INTRODUCTION

There has been a substantial increase in the number of individuals with opioid use disorder (OUD) over the past decade, particularly among women.¹ Historically, men have reported higher rates of OUD, however the increase in OUD among women has increased to rates that are closer to the OUD diagnoses rates in men, therefore reducing the gender gap among those with OUD.^{2, 3} From 1999 to 2017, the rate of overdose deaths among women aged 30–64 increased by 1634% for synthetic opioids and 915% for heroin.⁴ Women have a higher prevalence of pain syndromes and different response to analgesic drugs than men,⁵ contributing to higher rates of women being prescribed opioid pain medications than men.⁶ Furthermore, multiple studies have suggested that women progress from time to initial prescription opioid use to problematic use and seek-treatment faster than men, but this is not true for heroin use.^{7, 8} This information warrants a more in-depth understanding of this population.

Medication treatment for OUD (MOUD; e.g., buprenorphine, methadone, and extended-release naltrexone) are effective in reducing opioid use, risk of overdose, and all-cause mortality.⁹ Despite these benefits, a low proportion of women enter treatment.¹⁰ Women face unique barriers when initiating OUD treatment due to mental health conditions, past traumas, and stigma,¹¹ yet research continues to overlook critical gender differences in demographics, drug use severity, psychopathology, and other clinical characteristics among persons initiating MOUD.¹² Women initiating MOUD have higher rates of comorbid depression and anxiety,¹³ report greater psychiatric severity and higher levels of functional impairment compared to men.^{14, 15} Therefore, the aim of this manuscript is to explore the gender-specific differences in clinical characteristics including current and past psychiatric and substance use disorder diagnoses, depression and anxiety symptoms, quality of life (QoL) and reported drug use among a cohort of persons with OUD initiating MOUD.

METHODS

Study design

Project Medication-Assisted Therapy and BIological Outcomes (MAT BIO) is a prospective cohort NIH-funded study of persons with Diagnostic and Statistical Manual of Mental Disorders (DSM-5) diagnosed moderate to severe OUD living with and without HIV who are initiating treatment with methadone or buprenorphine. Participants were screened and enrolled when they began MOUD with biological and self-report measures obtained at baseline, Days 7 and 14, and Months 1, 3, and 6 postinitiation of MOUD. Study protocol and procedures were approved by Yale Internal Review Board and previously published.¹⁶ Differences in demographic and clinical characteristics were assessed by self-reported gender at baseline. Χ² and Fisher's exact test assessed differences in dichotomous variables, and T-test assessed differences in continuous variables. Data was analyzed using Stata®, version 17 software.

RESULTS

Of the 125 participants enrolled from March 2017 to August 2021, 33 (26.4%) identified as women, 90 (72.0%) as men, and 2 (1.6%) as transgender women based on current gender identity. The persons who identified as transgender women were included in the women grouping of the analyses. Items regarding sex were not collected in this project. Study research assistants who were trained and certified to administer all of the study instruments conducted interviews. All participants were seeking MOUD with 45.6% of men and 45.5% of women starting methadone, and 54.4% of men and 54.3% of women starting buprenorphine. Approximately one-third of participants were homeless and three-quarters were not currently in a controlled environment (e.g., prison or inpatient treatment center) in the month before baseline assessment. When compared to men, women were significantly younger, more likely to be White non-Hispanic, identify as a member of the LGBTQ + community, and have a lower mean lifetime number of months of incarceration (see Table 1). There were no significant differences in employment status, mean income, HIV or hepatitis C status, or their history of OUD treatments.

