Intended for healthcare professionals

Rapid response to:

Practice Therapeutics

Hormone replacement therapy

BMJ 2012; 344 doi: (Published 16 February 2012) Cite this as: BMJ 2012;344:e763

Rapid Response:

Re: Hormone replacement therapy

In her BMJ podcast about HRT, Martha Hickey makes it clear that she thinks the WHI and MWS results have been “unpicked” and HRT can be a safe option for some women.1 Professor Klim McPherson has described such arguments as ridiculous.2 Important trials were stopped prematurely because of increases in cancers and vascular diseases – if they had been continued the results would have been worse. So why is HRT still being promoted?

Professor Jim Thornton, a former President of the Royal College of Obstetrics and Gynaecologists, notes that Hickey and colleagues have drug company interests; the effect on mortality from all causes is in the opposite direction when only randomised trials are included; and many women get withdrawal hot flushes on stopping HRT.3

Progestogens and oestrogens can be addictive and difficult to stop.4 Former GP Margaret White wrote, “the menopause nature gave me was fine but the one that Premarin gave me was hell!” HRT is also a major cause of mental illness with an increased risk of suicide.5

It is no longer believed that HRT prevents colorectal cancer with no benefit from either estrogen-alone or estrogen plus progestogen in the WHI clinical trial and observational study after 7 to 8 years of intervention and follow-up.6 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 progestogen. Also there was no protective effect on colorectal mortality.

The bad effects of using progestogens and oestrogens are overwhelming:-

Doubling of mortality from breast cancer 7

Doubling of mortality from ovarian cancer 8

Doubling of mortality from lung cancer 9

Doubling of deaths from suicide and suspected suicide 5

Doubling of cervical adenocarcinomas 10

4-5 fold increase in invasive cervical cancers 11

5 fold increase in endometrial cancer (oestrogens) 12

Doubling (or up to 6 times) of primary venous thrombosis 13

81% increase in myocardial infarctions (at one year) 14

44 -55% increase in ischemic strokes 15,16

Doubling (or up to 5 times) increases in migraine headaches and vascular over-reactivity 17,18

Increases in osteoporosis due to micro-thrombi in bones, mineral deficiencies, and decreases in serum bone alkaline phosphatase 19,20

HRT has been a health disaster for too long.

1. Hickey M, Elliot J, Davison SL. Hormone replacement therapy. BMJ 2012;344:e763

2 Kmietowicz Z. Articles disputing link between HRT and breast cancer are “ridiculous”. BMJ 2012; 344:e513.

3 Thornton JG. Re: Hormone replacement therapy. BMJ 18 February 2012

4 White M, Grant ECG. Addiction to oestrogen and progesterone. J Nutr Environ Med 1998; 8:117-120.

5 Price EH. Increased risk of mental illness and suicide in oral contraceptive and hormone replacement therapy in studies. J Nutr Environ Med 1998; 8:121-127.

6 Prentice RL, Pettinger M, Beresford SA, et al. Colorectal cancer in relation to postmenopausal estrogen and estrogen plus progestin in the Women's Health Initiative clinical trial and observational study. Cancer Epidemiol Biomarkers Prev 2009;18:1531-7.

7 Chlebowski RT, Anderson GL, Gass M, et al; WHI Investigators. Estrogen plus progestin and breast cancer incidence and mortality in postmenopausal women. JAMA 2010;304:1684-92.

8 Beral V, Bull D, Green J, Reeves G for the Million Women Study Collaborators. Ovarian cancer and hormone replacement therapy in the Million Women Study. Lancet 2007;369:1703-1710.

9 Chlebowski RT, Schwartz AG, Wakelee H, et al; Women's Health Initiative Investigators. Oestrogen plus progestin and lung cancer in postmenopausal women (Women's Health Initiative trial): a post-hoc analysis of a randomised controlled trial. Lancet 2009;374:1243-51.

10 J Green, A Berrington de Gonzalez, et al.. Risk factors for adenocarcinoma and squamous cell carcinoma of the cervix in women aged 20–44 years: the UK National Case–Control Study of Cervical Cancer. Br J Cancer 2003; 89: 2078–2086.

11 Zondervan KT, Carpenter LM, Painter R, Vessey MP. Oral contraceptives and cervical cancer--further findings from the Oxford Family Planning Association contraceptive study. Br J Cancer 1996;73:1291-7.

12 Persson I, Yuen J, Bergkvist L, Schairer C. Cancer incidence and mortality in women receiving estrogen and estrogen-progestin replacement therapy--long-term follow-up of a Swedish cohort. Int J Cancer. 1996;67:327-32.

13 Daly E, Vessey MP, Hawkins MM, et al. Risk of venous thromboembolism in users of hormone replacement therapy. Lancet 1996; 348:977-80.

14 Manson JE, Hsia J, Johnson KC, et al; Women's Health Initiative Investigators. Estrogen plus progestin and the risk of coronary heart disease. N Engl J Med 2003;349:523-34.

15 Hendrix SL, Wassertheil-Smoller S, Johnson KC, et al; WHI Investigators. Effects of conjugated equine estrogen on stroke in the Women's Health Initiative. Circulation 2006;113:2425-34.

16 Wassertheil-Smoller S, Hendrix SL, Limacher M, et al; WHI Investigators. Effect of estrogen plus progestin on stroke in postmenopausal women: the Women's Health Initiative: a randomized trial. JAMA 2003;289:2673-84.

17 Grant ECG. Relation between headaches from oral contraceptives and development of endometrial arterioles. BMJ 1968;3:402-05.

18 Grant ECG. The pill, hormone replacement therapy, vascular and mood over-reactivity and mineral imbalance. J Nutr Environ Med 1998;8:105-116.

19 Little K. Progestogens:thrombosis and osteoporosis. J Nutr Environ Med 1998;8:139-52.

20 McLaren-Howard J, Grant ECG, Davies S. Hormone replacement therapy and osteoporosis: bone enzymes and nutrient imbalance. J Nutr Environ Med 1998;8:129-38.

Competing interests: No competing interests

13 March 2012
Ellen CG Grant
Physician and medical gynecologist
Kingston Upon Thames, KT2 7JU