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Oral contraceptive steroids —pharmacological issues of interest to the prescribing physician

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Advances in Contraception

Abstract

Oral contraceptive steroids (OCS) are well absorbed from the gastrointestinal tract in humans. However, while the progestogens are almost completely bioavailable, ethinylestradiol (EE2) is subject to extensive first pass metabolism consisting chiefly of conjugation with sulfate in the gut wall. Both EE2 and progestogens are well absorbed in patients with an ileostomy or with diseases such as cystic fibrosis or Crohn's disease. However in patients with celiac disease (gluten-sensitive enteropathy) the gut wall is less able to conjugate EE2 and thus its bioavailability is increased. The bioavailability returns to control values as the disease is improved following gluten withdrawal. Other drugs that are conjugated with sulfate, such as vitamin C and paracetamol, compete for available sulfate when coadministered with OCS leading to high plasma levels of EE2.

Enzyme-inducing agents such as rifampicin, phenobarbitone, phenytoin and carbamazepine reduce blood levels of the OCS leading to contraceptive failure. In the case of anticonvulsants (but not rifampicin) this can be easily overcome by increasing the dose of OCS used. Broad-spectrum antibiotics are reported to cause failure of contraception by interfering with the enterohepatic circulation of EE2 but limited systematic studies show no evidence of such an interaction. Nevertheless practitioners are advised to recommend the use of alternative contraceptive precautions for women receiving broad-spectrum antibiotics concurrently with their OCS preparation.

Resumé

Les contraceptifs oraux stéroïdes (OCS) sont bien absorbés par l'appareil gastro-intestinal humain. Toutefois, si les progestogènes sont presque entièrement biodisponibles, l'éthinyl oestradiol (EE2) doit passer par un premier métabolisme important qui consiste essentiellement en une conjugaison au sulfate dans la paroi de l'intestin. Aussi bien le EE2 que les progestogènes sont bien absorbés chez des patientes ayant une iléostomie ou souffrant de maladies telles que la fibrose kystique ou la maladie de Crohn. Cependant, chez les patientes souffrant de maladie coeliaque (entéropathie d'intolérance au gluten), la paroi intestinale est moins à même de conjuguer l'EE2, de sorte que la biodisponibilité est accrue. La biodisponibilité reprend des valeurs normales lorsque le gluten est éliminé. D'autres substances qui se conjuguent avec le sulfate, telles que la vitamine C et le paracétamol se font concurrence pour le sulfate disponible lorsqu'elles sont administrées en même temps que les OCS, entraînant des niveaux plasmatiques élevés de EE2.

Les agents inducteurs d'enzymes, tels que la rifampicine, le phénobarbital, la phénytoïne et la carbamazépine, réduisent les niveaux sanguins des OCS, entraînant l'échec du contraceptif. Dans le cas des anticonvulsifs (mais non de la rifampicine) ce phénomène peut facilement être surmonté en augmentant la dose de OCS administrée. On a rapporté que les antibiotiques à large spectre provoquent l'échec de la contraception du fait qu'ils compromettent la circulation entéro-hépatique du EE2, mais certaines études systématiques limitées n'ont pas fait ressortir cette interaction. Néanmoins, il est conseillé aux praticiens de recommander d'autres précautions anticonceptionnelles aux femmes qui reϑoivent, en même temps qu'un contraceptif oral stéroïde, un traitement aux antibiotiques à large spectre.

Resumen

Los anticonceptivos orales esteroides (AOE) son bien absorbidos por el aparato gastrointestinal humano. No obstante, si bien los progestágenos son casi totalmente biodisponibles, el etinilestradiol (EE2) debe pasar por un primer metabolismo importante que consiste esencialmente en una conjugación con sulfato en la pared intestinal. Tanto el EE2 como los progestágenos son bien absorbidos en las pacientes con una ileostomía o afectadas de enfermedades como fibrosis quística o la enfermedad de Crohn. Sin embargo, en pacientes con enfermedad celíaca (enteropatía de intolerancia al gluten), la pared intestinal en menos capaz de conjugar el EE2, de modo que la biodisponibilidad aumenta. La biodisponibilidad retoma valores normales cuando el gluten es eliminado. Otras sustancias que se conjugan con el sulfato, como la vitamina C y el paracetamol, compiten por el sulfato disponible cuando son administradas al mismo tiempo que los AOE, ocasionando niveles plasmáticos elevados de EE2.

Los agentes inductores de enzimas, como la rifampicina, el fenobarbital, la fenitoína y la carbamazepina, reducen los niveles sanguíneos de los AOE, provocando el fracaso de los anticonceptivos. En el caso de los anticonvulsivos (pero no de la rifampicina), este fenómeno puede ser fácilmente superado al aumentarse la dosis de AOE utilizada. Se ha informado de que los antibióticos de amplio espectro provocan el fracaso de la anticoncepción porque interfieren con la circulación entero-hepática del EE2, pero algunos estudios sistemáticos limitados no indican tal interacción. Sin embargo, se aconseja a los practicantes recomendar otras precauciones anticonceptivas a las mujeres que reciben antibióticos de amplio espectro juntamente con AOE.

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Orme, M., Back, D.J. Oral contraceptive steroids —pharmacological issues of interest to the prescribing physician. Adv Contracept 7, 325–331 (1991). https://doi.org/10.1007/BF02340178

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