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Sex and Gender Differences in Addiction and Addiction Treatment

A great deal has been written lately about the lack of gender balance in drug trials involving animals. A 2021 study examining the impact of cocaine addiction on the brains of mice found that 82 proteins were altered in the nucleus accumbens of male mice and only 50 proteins in female mice. It’s results like these that are throwing into question thousands of studies conducted with male-only animals.

New research by Jessica A. Loweth and Daniel Manvich, neuroscientists at Rowan University’s School of Osteopathic Medicine, indicates that the hormones estrogen and progesterone interact with opioid cravings and addiction. The researchers quickly point to a few known facts about women and opioid addiction:

  • Women are more likely than men to be prescribed opioid for pain relief
  • Women are more likely than men to use the pain relievers they are prescribed
  • Women transition faster from “initial use to more compulsive misuse” of opioids
  • Opioid-dependent women self-report stronger cravings than men
  • Opioid-dependent women self-report more severe withdrawal symptoms than men

Right from the start, based on a slew of studies, you can see there’s something going on with opioid dependency in women vs. men. What is the source of those gender differences? That’s what these researchers set out to discover:

Research indicates that increasing estrogen levels can increase both the number of opioid receptors and the levels of certain endogenous opioids in various parts of the brain. These changes could contribute to differences in opioid-induced pain relief across the menstrual cycle.

The researchers found that cocaine cravings are strongest leading up to the time of ovulation, when estrogen levels are increasing. Similarly, studies in rats found “the rewarding effects of the prescription opioid painkiller oxycodone are similarly reduced during cycle stages surrounding ovulation in which estrogen and progesterone levels are rising or have just fallen from peak levels.”

The researchers suggest that sex differences be considered when prescribing and monitoring the use of opioid painkillers, and that the patient’s menstrual cycle be taken into consideration. A similar conclusion was reached in a fascinating study involving ten thousand recovering heroin addicts in Italy. Known as the VEdeTTE Cohort, patients were tracked at 115 drug treatment centers in Italy from 1998 to 2001. What the study found were surprising gender differences:

  • Women addicts were on average younger and better educated than men
  • Male addicts were more often single and women addicts more often married, separated, divorced, or living with a partner
  • Women were more likely to report psychological comorbidities such as depression
  • Women were more often offered psychotherapy, and men pharmacology
  • Women stick with methadone treatment longer than men do

The authors concluded, “High methadone doses and the combination with psychotherapy improved treatment retention in both genders.” This interesting outcome matches other reporting here at AddictionNews that it may be the therapy, not the drugs, that’s doing the heavy lifting in addiction recovery. The VEdeTTE Cohort does not comment on estrogen, progesterone, or the interaction between the menstrual cycle and addiction.

A more recent article published by JAMA Network Open in 2020 found “sex differences in opioid overdose in adolescents and young adults using insurance claims data and found sex differences in both the prevalence of overdose and the factors associated with overdose.” As with the Italian study, the author cites a study showing that 66% of females receiving treatment for opioid addiction experience “depression or anxiety” and 16% had traumatic stress disorder. More than half the men also experienced “depression or anxiety,” leading the author to conclude that attention to psychiatric disorders is an important prevention strategy for both sexes.

We conclude with the most recent, and perhaps most discouraging, study of sex and gender differences in the efficacy of substance use disorder medications. This 2022 study found that, with the exception of tobacco cessation medications, there were scant studies into sex or gender differences in response to medications such as Naloxone, buprenorphine, methadone, or other drugs used to treat substance use disorders. The tobacco studies, for what it’s worth, showed “significant differences” between the sexes. It’s an important story and we’ll keep following it here at AddictionNews.

Written by Steve O’Keefe. First published July 22, 2024.

Sources:

“New research suggests estrogen and progesterone could play role in opioid addiction and relapse,” The Conversation, July 16, 2024.

“Gender Differences in Heroin Addiction and Treatment: Results from the VEdeTTE Cohort,” Substance Use & Misuse, February 2016.

“The Importance of Studying Sex and Gender Differences in Opioid Misuse,” JAMA Network Open, December 17, 2020.

“Consideration of sex and gender differences in addiction medication response,” Biology of Sex Differences, June 27, 2022.

Image Copyright: ricochet64.

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