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You feel different when it’s your mum

February 28, 2012

The risks and benefits of HT*

An extraordinary article in this week’s BMJ trying to revive hormone therapy (HT) for post menopausal women. The authors suggest, among other nonsense, that HT reduces overall mortality.

Here’s the rapid response I sent in.

Is this article an advertisement? I note the authors all have links with the HT industry.

The claim of a dramatic reduction in hot flushes fails to mention symptom recurrence when the HT is stopped, and that the largest WHI (Women’s Health Initiative) trial showed no benefit on quality of life.

The graphs appear to have been derived from, and give equal weight to, the largest randomised trial (WHI) and the largest observational study, the Nurses Health Study. If the latter were removed and the other eight randomised trials included, the effect on all cause mortality would be in the opposite direction (odds ratio 1.06; 95% CI 0.94 -1.19) (Sanchez et al. 2005).

For the 51 year old woman with hot sweats, HT provides short term relief. It increases the chance of some diseases, namely cardiovascular disease, strokes and breast cancer and reduces that of others, including osteoporosis, bowel cancer. The exact risk-benefit ratio varies with the woman’s prior risk of each disease but the precision of the estimates is insufficient to allow individualised risk assessments.

When they learn that there is no overall improvement in quality of life, and that in the trials overall mortality was increased, most women wisely decide to live with their hot flushes.

Gabriel Sanchez R, Sanchez Gomez LM, Carmona L, Roqué i Figuls M, Bonfill Cosp X. Hormone replacement therapy for preventing cardiovascular disease in post-menopausal women. Cochrane Database of Systematic Reviews 2005, Issue 2. Art. No.: CD002229. DOI: 10.1002/14651858.CD002229.pub2.

I also mentioned my own conflict of interest. Namely that my mother died of a stroke while taking HT six months before the Women’s Health Initiative trial was suspended because of the increased risk of stroke. But she was a good age and there’s only a small chance that the HT, which she was taking on my advice, killed her.

The important  lesson to take from the observational Nurses Health Study, and the randomised WHI trial is to be sceptical of observational epidemiology.

Jim Thornton

*Hormone replacement therapy (HRT) changed to hormone therapy (HT) Jan 2016

2 Comments leave one →
  1. March 7, 2012 9:25 pm

    Ellen Grant http://www.harmfromhormones/ writes:
    I don’t think it is true that HRT prevents coloractal cancers. WHI paper below.

    Cancer Epidemiol Biomarkers Prev. 2009 May;18(5):1531-7.
    Colorectal cancer in relation to postmenopausal estrogen and estrogen plus progestin in the Women’s Health Initiative clinical trial and observational study.
    Prentice RL, Pettinger M, Beresford SA, Wactawski-Wende J, Hubbell FA, Stefanick ML, Chlebowski RT.

    Colorectal cancer incidence was reduced among women assigned to active treatment in the Women’s Health Initiative (WHI) estrogen plus progestin-randomized trial, but the interpretation was obscured by an associated later stage of diagnosis. In contrast, the estrogen-alone trial showed no incidence reduction or differential stage at diagnosis. Here, data from the WHI observational study are considered, in conjunction with colorectal cancer mortality data from the hormone therapy trials, in an attempt to clarify postmenopausal hormone therapy effects. Participants and
    Postmenopausal women ages 50 to 79 years at WHI enrollment. Estrogen-alone analyses include 21,552 and 10,739 women who were posthysterectomy from the observational study and clinical trial, respectively. Estrogen plus progestin analyses include 32,084 and 16,608 observational study and clinical trial women with uterus. Colorectal cancers were verified by central medical and pathology report review.
    Hazard ratios (95% confidence intervals) from the WHI observational study were 0.80 (0.53-1.20) for estrogen and 1.15 (0.74-1.79) for estrogen plus progestin, with, respectively, 168 and 175 women diagnosed with colorectal cancer. Delayed diagnosis with estrogen plus progestin is not evident in the observational study. No protective effect on colorectal cancer mortality in the estrogen plus progestin trial is seen over an 8-year intervention and follow-up period.
    Hazard ratio patterns in the WHI clinical trial and observational study do not provide strong evidence of a clinically important colorectal cancer benefit with either estrogen-alone or estrogen plus progestin over 7 to 8 years of treatment and follow-up.

  2. March 11, 2012 10:07 am

    I also do not believe that HRT prevents osteoporosis.. Progestins can cause microthrombi in the bones as described in Dr Kitty Little’s book Bone Behaviour. Using progestins alone for contraception increases the risk of osteoporosis, especially in lactating women. We found that women taking HRT were more likely to be deficient in zinc and magnesium and have low levels of bone alkaline phosphatase and higher copper levels. They were also harder to replete to normal levels until they stopped taking hormones. .

    Reference McLaren-Howard J, Grant ECG,Davies S. Hormone replacement therapy and osteoporosis:bone enzymes and nutrient imbalance. bone enzymes and nutrient imbalance.
    J Nutr Environ Med.1998;8:129-138.

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