Intended for healthcare professionals

Rapid response to:


Which drugs should be available over the counter?

BMJ 2004; 329 doi: (Published 22 July 2004) Cite this as: BMJ 2004;329:182

Rapid Response:

Levonorgestrel is hazardous

Editor- Your Editorial author Robert Fenichel has served as a
consultant to a large number of drug companies, some of whom manufactured
synthetic progesterones.1 He says none of them have made the
levonorgestrel preparation which was rejected by the FDA as an “over the
counter” drug. He mentions Schering which made Anovlar, the first
synthetic progesterone we tested in 1962. Anovlar contained norethisterone
acetate. Like all progesterone dominant preparations, side-effects
included severe migraine, clotting and mood changes.2,3 Micronised
levonorgestrel is about ten times more powerfully progestogenic than
norethisterone acetate. Schering have produced a variety of products
containing levonorgestrel, such as Microgynon, Eugynon, Neogest, Logynon
and Norgeston and an emergency contraceptive pill containing

Where has Dr Fenichel been? Has he missed the studies finding that
progesterones are more powerful breast carcinogens than oestrogens?
Progesterones are among the most immunosuppressive, teratogenic and
carcinogenic drugs in existence. How can he possibly claim therefore that
the medical hazards of levonorgestrel are minimal? I attach my previous
Rapid Response the BMJ news item on this subject4 as a reminder of the
serious implications of exposures to progesterones seems to be needed for

1 Feichel RR. Which drugs should be available over the counter? BMJ
2004;329:182-183 (24 July), doi:10.1136/bmj.329.7459.182

2 Mears E, Grant ECG. "Anovlar" as an oral contraceptive. BMJ 1962;
2: 75-79.

3 Changing oral contraceptives. BMJ 1969;4:789-91 & Today's
Drugs (Grant ECG).

4 Grant ECG Progesterone emergency contraception, 23 May 2004

“Janis Hopkins Tanne reports that the rejection by the FDA of over
counter status for high dose synthetic progesterone emergency
contraception has aroused outrage.1 Are there not sound medical reasons
for the FDA's decision? The incidence of underage pregnancies world-wide,
like the diagnosis of breast cancer, appears to have increased with
increasing promotion of hormones. The USA and the UK have high incidences
of both.

Progesterone is strongly immuno-suppressive and carcinogenic. It
promotes growth in breast glands, ducts and blood vessels in untreated
luteal cycles and when women are exposed to exogenous hormones. Several
studies including the Million Women Study, the Women's Health Initiative
Study and the Nurses Study found progesterones increased the risk of
invasive, metastatic breast cancer more than estrogens given alone. The
risk increases with repeated or longer use for different reasons, whether
for contraception or menopausal symptoms.

Haiyhan Pang and colleagues write that progesterone may play a direct
role in breast cancer invasion and metastasis.2 While the effects of
progesterone on cell cycle progression are well known, its role in
spreading and adhesion of breast cancer cells is now receiving attention.
Cell adhesion protein desmoplakin is upregulated by progesterone – a
process that is suppressed by epidermal growth factor. This appears to be
a general but not universal effect in breast cancer cell lines.
Randomised trials of HRT have been stopped and older women are being
warned not to use hormones because of the unacceptably high risks of
invasive and metastatic cancer and vascular diseases.

It is unfair to subject teenagers to the dangers of life long
autoimmune diseases, such as systemic lupus erythematosus and anti-
phosphlipid syndome and increased risks of several cancers. Any use of
contraceptive hormones in the previous 20 years doubled the number of
breast cancers with over expression of cyclin-D in young women.3
The FDA has made a rational medical decision. Randomised hormone trials
have confirmed unacceptable risks for older women but the possible
deleterious long-term effects of repeated, large dose hormone exposures on
reproduction, and future health, are greatest for younger women.

1 Tanne JH. FDA rejects over the counter status for emergency
contraceptive. BMJ 2004; 328: 1219.

2 Pang H, Brian G Rowan, Mariam Al-Dhaheri and Lee E Faber. Epidermal
growth factor suppresses induction by progestin of the adhesion protein
desmoplakin in T47D breast cancer cells. Breast Cancer Research 2004,

3 Terry MB, Gammon MD, Schoenberg JB, Brinton LA, Arber N, Hibshoosh
H. Oral Contraceptive Use and Cyclin D1 over expression in Breast Cancer
among Young Women. Cancer Epidemiol Biomarkers Prev, 2002;11: 1100-1103.

Competing interests:
Tested oral contraceptives for the Council for the Investigation of Fertility Control in the 1960s

Competing interests: No competing interests

15 August 2004
Ellen C G Grant
physician and medical gynaecologist
20 Coomeb Ridings, Kingston-upon-Thames, KT2 7Ju, UK