Estrogen and Breast Cancer

In 2002, the Women’s Health Initiative (WHI) sent shockwaves through the media and especially through the menopausal community. This was a study that was stopped early because it seemed to show that “hormone replacement therapy causes breast cancer.” As a result, 70-80% of women who had been taking hormone replacement therapy (HRT) for menopausal symptoms stopped taking it.

The gross misinterpretation of the WHI that has scared women away from taking hormones is perhaps the greatest disservice towards women’s health that has ever been perpetuated. In fact, historically, estrogen replacement for menopausal symptoms has caused exactly ZERO breast cancer deaths.

So let’s talk about what the WHI study really showed. First off, the average age of women in the WHI was 63. So they were being started on HRT approximately 10 years after the menopausal transition. They were much older – and had more underlying health conditions – than our average menopausal woman. Some of the women in the WHI had used HRT for menopausal symptoms previously, and some had not – which you’ll see did make a difference.

The WHI had two groups: one group taking only estrogen, and the other taking estrogen plus a progestin (which is a synthetic form of progesterone, but not the same thing). The estrogen-only group actually showed a 20% lower risk of breast cancer as compared to the placebo (non-hormone) group. It was only the estrogen-plus-progestin group that showed an increased risk, which suggests that the risk is associated with the progestin component, not with the estrogen.

If you dive deeper into the estrogen-plus-progestin group, the effect is small: there was only one extra case of breast cancer per 1,000 patient-years. This risk completely disappeared for the patients who had used HRT prior to the study, or during the menopausal transition.

Subsequently, a 20-year follow-up study of the WHI patients showed that those in the estrogen-only group had a 40% reduction in breast cancer deaths. So the sound byte that “estrogen causes breast cancer” makes no sense. The women who were taken off their estrogen therapy and were made to suffer night sweats and hot flashes shouldn’t have been discontinued from their therapy.

Chlebowski et al 2020: CEE = conjugated equine estrogen, MPA = medroxyprogesteroe acetate (progestin)

If estrogen isn’t the culprit, should we be afraid of progestins? Yes, and no. The progestin used in the WHI was called medroxyprogesterone acetate, or MPA. MPA is no longer used for hormone replacement therapy. It is necessary to give some form of progesterone along with estrogen replacement for most women because estrogen can increase the thickness of a woman’s endometrial lining, predisposing to endometrial cancer. But we don’t use progestins anymore; instead we use bioidentical progesterone. Bioidentical just means that it has an identical chemical structure to the progesterone that women normally make on their own.

So here is a summary of what you should know about menopausal hormone replacement therapy and breast cancer:

• Estrogen replacement therapy given during menopause reduces breast cancer mortality

• Estrogen plus medroxyprogesterone acetate (a progestin) caused a small increased risk in breast cancer due to the progestin component

• Medroxyprogesterone acetate is no longer used for hormone replacement therapy

• The best time to start hormone replacement therapy for menopause is at the onset of symptoms, not 10 years afterwards

I hope that helps clarify some of the confusion and allow you to rest assured that if you are suffering from hot flashes, night sweats, vaginal dryness, and other menopausal symptoms associated with estrogen deficiency, you can have your hormones brought back into balance. But as always, this is not medical advice - please speak with your physician to ensure it is safe for you.

In good health,

Gina

References

Writing Group for the Women’s Health Initiative Investigators. Risks and benefits of estrogen plus progestin in healthy postmenopausal women. JAMA 2002;288(3):321-333.

Anderson et al. Prior hormone therapy and breast cancer risk in the Women’s Health Initiative randomized trial of estrogen plus progestin. Mauritas 2006 Sep 20;55(2):103-15.

Chlebowski et al. Association of menopausal hormone therapy with breast cancer incidence and mortality during long-term follow-up of the Women’s Health Initiative randomized clinical trials. JAMA 2020;324(4):369-380.

“Clearing the air on hormone replacement therapy.” Peter Attia, MD, www.peterattiamd.com