# Exploring the Role of Testosterone as a Novel Anti-Nociceptive Agent in Women with Chronic Pain and Opioid Use

> **NIH NIH R21** · BRIGHAM AND WOMEN'S HOSPITAL · 2021 · $268,500

## Abstract

PROJECT SUMMARY
There is abundant evidence that women and men do not experience pain equally. Compared to men, women
are overrepresented in the majority of clinical pain conditions and also exhibit greater sensitivity to
experimental pain. Similarly, use of analgesics is twice as common in women, compared to men, for conditions
of comparable severities. Women not only have 20-fold lower serum testosterone concentrations compared to
men but also experience a reduction in testosterone levels with age. Taken together, these data suggest that
testosterone has anti-nociceptive properties which may explain why women have a higher incidence and
severity of chronic pain compared to men. Additionally, patients who are prescribed opioid-analgesics for
chronic pain experience further reduction in testosterone levels as opioids potently suppress the gonadal axis.
Both pre- and postmenopausal women on chronic opioids demonstrate >50% reduction in testosterone levels
compared to women not using opioids. In recent years, the use of sustained-action opioids in the management
of chronic non-cancer pain has grown with many women taking multiple opioid analgesics. The development of
opioid-induced hypogonadism deprives these women of the anti-nociceptive properties of testosterone and
leads to a vicious cycle resulting in perpetuation of chronic pain despite being on opioids, subjecting patients to
long-term requirement of even higher doses of opiates. Previous trials of testosterone replacement in men with
opioid-induced hypogonadism have shown improvement in both clinical and experimental pain, and
improvement in quality of life (QOL). However, despite having significantly higher burden of chronic pain, the
efficacy of testosterone replacement on pain perception and tolerance has not been studied in women.
The overall goal of this proposal is to evaluate the efficacy of physiologic testosterone replacement in
improving clinical and experimental pain in a double-blind, randomized-controlled trial in postmenopausal
women with chronic back pain who are being treated with opioid-analgesics for at least 6 months and have low
testosterone. We will also assess the efficacy of testosterone replacement on QOL, mood and physical
function. We propose a 12-week double-blind, randomized-controlled, proof-of-concept trial to determine the
efficacy of physiologic testosterone replacement with weekly intramuscular injections versus placebo injections
in women age 60 years and older with chronic back pain and testosterone deficiency. The following outcomes
will be measured: 1) clinical pain, 2) experimental pain with quantitative sensory testing, and 3) QOL, mood
and physical function. Because chronic pain is a major public health problem for which existing therapies are
suboptimal and only provide partial relief, if this trial confirms benefits of testosterone therapy, patients will
have an inexpensive, relatively safe and easy to administer medication available that has the pot...

## Key facts

- **NIH application ID:** 10189910
- **Project number:** 1R21AG071907-01
- **Recipient organization:** BRIGHAM AND WOMEN'S HOSPITAL
- **Principal Investigator:** Shehzad Basaria
- **Activity code:** R21 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2021
- **Award amount:** $268,500
- **Award type:** 1
- **Project period:** 2021-06-01 → 2023-04-30

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/10189910

## Citation

> US National Institutes of Health, RePORTER application 10189910, Exploring the Role of Testosterone as a Novel Anti-Nociceptive Agent in Women with Chronic Pain and Opioid Use (1R21AG071907-01). Retrieved via AI Analytics 2026-05-22 from https://api.ai-analytics.org/grant/nih/10189910. Licensed CC0.

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