Adding nuance to hormone therapy risks

Apr 6, 2011

Whether or not to take hormones has become one of life’s difficult choices as women face menopause, and look for ways to relieve the symptoms. A new study suggests women may be able to minimize the risks if they start in their 50’s.

It also shows negative effects appear more common for women if they take estrogen after age 60.

It's unlikely, however, that this one study will end the hormone debate.

Two types of hormone therapy

The research comes out of the Women’s Health Initiative, based at Seattle’s Fred Hutchinson Cancer Research Center, which included two groups:

  • Combined hormone therapy, typically using estrogen and progestin, a synthetic form of progesterone.
  • Estrogen-only therapy,  for women who’ve had a hysterectomy, which is when the uterus is removed.   

The latest follow-up study, published this week in the Journal of the American Medical Association, applies to the hysterectomy group, who took estrogen alone for about 3-4 years and then stopped. 

Huge numbers of women have had hysterectomies. A quarter to a third of all women in their 50’s … and nearly half of all women by age 70.

Hormone replacement was a standard therapy until about nine years ago. That’s when results first came in from the Women’s Health Initiative (WHI).

Andrea LaCroix, an epidemiologist at the Hutch and the U.W. and co-leader of the WHI, says she was a young mother when the project first launched in the early 1990's.

"I was looking forward to having some good information when I got to the other side of menopause about hormone therapy," she says. "We really expected the news to be very good based on observational studies ... at the time."

Problems or benefits

By the time she reached menopause, the evidence was in, from more than 11,000 participating women -- and LaCroix decided not to take the pills. Hormone replacement had serious side effects. For some women it elevated their risk of heart attack and stroke. The study was stopped, early, because it looked like the risks outweighed the potential benefits.

Now that the women have been studied for what happens if they stop taking the hormones, LaCroix says women in both groups found the negative effects quickly went away.

But she was surprised to find minimal risks for women who start taking estrogen-only immediately at menopause. The data showed a clear difference by age.

"It means the overall picture around safety is reassuring for women in their 50's who want to try estrogen-only hormone replacement for hot flashes," she says, and quotes from her own article. "Our results emphasize the need to counsel women about hormone therapy differently depending on their age and hysterectomy status."

An earlier study looking at the combined-hormone group found no differences by age.

The last word?

LaCroix and her co-authors say their evidence is strong, because of the number of women in the WHI study and the way they included an equal number of women receiving placebo pills.

Still, a companion article in the same issue of the Journal of the American Medical Association, responding to the estrogen-only study, offers cautions for women in their 50's. The authors, Emily Jungheim and Graham Colditz of Washington University in St. Louis,  point out that all previous studies had shown a higher potential risk of breast cancer for women taking estrogen in their 50's. Even if those earlier studies had limitations, they suggest, the data on breast cancer may need more scrutiny.

Since the full article is behind a pay-wall, here's a fairly long (and technical) quote:

"Continued surveillance of long-term [hormone-therapy] users is necessary to refine the assessment of risks and benefits among women who choose to continue therapy beyond 5 years. The lack of an adverse effect of unopposed estrogen when used for a short period in the WHI does not counter the larger body of evidence of an elevated risk of breast cancer with increasing duration of use, the greater adverse effect among leaner women, and randomized controlled trial evidence that estrogen agonist/antagonists
(eg, tamoxifen) reduce the incidence of estrogen receptor–positive breast cancer by more than 50%."

LaCroix agrees this finding needs more study, but she expects her results to stand up.

Some doctors are bigger fans than others of hormone replacement therapy. One place to find an overview about hormones and menopause is at the National Cancer Institute website.