Binding of Levonorgestrel, Norethisterone and Desogestrel to Human Sex Hormone Binding Globulin and Influence on Free Testosterone Levels

Nilsson, B.; Schoultz, Bo von

doi:10.1159/000293644

Cited by 16 publications

(7 citation statements)

References 16 publications

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“…As a result, desogestrel in combination with oestrogens may enhance the oestrogenic potency resulting in a favourable effect on the lipid metabolism. The progestagen‐only preparations caused changes opposite to those of combined oral contraceptives, may be through the fact that desogestrel and levonorgestrel alone lower SHBG levels [30] resulting in higher levels of free testosterone [31, 32]. This will be even more pronounced for levonorgestrel‐only, because of its higher binding affinity to SHBG.…”

Section: Discussionmentioning

confidence: 99%

Effect of second and third generation oral contraceptives on lipid metabolism in the absence or presence of the factor V Leiden mutation

Kemmeren

Algra

Grobbee

2001

Journal of Internal Medicine

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Abstract. Kemmeren JM, Algra A, Grobbee DE (University Medical Center Utrecht, Utrecht, The Netherlands). Effect of second and third generation oral contraceptives on lipid metabolism in the absence or presence of the factor V Leiden mutation. J Intern Med 2001; 250: 441±448.Objectives. The effect of a second and third generation oral contraceptive and of the progestagens used in these pills on lipid metabolism was studied in the absence or presence of the factor V Leiden mutation. Design. A single centre, double blind randomized trial. Setting. University Medical Centre. Subjects. A total of 51 women without and 35 women with the factor V Leiden mutation. Interventions. A second generation (30 lg ethinylestradiol/150 lg levonorgestrel) or a third generation (30 lg ethinylestradiol/150 lg desogestrel) oral contraceptive. After two cycles of use and a wash-out period of two cycles, the participants received the corresponding progestagen-only preparation containing 150 lg levonorgestrel or 150 lg desogestrel. Main outcome measures. Mean difference in changes between the treatment groups on total cholesterol, HDL, LDL, triglycerides and total/HDL cholesterol ratio.Results. Compared with levonorgestrel, desogestrelcontaining oral contraceptives caused in women without the factor V Leiden mutation signi®cant changes in HDL (0.43; 95% con®dence interval [CI] 0.25±0.61), LDL (±0.55; 95% CI ±0.90 to ±0.20), triglycerides (0.19; 95% CI 0.06±0.32) and total/ HDL cholesterol ratio (±0.87; 95% CI ±1.21 to ±0.53). When the progestagen-only preparations were used, differential changes were found for HDL (0.16; 95% CI 0.03±0.29), LDL (±0.31; 95% CI ± 0.56 to ±0.05) and total/HDL cholesterol ratio ()0.55; 95% CI ±0.84 to ±0.26). Desogestrel-only caused changes opposite to those of desogestrelcontaining oral contraceptives. For cholesterol and triglycerides, this effect was also found for levonorgestrel-only in comparison with levonorgestrelcombined oral contraceptives. Levonorgestrel appeared to induce the effect on HDL. Almost all results were similar for women with the factor V Leiden mutation. Conclusion. It appears that desogestrel counteracts the effects of oestrogens to a lesser extent than levonorgestrel. Desogestrel-containing oral contraceptives have therefore a more favourable in¯uence on cholesterol metabolism in comparison with levonorgestrel-containing oral contraceptives.

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Section: Discussionmentioning

confidence: 99%

Effect of second and third generation oral contraceptives on lipid metabolism in the absence or presence of the factor V Leiden mutation

Kemmeren

Algra

Grobbee

2001

Journal of Internal Medicine

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“…We calculated non-SHBG-bound LNG concentration using Södergard' method [14] based on the law of mass action with the SHBG and albumin binding affinities given by Nilsson [15]. Non-SHBG-bound LNG concentration is a multiple of calculated free LNG concentration [14].…”

