Impact of Menopausal Hormone Therapy on Colorectal Cancer Risk

A Systematic Review

Livia Nakhostin; Aurelia Stadler; Petra Stute


Clin Endocrinol. 2021;95(3):390-397. 

In This Article

Abstract and Introduction


Colorectal cancer (CRC) is the second most frequently diagnosed cancer in females worldwide. Menopausal hormone therapy (MHT) has been proposed as a potential protective factor for the development of CRC. Yet, the available evidence is controversial. Thus, we aimed at summarizing the current evidence on the effect of MHT on CRC through a systematic review. A systematic literature search identified 1001 potentially relevant articles, out of which 57 original studies and nine meta-analyses were deemed eligible for the final synthesis. The evidence synthesis showed the following: (1) MHT showed a heterogeneity in findings for CRC risk with a slight tendency to a neutral or protective effect; (2) MHT effect was either neutral or protective on colorectal adenoma; (3) MHT had no impact on tumour grade, subsite and histologic types; (4) MHT was not associated with CRC mortality; and (5) MHT showed heterogeneous effects on CRC stage and invasiveness, respectively. In summary, despite some evidence pointing towards a protective effect of MHT on CRC, MHT is currently not recommended for primary CRC prevention by international guidelines due to several important, potentially harmful effects.


Menopausal hormone therapy (MHT) is considered to be the most effective treatment for disturbing menopausal symptoms such as vasomotor symptoms and sleeping disturbances.[1] MHT is prescribed in various forms, doses and regimens of oestrogens with (uterus present) or without (post-hysterectomy) progestogen. The onset of natural menopause at an average age of 51 years coincides with increasing risks for non-communicable diseases and some types of cancer, for example colon cancer. Before the publication of the Women's Health Initiative in 2002, MHT was commonly prescribed for primary prevention of cardiovascular disease, osteoporosis, cognitive impairment and some types of cancers in women with and without menopausal symptoms.[2] Colorectal cancer (CRC) is the second most frequently diagnosed cancer in women worldwide and therefore a substantial health risk. CRC incidence and mortality can be reduced by detection and removal of precancerous lesions through CRC screening, as well as adjustment of modifiable risk factors, such as diet, alcohol consumption, tobacco smoking and physical activity.[3] Whereas these factors are accepted modifiable risk factors for CRC, the debate about the potential protective role MHT on CRC remains controversial.[3] Thus, the purpose of this review was to update and synthesize the current evidence on the role of MHT on CRC risk. Study outcomes were differentiated by the risk for colorectal adenoma, risk for colorectal cancer, colon and rectal cancer, tumour stage and invasiveness, tumour grade, molecular and histologic characteristics, colon cancer site and mortality.