mTOR inhibitors and risk of ovarian cysts: a systematic review and meta-analysis

Fabio Parazzini, Sandro Gerli, Alessandro Favilli, M. Vignali, Elena Ricci, Sonia Cipriani, Francesça Chiaffarino, A. Dell’Acqua, Sergio Harari, Stefano Bianchi
In: BMJ Open · 2021 · vol. 11(9) , pp. e048190 · doi:10.1136/bmjopen-2020-048190 · PMID:34561260 · W3199340981
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This meta-analysis of seven studies found that ovarian cyst development occurred in 37.0% of women treated with mTOR inhibitors, with 17.3% experiencing clinically significant cysts.

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Abstract

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.

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