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Rapid response to:


Hormone replacement therapy

BMJ 2002; 325 doi: (Published 20 July 2002) Cite this as: BMJ 2002;325:113

Rapid Response:

Cancer and Hormone replacement therapy

Stevenson and Whitehead’s BMJ Editorial

Hormone replacement therapy

EDITOR - The Editorial by Stevenson and Whitehead minimises the
importance of the WHI Study’s results.1,2 The surprise is not that
progesterone causes breast cancer but that progestogens have been
prescribed to millions of women for the last 40 years. Bilateral
oophorectomy has been a treatment and preventative of premenopausal breast
cancer since1896. 3 Progesterone causes breast and ovarian cancer in mice
and dogs.4 Progestogens are breast carcinogens because they act
predominantly like progesterone.

Medroxyprogesterone acetate is mostly used for HRT in the USA, while
norgestrel derivatives or norethisterone (norethindrone) are used for
contraception in the USA and for both contraception and HRT in the UK.
Medroxyprogesterone acetate (MPA) is a third less powerful than
norethisterone, while levonorgestrel is five times more powerful.5,6
Weaker progestogens, like MPA, are given in higher doses and vice versa.
In most studies scarcity of genuine “never” users of any type of hormone
helps to minimise incidence and mortality risk estimates for all adverse

Most women in the WHI study had previously used contraceptive or
menopausal hormones. They were re-enrolled for at least 3.5 years and 42%
of takers discontinued HRT before the study was halted. Median length of
use was not given but the risk estimates nearly doubled when nonadherence
was taken into account. The study is therefore most useful for showing
that current use increases the main causes of death, namely: breast
cancer, coronary artery disease, strokes and pulmonary emboli. The study
was stopped prematurely to prevent the inevitable increases in mortality
with further HRT exposures.

Dr Ellen C G Grant
20 Coombe Ridings,
Surrey KT2 7JU


1.Stevenson JC, Whitehead MI. Hormone replacement therapy. BMJ

2. Writing Group for the Women’s Health Initiative Investigators. Risks
and benefits of estrogen plus progestin in healthy postmenopausal women:
principal results from the Women’s Health Initiative randomised controlled
trial. JAMA 2002; 288: 321-33.

3. Beatson G T. On the treatment of inoperable cases of carcinoma of the
mamma. Suggestions for a new method of treatment with illustrative cases.
Lancet 1896;ii:104-107.

4.Li JJ Perspectives in hormonal carcinogensis. In Cellular and Molecular
Mechanisms of Hormonal Carcinogenesis: Enviromental influences. Ed. James
Huff, Jeff Boyd, J.Carl Barrett 1996 Wiley-Liss Inc.

5. Grant ECG. The Hormone Balance of Oral Contraceptives. The Journal
of Obstetrics and Gynaecology of the British Commonwealth 1967; 74: 908-
6. Swyer GIM, Little V. Potency of progestogens and oral contraceptives:
Further delay-of-menses data. Contraception.1982;26;23.

Competing interests: No competing interests

24 July 2002
E.C.G. Grant
Physycian and medical gyaecologist
20 Coombe Ridings, Kingston-upon-Thames, Surrey, KT2 7JU