Hormone replacement therapy: Explaining the risks

Let me ask you a messing-with-your-mind type of question. Which of the following gives women the least relative risk of developing breast cancer?

1. Consuming an additional serving of french fries every week.
2. Eating more than a quarter of a grapefruit every day.
3. Working night shifts.
4. Being a Finnish or Icelandic flight attendant.
5. Taking antibiotics for things other than acne and rosacea.
6. Being a starving child in Holland at the end of the Second World War.
7. Using an electric blanket a lot.
8. Taking hormone replacement therapy to alleviate the effects of menopause.

The answer is ta-da hormone replacement therapy. I use the ta-da because if you are a sweaty, irritable, sleepless, achy, libido-challenged menopausal woman the ordering might surprise you.

In 2002, what was known as theWomen's Health Initiative a randomized study of more than 16,600 post-menopausal American women aged 50 to 79 was stopped more than three years early because it seemed evident that HRT was risky. The relative breast cancer rate increase cited originally as 26 per cent garnered the biggest headlines, but there was also some evidence that instead of protecting against heart disease and stroke as once thought, the data indicated HRT might increase the risk.

The response of the world's menopausal and post-menopausal women to the news is now seen as almost an object lesson in patients voting down risky treatments. Within a year, the number of HRT-related prescriptions in the U.S. think 90 million a year declined by two-thirds for the combined estrogen/progesterone treatment and by one-third for estrogen alone. Today, the number of U.S. HRT-related prescriptions is estimated to be half what it was before the WHI study came out. Similar trends are found in the rest of the developed world.

Only the scientific cat-and-dog fight over whether it was sensible for many women to quit HRT holus-bolus continues on two fronts.

One, summed up by Spanish gynecologist Santiago Palacios in a recent article, is that "despite the drawback in hormone treatment for menopausal women during the last three to five years, there has been no argument about the efficacy and superiority of estrogen as a treatment of choice for menopausal symptoms."

The other is that there is no ending to the debate over HRT risk and benefits. This month the world was told HRT increased lung cancer death risk. In April, it was said to lower colon cancer risk. In February, it increased breast cancer. In January, the Society of Obstetricians and Gynaecologists of Canada declared it safe and effective just as another study was declaring that using it could shrink the brains of post-menopausal women.

The fundamental question all these disagreements raise is whether there is a better way for a woman, who is trying to balance HRT's undisputed abilities to lessen the ills of menopause with other potential ills from the treatment itself, to make a more sound decision?

It was almost enough to make a man (well this man) say hallelujah he was never born a menopause-experiencing, HRT-considering woman.

But the fundamental question all these disagreements raise is whether there is a better way for a woman, who is trying to balance HRT's undisputed abilities to lessen the ills of menopause with other potential ills from the treatment itself, to make a more sound decision?

The issue is beyond complicated.

Not only are there all those contradictory findings, but as Avrum Bluming, a California oncologist and professor of medicine at the University of Southern California, explained to me over the phone, "not all risks are perceived in the same way." Some are, "written in red," says Bluming, who recently co-wrote a review article in The Cancer Journal entitledHormone Replacement Therapy: Real Concerns, False Alarms.

In essence, what you must balance is a potentially fatal disease cancer, heart attack, stroke against an often extremely uncomfortable but generally non-fatal set of ills associated with menopause - hot flashes, sleeplessness, depression, brain fatigue, and so on. The two categories just don't talk to one another in the same language of risk.

The disconnect is compounded by another aspect of the debate. Replacing the hormones the body stops making hasn't only been held up as a way of mitigating the effects of menopause-related conditions effects which can last in some women for decades it has also been touted as a virtual fountain of youth.

Gynecologist Robert Wilson in his 1966 bestseller Forever Young famously talked about HRT allowing women to come "back into the bedroom, back into the kitchen, and back to looking and feeling young." Actress Suzanne Somers promotes a version of the treatment in her book Ageless and talks openly of taking 60 pills a day and injecting hormones into her vagina.

Women have to ask themselves how the allure of at least looking forever young relates to the maybe/could-be/could-not-be risk of breast cancer, heart attack, brain shrinkage or whatever?

I truthfully don't know if the issues will ever be completely resolved, but I do have a suggestion to help women decide what to do. There should be an international statistical effort that takes new findings about HRT, benefits and risks, and assembles them in a way in which they speak as a whole. In an area where 80 per cent of all women going through menopause will have symptoms of the changeover, you don't want medical communication by news headline, contradictory individual studies or Suzanne Somers.

Meta-analysis

You want what is called in science a meta-analysis a compilation of data from all previous studies into one view of the field. But you want it to take place not whenever some random statistician decides a meta-analysis should be done, but as instantaneously as possible. You want it to be a virtual thing, a Google search thing. A woman either considering going on HRT or who is on it already should be able to visit a site to see what the most recent report says about risks and benefits from HRT in general. She should be able to go online and see, as the list which started this column outlines, where newly reported risks fit in with other risks of the same condition.

In order for this to work, the numbers which express risk and benefit have to translate into a graphic which an ordinary, statistically challenged, worried, maybe vain, menopausal woman can easily understand. The 2002 WHI paper formally presents effects of HRT on its study group in the following way:

"Estimated hazard ratios (HRs) (nominal 95 per cent confidence intervals [CIs]) were as follows: CHD, 1.29 (1.02-1.63) with 286 cases; breast cancer, 1.26 (1.00-1.59) with 290 cases; stroke, 1.41 (1.07-1.85) with 212 cases; PE, 2.13 (1.39-3.25) with 101 cases; colorectal cancer, 0.63 (0.43-0.92) with 112 cases; endometrial cancer, 0.83 (0.47-1.47) with 47 cases; hip fracture, 0.66 (0.45-0.98) with 106 cases; and death due to other causes, 0.92 (0.74-1.14) with 331 cases."

Gasp. Can anyone but a statistical god understand what that means?

Trying to be more colloquial, it then said:

"Absolute excess risks per 10,000 person-years attributable to estrogen plus progestin were seven more CHD events, eight more strokes, eight more PEs, and eight more invasive breast cancers, while absolute risk reductions per 10,000 person-years were six fewer colorectal cancers and five fewer hip fractures. The absolute excess risk of events included in the global index was 19 per 10,000 person-years."

Gasp again.

What ordinary people want, I think, and what the menopausal women of the world should be given, is a graph which shows in a personal, visual fashion what could happen if they are given a treatment.

Bluming recently presented his findings at a symposium at Johns Hopkins University in Baltimore on communicating and understanding health benefits and risks. At the same meeting there was much discussion of the concert hall graphic proposed in 2007 by Eric Rifkin and Ed Bouwer. These graphics use filled in chairs in a seating plan to show what happened when you did certain things. You visually get to see something like how many more people in a group of a given number (in this case a concert hall audience) will be dead by age 80 if they smoked, according to statistical predictions.

What's good about the seating plan graphic is that it personalizes risk and benefit. You see representations in the chairs of those who died following smoking and you get a visual feeling for the size of the risk. You see yourself maybe sitting in a chair and get a personalized feel for the consequences of your choices.

This is what we want in medical decision-making when it comes to HRT, and many other things.

In a field where data remains confused, we may never be able to make a truly informed choice, but at the very least we can go away saying: That was a self-affirming guess.