Table 1. Participant characteristics by gender, bivariate results

Psychiatric disorders

As depicted in the table, women and men had similar prevalence of DSM-5 psychiatric disorders on the Mini-International Neuropsychiatric Interview (MINI)¹⁷ at baseline for major depressive, bipolar disorders, and generalized anxiety disorder. Nine participants did not complete the MINI. However, women had a significantly higher prevalence of posttraumatic stress disorder (PTSD). Although not significant, women also had a higher prevalence of moderate to severe depressive symptoms as per the Patient Health Questionnaire (PHQ-9).¹⁸ Women were also more likely to be told they should be taking psychiatric medications by a medical professional, but there was no statistical difference in ‘currently prescribed psychiatric medications’.

Quality of life (QoL)

Women had poorer health-related World Health Organization QoL-Bref¹⁹ mean scores across all domains (physical, psychological, social relationships, and environment), although only the psychological scores were significantly different.

Substance use

There was no difference in the types of substances used in the three months before the baseline assessment. However, when exploring DSM-5 substance use disorder diagnoses at baseline as per the Alcohol, Smoking and Substance Involvement Screening Test (ASSIST)²⁰ nonprescribed sedative/sleeping pill (31.4% of women vs. 7.8% of men; p < .001) and hallucinogens (14.3% of women vs. 2.2% of men; p = .02) use was statistically significantly different.

Based on the timeline followback (TLFB), the majority of participants reported approximately 19 days of any opioid use in the 30 days before baseline, no significant difference between genders. When exploring the type of opioid used, 94 participants (81.1% of men and 60.0% of women) reported heroin use in the 30 days before baseline (p = .01). Statistical analyses could not be performed on other opioid use (morphine, fentanyl, oxycodone, and oxycontin) due to the small number of participants (1–4 per type of opioid) who reported use.

DISCUSSION

This is a cross-sectional analysis of gender differences of baseline characteristics of a cohort of persons with OUD seeking MOUD. Women had a higher prevalence of DSM-5 generalized anxiety disorder and PTSD, and greater depression severity as compared to men. Prior research indicates that participants with an anxiety disorder are more likely to meet OUD criteria,²¹ and opioid relapse is more likely in women with co-occurrence of affective and anxiety disorders.¹⁰ Women had poorer psychological QoL compared to men in this study which aligns with previous research on those seeking MOUD,^{15, 22, 23} and may be associated with worse MOUD retention and outcomes.²⁴ Concurrent psychosocial treatment and MOUD are associated with improved outcomes indicating that psychiatric comorbidity is a critical treatment target.²⁵ Our findings reflect that women were significantly more likely to be told by medical providers that they should be prescribed medications for their mental health conditions, however they were less likely to be currently prescribed these medications as compared to men.

In this study, women reported higher rates of nonprescribed hallucinogen and sedative/sleeping pill use. This is important given among those on MOUD, sedative use has been associated with poorer MOUD retention.²⁶ In addition, sedative (benzodiazepine) misuse is implicated in 40–80% of methadone deaths^{27, 28} and up to 80% of buprenorphine-related deaths.^{29, 30} Given the age of our sample and that maternal mortality involving opioids doubled between 2007 and 2016,³¹ with overdose as a leading cause,³² the results from this analysis highlights the importance of addressing sedative misuse with MOUD particularly among reproductive-age women.

These findings are relevant in the context of treatment outcomes; programs for women may benefit from a multidisciplinary approach that addresses psychiatric comorbidities as suggested by the American Society of Addiction Medicine³³ compared to traditional siloed care. To combat this risk for relapse for women, concurrent psychiatric therapy may help manage symptoms that emerge with MOUD initiation. Women-specific programming may be beneficial as mixed-gender treatments often fail to address their needs, including childcare assistance, pregnancy care, parenting, domestic violence, sexual trauma, psychiatric comorbidity, housing, income support, and social services.^{10, 34, 35} Furthermore, our results support the need for integrated HIV harm-reduction services, although women were significantly less likely to be diagnosed with HIV, their injection drug use behavior did not differ. This may be due to the younger age of the women. Therefore, engaging women in harm reduction services before they seek treatment including syringe exchange, access to pre-exposure prophylaxis (PrEP) for HIV, and increased HIV testing are essential.

