Researchers studying a large population of women in Denmark found that those who took hormone replacement therapy (HRT) after menopause had a significantly higher risk of developing ovarian cancer than those who did not. However, one independent expert suggested the findings don’t prove that HRT causes ovarian cancer and aren’t clear enough to help women weigh up the pros and cons of going on HRT.
The study was the work of first author Lina Steinrud Morch of Copenhagen University and colleagues and is published in the 15 July issue of the Journal of the American Medical Association, JAMA.
While other studies have suggested a link between ovarian cancer and postmenopausal hormone therapy, they don’t reveal how this might depend on the type, dose and duration of therapy, wrote the researchers.
Using national registries, they followed a cohort of 910,000 Danish women aged 50 to 79 for an average of 8 years (equivalent of 7.3 million women-years). During that time 3,068 incident ovarian malignancies (2,681 of which were epithelial cancers) were diagnosed. Epithelial ovarian cancers are those that start on the surface layer of the ovaries as opposed to in the eggs (germ cell cancers).
At the end of the follow up period, 63 per cent of the women had never used HRT, 22 per cent had used it but were using it no longer, and 9 per cent were still using it (current users).
The results showed that:
- Compared to women who never took HRT, current and previous users had a higher risk of developing an ovarian cancer (relative risk, 1.38 and 1.15, respectively).
- The incidence rates in current and never users of hormones were 0.52 and 0.40 per 1000 years, respectively, ie, an absolute risk increase of 0.12 per 1000 years.
- This is approximately the equivalent to 1 extra ovarian cancer for roughly 8,300 women taking HRT each year.
- Excess risk was observed even with short-term use of HRT (for instance for up to 4 years of use the relative risk was 1.33).
- The excess risk did not rise substantially with longer use.
- The risk declined with years since last use.
- By 2 years after stopping use of HRT, the risk of developing any ovarian cancer was the same as that of never users.
- By 6 years after stopping use of HRT, the relative risk was 0.63.
- The risk was similar among women who took estrogen only HRT as those who took estrogen plus progestin, and the type of progestin made no difference.
- Among women who took estrogen only, the oral method but not the transdermal (skin patch) was linked to a much higher risk than never users (relative risk 1.34 for oral and 1.13 for transdermal).
- Vaginal estrogen was also linked to a marginally higher risk (relative risk compared with never users was 1.23).
The researcher concluded that:
“Regardless of the duration of use, the formulation, estrogen dose, regimen, progestin type, and route of administration, hormone therapy was associated with an increased risk of ovarian cancer.”
These findings appear to confirm those from the 2002 Women’s Health Initiative study, which was stopped early because researchers found an increased risk of ovarian cancer, breast cancer, and other diseases linked to use of HRT.
Dr Garnet Anderson, an ovarian cancer researcher at the Fred Hutchinson Cancer Research Center in the US was quoted by NCI Cancer Bulletin as saying that:
“Here we see that combination therapy had essentially the same amount of increased risk as estrogen-alone therapy.”
Anderson said these findings are not likely to affect the current US guidelines on hormone therapy, which urge women to use the smallest possible dose for the shortest time period.
Commenting in Journal Watch, editor in chief Dr Andrew M Kaunitz, Professor and Associate Chair of the Department of Obstetrics and Gynecology at the University of Florida College of Medicine-Jacksonville, suggested that the “modest elevations in risk for ovarian cancer” from menopausal HRT use found in this large study could be the result of detection bias arising from the greater likelihood that HRT users would be receiving more medical attention (including diagnostic services) than non users.
“The observation of excess ovarian cancer risk among women who had just initiated HT suggests the presence of such bias,” wrote Kaunitz.
Moreover, he commented that the fact that the researchers found similar risks with short and long term use of HRT, and that risk in women who stopped taking it rapidly approached that of never users should be taken into account when considering whether the extra risk was caused by HRT or not.
“Although risk-reduction strategies for ovarian cancer should remain high priorities, whether these findings should be used to counsel women who are weighing the pros and cons of HT is not clear,” wrote Kaunitz.
“Hormone Therapy and Ovarian Cancer.”
Lina Steinrud Morch; Ellen Lokkegaard; Anne Helms Andreasen; Susanne Kruger-Kjaer; Ojvind Lidegaard.
Vol. 302 No. 3, July 15, 2009
Source: JAMA Archives, Journal Watch, NCI Cancer Bulletin.
Written by: Catharine Paddock, PhD