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Sex Differences in Drug Effects: Interaction with Sex Hormones in Adult Life

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Sex and Gender Differences in Pharmacology

Part of the book series: Handbook of Experimental Pharmacology ((HEP,volume 214))

Abstract

In recent years, it has become clear that women and men may differ for drug response. Also, there is an increasing recognition on the role of sex hormones on pharmacokinetics and pharmacodynamics as mechanism accounting for sex differences in drug effects.

In women, the phases of menstrual cycle, of reproductive life and fluctuations in the concentrations of sexual steroids on pharmacokinetics and pharmacodynamics must be considered. Furthermore, the use of oral contraceptives or hormonal replacement therapy, the sex hormone-related changes in total body water or in the amount of fat influence the overall effect of drugs.

On the contrary, the influence of androgens on drug effects is minimal because of the even plasma levels of these hormones in adult males.

Nevertheless, since women have been scarcely included in the early phases of clinical trials, the results obtained in men have been often translated to women and their exact response to drugs is still not well known.

The available evidence suggests that sex hormones influence drug absorption, distribution, metabolism, pharmacodynamics, and adverse effects. For instance, many cardiovascular drugs are metabolized by enzymes of the cytochrome P450 mono-oxygenases system, which is more expressed in females than in males, showing sex differences in drug response.

Upcoming pharmacological research should aim to further clarify the influence of sex hormones on drug effects and, for this purpose, to increase the number of women enrolled in all phases of clinical trials. An evidence-based pharmacotherapy in women is therefore auspicable for women’s health.

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Abbreviations

ACE:

Angiotensin-converting enzyme

CYP:

Cytochrome P450 mono-oxygenases

RAS:

Renin-angiotensin system

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Acknowledgments

Supported by a grant of the Italian Ministry of Health—Ministero della Salute, Ricerca Corrente 2011.

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Authors and Affiliations

  1. Department of Medical Sciences, Centre for Clinical and Basic Research, IRCCS San Raffaele Pisana, via della Pisana, 235, 00163, Rome, Italy

    Ilaria Spoletini PhD, Cristiana Vitale MD, PhD & Giuseppe M C Rosano MD, FESC, FACC

  2. Department of Therapeutic Research and Medicine Evaluation, National Institute of Health, Rome, Italy

    Walter Malorni PhD

  3. Centre for Clinical Research San Raffaele Sulmona, Sulmona, Italy

    Giuseppe M C Rosano MD, FESC, FACC

Authors
  1. Ilaria Spoletini PhD
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  2. Cristiana Vitale MD, PhD
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  3. Walter Malorni PhD
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  4. Giuseppe M C Rosano MD, FESC, FACC
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Corresponding author

Correspondence to Giuseppe M C Rosano MD, FESC, FACC .

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Editors and Affiliations

  1. Institute of Gender in Medicine (GiM), Center for Cardiovascular Research (CCR), Charité - Universitätsmedizin Berlin, Hessische Str. 3-4, Berlin, 10115, Germany

    Vera Regitz-Zagrosek

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Spoletini, I., Vitale, C., Malorni, W., Rosano, G.M.C. (2013). Sex Differences in Drug Effects: Interaction with Sex Hormones in Adult Life. In: Regitz-Zagrosek, V. (eds) Sex and Gender Differences in Pharmacology. Handbook of Experimental Pharmacology, vol 214. Springer, Berlin, Heidelberg. https://doi.org/10.1007/978-3-642-30726-3_5

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