This analysis is subject to limitations including only gathering information on current gender identification, items regarding sex at birth were not collected. The sample had a small number of women participants, which is typical of most analyses of MOUD treatment studies.^36-40 Although untreated/undertreated ADHD is associated with substance use,^{41, 42} items regrading ADHD were not asked in this project. Additionally, information collected on psychiatric medications was based on self-report, rather than medical records, which may have introduced recall bias and under/over-reporting. Nevertheless, among this population, we found similar results to other studies of gender differences among persons with OUD initiating MOUD.^{1, 13-15, 23} Analyses included in this manuscript report differences among baseline characteristics of this on-going project. Future analysis will explore gender differences over the 6-month study period.

CONCLUSION

This evaluation provides insights into gender differences in persons with OUD seeking MOUD that may help develop women-specific OUD treatment. More prospective research is required to understand these gender differences in baseline characteristics and how they may affect MOUD initiation and retention, as well as other outcomes including reduction in relapse, opioid overdose, and death among women.

ACKNOWLEDGMENTS

This study was funded by the National Institutes on Drug Abuse (NIDA; North Bethesda, MD; R01DA043337, Springer & Shaw) and for career development by NIDA (K02 DA032322, Springer). The funders were not involved in the research design, analysis or interpretation of the data or the decision to publish the manuscript.

CONFLICTS OF INTEREST

Author Springer has provided scientific consultation to Alkermes Inc. and received NIH and VA grant funding. Dr. Shaw received NIH funding. Dr. Springer has received in-kind study drug donations from Alkermes Inc and Indivior Pharmaceutical Company for NIH-funded research. The authors alone are responsible for the content and writing of this paper.

Summary

A notable surge in opioid use disorder (OUD) has been observed over the past decade, with a significant increase among women, narrowing the previously larger gender gap in OUD diagnoses. Women exhibit a higher prevalence of pain syndromes and demonstrate differing responses to analgesic medications compared to men, potentially contributing to higher rates of opioid prescriptions. While women often transition more rapidly from initial opioid prescription to problematic use and treatment-seeking than men (excluding heroin use), a comprehensive understanding of this population remains warranted.

Medication-Assisted Treatment (MAT) and Gender Differences

Medication-assisted treatment for OUD (MOUD), including buprenorphine, methadone, and extended-release naltrexone, effectively reduces opioid use, overdose risk, and mortality. However, women have lower treatment initiation rates, facing unique challenges such as mental health conditions, trauma, and stigma. Existing research frequently overlooks critical gender differences in demographics, drug use severity, psychopathology, and other clinical characteristics among individuals commencing MOUD. Women initiating MOUD experience higher rates of comorbid depression and anxiety, reporting greater psychiatric severity and functional impairment compared to men. This study aims to analyze gender-specific differences in clinical characteristics, including psychiatric and substance use disorders, depressive and anxiety symptoms, quality of life (QoL), and reported drug use in a cohort of individuals with OUD beginning MOUD.

Study Design and Methods

The Medication-Assisted Therapy and Biological Outcomes (MAT BIO) study, a prospective cohort study, enrolled individuals with DSM-5 diagnosed moderate to severe OUD, with and without HIV, initiating methadone or buprenorphine treatment. Data collection involved biological and self-report measures at baseline and at multiple time points following MOUD initiation. Gender differences in demographic and clinical characteristics were analyzed using appropriate statistical tests.

Results

Of 125 participants, 33 (26.4%) identified as women, 90 (72%) as men, and 2 (1.6%) as transgender women. Women were significantly younger, more likely to be White non-Hispanic, identify as LGBTQ+, and had a lower mean lifetime incarceration duration compared to men. No significant differences were found in employment status, income, HIV/hepatitis C status, or history of OUD treatment. Women and men showed similar prevalence rates of major depressive, bipolar, and generalized anxiety disorders. However, women demonstrated a significantly higher prevalence of posttraumatic stress disorder (PTSD) and higher rates of moderate to severe depressive symptoms. Women reported poorer health-related QoL scores, with significantly lower psychological scores. While there were no differences in substance use types in the preceding three months, women exhibited significantly higher rates of nonprescribed sedative/sleeping pill and hallucinogen use. Heroin use in the 30 days prior to baseline was more prevalent among men.

