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

BMJ Open. 2021 Sep 24;11(9):e048190. doi: 10.1136/bmjopen-2020-048190.


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.

Keywords: adverse events; epidemiology; gynaecology.

Publication types

  • Meta-Analysis
  • Systematic Review

MeSH terms

  • Everolimus
  • Female
  • Humans
  • Incidence
  • Ovarian Cysts* / chemically induced
  • Ovarian Cysts* / epidemiology
  • Pelvis
  • TOR Serine-Threonine Kinases


  • Everolimus
  • MTOR protein, human
  • TOR Serine-Threonine Kinases