February 13, 2015

expert reaction to study associating hormone replacement therapy (HRT) with increased risk of ovarian cancer

Researchers publishing in The Lancet have conducted a meta-analysis of 52 studies with the aim of evaluating a possible link between the use of hormone replacement therapy and ovarian cancer. They report that there was an increased risk of ovarian cancer in those who used hormone replacement therapy, and that this declined after its use ceased.

Prof. Anne Gompel, Professor of Medical Gynaecology, University Paris, said:

“This study is a meta-analysis of 52 epidemiological studies. A total of 21488 cases and 63846 controls were gathered from retrospective and prospective studies; 12110 cases came from the prospective studies among which 6601 were observed in women who had used MHT with median duration 6 years. Analyzing the global risk for ever users compared to non-users, (see Appendix), the RR= 1.20 (95% CI,1.13-1.28) in prospective studies, RR= 1.02(0.93-1.11) in retrospective studies and  RR=1.14 (1.09-1.20) in all studies. Analysis according to duration of use gathered from prospective studies showed that duration is not associated with an increased risk in current users, which is quite unusual for a causal factor.

“In addition, a major flaw can be discussed: in the prospective studies, two studies represented about 75% of the population, the Million Women Study (MWS) and the Danish Sex Hormones Register Study (DaHoRS). In the DaHoRS, no information was available on contraception use, BMI, age at menopause, which are well established risk factors for ovarian cancer. Thus the results published here represent mostly the MWS data in terms of adjustments. This meta-analysis “appears” to give a confirmation of an increased risk of ovarian cancer especially serous and endometriod tumors. Unfortunately this relies on possible flaws and reflects mostly the previous data from the MWS and does not contribute to evaluate more specifically the level of increase in the risk if any.

“As a reassuring observation, the mortality rates from ovarian cancer obtained from the WHO data,( http://www-dep.iarc.fr/WHOdb/WHOdb.htm) show a continuous decrease since the mid-90s in France, a progressive decrease also in the UK and USA, with somehow an acceleration of this decrease since 2006/2007 only in UK and USA.”

Prof. Montserrat Garcia-Closas, Professor of Epidemiology, The Institute of Cancer Research, said:

“This new study provides convincing evidence for a link between HRT use and a modest increase in risk of developing two of the most common types of ovarian cancer. It means it will be important to consider the risk of ovarian cancer in the balance between benefits and risks of taking HRT.

“A woman’s decision on taking HRT needs to take into account the risk-benefit trade-offs of multiple factors, not just ovarian cancer – for instance her underlying individual risk of HRT-related diseases such as blood clots in the veins, and her risk of developing breast and ovarian cancer due to other factors. This underlines the need for better tools to assess individual disease risk, to allow women to take better informed decisions on whether to take HRT or not.”

Prof. Rod Baber, Clinical Associate Professor of Obstetrics and Gynaecology, University of Sydney, and President of the International Menopause Society, said:

“The authors are to be congratulated on their efforts to try to provide some clarity on the subject of ovarian cancer risk and hormone replacement therapy (HRT). This has for some time been a contentious issue. The largest randomised trial of HRT use, The Women’s Health Initiative, found no increased risk of ovarian cancer with use of HRT for 5 years.

“This meta-analysis of 52 epidemiological studies has reported an increased risk of ovarian cancer with use of HRT.

“Interestingly, and perhaps surprisingly, this risk is the same for both oestrogen only use and for combined oestrogen plus progestogen use and is unrelated to duration of therapy.

“There is no correlation with dose of HRT, although this is, on average, probably higher than that used today, nor is there any distinction between oral and non-oral administration or between sequential and continuous progestogen use.

“The prospective data is heavily influenced by two studies, MWS and DahoRS neither of which corrected for previous use of oral contraceptives and the retrospective data contains only one study (Negri et al) which found a significant increase in risk. The total American and other region studies found no increase in risk overall.

“Therefore, this study looks at a heterogeneous study population, with, in some cases, incomplete data and tries to attribute cause and effect between HRT use and a heterogeneous group of ovarian cancers of which two types out of four purportedly showed an increased risk.

“That this risk in absolute terms then comes down to one excess case of ovarian cancer per 2000 users after 5 years of use means that for women using HRT this risk is very very low in absolute terms and may be beyond the capacity of a meta-analysis of observational studies to accurately predict.

“My advice to women using HRT would be that this study at worst suggests a very small increase in risk with use of HRT, that this is no reason for them to stop taking their HRT, that the benefits of HRT in their own individual case should be weighted up against this information and that they should discuss this with their own doctor.”

‘Menopausal hormone use and ovarian cancer risk:  by name of Beral et al. will be published in The Lancet at 00:01 UK time on Friday 13th February 2015, which is also when the embargo will lift. 

All our previous output on this subject can be seen at this weblink: http://www.sciencemediacentre.org/?s=hormone%20replacement%20therapy&cat

Declared interests

Prof. Anne Gompel: Is a member if IMS, EMAS, GEMVI (French society of menopause), ESE, Endocrine Society, a past board member of EMAS and IMS, and a current board member of GEMVI.

She has the following grant funding: on estetrol research on breast cells. Luteron  (Pharma) (2012), on Ulipristal acetate on the breast . HRA-Pharma (2009-12), in the past lectures for Besins on progesterone and the bebreast/endometrium (no honorarium)

Prof Rod Baber – I have conducted research for various pharma companies involved with menopausal health. All moneys have been paid into a trust account administered by Royal North Shore Hospital in Sydney and I have received no financial benefit from these trials

I have acted as a speaker for various pharma companies as above.  My presentations have always been of my own choosing and independent of any outside influence. I have received honoraria for the presentations of these lectures.

I am not on any speaker bureau, I am not on any advisory boards and I hold no relevant shares

No other interests declared.