In vivo conversion of norethisterone and norethisterone acetate to ethinyl etradiol in postmenopausal women

Kuhnz, W.; Heuner, Almut; Hümpel, M.; Seifert, Wilfried; Michaelis, K.

doi:10.1016/s0010-7824(97)00174-1

Cited by 91 publications

(39 citation statements)

References 18 publications

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“…The methods were described in detail previously (22,23). In brief, the plasma samples for the estimation of ethinyl estradiol were extracted from acidified plasma into toluene and, after two further clean-up steps, back-extracted into dichloromethane.…”

Section: Analytic Methodsmentioning

confidence: 99%

Levetiracetam Does Not Alter the Pharmacokinetics of an Oral Contraceptive in Healthy Women

Ragueneau‐Majlessi

Levy

Janik³

2002

Epilepsia

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Summary:Purpose: This study was designed to evaluate whether levetiracetam, a novel antiepileptic drug (AED), influences the pharmacokinetics of steroid oral contraceptives.Methods: During a run-in phase, 18 healthy female patients received an oral contraceptive containing ethinyl estradiol, 0.03 mg, and levonorgestrel, 0.15 mg, for the first 21 days of two consecutive menstrual cycles. In a subsequent double-blind, randomized, two-way crossover treatment phase, subjects received either levetiracetam, 500 mg, or placebo twice daily concomitant with the oral contraceptive. Plasma concentrations of ethinyl estradiol and levonorgestrel were measured on days 14 and 15 of the two treatment periods for the evaluation of the 24-h kinetic parameters, and an additional sample was collected on day 21 to determine the trough plasma concentrations. Serum progesterone and luteinizing hormone (LH) levels were determined on days 13, 14, 15, and 21 of each cycle of the treatment phase.Results: The plasma concentration-time curves and pharmacokinetic parameters of ethinyl estradiol and levonorgestrel were not statistically different during concomitant treatment with either levetiracetam or placebo. The ratios of the logtransformed geometric mean areas under the plasma concentration-time curves (AUCs), maximal (C max ) and minimal (C min ) plasma concentrations, and trough concentrations on day 21 (C 21 ) ranged from 99.12 to 99.96% for ethinyl estradiol and from 97.13 to 99.41% for levonorgestrel. The 90% confidence intervals of these ratios were well within the 80 to 125% acceptance range for lack of interaction. Serum progesterone and LH concentrations were fairly constant during the run-in and treatment phases and remained markedly below their respective physiologic levels. Safety and menstrual-bleeding patterns were comparable during levetiracetam and placebo administration.Conclusions: Levetiracetam does not affect the pharmacokinetics of an oral contraceptive containing ethinyl estradiol and levonorgestrel, and on the basis of serum progesterone and LH levels, it does not affect the contraceptive efficacy.

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Section: Analytic Methodsmentioning

confidence: 99%

Levetiracetam Does Not Alter the Pharmacokinetics of an Oral Contraceptive in Healthy Women

Ragueneau‐Majlessi

Levy

Janik³

2002

Epilepsia

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“…In one study the use of norethisterone acetate was accompanied with a higher risk after 5 years of use (2.03, 1.88-2.18) than that of medroxyprogesterone acetate (1.64, 1.49-1.79) (Lyytinen et al, 2009). It is known that NET can be converted in vivo into ethinylestradiol (Kuhnz et al, 1997). In as far this conversion may influence the observed NET effect is currently unknown and is under investigation.…”

Section: Discussionmentioning

confidence: 99%

Progestogens and Breast Cancer Risk – In Vitro Investigations with Human Benign and Malignant Epithelial Breast Cells

Mueck¹,

Seeger²,

Neubauer³

2011

Breast Cancer - Recent Advances in Biology, Imaging and Therapeutics

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“…However, (NETA) can be aromatised to ethinylestradiol [ 27 ]. Kuhnz et al [ 28 ] reported that this conversion resulted in a dose that was equivalent to taking 4-6 μg of ethinyl estradiol for each 1 mg of NETA ingested. The conversion ratio of NETA to EE has been subsequently estimated to be between 0.2 and 0.33 % for different doses [ 29 ], Chu et al [ 30 ] concluded that a daily dose of 10-20 mg NETA equates to taking a 20-30 μg ethinyl estradiol COC, Conversion to estrogen and the estrogenic effects are of no relevance when these progestogens are taken in low-dose progestogen-only, or combined oral contraceptive pills [ 31 ] but probably explains why high-dose norethisterone and its ester are effective at delaying and regulating menstrual bleeding.…”

Section: Adolescent Aubmentioning

confidence: 99%

Abnormal Uterine Bleeding

Shavit¹,

Rabinovici²,

Carp³

2015

Progestogens in Obstetrics and Gynecology

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In vivo conversion of norethisterone and norethisterone acetate to ethinyl etradiol in postmenopausal women

Cited by 91 publications

References 18 publications

Levetiracetam Does Not Alter the Pharmacokinetics of an Oral Contraceptive in Healthy Women

Levetiracetam Does Not Alter the Pharmacokinetics of an Oral Contraceptive in Healthy Women

Progestogens and Breast Cancer Risk – In Vitro Investigations with Human Benign and Malignant Epithelial Breast Cells

Abnormal Uterine Bleeding

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