Menopausal hormone therapy and ovarian cancer

It is clear from the data discussed above and from the recent meta-analysis[ 1 ] that when considering a possible link between MHT and risk of ovarian cancer, there remain a number of inconsistencies. To confidently attribute cause and effect for a risk as small as that suggested for MHT on ovarian cancer is testing the limits of meta-analysis and would require complete data. Unfortunately, despite the best efforts of the investigators, in this meta-analysis the data were incomplete. Two studies, The Million Women Study[ 7 ] and The Danish Sex Hormones Register Study[ 8 ] contributed 76% of the prospective data and one of these provided no information at all on oral contraceptive use, BMI, family history, neither age at menopause nor on women younger than 55, and the age group most likely to use MHT. All hysterectomized women <55 were excluded from the analyses and no information was available regarding an indication for the surgery. As estrogen only therapy is only prescribed for hysterectomized women, it is difficult to see how the investigators accurately calculated a risk for estrogen only therapy in the under 55 cohort. Data on the removal of fallopian tubes among women undergoing hysterectomy were unavailable. It is also quite unusual to see a lower risk from retrospective, case- control studies, which usually amplify the risk. It is also unusual not to see an effect if the duration of therapy such as had been reported in some earlier studies. This may be a sign of possible detection bias. In addition, not all confounders were identified or considered which may have affected final results. In a sub-analysis of the 17% of women for whom appropriate details were available, it was surprising to see no effect for commonly known risk factors for ovarian cancer. Finally, the issue of detection bias (women receiving treatment are more likely to have had examinations and investigations than those not) was not considered. Receptors for estradiol may be found on epithelial ovarian cancer cells thus providing some biological plausibility for a link between MHT and ovarian cancer. However the failure of this meta-analysis and earlier epidemiological studies to find any association between dose or duration of MHT and change in risk, argues against cause and effect, as does the overall inconsistency of effect on the different subtypes of epithelial ovarian cancer. A number of established risk factors for ovarian cancer suggest that rather than estrogen itself being a risk factor, it may be more frequent ovulation, which is the culprit. Factors such as increased parity, breastfeeding, and the combined oral contraceptive all lead to less frequent ovulations and are also associated with a reduced lifetime risk of ovarian cancer. In support of this proposition, a recent study in poultry found that hens bred to lay eggs daily had a greater risk of ovarian cancer than hens, which did not, a finding possibly linked to the overexpression of oviduct-related genes. This new meta-analysis has been a brave attempt to bring some clarity to the vexed question of whether or not there is an association between MHT use and the risk of ovarian cancer. That it has not succeeded, should not be seen as a failure but, rather, as an acknowledgment that the instruments used are not powerful enough to measure any possible tiny change in the risk of a rare condition. What does this new study mean for women? It does not mean women should stop taking MHT. Rather, it is a reminder that the principal reason for taking MHT is the alleviation of troublesome menopausal symptoms. Considerations such as quality of life, protection against osteoporosis and cardiovascular disease, and risk of breast cancer far outweigh any risk of ovarian cancer and each individual woman should evaluate her own individual risk: benefit profile in consultation with her personal physician before deciding whether starting or continuing MHT, is the right choice for her. The link between MHT and ovarian cancer remains unproven and consequently there should be no need for any change in clinical practice.

The link between MHT and ovarian cancer remains unproven. The principal indication for MHT use is alleviation of menopausal symptoms. Each woman should discuss her own individual risk factors before commencing or continuing MHT. Current evidence regarding MHT and ovarian cancer risk does not suggest a need for any change in clinical practice. The link between MHT and ovarian cancer remains unproven. The principal indication for MHT use is alleviation of menopausal symptoms. Each woman should discuss her own individual risk factors before commencing or continuing MHT. Current evidence regarding MHT and ovarian cancer risk does not suggest a need for any change in clinical practice. Nil. There are no conflicts of interest.