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Postmenopausal estrogen therapy: which route to take?

Nature Reviews Endocrinology volume 5, pages 146–147 (2009)Cite this article

The efficacy and safety of therapy with oral estrogen and nonoral estrogen formulations (i.e. transdermal patches, percutaneous gel or lotion, and intravaginal gel, tablet or ring), which are widely used to treat menopausal symptoms, have been compared in previous reviews.1,2 In some areas, the optimum administration route for estrogen is still to be clarified, in particular when it is used in combination with progesterone or progestogen. Here, I will focus on the main differences in pharmacological effects of oral versus nonoral estradiol therapies. Most studies on nonoral estrogen therapy have used transdermal patches or percutaneous gel, and it is assumed that other nonoral forms would have similar effects.

Oral administration of estrogen requires higher doses than transdermal therapy. This difference occurs mainly because estrogen undergoes first-pass metabolism in the liver (known as the first-pass effect) that induces a variety of metabolic effects. Metabolism of orally administered estrogen also depends on the coadministration of other substances that might enhance its bioavailability, such as alcohol, grapefruit, hypnotic agents and cimetidine, or reduce it, such as smoking, antibiotics and antiepileptic drugs. A further consequence of oral estrogen administration is the extensive accumulation of estrone and other metabolites in the liver and systemic circulation.3 In my opinion, this phenomenon is overlooked all too often, even though it might account for substantial estrogenicity, including both beneficial effects (reduced dose requirements), and adverse events.3,4,5,6,7,8,9,10

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  1. 1850 M Street NW, Suite 450, Washington, DC 20036, USA jsimon@jamesasimonmd.com

Authors and Affiliations

  1. JA Simon is Clinical Professor at George Washington University School of Medicine and Medical Director of Women's Health & Research Consultants, Washington, DC, USA.,

    James A Simon

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Competing interests

The author declared associations with the following companies:

Consultant/advisory board member: Allergan, Alliance for Better Bone Health, Ascend, Barr, Bayer, BioSante, Concert Pharmaceuticals, Corcept Therapeutics Inc., Depomed Inc., GlaxoSmithKline, KV, Meditrina, Merck, Merrion, Nanma/Tripharma/Trinity, Novo Nordisk, Novogyne, Pear Tree, QuatRx, Roche, Sciele, Solvay, Ther-Rx, Warner Chilcott, Wyeth;

Grant/research support: BioSante, Boehringer Ingelheim, FemmePharma, GlaxoSmithKline, Nanma/Tripharma/Trinity, Novartis, Procter and Gamble;

Speakers' bureau: Ascend, Barr, Bayer, GlaxoSmithKline, KV, Merck, Novartis, Novogyne, Sciele, Ther-Rx, Warner Chilcott, Wyeth.

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Simon, J. Postmenopausal estrogen therapy: which route to take?. Nat Rev Endocrinol 5, 146–147 (2009). https://doi.org/10.1038/ncpendmet1073

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