Hormonal markers predict treatment response in alcohol use disorder

A new study reveals hormonal and biochemical factors that affect alcohol dependence (also known as Alcohol Use Disorder), suggesting that men and women with alcohol problems may benefit from different treatments.

Scientists have known that men and women have different risks related to alcohol misuse and related problems and that alcohol treatments may need to be tailored differently to men and women. However, the biological mechanisms underlying those differences are not well understood.

"This is the first large study to confirm that some of the variability in Alcohol Use Disorder (AUD) and related problems is associated with particular combinations of hormones and chemical biomarkers in men and in women. It may mean that sex-specific treatments can be tailored to improve responses for men and women with alcohol problems" said lead researcher Victor Karpyak, Professor of Psychiatry at Mayo Clinic in Rochester, Minnesota (USA). This work is presented at the ECNP Congress in Milan, Italy.

As part of a research project researching the alcohol dependence medication acamprosate, the researchers looked at hormonal and protein markers of 268 men and 132 women with Alcohol Use Disorder. They correlated these markers with psychological markers, such as depressed mood, anxiety, craving, alcohol consumption and treatment outcomes during the first 3 months of treatment.

At the beginning of the trial – before anyone had taken any medication – the researchers tested men and women for several sex-specific blood markers, including sex hormones (testosterone, estrogens, progesterone) as well as proteins known to impact their reproduction (such as follicle stimulating hormone, and luteinizing hormone) or bioavailability of these hormones in the blood (albumin and sex hormone-binding globulin).

They found that at the beginning of the trial men with Alcohol Use Disorder, symptoms of depression, and higher craving for alcohol, also had lower levels of the hormones testosterone, estrone, estradiol, as well as the protein sex hormone binding globulin. No such associations were found in women with AUD.

We found that there were different associations in men and women. For example, women who had higher levels of testosterone, sex hormone binding globulin, and albumin were also more likely to relapse during the first three months of treatment compared to women with lower levels of those biochemical markers. No such relationships were found in men."

Victor Karpyak, Professor, Psychiatry, Mayo Clinic in Rochester

 "These hormones and proteins are known to have an influence on behaviour, and indeed we see an association between different levels of these compounds and different behavioural aspects of alcohol use disorder, although we can't for sure say that one directly causes another. What it does mean is that if you are treating a man and a woman for alcoholism, you are dealing with different biochemical and psychological starting points. This implies that what works for a man may not work for a woman, and vice versa.

"This is the first study large enough to be able to confirm that particular combinations of sex hormones and related proteins may be part of the biological differences in how alcoholism manifests itself in men and women. We need more research to understand what this means for disease progression and its treatment. Given that many of those differences are related to sex hormones, we particularly want to see how the dramatic hormonal change women experience during menstrual cycle and at menopause may affect the biochemistry of alcoholism, and guide treatment efforts".

Commenting, Dr Erika Comasco, Associate Professor in Molecular Psychiatry, Uppsala University, Sweden, said," This research is an important step forward to gender equity in medicine. The findings provide an important first insight into the relationship between sex hormones and alcohol use disorder treatment. While sex differences in the way the disorder manifests itself are known, these results suggest that sex hormones may modulate treatment response, potentially supporting sex-specific pharmacological intervention. However, hormone fluctuations related to the menstrual cycle are also potential modulators of alcohol misuse, warranting further investigation into their role in treatment and relapse outcomes for female patients."

This is an independent comment, Professor Comasco was not involved in this work.

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