title: "GnRH Agonist Leuprorelin and Liver Volume in Premenopausal Women With Severe Polycystic Liver Disease"
description: "A small randomized trial found that medically induced menopause with leuprorelin did not reduce liver volume in premenopausal women with severe polycystic liver disease, and side effects were substantial."
date: "2025-01-01"
category: "research-update"
studyType: "RCT"
sampleSize: 14
evidenceTier: "B"
pubmedId: "42900154"
In a small open-label randomized trial (14 premenopausal women), leuprorelin-induced menopause did not reverse liver enlargement in severe polycystic liver disease, did not improve disease-related quality of life, and produced more adverse events than standard care. The study was stopped early.
Polycystic liver disease (PLD) is a condition in which multiple fluid-filled cysts develop in the liver, sometimes causing marked enlargement with abdominal discomfort and reduced quality of life. Female sex is a known risk factor, and the observation that liver size tends to increase with estrogen exposure and shrink after menopause suggested that lowering estrogen might be a useful therapeutic target. This study tested that idea directly.
The investigators randomized premenopausal women aged 18 to 45 with severe PLD, 1:1, to either an immediate start of leuprorelin or standard care with a delayed leuprorelin start at 18 months. Leuprorelin is a gonadotropin-releasing hormone (GnRH) agonist, given as an 11.25 mg injection every three months, which suppresses estrogen and progesterone and produces a medically induced menopause. Six women were assigned to immediate leuprorelin and eight to standard care. The primary outcome was the rate of liver growth at 18 months.
Liver growth did not differ meaningfully between groups. In the immediate-start group, liver volume still increased in half of participants. The median liver growth rate was 4.04 percent per year (range -4.62 to 6.84) with leuprorelin versus 11.0 percent per year (range 0.70 to 13.2) with standard care, a difference that was not statistically significant (p=0.15). Given the very small sample, this result cannot establish that leuprorelin has no effect on liver volume, only that no benefit was detected in this trial.
Secondary outcomes were less favorable. PLD-related quality of life did not improve with treatment. Menopausal side effects were severe enough that one participant discontinued treatment early. The total number of adverse events was 38 in the immediate-start group compared with 9 in the standard care group (p<0.001). Because of these findings, the investigators terminated the study early after an interim analysis.
The authors' conclusion is direct: leuprorelin did not reverse liver volume, and the menopausal side effects and adverse events were substantial. The trial's small size, open-label design, and early termination mean the findings should be read as preliminary, but they do not support estrogen suppression as a routine option for this population on the basis of this evidence. The hypothesis that estrogen drives liver growth in PLD remains plausible given earlier observations, but this trial did not confirm that lowering estrogen slows liver enlargement in a clinically meaningful way.
| Field | Detail |
|---|---|
| Study type | Prospective, open-label randomized controlled trial |
| Population | Premenopausal women aged 18 to 45 with severe polycystic liver disease |
| Sample size | 14 (6 immediate leuprorelin, 8 standard care with delayed start) |
| Intervention | Leuprorelin 11.25 mg injection every 3 months (GnRH agonist) |
| Comparator | Standard care with leuprorelin start at 18 months |
| Primary outcome | Liver growth rate at 18 months |
| Key secondary outcomes | Quality of life, menopausal side effects, adverse events |
| Result (liver growth) | 4.04 vs 11.0 %/year, p=0.15 (not significant) |
| Result (adverse events) | 38 vs 9, p<0.001 |
| Journal | Hepatology Communications |
| Evidence tier | B |
1. Study: Effects of the GnRH agonist leuprorelin on liver volume in premenopausal women with severe polycystic liver disease. *Hepatology Communications*. PubMed. https://pubmed.ncbi.nlm.nih.gov/42900154/
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