Discussion

This cross-sectional analysis reveals significant gender differences in baseline characteristics among individuals with OUD seeking MOUD. Women displayed a higher prevalence of anxiety disorders, PTSD, and greater depression severity, aligning with findings linking anxiety disorders to OUD criteria and increased relapse risk in women with co-occurring affective and anxiety disorders. Women also experienced poorer psychological QoL, potentially impacting MOUD retention and outcomes. The study highlights higher rates of nonprescribed sedative/sleeping pill and hallucinogen use among women, factors significantly associated with poorer MOUD outcomes and increased mortality risk. These findings underscore the importance of integrated care addressing psychiatric comorbidities, particularly in women, potentially improving MOUD outcomes and reducing risk.

Conclusion

This study provides valuable insights into gender-specific differences in individuals with OUD initiating MOUD, informing the development of tailored treatment approaches for women. Future research should focus on longitudinal data to understand how these baseline characteristics affect MOUD initiation, retention, and outcomes.

Summary

A significant rise in opioid use disorder (OUD) has been observed over the past decade, particularly among women, narrowing the historical gender gap in OUD diagnoses. Women experience higher rates of overdose deaths and exhibit a higher prevalence of pain syndromes and varying responses to analgesic medications, potentially contributing to higher opioid prescription rates. While women may progress faster to problematic opioid use and treatment-seeking compared to men (except for heroin), this necessitates a deeper understanding of this population's unique characteristics.

Study Design

The Medication-Assisted Therapy and Biological Outcomes (MAT BIO) study, a prospective cohort study, investigated individuals with moderate to severe OUD initiating methadone or buprenorphine treatment. Data collection included biological and self-reported measures at baseline and various intervals post-treatment initiation. The study protocol was approved by the Yale Internal Review Board. Gender differences were analyzed using appropriate statistical methods.

Results

Among 125 participants, 33 (26.4%) identified as women. Women were significantly younger, more likely to be White non-Hispanic, identify as LGBTQ+, and have fewer months of lifetime incarceration than men. No significant differences were found in employment, income, HIV/Hepatitis C status, or history of OUD treatment.

Psychiatric Disorders

Women and men exhibited similar prevalence of major depressive, bipolar, and generalized anxiety disorders. However, women showed a significantly higher prevalence of post-traumatic stress disorder (PTSD) and a higher, though not statistically significant, prevalence of moderate-to-severe depressive symptoms. A greater proportion of women reported being advised by medical professionals to take psychiatric medications, despite no significant difference in current prescriptions.

Quality of Life

Women reported poorer health-related quality of life (QoL) across all domains, with significantly lower scores in the psychological domain.

Substance Use

While there were no differences in substance use types within three months of baseline, women had significantly higher rates of non-prescribed sedative/sleeping pill and hallucinogen use. Most participants reported approximately 19 days of any opioid use in the preceding 30 days, with no significant gender difference. A significantly higher percentage of men reported heroin use in the 30 days prior to baseline.

Discussion

This cross-sectional analysis reveals that women initiating MOUD exhibit higher rates of PTSD, greater depressive symptom severity, and poorer psychological QoL compared to men. These findings highlight the importance of addressing co-occurring psychiatric disorders, particularly for women, as these factors may influence MOUD retention and outcomes. Women also demonstrated higher rates of non-prescribed sedative/sleeping pill and hallucinogen use, emphasizing the need to address poly-substance use in treatment strategies, especially given the link between sedative misuse and poorer MOUD outcomes and increased mortality.

