By: Alfred O. Mueck* and Harald Seeger

Read the whole article here

Abstract: Many women receiving hormone replacement therapy (HRT) smoke; in the Women’s Health Initiative (WHI),
one of the largest interventional studies on HRT to date and which recently had to be discontinued, 50% of the 8,500
women on HRT had smoked before or continued to smoke during the study. Remarkably, there is little knowledge about
the impact smoking has on the efficacy and side effects of HRT. However, it has been proven that, depending on the type,
duration and intensity of nicotine consumption, smoking can reduce or completely cancel the efficacy of orally
administered estrogens. Not only does smoking diminish the otherwise well-established beneficial effects of estrogen on
hot flashes and urogenital symptoms and its positive effects on lipid metabolism, i.e. by reducing cholesterol, but smoking
also specifically reduces estrogen’s ability to prevent osteoporosis.
The reduction or loss of therapeutic efficacy is mainly caused by dose-dependent elevated hepatic clearance, partially in
conjunction with lower estrogen levels, and has been demonstrated only with oral estrogen applications. This failure of
therapeutic action should not be compensated for by increasing the dose in smokers as this might result in the production
of toxic, even potentially mutagenic estrogen metabolites – compounds recently associated with a higher risk of breast
cancer. The favorable effects of estrogens are not lost in smokers when they are applied transdermally. This route enables
low dosage and also avoids the formation of unphysiological metabolites by bypassing the liver. Women who continue to
smoke despite all warnings should therefore only be treated via the transdermal route.
Oral contraceptives, but not HRT, are contraindicated in elderly smokers. However, the principal conclusion of the WHI
study was that the lowest dose possible should be chosen, especially in patients with an increased cardiovascular risk, as is
the case in smokers.