Million Women Study

- Novo Nordisk position statement

11 August 2003

This was an epidemiological study, which involved 1.084.110 women in the UK aged 50-64 years. Women who were invited for a routine breast screening were asked to participate in this study and to fill in the questionnaire. They were recruited between 1996 and 2001, the average period of follow up was 2.6 years for breast cancer incidence.

The results of this study are similar to some other findings that current and recent use of HRT increases the risk of diagnosing breast cancer. The absolute numbers of additional cases remain low (0 – 3 in women using unopposed estrogens, 5 – 7 in women using oestrogen-progestogen combinations per 1.000 women after 5 years HRT use). The WHI study showed a lower relative risk for the diagnosis of breast cancer: RR 1.26, over 5.2 years of the follow up. This risk was significant only after 4 years of treatment in pre-treated patients who had previously been on HRT. It is widely accepted that the results of randomized trials have greater validity than epidemiological observations.

It is relevant to point out that the Million Women Study did not show any dose relationship with regard to the risk of diagnosing breast cancer. The classification of the two estradiol dose groups is not appropriate, because the < 1 mg estradiol group includes all transdermal preparations, which are not comparable to oral preparations (e.g. 0.05mg - 0.1mg patches are equivalent to 2 – 4mg oral estradiol). In addition oral 1 mg estradiol represented 3.1 % of the unopposed oestrogen market in 1999. However, assuming that oestrogen plays a role in changing the growth pattern of a pre-existing tumor, it is reasonable to hypothesize that this is a dose-related phenomenon.

There were no significant differences between different HRT combinations containing different progestogens.

The results of this study demonstrate that the use of local HRT such as Vagifem are not associated with any increased risk of breast cancer (RR 0.67).

Novo Nordisk’s low dose preparations (Activelle, Novofem, Estrofem 1mg) were either not included in the study (Novofem and Estrofem 1mg were not on the UK market at the time of the study) or, if used could only have been marginally used (Activelle had a market share of 0.6% in 1999). In 1999 Novo Nordisk had a market share of 8.4% (Kliogest 5.5%, Trisequens 2.3%) of the total systemic HRT market (volume, cycles).

Novo Nordisk has continuously updated the prescribing information to reflect the most current medical beliefs concerning all potential adverse events. The prescribing information includes reference to the increased risk of diagnosis of breast cancer, associated with the use of the HRT medicines studied in both the warning and adverse reactions sections of Novo Nordisk’s HRT medicines.

HRT is indicated for the relief of menopausal symptoms and as a second line therapy for the prevention of osteoporosis. Each decision to start HRT should be made on an individual basis, and treatment should be regularly reappraised (at least once a year). Women, who wish to stop HRT, or change their current preparation, should make a routine appointment to discuss their treatment options with their doctor.

Please refer to the British Menopause Society press release for further information regarding the Million Women study.