Conclusion

The study underscores the need for gender-specific OUD treatment approaches. Future research should investigate how these gender differences influence MOUD initiation, retention, and long-term outcomes, aiming to reduce relapse, overdose, and mortality among women with OUD.

Summary

Opioid use disorder (OUD) is rising, especially among women. While historically men had higher rates, the gap is narrowing. Women experience higher rates of overdose deaths and are more often prescribed opioid pain medication. Studies suggest women transition faster from prescription opioid use to problematic use and treatment seeking than men, but this doesn't apply to heroin. This necessitates a deeper understanding of women with OUD.

Study Design

The Medication-Assisted Therapy and Biological Outcomes (MAT BIO) study followed individuals with OUD starting methadone or buprenorphine treatment. Data was collected at baseline and at various intervals after treatment began. The study was approved by the Yale Internal Review Board. Statistical tests (chi-squared, Fisher's exact, t-test) analyzed the data.

Results

Of 125 participants, 33 identified as women. Women were significantly younger, more likely to be White and non-Hispanic, and LGBTQ+, and had shorter average incarceration times than men. There were no significant differences in employment, income, HIV or Hepatitis C status, or prior OUD treatments.

Psychiatric Disorders

Women and men showed similar rates of major depressive, bipolar, and anxiety disorders. However, women had significantly higher rates of post-traumatic stress disorder (PTSD) and tended to have more severe depression symptoms. More women were advised by medical professionals to take psychiatric medication, but there was no difference in actual prescription rates.

Quality of Life

Women reported lower quality of life (QoL) across all domains, with significantly lower psychological QoL scores.

Substance Use

There were no differences in substance use types in the three months before treatment. However, women had significantly higher rates of non-prescribed sedative/sleeping pill and hallucinogen use. Most participants reported recent heroin use, with a higher percentage of women reporting heroin use compared to men. Other opioid types couldn’t be analyzed due to low numbers.

Discussion

This study highlights gender differences in OUD, showing higher rates of PTSD, depression severity, and poorer psychological QoL among women. These factors affect treatment outcomes and retention. Women also reported higher rates of sedative/sleeping pill and hallucinogen misuse, which is linked to poorer treatment outcomes and overdose risk.

Conclusion

This study suggests that OUD treatment programs should incorporate a multidisciplinary approach addressing psychiatric comorbidities, particularly for women. More research is needed to understand how these gender differences influence treatment success and long-term outcomes.

Summary

Lots more women are having problems with opioid drugs than before. Doctors gave women opioid pain medicine more often than men. Women tend to get help for opioid problems sooner than men, but not for heroin. This study looks at the differences between men and women getting help for opioid problems.

Study design

Researchers studied people with serious opioid problems who were starting a medicine to help them. They collected information when the people started the medicine and then again at different times.

Results

Of the 125 people in the study, about one-fourth were women. Women were usually younger and more likely to be white, part of the LGBTQ+ community, and spent less time in jail than men. There was no big difference in things like jobs, money, or having HIV or hepatitis C.

Psychiatric disorders

Women and men had similar problems with depression, bipolar disorder, and anxiety. However, women were much more likely to have post-traumatic stress disorder (PTSD) and had more severe depression symptoms. More women were told by a doctor that they should take medicine for mental health, but it wasn't always the case that they were actually taking medicine.

Quality of life

Women had a worse quality of life, especially in how they felt mentally.

Substance use

Men and women used similar drugs in the months before the study. But women used more sleeping pills and hallucinogens that weren't prescribed. Most people used heroin, but a higher percentage of women reported using heroin compared to men.

Discussion

This study shows women with opioid problems often have other mental health issues like anxiety and depression. Women also have a lower quality of life. They also used more non-prescribed drugs that can be dangerous with opioid medicine.

Conclusion

This study helps show how men and women are different when it comes to opioid problems and getting help. More research is needed to understand these differences and how to best help women.