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Estrogen and Drug Addiction - An Overview

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The dopamine reward system in the brain is strengthened by estrogen, which increases happy emotions. To know more about it, read the article below.

Written by

Dr. Palak Jain

Medically reviewed by

Dr. J. N. Naidu

Published At December 7, 2022
Reviewed AtMay 10, 2023

Introduction:

Estrogen enhances sex differences in all stages of drug abuse. Still, there is no evidence that other sex hormones, such as progesterone in females and testosterone in males, have a role. In studies, animals received controlled hormone replacement while having their ovaries removed in the case of females and having their testicles removed in the case of males. There is a significant link between estrogen and the development of drug misuse. Women with higher estrogen levels may be more sensitive to the side effects of some medications. When a woman goes through the high-estrogen period of her cycle, she could take another substance for fun without realizing the changes it causes in her body.

How Does the Menstrual Cycle Work?

The follicular and luteal phases closely correspond to the length of the human female reproductive cycle, usually 28 days. When menstruation occurs early in the follicular phase, estrogen and progesterone levels are low and largely stable. While progesterone levels stay low, estrogen levels rise during the mid-follicular phase and peak just before ovulation. Following ovulation, the luteal phase begins. Progesterone levels start to climb 3 to 8 days after ovulation, reach a peak, and then start to fall before menstruation.

What Part Does the Stimulant Play in Drug Addiction?

Stimulants like cocaine and Methamphetamine have been the main subjects of research on the effects of ovarian hormones (estrogen) on responses to drug abuse. Clinical research has generally shown that the euphoria and positive reinforcing effects of cocaine and Methamphetamine are more pronounced during the follicular phase than during the luteal phase.

These findings support preclinical research suggesting progesterone during the luteal phase reduces the reinforcing effects of stimulants, or estrogen during the follicular phase increases the reinforcing effects of stimulants. Other clinical research, however, has been unable to show a relationship between the menstrual cycle phase and the subjective reactions to cocaine administered intravenously or intranasally.

These inconsistent outcomes could result from different methods to track menstrual cycle-related hormonal changes, such as smoking cocaine versus injecting it or administering it intravenously. Each menstrual cycle phase is marked by large changes in ovarian hormone levels, as was already mentioned. As a result, direct measurements of endogenous estrogen and progesterone levels may be the more reliable way to determine how ovarian hormones affect women who depend on stimulants' effects for their good mood and behavior.

According to a study, women who use cocaine and have high levels of endogenous progesterone (> 4 ng/ml) report much less stress-induced cravings than those who have low levels of endogenous progesterone. Another study compared the endogenous levels of estrogen and progesterone in cocaine-dependent women who had just stopped using the drug to those in healthy women used as control.

For 28 days, salivary estrogen and progesterone levels were measured daily. Cocaine-dependent women showed considerably higher salivary progesterone levels and lower estrogen-to-progesterone ratios throughout the menstrual cycle than the control group. Although cycle length and ovulation are unaffected in cocaine-dependent women, these data imply that long-term cocaine use and/or withdrawal may change the hormonal environment.

In women addicted to cocaine, exogenous progesterone therapy reduces the favorable subjective effects of smoked and intravenous cocaine. Therefore, boosting progesterone may mitigate the danger of drug-primed craving and relapse and shield against the reinforcing effects of stimulants. Stress and drug-paired indicators both significantly predict desire and relapse.

The results of clinical trials on nicotine-dependent women point to the influence of ovarian hormones on Nicotine withdrawal symptoms and reactions to smoking triggers. For instance, as progesterone levels start to fall in the late luteal phase, nicotine cravings and withdrawal symptoms increase. Female smokers desire more smoke signals during the luteal phase than in the follicular period. Other research has revealed no relationship between the menstrual cycle phase and the subjective reactions of female smokers who have quit smoking or their ability to think clearly.

How Does Alcohol Addiction Influence the Menstrual Cycle?

Studies have conflicting findings on the influence of menstrual cycle phases on alcohol subjectivity. Alcohol has anxiogenic effects during the luteal phase when the progesterone hormone is elevated during the menstrual cycle but no impact on anxiety during the follicular phase is seen when the estrogen hormone is elevated, according to research on healthy, non-dependent women.

Alcohol has been shown to produce anxiogenic effects during the follicular phase but not the luteal phase, according to others. The inconsistent outcomes may be due to different alcohol doses being used. Studies on the menstrual cycle phase's ability to reinforce alcohol use have produced mixed results. Alcohol intake increased more during the luteal phase than during the follicular phase.

How Does Estrogen Affect Opioid Addiction?

In the past 25 years, there has been a major rise in the non-medical use of prescription opioids, which presents a huge clinical obstacle to effective pain management. According to recent epidemiologic statistics, women are more likely than males to endure chronic pain, and the incidence of prescription opioid usage among women is rising. The effects of the menstrual cycle phase on the antinociceptive effects of opioids have traditionally been the subject of clinical studies. In one study, the antinociceptive effects of Fentanyl after laparoscopic surgery were found to be constant throughout the menstrual cycle.

In a clinical laboratory experiment, researchers looked at the impact of menstrual cycle phases on the strength of Morphine or Pentazocine analgesia in healthy women and those using oral contraceptives. Women who cycle normally showed more Morphine analgesia for pain during the menstrual cycle's follicular phase than during the luteal phase. Researchers discovered that the menstrual cycle phase had no impact on the analgesic effects of Morphine in women using oral contraceptives.

How Does Marijuana Use Affect Ovarian Hormones?

There have not been many clinical investigations into how ovarian hormones affect behavior and marijuana use. There is no relationship between the menstrual cycle phase and either alcohol or marijuana usage, according to several studies of marijuana users. Additionally, the menstrual cycle phase seems to have little impact on marijuana users' negative affect, arousal, mood, and attention, considering the rise in female marijuana use over the last couple of decades.

Conclusion:

The effects of estrogen and progesterone that are most consistently seen seem to be in response to the administration of stimulants, with progesterone attenuating and estrogen boosting positive subjective responses to cocaine and Amphetamine. Furthermore, elevated endogenous progesterone levels in cocaine-dependent women appear to decrease reactions to stress and drug-paired stimuli.

According to significant research, variations in ovarian hormone levels over time and/or the ratio of progesterone to estrogen may serve as better indicators of responses to drug abuse than absolute levels of either estrogen or progesterone. According to clinical research, exogenous progesterone is an effective treatment for drug-dependent women. Most preclinical and clinical laboratory investigations have indicated that progesterone reduces the drug's reinforcing effects.

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Dr. J. N. Naidu
Dr. J. N. Naidu

General Practitioner

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