel upon various hormonal parameters.

The effect of two oral contraceptives containing 30 micrograms ethinylestradiol + 75 micrograms gestodene or 30 micrograms ethinylestradiol + 150 micrograms desogestrel upon various hormonal parameters were measured in 11 women each on days 1, 10, and 21 of the first, second, third, sixth, and twelfth treatment cycle and compared to the levels on days 1, 10, and 21 of the preceding control cycle. There was no significant difference in the clinical effects or in the influence on the serum hormone parameters between both formulations. A significant decrease in the serum concentrations of luteinizing hormone and follicle stimulating hormone was observed during each cycle which was dependent on the duration of intake. Contrary to this, prolactin was not significantly altered, but 6 out of the 22 women showed episodically elevated prolactin levels. Serum estradiol and progesterone were profoundly suppressed, except one woman who ovulated during the twelfth cycle probably due to a therapy with metamizol, trimethoprim and sulfamethoxazole. The concentrations of dehydroepiandrosterone-sulphate were significantly and time-dependently reduced by 20 to 25% during each treatment cycle. There was also a significant decrease in the serum levels of testosterone by 20 to 30% and of free testosterone by 40 to 60%, while sex hormone-binding globulin increased by 250 to 300%. It could be observed that during the pill-free interval of 7 days the pituitary and ovarian function recovered, while the sex hormone-binding globulin levels remained elevated by 100%.

Adolescent↗
PubMed1988

Alterations in the serum levels of gestodene and SHBG during 12 cycles of treatment with 30 micrograms ethinylestradiol and 75 micrograms gestodene.

The serum concentrations of gestodene have been measured radioimmunologically in 11 female volunteers on Day 1, 10, and 21 of the 1st, 3rd, 6th, and 12th cycle of treatment with an oral contraceptive containing 30 micrograms ethinylestradiol and 75 micrograms gestodene during the first 4 hours and 24 hours after intake. During the 1st cycle the maximal gestodene levels increased from 2.1 to 6.2 ng/ml on Day 1 to values between 7.5 and 22.0 ng/ml on Day 21. During the 3rd and 6th treatment cycle the levels were still higher with maxima between 10.1 and 26.3 ng/ml, while during the 12th cycle the gestodene concentrations were slightly lower. The serum levels of SHBG rose significantly during intake of the pill up to values between 210 and 240 nmol/l on Day 21 of each cycle, and were reduced to a certain degree during the pill-free interval. The SHBG concentrations correlated closely with the area under the gestodene concentration-versus-time curves (AUC) indicating a pronounced influence of serum protein binding upon the pharmacokinetics of gestodene. The gestodene levels of the individual women remained relatively constant during the 12 treatment cycles, although great interindividual differences were found. It is concluded that the relatively high serum concentrations of gestodene are not only based on the binding to SHBG, but probably also on an impeded metabolism of gestodene.

Adolescent↗
PubMed1988

Serum levels of 3-keto-desogestrel and SHBG during 12 cycles of treatment with 30 micrograms ethinylestradiol and 150 micrograms desogestrel.

The serum concentrations of 3-keto-desogestrel (KDG) have been determined radioimmunologically in 11 female volunteers on Day 1, 10, and 21 of the 1st, 3rd, 6th, and 12th cycle of treatment with 30 micrograms ethinylestradiol and 150 micrograms desogestrel during the first 4 hours and 24 hours after intake. On the first day of each cycle the KDG levels were low, but increased thereafter until Day 21. Highest serum concentrations were measured on Day 21 of the 3rd and 6th cycle with peak levels between 1.5 and 6.2 ng/ml. Contrary to this, the KDG levels were significantly reduced during the 12th treatment cycle. The serum concentrations of SHBG rose significantly between Day 1 and Day 21 of each cycle reaching values which were 3-fold of those at the beginning of treatment. During the pill-free intervals, SHBG levels decreased but remained elevated as compared to controls. There was a significant correlation between the SHBG levels and the area under the KDG-concentration-versus-time curves (AUC) indicating a pronounced influence of the serum steroid-binding protein upon the pharmacokinetics of KDG. There were great interindividual differences in the KDG levels. The serum levels of the individual woman remain, however, in a relatively constant range throughout the treatment period of 12 months, possibly due to genetic factors.

Adult↗
PubMed1988

[Prevention of atherosclerosis by estrogen substitution?].

Epidemiological, experimental and clinical data verify that the risk of cardiovascular diseases is increased by a long-term estrogen deficiency. This is, among other things, caused by alterations of lipid metabolism (e.g., rise in total cholesterol and LDL-cholesterol, decrease in HDL-cholesterol) due to the estrogen dificit which are involved in an accelerated development of atherosclerosis. If there is an estrogen deficiency, an elevated serum level of cholesterol or LDL-cholesterol can be reduced and the HDL-cholesterol level can be increased by an adequate estrogen replacement therapy, i.e., treatment with an estrogen and progestogen the type and dose of which are adjusted to the clinical picture. When the present knowledge about the physiological and pathological pathways is weighed and the epidemiological data are critically valued - whereby the extent and duration of the stage of estrogen deficit has to be regarded as an important criterion -, it can be assumed that an estrogen therapy prevents a premature atherosclerosis and coronary heart disease provided that they are related to an estrogen deficiency. The differences in the degree of estrogen deficit and the symptoms as well as in the pharmacological and pharmacodynamic peculiarities if the individual women render it necessary to adjust individually the estrogen therapy, to avoid overdosing and to pay attention to risk factors. Therefore, an undifferentiated treatment with estrogens (e.g. estrogen for every woman) does not appear to be appropriate.

