Professor Franconi, can we say that the years do not pass in the same way for men and women?

“Aging is a biological phenomenon that occurs quite differently between the sexes due to their different physiology. We have known for some time that on average, women live longer than men, so they age longer (suffice it to say. over 90 years of age men are 25 out of 100 while women are 75 out of 100) and have to cope with a poorer quality of life because of the diseases that arise over the years. But for once, instead of physiological differences, let us try starting from gender differences, that is, the different conditions of men and women within our society. This view presents us with a disturbing scenario. First of all, elderly women are often poorer than men of the same age: perhaps because they have lost their husbands’ pensions, or because they have lower pensions than that of men. Socioeconomic level is one of the most important determinants of health: poverty leads people to seek less care, take less care of themselves, and do not exercise (if they cannot afford the cost of a gym). Not only that, poverty also results in a poor quality diet, which is certainly not good for health. Finally, in addition to being poorer, older women are also lonelier: perhaps they are widows, they have grown children who are far from home, and so they find themselves abandoned and depressed. It is easy to imagine how these factors negatively affect health.”

It is right to start from gender issues. But what, then, are the physiological aspects that make men and women different with regards to aging?

“We know well that before a certain age, cardiovascular disease affects the male sex more. Then, when the woman goes through menopause, the relationship reverses, and she also becomes more at risk because of the closing of the so-called “hormonal umbrella” that had protected her during her childbearing years. In addition, at menopause women begin to get type 2 diabetes, a disease that brings more complications (heart attack and heart failure) in women than in men. Not forgetting, as the father of Western medicine Hippocrates had already observed, that women only get gout after menopause. Older women also have an increased risk of developing some form of dementia, such as Alzheimer’s, while men are more likely to go on to Parkinson’s.

We then know that some organs age differently between the two sexes. Kidney function, for example, declines with age more in men than in women, although the reason for this phenomenon is not yet clear. Also, in women, lipids tend to increase after menopause, while in men they remain constant. Aging also then results in a difference in the distribution of body fat. At the intersection of sex and gender is also the case of osteoporosis: this is a disease that occurs in men as well, although much less than in women. In Italy, 5 million women and 800,000 men suffer from it, but the latter are more often victims of fractures.”

How should physicians take these differences into account when prescribing medication?

“One of the things that is always said is that it is necessary to adjust the dosage of drugs or nutraceuticals according to gender. But it’s more complex than that, and it involves the different ways in which men and women process molecules. For example, let’s talk about medications taken by mouth (because the differences also vary depending on the route of administration, whether oral, intramuscular, or subcutaneous): the first stage is the stomach. In men, this environment has a lower pH than in women, so the environment is more acidic, and this affects the absorption of the drug, depending on whether it is an acidic or basic drug. Not only that, the gastrointestinal tract motility is also different, slower in women, and this too has an impact on how the drug performs its action. From the intestines, the active ingredients must then pass into the liver to be metabolized, thanks to certain enzymes that are expressed differently in the two sexes: some more in the male, others more in the female. The result is that, for example, the enzymes that metabolize antidepressants are generally more numerous in men, while those that metabolize statins are on average more present in women, although of course there may be exceptions. But that’s not the end of the story: these enzymes are sensitive to hormones, so that in women, conditions can change with menopause, with menstruation, with the use of oral contraceptives, and with Hormone Replacement Therapy. These 4 different “hormonal situations” make us realize that in pharmacology “the” woman does not exist: there are at least four different types. If we then also want to consider the variations in these enzymes due to age and the action of the microbiota, which also differs between the sexes and varies according to diet, therefore also according to where one lives, it all becomes terribly complicated, although very fascinating to study. And this applies not only to the active ingredients, but also to the excipients, which are wrongly considered inert. So the challenge is not so much to prescribe different doses, but to produce different drugs and supplements for men and women based on this knowledge.”

Returning to the topic of gender, is the way men and women behave in relation to treatment adherence also different?

Unfortunately, we still have little data on this issue. But what we have tells us that men are generally more adherent to therapy, both in the cardiovascular and nervous system areas. True, it sounds strange because women generally follow rules more than men, but more so they make other family members follow them. However, when it comes to the lonely and depressed women mentioned earlier, it is obvious that adherence to therapy decreases. But so-called compliance is determined by many factors, some even related to where you live. City people are on average more adherent than those living in rural areas. It also depends on the person prescribing the treatment. Here we know that there is a different prescriptive attitude between male and female physicians. And although there is very little data in this area as well, we know in general that women physicians prescribe less, and talk to patients more. We also know that female patients followed by a female physician reach therapeutic targets more easily. For male patients, however, it seems to be unimportant for them to be cared for by male or female physicians.

We have talked about medication, but does what we have said also apply to supplements?

That of sex-gender differences in supplements is still a largely unexplored area, and there is much work to be done. For example, I am working on taurine and its effects on male and female cells, and the differences are obvious, as are also those of acetylcysteine. Soon to be published, though, will be data on extracts derived from olive tree leaves. Then I remember that we have information about nutrition when exercising, for example in sports, but this is mostly obtained from men. Women’s needs, which as we have seen change during menstruation or menopause, have been neglected. It seems clear, in short, that medicine must abandon its androcentrism in order to produce data to enable appropriate care and nutrition for all.

Flavia Franconi, a psychiatrist and pharmacologist, is one of Italy’s leading experts in gender-specific medicine. She received her medical degree from the University of Florence, Italy, and was a full professor of Molecular Cellular Pharmacology and coordinator of the Doctoral Program in Gender Pharmacology at the University of Sassari. She has more than 170 publications to her credit, in addition to editing the quarterly journal “Quaderni della SIF” of the Italian Society of Pharmacology. She is chair of the Health Commission of the Women20 Initiative. She has served on various committees on Health at the national and regional levels. She was elected to the Consiglio Comunale of the Basilicata Region in 2013, serving as Vice President and Assessor for Health and Safety.