#42–Avrum Bluming, M.D. and Carol Tavris, Ph.D.: A compelling case for hormone replacement therapy

KEYPOINTS

• 01

  Estrogen Matters argues that women have been wrongly denied HRT

  Oncologist Avrum Bluming and social psychologist Carol Tavris wrote Estrogen Matters, building on their 2009 review. They argue that the belief that estrogen causes breast cancer has kept women off hormone replacement therapy for about 30 years, especially since 2002. Attia frames the episode as a story of bad science rather than a blanket endorsement. Not every woman needs HRT, and the clinical task is identifying who benefits most and for whom the risks outweigh the benefits.

• 02

  Uterine cancer scare, then the fix

  Premarin (named for pregnant mare urine) was cheap to make and remains the dominant US estrogen. In the early 1970s, estrogen alone was found to raise uterine cancer risk up to about fivefold, and prescriptions fell sharply. By the late 1970s, adding a progestogen, cyclically or continuously, was shown to cancel that risk, and use climbed again. A 1991 NEJM article by Goldman and Tosteson said it was 'time for action, not debate'.

• 03

  The Women's Health Initiative enrolled the wrong population

  About 16 million US women, roughly 22% of those of eligible age, used HRT in 2002. WHI participants averaged 63, about a decade past menopause. Around 70% were overweight or obese, and many smoked or had hypertension. Older women were chosen so heart events would show up sooner and cost less. Women with significant hot flashes were excluded for fear they would drop out of the placebo arm. Yet the results were 'immediately extrapolated to all women everywhere'.

• 04

  The breast-cancer finding was small and not significant

  The reported 26% relative increase (hazard ratio about 1.26, later 1.24) 'almost reached nominal statistical significance'. In absolute terms, Bluming calculates it as about 0.9 extra cases per 1,000 women, under 1%. By 2006 a follow-up reported that the increased risk in that population had disappeared. Bluming and Tavris also note the WHI's leader had published 'time to bring the HRT bandwagon to a halt' beforehand. Tavris calls it confirmation bias, not a conspiracy.

• 05

  A 50–70% collapse in HRT use followed

  By 2004, use had fallen from 22% to about 10%. Bluming and Tavris cite one estimate that about 50,000 women died prematurely of heart disease after stopping HRT in the years after 2002. That figure is a modelled estimate and is contested.

• 06

  The heart-disease window matters

  Women who start within about 10 years of menopause, without existing cardiovascular disease, are a very different group from the WHI's 63-year-olds with existing risk factors. Attia's example is a healthy 60-year-old who went through menopause at 50 and has no evidence of heart disease.

• 07

  Bones, brain and colon

  Bluming says estrogen can reduce hip fracture risk by up to 50%, better than any long-term alternative. About 21% of women who fracture a hip die within a year, roughly 40,000 a year, similar to US breast-cancer deaths. Studies, including the Nurses' Health Study, show about 20–25% less colon cancer. He says estrogen may cut Alzheimer's incidence by 20–50% depending on the study. The authors say animal, lab, field and randomised studies all point the same way on cognition.

• 08

  Breast-cancer survivors are a contested group

  Bluming points to his own small 14-year study, which reported results yearly and fit alongside 14 others in showing no increased local recurrence, contralateral cancer or distant recurrence in survivors who took hormones. He notes that as early as 1944 researchers reported about a 25% response rate treating breast cancer with high-dose estrogen. He also notes progesterone did slightly better than tamoxifen in an early 1970s randomised trial. His position remains contested.