Arteriosclerosis↗
PubMed1988

Investigations upon the mechanism of inhibition of spermatogenesis in the rat by a dimeric ethynodiol-testosterone ester.

The combination of androgens and progestogens has been shown to be a suitable male contraceptive. Previous experiments revealed that injection of a dimeric testosterone-ethynodiol ester into rats and monkeys induces azoospermia for several weeks. In order to investigate the mechanism of action, we compared the endocrine effects of a single injection of 10 mg of the dimeric ester into intact male rats with that of 6 mg of norethisterone enanthate + 6 mg of testosterone enanthate. After the injection of the dimer there was a transitory reduction of serum FSH and a strong suppression of serum LH and testosterone, of testicular testosterone and of androgen-binding protein (ABP) in the testis and epididymis for at least 8 weeks, whereas spermatogenesis was totally depressed between the 4th and 8th week. Contrary to this, the enanthates caused only a slight suppression of spermatogenesis, although serum LH, testicular testosterone and ABP were profoundly reduced. The only conspicuous difference in the endocrine pattern of both groups during the first 4 weeks was in the serum testosterone level which remained normal in the rats treated with the enanthates. The results suggest that testicular testosterone and ABP concentrations are of minor significance for an intact spermatogenesis, and that some other factors produced by Sertoli cells might be involved and possibly maintained by normal serum testosterone levels.

Androgen-Binding Protein↗
PubMed1988

[Effect of 2 low-dosage Gestodene or desogestrel containing ovulation inhibitors on sex hormones and lipid metabolism].

In a randomised study on 20 healthy female subjects we compared the effect of two low-dosage antiovulants containing gestodene or desogestrel on ovarial and adrenal function and on fatty metabolism. Both antiovulants produced a moderate inhibition of gonadotropin secretion and a marked suppression of serum levels of oestradiol, testosterone and free testosterone; there was a strong increase in sex hormone-binding globulin, and an increase in cortisol--probably due to the increase on corticosteroid-binding globulin--and a continuous drop in dehydroepiandrosterone S. In all cases there was no significant difference between the effect of both preparations. Whereas there was no change in total and LDL cholesterol, total phospholipids and VLDL triglycerides, there was a significant increase in the concentrations of apolipoprotein B, total triglycerides, the cholesterol and phospholipid properties of VLDL as well as of all components of HDL. The LDL triglycerides were also elevated, whereas the LDL phospholipids dropped. On the whole the changes in lipid metabolism, which indicate a certain predominance of the oestrogen effect, were low. However, it became that the duration of intake exercises considerable influence.

Adolescent↗
PubMed1987

[Progestagens in contraception].

The different spectrum of biological actions of the various synthetic progestogens is compared on the basis of their chemical structure, pharmacokinetics and interaction with the multiple receptors. In detail, the mechanism of action of the progesterone derivatives (medroxyprogesterone acetate, chlormadinone acetate and cyproterone acetate), the norethisterone-related (norethisterone, ethynodiol diacetate, lynestrenol and norethynodrel) and the norgestrel-related progestogens (levonorgestrel, desogestrel, gestodene and norgestimate), and a possible influence of some metabolites upon the biological profile are discussed. With regard to the progestogenic activity, the time-course of the serum concentrations of the steroids after the application (pharmacokinetics) which is dependent upon absorption, metabolization in the gastro-intestinal tract and liver (first-pass effect), distribution and storage in fat and other tissues, binding to serum proteins, inactivation, and conjugation, is of particular importance. The various side-effects of the progestogens are mainly based on their influence upon hepatic metabolism (lipids, lipoproteins, serum proteins) and upon other organs which is dependent on their different estrogenic, antiestrogenic, androgenic, antiandrogenic, glucocorticoid and antimineralocorticoid actions.

Contraceptives, Oral, Synthetic↗
PubMed1987

Divergent effects of two low-dose oral contraceptives on sex hormone-binding globulin and free testosterone.

The effect of a triphasic combination of ethinyl estradiol and levonorgestrel on the serum concentrations of total testosterone, free testosterone, and sex hormone-binding globulin as measured directly by radioimmunoassay and on the binding capacity of sex hormone-binding globulin was compared with that of a preparation containing ethinyl estradiol and desogestrel. Blood samples were taken on days 6, 11, 21, and 28 of a control cycle, the third cycle of treatment with either ethinyl estradiol-levonorgestrel or ethinyl estradiol-desogestrel (11 volunteers each), the third cycle of a 3-month washout period, and the third treatment cycle after crossover change of the preparations. There was a significant reduction in total testosterone by 16% during treatment with both preparations. Ethinyl estradiol-desogestrel increased the concentration (+175%) and binding capacity (+330%) of sex hormone-binding globulin to a much greater extent than with ethinyl estradiol-levonorgestrel (+92% and +160%). Contrary to this, a significant suppression of non-protein-bound testosterone by 35% was found during treatment with both oral contraceptives. The results demonstrate that an excessive elevation of the levels of sex hormone-binding globulin above the normal range does not cause a corresponding suppression of free testosterone. It is assumed that the decrease in the apparent binding affinity of high sex hormone-binding globulin concentrations to testosterone may be due to protein-protein interactions.

Adult↗