What’s News: Ovarian Cancer and HRT

One of the nice things about being friends with the country’s best menopause blogger, is that I sometimes get a heads-up about controversial new articles regarding Hormone Replacement Therapy (HRT). So hat’s off to Ellen Dolgen for tipping me off to this new study in the British journal Lancet which says that HRT causes a small increase in the risk of Ovarian cancer. “What do you think of this?” she asked, casually turning my evening upside down…

Well, my first thought is:


First, we need to remember why enlightened doctors recommend hormone replacement after menopause: because estrogen cuts the risk of heart disease in half– and heart disease is the number one killer of women!

So it is very important to keep things in perspective: if you are a woman at menopause, starting HRT is almost four times more likely to save your life than it is to give you breast or ovarian cancer.

With that in mind, I can unequivocally say that this article does not change my opinion: women should absolutely still use HRT, starting shortly after menopause and continuing for decades.

That opinion is probably not too surprising to those of you who have read my prior blog posts on HRT and cancer risk (and if you haven’t, jump right in here and here).

What may be surprising however, is that I’m going to go one step further and say that I think that this new article is great news for women!

Ovarian Cancer?? WHEW!

“What??”, you may ask? “How can ovarian cancer –caused by a therapy you are recommending!– be great news??”

Sit back, put your feet up, I’ll tell you…

First, and most important: If this new study is accurate, how significant is the increased risk of ovarian cancer due to HRT?

The authors state:

The increased risk may well be largely or wholly [caused by HRT]; if it is, women who use hormone therapy for 5 years from around age 50 would have about one extra ovarian cancer diagnosis per 1000 users and, if its prognosis is typical, about one extra ovarian cancer death per 1700 users.

A brief stroll down Memory Lane

Here is a quick review of the analysis I wrote looking at the Danish HRT study published in December 2012 (that news outlets completely ignored):

The Danish Osteoporosis Prevention Study was a prospective, placebo controlled trial of HRT (using bio-identical estradiol, no less) that included 1000 women. Two years before that study was published, the Endocrine Society (as mainstream a group of docs as you can find!) reviewed ALL studies on HRT, and published a 66 page report. One of their findings was particularly astounding:

Menopausal Hormone Therapy was associated with a 40% reduction in mortality in women in trials in which participants had a mean age below 60 yr or were within 10 years of menopause onset.

JCEM July 1, 2010 vol. 95 no. 7 Supplement 1

That’s right: they said that women on HRT had a 40% lower risk of death, as long as they started within ten years of menopause! Is that really possible? Well, the Danish trial results were published two years later, so the Endocrine Society had not seen those results– so let’s take a look:
The Endocrine Society’s criteria fit the participants in the Danish trial: the women were all within ten years of menopause onset. And sure enough: over the ten years of the Danish study, 15 of the women who took HRT died —but in the control group (women who did NOT take HRT), 26 women died! HRT lowered their mortality rate by 42%, right in line with what the Endocrine Society review predicted back in 2010.

So, that is something that we have seen across all HRT studies, whether using bio-identical estrogen or not: women who start HRT around age 50 and continue for ten years, have a 40% lower risk of death from any cause while they take hormones– mostly due to the incredible cardiovascular prevention that estradiol confers, but also due to prevention of osteoporosis.

If the women stop using HRT, their risk of death slowly goes up, back towards that of women who did not have the benefit of hormones. If you would like more detail about that, click here—...

After ten years, the women in the Danish stopped using HRT. But the authors followed the women for six more years. How did they do after stopping HRT? At the end of the 16 years,

In the control group there were 23 deaths due to cardiovascular causes and 17 due to non-cardiovascular causes. In the treatment group there were six deaths due to cardiovascular causes and 21 due to non-cardiovascular causes.

So: after 16 years, there had been 40 deaths in the women NOT on hormones (the control group), vs. 27 deaths in the women using HRT (ten years on HRT, 6 more not on HRT). In other words, their risk of death slowly headed back towards baseline after they stopped HRT, so that after six years not on HRT, their risk of death was lower by only 33%, not 42%. To put it another way: HRT = good; stopping HRT = bad.

–but the gist of it is: for most women, using hormone replacement for 15 years is much better than using HRT for just ten years, in spite of what your gynecologist may tell you.

40% lower mortality is amazing… But can we do even better??

Believe me, I am well aware of how awful a battle with ovarian cancer can be. One of my dear friends (who is not on HRT) just started chemo for ovarian cancer this week, and even as I write this my heart aches for her and her husband. I know they are going to beat it, but the fight will be long and draining, and I wish with all my heart that they did not have to go through it.

