Can Hormones Guide Sex-Specific Treatments for AUD?

MILAN — Specific combinations of hormonal and biochemical factors were associated with different clinical characteristics and treatment outcomes of alcohol use disorder (AUD) between men and women.

“These hormones and proteins are known to have an influence on behavior, and indeed we see an association between different levels of these compounds and different behavioral aspects of [AUD], although we can’t for sure say that one directly causes another,” said lead researcher Victor M. Karpyak, MD, PhD, professor of psychiatry at the Mayo Clinic, in a release.

The findings were presented at the 37th European College of Neuropsychopharmacology (ECNP) Congress.

Sex Hormone Signatures

Previous research has highlighted differences in symptoms including cravings, withdrawal, consumption patterns, depression, and anxiety between men and women with AUD, said Karpyak. Differences in hormones and biochemicals have also been observed between individuals with and without AUD.

However, specific biochemical and hormonal “signatures” associated with male and female responses to treatment have thus far not been explored, he told Medscape Medical News.

The study included 400 treatment-seeking individuals (132 women and 268 men; mean age, 41.8 years; 93% White) who met Diagnostic and Statistical Manual of Mental Disorders, Fourth Edition, criteria for AUD and were enrolled in a clinical trial of acamprosate.

Baseline assessment included psychiatric comorbidities and substance use with the Psychiatric Research Interview for Substance and Mental Disorders, alcohol consumption pattern over the past 90 days by Timeline Follow-Back calendar, recent craving on the Penn Alcohol Craving Scale (PACS), situations at the risk of drinking on the Inventory of Drug-Taking Situation, recent depression severity on the Patient Health Questionnaire 9 (PHQ-9), and recent anxiety severity on the Generalized Anxiety Disorder 7 scale.

Plasma sex-related hormone and protein measurements were taken at baseline — after detoxification but before treatment. These included total testosterone, estradiol, estrone, progesterone, follicle-stimulating hormone (FSH), luteinizing hormone (LH), sex hormone–binding globulin (SHBG), and albumin.

“The important thing is that these measurements were taken during sobriety,” said Karpyak. Study participants were already in residential treatment programs, and the average time since their last drink was approximately 3 weeks. Relapse was defined as any alcohol consumption during the first 3 months.

What Works for Men May Not Work for Women

Results showed that men with symptoms of depression and a higher craving for alcohol, as shown on baseline PHQ-9 and PACS scores, had lower baseline levels of testosterone, estrone, estradiol, and SHBG than those without these symptoms (P = .0102 and P = .0014, respectively).

In addition, a combination of higher progesterone and lower albumin was associated with a lower risk for relapse during the first 3 months (odds ratio [OR], 0.518; P = .0079).

In women, a combination of lower estrone and estradiol and higher FSH and LH levels was associated with higher maximum number of drinks per day (P = .035).

In addition, women who were more likely to relapse during the first 3 months of treatment had higher baseline levels of testosterone, SHBG, and albumin than those at lower relapse risk (OR, 4.536; P = .0057).

Karpyak noted that these “hormone signatures” were associative and not predictive.

What this means, he said, “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.”

Toward Gender Equity

The findings may eventually lead to a way to predict treatment responses in patients with AUD, Karpyak added, but cautioned that despite statistical significance, these are preliminary findings.

Before these results can be integrated into clinical practice, they need to be replicated. Karpyak emphasized the need for follow-up research that builds on these findings, using them as preliminary data to determine whether prediction holds real significance.

“Given that many of these differences are related to sex hormones, we particularly want to see how the dramatic hormonal change women experience during the menstrual cycle and at menopause may affect the biochemistry of alcoholism and guide treatment efforts,” he said.

In a statement, Erika Comasco, PhD, associate professor in molecular psychiatry, Uppsala University, Uppsala, Sweden, said the 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,” she explained. “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.”

Comasco shares Karpyak’s view that hormonal fluctuations linked to the menstrual cycle may influence alcohol misuse and believes more research is needed to explore their impact on treatment and relapse outcomes in female patients.

This study was funded by the National Institute on Alcohol Abuse and Alcoholism (National Institutes of Health) and the Samuel C. Johnson Genomics of Addiction Program at Mayo Clinic. Karpyak and Comasco reported no relevant disclosures.