HRT Worries – This Time, It’s Ovarian Cancer Again….

HRT once again takes the media center stage, this time with new research linking post-menopausal estrogen use to ovarian cancer.

The data comes from a large European study  – the European Prospective Investigation into Cancer and Nutrition – and was presented as a poster (abstract B101 in the linked pdf) at the American Association for Cancer Research Meeting in Philadelphia.

In this study of over 160,000 women with 9 years of follow-up, use of post-menopausal estrogen-only therapy for more than five years was associated with a small but significantly increased of ovarian cancer. The increased risk occurred across all types of estrogens (sorry, Suzanne….) and all routes of administration, and increased with duration of estrogen use.

No increase in ovarian cancer risk was found for women taking estrogen plus progestin therapy.

This is not the first study to suggest that postmenopausal estrogen use may increase the risk of ovarian cancer.

  • The Breast Cancer Detection Demonstration project reported an increased ovarian cancer risk among users of estrogen-only (E) therapy. Similarly, that study found no increase in risk among users of estrogen plus progestin therapy.
  • The Womens’ Health Initiative reported an increase in ovarian cancers among users of combination hormone therapy (E+P) , but that risk was not statistically significant, since the data was based on only 32 cancers. To my knowledge, they have not yet reported ovarian cancer data from the estrogen-only arm of that study.
  • A Swedish study also reported ovarian cancer risks with estrogen only therapy, as well as with sequential estrogen + progestin, but not with combination daily E+P. In that study, a small increase in risk was also seen for low dose vaginal but not oral estrogen, and women who had had a hysterectomy did not have an increased risk of ovarian cancer with any regimen.

Just how big a risk are we talking about?

Unfortunately, I don’t have much to go on here, other than the research abstract (don’t get me started again on the publicity surrounding poster presentations instead of waiting for the peer-reviewed published papers), but let’s see what I can do….

There were 424 cases of ovarian cancer among 162,920 study participants during nine years of follow up, for an overall annual incidence about 3.7 per 10,000.  That number is remarkably similar to the risk for ovarian cancer among WHI participants – 3.4 per 10,000. Both seem a bit high given that the population incidence of ovarian cancer here in the US is 1.3 per 10,000 annually, and may be related to the age of the women in these studies. But lets go on….

Users of estrogen-only therapy had a relative risk for ovarian cancer of 1.65, meaning that their risk was 65% higher than that in women not using hormone therapy. Unfortunately, the abstract does not give us the risk in hormone non-users. But for argument’s sake, let’s suppose it is the same as the US background risk of 1.3 per 10,000.* Then the risk among users of estrogen-only HT would be 2.1 per 10,000, or an additional .02% per year.

What does this mean for you?

Let’s assume the association is real. Let’s also assume you are miserable with hot flashes or some other menopausal symptom and want to take hormone therapy.

What are your risks?

Well, that depends what regimen you take – estrogen alone or estrogen + progestin. And that, in turn, depends on if you have a uterus. Your risk for ovarian cancer will be further affected by whether or not you actually still have your ovaries.  Combining this data with that from the WHI (statistically, this is not permissible, but I have to practice medicine in real life, so I’m gonna’ do it.), let’s graph it out –


Notice that the risk for breast cancer among users of estrogen alone, at least in the WHI, was actually lowered. I put a question mark there because it remains a bit of a puzzle how that data came about, and no one is convinced yet, but there it is. (Update – I think I am beginning to understand how this might be possible. See this post for a possible explanation of these findings)

You can also see that no matter how you look at it, for an individual woman, these are small numbers. What makes them big is when millions of women use HRT – now we are increasing disease rates across a population.

What also becomes obvious is that the best cancer hand, so to speak, is dealt to the woman who has had a hysterectomy with removal of the ovaries. Of course, that woman has also had a major operation, which carries its own risks, so consider that before you go asking for a hysterectomy so you can take your hormones without any increased cancer risks.

Bottom Line

If you choose to take hormone replacement, you should consider both its risks as well as its benefits in making your decision.

Use of estrogen for less than 5 years did not increase ovarian cancer risks in this reported study, and in the WHI, the breast cancer risks did not kick in for the first 3-4 years of use. This suggests that short term use of HRT around menopause carries little risk, and goes along with recommendations that women use the lowest dose for the shortest period of time and reassess the need for continued use on an annual basis.

If you are one of those women who choose to take hormone therapy for prolonged periods of time, your risks, though real, are not large.

Remember too, that there are non-hormonal options for treating many of the symptoms of menopause.
* I am not a statistician, just a doc trying to figure out how to make this stuff make sense to my patients and inform my own medical practice. If any of my readers having more expertise in this arena wish to jump in to correct me or suggest better numbers, I’m all ears.

Photo credit – Picasso’s Portrait of Dora Maar. From Musee national Picasso, Paris


12/29/10 UPDATE – I’ve begun rethinking the breast cancer data on estrogen alone, based on something called the Gap Time Theory, which states that it is only because the women in the WHI were 10 years post menopausal that breast cancer risks were lower in the estrogen only arm. If this theory were true, it would remove that potential benefit in women starting estrogen only treatment at menopause. Until we have better studies, all of this is hypothetical, unfortunately.

5 Responses to HRT Worries – This Time, It’s Ovarian Cancer Again….

  1. this story re HRT is really bothering me: it does not discuss ovarian cancer risk at all. but the main reason i’m troubled is that it advocates a one-size-fits-all very pro-HRT approach, discounts risks, and does not address the need for an individual assessment based on the woman’s actual health and history. the authors promote use of HRT even for women who do not have menopausal symptoms, and suggest that long-term use will prove to be “more protective,” a virtual fountain of youth, although studies do not show that. [“yet.”] concerns are written off as “BS,” which is not to be believed.

    i find it insulting that this article urges the “smart” approach for a patient is to take the advice of internet doctors who have never seen them, rather than emphasizing the need for patients to discuss their individual circumstances with their own doctor. “ladiez, don’t worry your pretty little heads” is never a big seller with me. it also did not escape my attention that they refer to other works written by themselves to support this “advice.”

    in fact, there are reasons i am not taking HRT despite some significant life disruptions due to menopausal symptoms. i’m not the only one in this boat.

  2. I remember when I went through early menopause, at the age of 37, and my doc started me on estrogen replacement. Three months later, I landed in his office and said, “This makes me feel lousy.” To his ever-lasting credit (this was back when hormones were touted as ESSENTIAL), he said, “Then let’s stop.” Sure, I had some hot flashes, but I got through it. And here I am at the grand old age of 58, with nary a problem.

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