Leuprorelin did not shrink polycystic livers and caused heavy menopausal side effects

Design

Prospective, open-label randomised trial, stopped early

Population

14 premenopausal women aged 18–45 with severe polycystic liver disease, the Netherlands

Primary outcome

Liver growth rate at 18 months

Effect

Median 4.04 vs 11.0 %/year (p = 0.15); adverse events 38 vs 9 (p < 0.001)

Oestrogen drives cyst growth in polycystic liver disease, and livers often shrink after menopause, so inducing menopause medically was a logical idea. This open-label Dutch trial randomised premenopausal women aged 18 to 45 with severe disease to start leuprorelin 11.25 mg every three months immediately (6 women) or after 18 months of standard care (8 women). The primary outcome was liver growth rate at 18 months.

Liver volume still increased in half the treated women. Median growth was 4.04% a year with leuprorelin against 11.0% with standard care, a difference that was not significant (p = 0.15). Disease-related quality of life did not improve, menopausal side effects were severe enough for one woman to stop, and adverse events totalled 38 against 9 (p < 0.001). The trial was ended early.

With 14 participants, a modest effect cannot be ruled out, but any benefit would have to be weighed against substantial harm in young women. Somatostatin analogues remain the main medical option for symptomatic disease, with procedures or transplantation for the most severe.

• Do not use GnRH agonists to treat polycystic liver disease outside a trial.
• Advise women with polycystic liver disease to avoid oestrogen-containing contraception and hormone therapy where possible.
• Somatostatin analogues are the established medical option for symptomatic, enlarging polycystic livers.
• Refer severe, symptomatic disease to a centre offering fenestration, resection or transplant assessment.

Why it matters

It closes off a hormonal approach that looked plausible and would have meant medical menopause for young women.

Don't overread it

With 14 participants, the trial cannot exclude a small effect on liver growth.

The statistics, in plain English

A p value of 0.15 with only 14 women means the trial could not detect anything but a large effect. The fourfold excess of adverse events is the firmer finding.

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