Effects of the GnRH agonist leuprorelin on liver volume in premenopausal women with severe polycystic liver disease

Background: Polycystic liver disease (PLD) is characterized by multiple liver cysts, sometimes leading to severe liver enlargement, with associated physical and psychosocial complaints. Treatment options are limited. Female gender is a risk factor for PLD; estrogen supplementation increases liver size in women with PLD, whereas the polycystic liver decreases after menopause. Estrogens may therefore be a target for therapy.

Methods: In this prospective, open-label study, premenopausal women aged 18−45 years with severe PLD were randomized 1:1 to a direct start of the gonadotropin-releasing hormone agonist leuprorelin (n=6) or to standard care with delayed start of leuprorelin 18 months after randomization (n=8). The gonadotropin-releasing hormone agonist (11.25 mg injections once every 3 mo) leads to a reduction in estrogens and progesterone, and consequently to medically induced menopause. The primary outcome was liver growth rate at 18 months. Secondary outcomes comprised quality of life, menopausal side effects, and adverse events. An interim analysis was performed when all participants had reached month 18, as notable side effects were expressed.

Results: In the group with direct start of leuprorelin, liver volume still increased in half of the participants, with the median liver growth rate not significantly different from the standard care group (4.04 [−4.62 to 6.84] vs. 11.0 [0.70−13.2] %/year, respectively, p =0.15). Importantly, PLD-related quality of life did not improve with treatment, whereas menopausal side effects were severe, leading one participant to stop treatment early. The total number of adverse events in the direct versus standard care group was 38 versus 9, respectively ( p <0.001). Because of these results, the study was terminated early.

Conclusions: leuprorelin treatment did not reverse liver volume, while menopausal side effects and adverse events were substantial.