Randomised trial, 1996

Do women with PMS have lower brain opioid activity than women without PMS?

This small study found that women with PMS lacked the normal rise in a brain-opioid-linked hormone response seen in women without PMS, suggesting reduced opioid activity may be involved in PMS.

Early or limited evidence Women with prospectively confirmed PMS compared with control women without PMS, tested at two points in their menstrual cycle.

What they did

Researchers studied women with confirmed PMS and a comparison group of women without PMS. During two phases of the menstrual cycle, each woman was given naloxone (a drug that blocks opioid receptors) at one of two doses, or a placebo, and blood was tested every 15 minutes before and after to measure a hormone called LH (luteinizing hormone).

What they found

In the control (non-PMS) women, LH rose significantly after naloxone during the mid-luteal phase (P < .001), showing active opioid activity at that point in the cycle. Women with PMS did not show this rise. Neither group responded to naloxone later in the cycle (late luteal phase). Levels of other hormones (estradiol, progesterone, prolactin) were similar between the groups.

What it means for you

The results suggest that women with PMS may have weaker brain opioid activity at a key point in the cycle, which could contribute to PMS symptoms. This was a small, mechanistic hormone study, not a treatment trial, no overall sample size was stated, and it cannot prove that this difference causes PMS.

P < .001

LH rise in controls (mid-luteal, with naloxone)

1 mg, 4 mg

Naloxone doses tested

About the study

Original title: Decreased central opioid activity in premenstrual syndrome: luteinizing hormone response to naloxone
Authors: Rapkin AJ, Shoupe D, Reading A et al.
Journal: Journal of the Society for Gynecologic Investigation
Year: 1996
Study design: Randomised trial
What was tested: Naloxone (1 mg or 4 mg) or placebo, given to test opioid-related hormone response.
Read the paper: doi.org/10.1016/1071-5576(95)00045-3

Topics

Premenstrual syndrome (PMS)Cognition, concentration and memory

Systematic review, 2025

Does zinc supplementation help with PMS symptoms?

Systematic review, 2025

Does teaching adolescent girls about their menstrual cycle and health help reduce period pain and PMS?

Review, 2024

What are the most effective treatments for PMDD?

Systematic review, 2024

Do SSRI antidepressants help treat PMS and PMDD?

Cohort study, 2023

Are PMS symptoms linked to genetic factors for psychiatric disorders?