MTOR inhibitors and risk of ovarian cysts : A systematic review and meta-analysis

Objective To summarise the available evidence on frequency of ovarian cyst development during mammalian target of rapamycin inhibitors (mTORi) treatment. Methods PubMed/Medline and EMBASE databases were searched, from 1990 up to March 2020, using the following keywords: 'tacrolimus', 'sirolimus', 'temsirolimus', 'everolimus', 'deforolimus', 'mTOR' and 'ovarian cysts' (Limit: Human, English, full article). Studies were selected for the review if they met the following criteria: clinical studies, studies reporting original data, studies reporting the number of patients using mTORi, studies reporting the number of patients with ovarian cysts. We selected 7 of 20 retrieved studies. Study design, population, sample size, criteria for diagnosis of ovarian cysts, drug doses and follow-up length were extracted. Pooled estimate of incidence was calculated for ovarian cysts as a percentage, with 95% CI. Results Four hundred-six women were included in the selected studies. The pooled incidence was 37.0% (95% CI 16.0% to 58.1%) for all ovarian cysts, and 17.3% (95% CI 5.6% to 29.1%) for clinically significant ovarian cysts. Based on two articles, comparing mTORi and non-mTORi for immunosuppression, pooled OR for ovarian cyst incidence was 4.62 (95% CI 2.58 to 8.28). Conclusion Ovarian cyst development is a common adverse event during immunosuppression treatment with mTORi. These cysts are benign conditions, but they require pelvic ultrasound follow-up and in some cases hospital admission and surgery.