# IMPACT OF SEX-RELATED HORMONE LEVELS AND GENETIC VARIATION ON ALCOHOL USE DISORDERS AND RELATED PHENOTYPES IN MALES AND FEMALES

> **NIH NIH R21** · MAYO CLINIC ROCHESTER · 2020 · $228,563

## Abstract

Sex-related differences have been previously reported in the susceptibility and progression of
alcohol use disorders, presence or absence of comorbid conditions, and treatment response.
For example, alcohol consumption is higher and alcohol dependence is more common in males,
whereas females are more likely to drink heavily when experiencing unpleasant emotions or in
effort to relieve psychological distress. Our previous research suggests that genetic variation
may contribute to these sex-related differences. Specifically, we have shown that variants in the
PDYN gene increased risk for alcohol dependence in males, but increased the risk for negative
(relief) craving in females. We have observed that sex-dependent effects of genetic variants are
also phenotype-specific, suggesting complex relationships with endophenotypes, comorbidities,
or other biological factors (such as sex hormones). However, the biological mechanisms
underlying these genetic associations and other sex-specific differences in alcohol-related traits
are not well understood. It is reasonable to suggest that differences in sex-related hormone
levels across the sexes and/or genetic differences between the sexes may play an important
role in these biological sex differences. Yet, there is a lack of systematic research addressing
the impact of sex-related hormone levels on the risk of development of alcohol use disorders
and no attempts to comprehensively investigate associations between alcoholism, sex-related
hormone levels and genetic variation in male and female alcoholics. Importantly, our pilot study
indicates that plasma levels of some of the sex-related hormones differ significantly between
alcohol dependent cases and non-alcoholic controls. We hypothesize that both sex-related
hormone levels and genetic factors are associated with sex differences in alcoholism and
related traits. In a sample of 235 male and 118 female alcoholics matched to 235 male and 118
female non-alcoholic controls, we will 1) investigate the association between plasma levels of
sex-related hormones (testosterone, estrogens, progesterone, LH, FSH and SHBG) and alcohol
dependence; 2) investigate associations between plasma levels of sex-related hormones with
alcoholism-related phenotypes, such as alcohol consumption, craving, withdrawal, comorbid
depression and anxiety among alcohol-dependent males and females; and 3) examine the
association between genetic variation and sex-related hormone levels in subjects with and
without alcohol dependence. The findings of this study will lead to a better understanding of the
biology of sex differences in alcohol use disorders, facilitating development of more effective
and individualized treatment strategies.

## Key facts

- **NIH application ID:** 10020301
- **Project number:** 5R21AA026875-02
- **Recipient organization:** MAYO CLINIC ROCHESTER
- **Principal Investigator:** VICTOR M. KARPYAK
- **Activity code:** R21 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2020
- **Award amount:** $228,563
- **Award type:** 5
- **Project period:** 2019-09-20 → 2022-02-28

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/10020301

## Citation

> US National Institutes of Health, RePORTER application 10020301, IMPACT OF SEX-RELATED HORMONE LEVELS AND GENETIC VARIATION ON ALCOHOL USE DISORDERS AND RELATED PHENOTYPES IN MALES AND FEMALES (5R21AA026875-02). Retrieved via AI Analytics 2026-05-23 from https://api.ai-analytics.org/grant/nih/10020301. Licensed CC0.

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