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

  • Ilaria Spoletini
  • Cristiana Vitale
  • Walter Malorni
  • Giuseppe M C Rosano
Part of the Handbook of Experimental Pharmacology book series (HEP, volume 214)


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.


Pharmacokinetics Pharmacodynamics Sex Progesterone Estrogen Testosterone Drug adverse effects 



Angiotensin-converting enzyme


Cytochrome P450 mono-oxygenases


Renin-angiotensin system



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


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Copyright information

© Springer-Verlag Berlin Heidelberg 2013

Authors and Affiliations

  • Ilaria Spoletini
    • 1
  • Cristiana Vitale
    • 1
  • Walter Malorni
    • 2
  • Giuseppe M C Rosano
    • 1
    • 3
  1. 1.Department of Medical Sciences, Centre for Clinical and Basic ResearchIRCCS San Raffaele PisanaRomeItaly
  2. 2.Department of Therapeutic Research and Medicine EvaluationNational Institute of HealthRomeItaly
  3. 3.Centre for Clinical Research San Raffaele SulmonaSulmonaItaly

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