Section: Methodsmentioning

confidence: 99%

Estimating systemic exposure to levonorgestrel from an oral contraceptive

et al. 2017

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Objective The gold standard for measuring oral contraceptive (OC) pharmacokinetics is the 24-hour steady-state area-under-the-curve (AUC). We conducted this study to assess whether limited sampling at steady state or measurements following use of one or two OCs could provide an adequate proxy in epidemiological studies for the progestin 24-hour steady-state AUC of a particular OC. Study Design We conducted a 13-sample, 24-hour pharmacokinetic study on both day 1 and day 21 of the first cycle of a monophasic OC containing 30 μg ethinyl estradiol and 150 μg levonorgestrel (LNG) in 17 normal-weight healthy white women, and a single-dose 9-sample study of the same OC after a one-month washout. We compared the 13-sample steady-state results with several steady-state and single-dose results calculated using parsimonious sampling schemes. Results The 13-sample steady-state 24-hour LNG AUC was highly correlated with the steady-state 24-hour trough value (r = 0.95; 95% CI [0.85, 0.98]) and with the steady-state 6, 8, 12 and 16-hour values (0.92 ≤ r ≤ 0.95). The trough values after one or two doses were moderately correlated with the steady-state 24-hour AUC value (r = 0.70; 95% CI [0.27, 0.90] and 0.77; 95% CI [0.40, 0.92], respectively). Conclusions Single time-point concentrations at steady-state and after administration of one or two OCs gave highly to moderately correlated estimates of steady-state LNG AUC. Using such measures could facilitate prospective pharmaco-epidemiologic studies of the OC and its side effects.

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“…Both substances do not bind to the estrogen receptor in a measurable amount (Bergink et al, 1983;Hoppen and Hammann, 1987). It must be considered that gestagens can bind to SHBG and displace testosterone, and can decrease levels of SHBG, thus increasing free testosterone levels (Nilsson and von Schoultz, 1989;Van der Vange et al, 1990;Raudaskoski et al, 1998).…”

Section: Discussionmentioning

confidence: 99%

Contraceptive Steroids Influence the Hemostatic Activation State in Healthy Men

ZITZMANN,

JUNKER,

KAMISCHKE

et al. 2002

Journal of Andrology

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Hormonal contraception for men requires administration of testosterone and gestagens. The effects of a long‐acting testosterone ester and 2 different progestins on hemostatic activation parameters were studied in relation to cardiovascular risk. In phase 1, 7 healthy men aged 28–38 years received a single intramuscular injection of 200 mg norethisterone‐enanthate (NET‐EN) on Day 0. Plasma samples were obtained on Days 0, 14, 41, and 84. In phase 2, 3 groups of 14 healthy men aged 18–45 years received four injections (every 6 weeks) of 1000 mg testosterone undecanoate (TU), plus daily oral placebo or daily oral levonorgestrel (LNG, 250 μg); or four injections (every 6 weeks) of NET‐EN. Treatment lasted 24 weeks. Plasma samples were obtained at weeks 0, 16, 24, and 52. All samples were assayed for levels of coagulation factors VIIc, VIIa, XIIc, and XIIa; prothrombin fragment F1+2 (F1+2); antithrombin; plasmin‐α2‐anti‐plasmin‐complex (PAP); and fibrinogen. NET‐EN alone led to a depletion of sexual hormones and a marked shift in hemostatic parameters with increasing levels of FXIIc, fibrinogen, antithrombin, and F1+2, whereas FVIIc and FVIIa levels decreased. PAP levels increased significantly. Opposite effects were seen in the TU/placebo group, with a significant down‐regulation of fibrinolysis and the hemostatic turnover rate. Testosterone effects were attenuated by additional administration of gestagens. The effect of hormonal male contraception using long‐acting testosterone esters with or without gestagens was significantly measurable within the hemostatic system. Down‐regulation of the hemostatic system with testosterone alone may indicate an antithrombotic effect, whereas clinical consequences of an additional gestagen compound cannot be derived.

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Binding of Levonorgestrel, Norethisterone and Desogestrel to Human Sex Hormone Binding Globulin and Influence on Free Testosterone Levels

Cited by 16 publications

References 16 publications

Effect of second and third generation oral contraceptives on lipid metabolism in the absence or presence of the factor V Leiden mutation

Effect of second and third generation oral contraceptives on lipid metabolism in the absence or presence of the factor V Leiden mutation

Estimating systemic exposure to levonorgestrel from an oral contraceptive

Contraceptive Steroids Influence the Hemostatic Activation State in Healthy Men

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