So why would I say that this new study, which apparently shows a small increase in ovarian cancer due to HRT, is actually GOOD news??

I say that because a death from ovarian cancer is already accounted for in that “40% lowered mortality” statistic– but now we know of something in particular to watch out for.

Meaning, a woman who is using HRT has a 40% lower risk of death from any cause– which is truly amazing, and makes HRT better than any drug ever invented– but it doesn’t make her immortal: obviously, she can still die. This study now tells us, “Hey, we have a hint as to one of the things that is slightly more likely to kill her than average. So now you know: if she’s on HRT, be extra vigilant for ovarian cancer– and maybe you can drop her risk of death by even MORE than 40%.”

Let’s go through that in more detail:

What is the ten-year risk of death (from any cause) for a 50 year old woman? Based on this website from the American Academy of Family Physicians, if you track a thousand 50-yr-old women, 42 will die before they reach 60.

So: For every thousand women who are 50 years old, over the next ten years,

  • 2.2 will get diagnosed with ovarian cancer,
  • and 42 will die (from all causes: heart attack, stroke, cancer, you name it).

But what if those same thousand women start taking HRT? Remember the Endocrine Society statement: .

Menopausal Hormone Therapy was associated with a 40% reduction in mortality in women in trials in which participants had a mean age below 60 yr or were within 10 years of menopause onset.

JCEM July 1, 2010 vol. 95 no. 7 Supplement 1

A 40% reduction in death!  Of those 42 women who would have died before age 60: If they use HRT, 40% of them will live! 40% x 42 women = 17 more women will live because those thousand women used HRT.

And what about ovarian cancer? Over that same ten years, will HRT cause some of those women to be diagnosed with ovarian cancer? Well, according to this new study, women who use hormone therapy for 10 years from around age 50 would have about two extra ovarian cancer cases per 1000 users and, if its prognosis is typical, about 1.2 extra ovarian cancer deaths per 1000 users.

So, let’s put it all together:

  • If you look at 1000 women who are age 50, on average over the next ten years 42 of them will die—UNLESS you give them HRT
  • If you give them HRT, 40% fewer will die: meaning if they use HRT, over that same ten years only 25 women will die instead of 42 women; i.e.  HRT will save 17 lives
  • but here is the kicker: of those 25 women who will nevertheless die despite getting HRT– now we know that 1.2 of those deaths may be due to ovarian cancer, which is above average
  • And that is why I say that this study is good news: we already knew that of those thousand 50-yr-old women who start HRT, HRT will save the lives of 17 of them– and now we have some added useful information:
    Of the 25 women who, despite using HRT, will die before they reach age 60, we now have a hint of what they might die from.
    Obviously, that means now we are empowered to be more vigilant: we can recommend more regular CA-125 with pelvic ultrasounds (and MRIs if there is any doubt), and hopefully catch them before it is too late. The risk of death from ovarian cancer is MUCH lower if it is caught early. So, this article gives us a heads-up as to how we can save a couple more lives.

(But traditional screening for ovarian cancer is notoriously inadequate– aren’t I being cavalier??
I don't believe so. Click here for more detail.)

It is true that traditional screening for ovarian cancer has a high failure rate. But this is why it’s important to maintain proper perspective: Even if no additional screening is done, HRT still saves lives and is the right answer from a public health standpoint. Remember that ovarian cancer screening is only recommended for high-risk women. For the vast majority of women, ovarian cancer screening is not recommended at all, and this article isn’t going to change that: i.e. the public health recommendations are not going to change to say that women on HRT now fall into a “high risk” category. This minimal increase in risk from HRT does not in any way compare with the increased risk of a BRCA carrier. So, unless you are in a high-risk category based on your family and genetic history, public health recommendations are going to say that this study should yield no change in your behavior: even though you are on HRT, no additional screening is warranted.

It is also worth pointing out that traditional — relatively ineffective– screening consists of serial CA-125 plus transvaginal ultrasound. In my practice, women can usually pay for screening that their insurance won’t cover, so I have the option of getting an MRI if we have any concern. MRI does increase sensitivity and specificity significantly in looking for ovarian cancer. (If there is any doubt, or certainly if the woman is a BRCA1 carrier, I would probably suggest getting an oophorectomy and using HRT.)
So, it is true that in my practice we have some screening options that may not make sense from a public health standpoint– but as I said, even without any additional screening, HRT would still be the way to go.

Knowledge is Power… and Prevention is the name of the game!

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