Medication: how gender can influence efficacy

Gender and age can affect how quickly the body breaks down medication and therefore the length of time for which it is effective and the intensity of its effect. With most forms of medication, this is not a problem: the approved dosages have been selected to offer sufficient efficacy for the majority of all patient groups. In the case of a few forms of medication, however, gender differences apply – with regard to both the efficacy of medication and its side-effects. 

In the past, the differences between men and women were not considered when developing medicinal products: Medication was primarily tested on young men so as to protect women of child-bearing age and unborn children. Often, medication was only noticed to affect women differently to men if they regularly complained about side-effects.

To ensure that medication is equally safe and effective for both men and women, precise legal regulations now exist on gender diversity in clinical trials. According to pharmaceutical associations, women account for between 30 and 80 percent of participants in phases II and III of clinical trials in Germany. However, data analyses of major international trials show that, even in recent times, women are still underrepresented in many important trials on cardiovascular medication. In addition, no research has been conducted into the gender-specific effects of many forms of medication that were approved a long time ago. As such, these have not yet been sufficiently investigated so women may receive too high or too low a dosage. It is also possible for gender-specific side-effects to be missed in trials if not enough representatives of both genders are involved.

Men and women’s bodies not only differ in size and weight but also in the amount of fat, muscle and bone mass. This influences the distribution of medication in the body: Women are generally smaller and lighter. If men and women take the same amount of a medicine, women often receive a higher dose compared to their bodyweight. In some cases, a high dose can have more severe side-effects. The fact that women have a higher body fat content and lower muscle mass leads to fat-soluble medication being stored in the fatty tissue and therefore remaining in women’s bodies for longer than it does in men’s.

Other gender-specific factors also affect the way the body distributes, converts and excretes medication. For example: 

• Different hormonal and enzymatic activities: for example, the higher pH level in women’s stomachs combined with their gender hormones can influence the solubility of medication in the stomach.
• Differences in the metabolization in the stomach, intestines and liver: in women, it takes longer for a tablet to pass through the stomach into the intestines and for the active ingredients to be broken down by the liver. Beta blockers for lowering blood pressure are therefore often administered to women in a lower dosage, for example. 
• Differences in excretion by the kidneys: men’s kidneys excrete medication quicker then women’s.

Even if trials determine that the concentration and length of time for which medication remains in the body differ for men and women, this does not necessarily impact its efficacy. After all, major differences also exist between people of the same gender, which cause their body to process medication in different ways. When developing medication, attention is therefore paid to finding a dosage that is suitable for as many patient groups as possible. As a result, the application areas and recommended dosages of most medicinal products are the same for both men and women.

There are, however, a few types of medication where gender-related differences in the efficacy have been found, so men and women have to receive different dosages. These include the following:

Painkillers

• Certain opiates such as morphine have a stronger effect on women and a higher risk of side-effects.
• Ibuprofen probably has a stronger effect on men.

Beta blockers

• The blood-pressure-lowering medication metoprolol has a stronger effect and a higher risk of side-effects in women.

Medication for treating depression

• The antidepressants fluvoxamine and sertraline have a stronger effect on women.

Anticoagulants 

• Women are at higher risk of bleeding when taking clopidogrel or heparin.
• If acetylsalicylic acids (ASA) are taken as anticoagulants, they have a weaker effect with regard to the prevention of coronary heart disease (CHD) in women who have not yet gone through the menopause and do not use hormonal contraception.

Other medication

• Romosozumab for treating osteoporosis often causes severe side-effects for men and is therefore only approved for (post-menopausal) women.
• Zolpidem for treating sleep disorders is broken down far more slowly by women’s bodies than by men’s and its effect therefore lasts longer.

If doctors are aware of gender-specific differences in relation to medication, they will adjust the dosage accordingly. In some cases, the package insert also provides information about what men and women should note when taking the medication. Any patients particularly affected by side-effects should always contact their doctor. The dosage can then be adjusted upon medical recommendation.

To prevent potential negative effects on their fertility and the development of unborn children, women of child-bearing age were previously excluded from clinical trials. Even today, this is still the case in the early phase of medicinal product development: If healthy people are to test the behavior of a new active ingredient in the body, in most cases only men are recruited. Often, the reason given for this is that men are not subject to the same level of hormonal fluctuations as women and do not take hormonal contraception that could influence the efficacy of the medication. Women therefore account for 10 to 40 percent of participants in phase I trials. The proportion of women in later phases is higher.

An EU directive entered into force in 2022 that stipulates that all human subjects involved in clinical trials must be representative of the population groups that will use the medicinal product subject to the trial. For example, if the illness that the active ingredient is intended to treat affects 70 percent of men, 70 percent of the subjects involved in the trial should be male. It is therefore not about a 50-50 split as with other gender ratios. Instead, the split should be based on the actual gender distribution of the medical conditions.